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Sample records for osteopontin opn levels

  1. Osteopontin (OPN) as a CSF and blood biomarker for multiple sclerosis: A systematic review and meta-analysis.

    Science.gov (United States)

    Agah, Elmira; Zardoui, Arshia; Saghazadeh, Amene; Ahmadi, Mona; Tafakhori, Abbas; Rezaei, Nima

    2018-01-01

    Identifying a reliable biomarker may accelerate diagnosis of multiple sclerosis (MS) and lead to early management of the disease. Accumulating evidence suggest that cerebrospinal fluid (CSF) and peripheral blood concentration of osteopontin (OPN) may have diagnostic and prognostic value in MS. We conducted a systematic review and meta-analysis of studies that measured peripheral blood and CSF levels of OPN in MS patients and controls to evaluate the diagnostic potential of this biomarker better. We searched PubMed, Web of Science and Scopus databases to find articles that measured OPN concentration in peripheral blood and CSF samples from MS patients up to October 19, 2016. Q statistic tests and the I2 index were applied for heterogeneity assessment. If the I2 index was less than 40%, the fixed-effects model was used for meta-analysis. Random-effects meta-analysis was chosen if the I2 value was greater than 40%. After removal of duplicates, 918 articles were identified, and 27 of them fulfilled the inclusion criteria. We included 22 eligible studies in the final meta-analysis. MS patients, in general, had considerably higher levels of OPN in their CSF and blood when compared to all types of controls (pCSF of MS subgroups (pCSF concentrations of OPN between MS patient subtypes. CIS patients had significantly lower levels of OPN both in their peripheral blood and CSF compared to patients with progressive subtypes of MS (pCSF concentration of OPN was significantly higher among RRMS patients compared to the CIS patients and SPMS patients (PCSF compared to patients with stable disease (P = 0.007). The result of this study confirms that increased levels of OPN exist in CSF and peripheral blood of MS patients and strengthens the evidence regarding the clinical utility of OPN as a promising and validated biomarker for MS.

  2. Association between Serum Osteopontin Levels and Cardiovascular Risk in Hypothyrodism

    OpenAIRE

    Türkan Mete; Gülhan Duman; Eda Melek Ertörer; Emre Bozkırlı; Okan Sefa Bakıner; Neslihan Başçıl Tütüncü

    2016-01-01

    Purpose: Cardiovascular effects of hypothyroidism are well known. Osteopontin (OPN) is a new inflammatory marker which was first isolated from the bone. Flow-mediated dilatation (FMD), a noninvasive technique to measure this endothelium-dependent function, has been used in several clinical studies to show cardiovascular risks. The aim of our study was to assess FMD value in hypothyroidism patients and to investigate whether plasma OPN level is a parameter which can predict cardiovascular risk...

  3. Osteopontin (OPN is an important protein to mediate improvements in the biocompatibility of C ion-implanted silicone rubber.

    Directory of Open Access Journals (Sweden)

    Shao-liang Wang

    Full Text Available Medical device implants are drawing increasing amounts of interest from modern medical practitioners. However, this attention is not evenly spread across all such devices; most of these implantable devices can cause adverse reactions such as inflammation, fibrosis, thrombosis, and infection. In this work, the biocompatibility of silicone rubber (SR was improved through carbon (C ion implantation. Scanning electron microscopy (SEM, atomic force microscopy (AFM, X-ray photoelectron spectroscopy (XPS, and X-ray diffraction (XRD results confirmed that these newly generated carbon-implanted silicone rubbers (C-SRs had large, irregular peaks and deep valleys on their surfaces. The water contact angle of the SR surface decreased significantly after C ion implantation. C ion implantation also changed the surface charge distribution, silicone oxygen rate, and chemical-element distribution of SR to favor cell attachment. The dermal fibroblasts cultured on the surface C-SR grew faster and showed more typical fibroblastic shapes. The expression levels of major adhesion proteins, including talin-1, zyxin, and vinculin, were significantly higher in dermal fibroblasts cultured on C-SR coated plates than in dermal fibroblasts cultured on SR. Those same dermal fibroblasts on C-SRs showed more pronounced adhesion and migration abilities. Osteopontin (OPN, a critical extracellular matrix (ECM protein, was up-regulated and secreted from dermal fibroblasts cultured on C-SR. Matrix metalloproteinase-9 (MMP-9 activity was also increased. These cells were highly mobile and were able to adhere to surfaces, but these abilities were inhibited by the monoclonal antibody against OPN, or by shRNA-mediated MMP-9 knockdown. Together, these results suggest that C ion implantation significantly improves SR biocompatibility, and that OPN is important to promote cell adhesion to the C-SR surface.

  4. Blocking the expression of both bone sialoprotein (BSP) and osteopontin (OPN) impairs the anabolic action of PTH in mouse calvaria bone.

    Science.gov (United States)

    Bouleftour, Wafa; Bouet, Guenaelle; Granito, Renata Neves; Thomas, Mireille; Linossier, Marie-Thérèse; Vanden-Bossche, Arnaud; Aubin, Jane E; Lafage-Proust, Marie-Hélène; Vico, Laurence; Malaval, Luc

    2015-03-01

    Osteopontin (OPN) and bone sialoprotein (BSP) are coexpressed in osteoblasts and osteoclasts, and display overlapping properties. We used daily injection of parathyroid hormone 1-84 (iPTH) over the calvaria of BSP knockout (-/-) mice to investigate further their functional specificity and redundancy. iPTH stimulated bone formation in both +/+ and -/- mice, increasing to the same degree periosteum, osteoid and total bone thickness. Expression of OPN, osterix, osteocalcin (OCN) and DMP1 was also increased by iPTH in both genotypes. In contrast to +/+, calvaria cell cultures from -/- mice revealed few osteoblast colonies, no mineralization and little expression of OCN, MEPE or DMP1. In contrast, OPN levels were 5× higher in -/- versus +/+ cultures. iPTH increased alkaline phosphatase (ALP) activity in cell cultures of both genotypes, with higher OCN and the induction of mineralization in -/- cultures. siRNA blocking of OPN expression did not alter the anabolic action of the hormone in BSP +/+ calvaria, while it blunted iPTH effects in -/- mice, reduced to a modest increase in periosteum thickness. In -/- (not +/+) cell cultures, siOPN blocked the stimulation by iPTH of ALP activity and OCN expression, as well as the induction of mineralization. Thus, full expression of either OPN or BSP is necessary for the anabolic effect of PTH at least in the ectopic calvaria injection model. This suggests that OPN may compensate for the lack of BSP in the response to this hormonal challenge, and provides evidence of functional overlap between these cognate proteins. © 2014 Wiley Periodicals, Inc., A Wiley Company.

  5. Osteopontin and splice variant expression level in human malignant glioma: Radiobiologic effects and prognosis after radiotherapy

    International Nuclear Information System (INIS)

    Güttler, Antje; Giebler, Maria; Cuno, Peter; Wichmann, Henri; Keßler, Jacqueline; Ostheimer, Christian; Söling, Ariane; Strauss, Christian; Illert, Jörg; Kappler, Matthias; Vordermark, Dirk; Bache, Matthias

    2013-01-01

    Background and purpose: We investigated the role of the hypoxia-associated secreted glycoprotein osteopontin (OPN) in the response of malignant glioma to radiotherapy by characterizing OPN and its splice variants in vitro and in patient material. Material and methods: The effect of siRNA knockdown of OPN splice variants on cellular and radiobiologic behavior was analyzed in U251MG cells using OpnS siRNA (inhibition of all OPN splice variants) and OpnAC siRNA (knockdown only of OPNa and OPNc). OPN and splice variant mRNA levels were quantified in archival material of 41 glioblastoma tumor samples. Plasma OPN was prospectively measured in 33 malignant glioma patients. Results: Inhibition of OPNa and OPNc (OpnAC) reduced clonogenic survival in U251MG cells but did not affect proliferation, migration or apoptosis. Knockdown of all OPN splice variants (OpnS) resulted in an even stronger inhibition of clonogenic survival, while cell proliferation and migration were reduced and rate of apoptosis was increased. Additional irradiation had additive effects with both siRNAs. Plasma OPN increased continuously in malignant glioma patients and was associated with poor survival. Conclusions: OPNb is partially able to compensate the effects of OPNa and OPNc knockdown in U251MG cells. High OPN plasma levels at the end of radiotherapy are associated with poor survival

  6. cDNA cloning, mRNA distribution and heterogeneity, chromosomal location, and RFLP analysis of human osteopontin (OPN)

    DEFF Research Database (Denmark)

    Young, M F; Kerr, J M; Termine, J D

    1990-01-01

    A human osteopontin (OP) cDNA was isolated from a library made from primary cultures of human bone cells. The distribution of osteopontin mRNA in human tissues was investigated by Northern analysis and showed that the human message was predominant in cultures of bone cells and in decidua cells...... osteopontin cDNA indicated that the gene is a single copy with an approximate length of 5.4-8.2 kb....

  7. [ORMDL3 polymorphisms and their relationship with OPN and TGF-β1 levels in children with asthma in Hunan, China: an analysis of 98 cases].

    Science.gov (United States)

    Yang, Ai-Mei; Huang, Rong; Jin, Shi-Jie

    2016-04-01

    To investigate ORMDL3 polymorphisms in children with asthma in Hunan, China, and to determine the relationship between ORMDL3 polymorphisms and serum osteopontin (OPN) and transforming growth factor-β1 (TGF-β1) levels. Peripheral blood samples were collected in children with asthma (n=98; astma group) or without asthma (n=30; control group) from Hunan, China. The asthma group was subdivided into atopic (n=62) and non-atopic (n=36) subgroups. Single nucleotide polymorphism (SNP) analysis was performed, and serum OPN and TGF-β1 levels were measured. There were no significant differences in genotype and allele frequencies of rs7216389 of the ORMDL3 gene between the asthma and control groups. The serum level of OPN in the asthma group was significantly higher than in the control group (P<0.05). Both the atopic and non-atopic subgroups showed increased serum levels of OPN compared with the control group (P<0.05). The serum level of TGF-β1 in the atopic subgroup was significantly higher than in the control group (P<0.05). The serum levels of OPN and TGF-β1 showed no significant differences in asthmatic children with different genotypes. The serum levels of OPN and TGF-β1 were in a positive linear correlation in the asthma group (r=0.620; P<0.01) and its two subgroups (r=0.734, 0.649 respectively; P<0.01). In children from Hunan, China, the SNP (rs7216389) of ORMDL3 is not related to asthma susceptibility. OPN and TGF-β1 may be involved in the development of asthma, and they are in a positive linear correlation. The SNP (rs7216389) of ORMDL3 does not influence the expression of OPN and TGF-β1, suggesting that it may not be associated with airway remodeling.

  8. Evaluation of serum osteopontin level and gene polymorphism as biomarkers

    DEFF Research Database (Denmark)

    Prasmickaite, Lina; Berge, Gisle; Bettum, Ingrid J

    2015-01-01

    samples from 275 high-risk melanoma patients enrolled in the Nordic Adjuvant IFN Melanoma trial were analyzed for circulating OPN concentrations and OPN promoter polymorphisms in position -443. The potential relation between serum OPN levels, the genotypes and survival in non-treated patients and patients...... receiving adjuvant IFN-α was investigated. Although slightly better survival was observed in the treated patients that had high levels of OPN, the difference was not statistically significant. In conclusion, serum OPN (its level or the genotype) cannot distinguish melanoma patients with poor prognosis...

  9. Relationship between radiobiological hypoxia in a C3H mouse mammary carcinoma and osteopontin levels in mouse serum

    DEFF Research Database (Denmark)

    Lukácová, Slávka; Khalil, Azza Ahmed; Overgaard, Jens

    2005-01-01

    To investigate the possible relationship between radiobiological hypoxia in a C3H mouse mammary carcinoma and osteopontin (OPN) levels measured in mouse serum. MATERIAL AND METHODS: Experiments were performed in CDF1 mice that were either non-tumour bearing or with different sized tumours implanted...... in the right rear foot. Osteopontin levels in extracted mouse blood serum and tissue from the transplanted tumours were measured using an ELISA assay. The tumour oxygenation status was estimated using the Eppendorf Histograph and the fraction of oxygen partial pressure (pO2) values =5 mm Hg (HF5...

  10. Levels of matrix metalloproteinase-7 and osteopontin in human gingival crevicular fluid during initial tooth movement

    Directory of Open Access Journals (Sweden)

    Dhaval Oswal

    2015-01-01

    Full Text Available Purpose: During orthodontic treatment, the early response of periodontal tissues to mechanical stress involves several metabolic changes that allow tooth movement. The purpose of this investigation was to evaluate osteopontin (OPN and matrix metalloproteinase (MMP-7 in the gingival crevicular fluid (GCF of human teeth exposed to orthodontic force. Materials and Methods: GCF samples were obtained from 15 healthy orthodontic patients (age, 12-22 years. In each patient, the left maxillary canine having the fixed orthodontic appliance was used as the test tooth, and its antagonist, with no appliance, was the control. Orthodontic force, 75 g was applied using a 16 × 22 beta titanium closing loop. The GCF sampling on the disto-buccal aspects of experimental and control tooth was performed at specific time interval with sterilized absorbent paper point. Processing was carried out with enzyme-linked immunosorbent assay to detect OPN and MMP-7 levels. Results: The peak level of OPN was seen after 1 h application of orthodontic force which was 1280.36 pg/ml ± 185.02. The peak level of MMP-7 was seen at 0 h which was 598.3 pg/ml ± 107.5. The levels of OPN after 1 h increased to 1280.36 pg/ml ± 185.02, and they decreased at 24 h to 1012.86 pg/ml ± 168.47 (P = 0.001. The levels of MMP-7 after 1 h decreased to 478 pg/ml ± 99.7 which increased at 24 h to 526.9 pg/ml ± 99.2. Conclusions: Orthodontic forces affect both OPN and MMP-7 protein levels on the compression side in a time-dependent fashion.

  11. Deletion of PTH rescues skeletal abnormalities and high osteopontin levels in Klotho-/- mice.

    Directory of Open Access Journals (Sweden)

    Quan Yuan

    Full Text Available Maintenance of normal mineral ion homeostasis is crucial for many biological activities, including proper mineralization of the skeleton. Parathyroid hormone (PTH, Klotho, and FGF23 have been shown to act as key regulators of serum calcium and phosphate homeostasis through a complex feedback mechanism. The phenotypes of Fgf23(-/- and Klotho(-/- (Kl(-/- mice are very similar and include hypercalcemia, hyperphosphatemia, hypervitaminosis D, suppressed PTH levels, and severe osteomalacia/osteoidosis. We recently reported that complete ablation of PTH from Fgf23(-/- mice ameliorated the phenotype in Fgf23(-/-/PTH(-/- mice by suppressing serum vitamin D and calcium levels. The severe osteomalacia in Fgf23(-/- mice, however, persisted, suggesting that a different mechanism is responsible for this mineralization defect. In the current study, we demonstrate that deletion of PTH from Kl(-/- (Kl(-/-/PTH(-/- or DKO mice corrects the abnormal skeletal phenotype. Bone turnover markers are restored to wild-type levels; and, more importantly, the skeletal mineralization defect is completely rescued in Kl(-/-/PTH(-/- mice. Interestingly, the correction of the osteomalacia is accompanied by a reduction in the high levels of osteopontin (Opn in bone and serum. Such a reduction in Opn levels could not be observed in Fgf23(-/-/PTH(-/- mice, and these mice showed sustained osteomalacia. This significant in vivo finding is corroborated by in vitro studies using calvarial osteoblast cultures that show normalized Opn expression and rescued mineralization in Kl(-/-/PTH(-/- mice. Moreover, continuous PTH infusion of Kl(-/- mice significantly increased Opn levels and osteoid volume, and decreased trabecular bone volume. In summary, our results demonstrate for the first time that PTH directly impacts the mineralization disorders and skeletal deformities of Kl(-/-, but not of Fgf23(-/- mice, possibly by regulating Opn expression. These are significant new perceptions into

  12. Plasma osteopontin levels in patients with head and neck cancer and cervix cancer are critically dependent on the choice of ELISA system

    International Nuclear Information System (INIS)

    Vordermark, Dirk; Said, Harun M; Katzer, Astrid; Kuhnt, Thomas; Hänsgen, Gabriele; Dunst, Jürgen; Flentje, Michael; Bache, Matthias

    2006-01-01

    The tumor-associated glycoprotein osteopontin (OPN) is discussed as a plasma surrogate marker of tumor hypoxia and as an indicator of the presence of pleural mesothelioma in asbestos-exposed individuals. The clinical introduction of plasma OPN measurements requires the availability of a reliable enzyme-linked immunosorbence assay (ELISA). We compared previously described and currently available ELISA systems on 88 archival plasma samples obtained from patients with head and neck or cervix cancer between 20 days before and 171 after the start of radiotherapy. Median (range) plasma OPN levels were 667 (148.8–2095) ng/ml and 9.8 (3.5–189.5) ng/ml for a previously described and a newly marketed assay, respectively. Although results for different assays were significantly correlated (r = 0.38, p < 0.05, Spearman rank test), between-assay factors ranged from 2.0 to 217.9 (median 74.6) in individual patients. OPN levels in cervix cancer patients were comparable to those of head and neck cancer patients. Commercially available OPN ELISA systems produce different absolute plasma OPN levels, compromising a comparison of individual patient data with published results. However, different assays appear to have a similar capacity to rank patients according to plasma OPN level. A review of literature data suggests that plasma OPN levels measured even with identical ELISA systems can only be compared with caution

  13. Serum osteopontin and vitronectin levels in systemic sclerosis.

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    Gundogdu, Baris; Yolbas, Servet; Yilmaz, Musa; Aydin, Suleyman; Koca, Sulayman Serdar

    2017-11-01

    Osteopontin a matricellular protein has pro-fibrotic effects and binds integrin such as αvβ1 and αvβ3. Vitronectin is one of the integrin αvβ3 ligands and is a multifunctional glycoprotein. The aim of the present study was to evaluate serum osteopontin and vitronectin levels in a cohort of patients with systemic sclerosis (SSc). Eighty-six patients with SSc, 46 patients with systemic lupus erythematosus (SLE), and 38 healthy controls (HC) were enrolled in the study. Serum osteopontin, vitronectin, IL-6, and TGF-β levels were analyzed. Serum osteopontin levels were higher in the SSc and SLE groups compared to the HC group (p < 0.01 and p < 0.001, respectively). However, it was not correlated with disease activity and severity scores in the SSc group. On the other hand, serum vitronectin levels were lower in the SSc group than in the SLE and HC groups (p < 0.001 for both). These results may suggest that osteopontin levels may be increased due to the inflammatory process and osteopontin has not a specific role on fibrosis in SSc. On the other hand, serum vitronectin levels decrease in SSc in contrast to SLE. It may be concluded that the one cause of decreased serum vitronectin levels in SSc may be its accumulation in fibrotic area.

  14. Osteopontin induces β-catenin signaling through activation of Akt in prostate cancer cells

    International Nuclear Information System (INIS)

    Robertson, Brian W.; Chellaiah, Meenakshi A.

    2010-01-01

    Secretion of osteopontin (OPN) by cancer cells is a known mediator of tumorigenesis and cancer progression in both experimental and clinical studies. Our work demonstrates that OPN can activate Akt, an important step in cancer progression. Both ILK and PI3K are integral proteins in the OPN/Akt pathway, as inhibition of either kinase leads to a loss of OPN-mediated Akt activation. Subsequent to OPN-induced Akt activation, we observe inactivation of GSK-3β, a regulator of β-catenin. Osteopontin stimulation leads to an overall increase in β-catenin protein levels with a resultant transfer of β-catenin to the nucleus. Through the nuclear import of β-catenin, OPN increases both the transcription and protein levels of MMP-7 and CD44, which are known TCF/LEF transcription targets. This work describes an important aspect of cancer progression induced by OPN.

  15. Plasma osteopontin in acute liver failure

    DEFF Research Database (Denmark)

    Srungaram, Praveen; Rule, Jody A; Yuan, He Jun

    2015-01-01

    BACKGROUND: Osteopontin (OPN) is a novel phosphoglycoprotein expressed in Kupffer cells that plays a pivotal role in activating natural killer cells, neutrophils and macrophages. Measuring plasma OPN levels in patients with acute liver failure (ALF) might provide insights into OPN function...... in the setting of massive hepatocyte injury. METHODS: OPN levels were measured using a Quantikine® ELISA assay on plasma from 105 consecutive ALF patients enrolled by the US Acute Liver Failure Study Group, as well as controls including 40 with rheumatoid arthritis (RA) and 35 healthy subjects both before, and 1...... and 3 days after undergoing spine fusion (SF) surgery as a model for acute inflammation. RESULTS: Median plasma OPN levels across all etiologies of ALF patients were elevated 10- to 30-fold: overall median 1055ng/mL; range: 33-19,127), when compared to healthy controls (median in pre-SF patients: 41ng...

  16. Osteopontin Levels in Human Milk vary Across Countries and within Lactation Period

    DEFF Research Database (Denmark)

    Bruun, Signe; Jacobsen, Lotte Neergaard; Ze, Xiaolei

    2018-01-01

    OBJECTIVES: Osteopontin (OPN) is a multifunctional protein expressed in many cell types, tissues and body fluids with the highest concentrations found in milk; significantly higher in human than in bovine milk. Intervention studies have indicated beneficial effects of supplementing infant formula...... with bovine OPN. In this multicenter study, we determined the OPN content in human milk samples from 629 Chinese, Danish, Japanese and Korean mothers. METHODS: At each study site, milk samples were collected and analyzed for OPN and protein concentration using ELISA and infrared spectroscopy, respectively....../L in Korean to 266.2 mg/L in Chinese mothers (p mothers delivering more than one sample, multilevel (mixed model) linear regression analysis showed...

  17. Immunohistochemical detection of osteopontin in advanced head-and-neck cancer: Prognostic role and correlation with oxygen electrode measurements, hypoxia-inducible-factor-1α-related markers, and hemoglobin levels

    International Nuclear Information System (INIS)

    Bache, Matthias; Reddemann, Rolf; Said, Harun M.; Holzhausen, Hans-Juergen; Taubert, Helge; Becker, Axel; Kuhnt, Thomas; Haensgen, Gabriele; Dunst, Juergen; Vordermark, Dirk

    2006-01-01

    Purpose: The tumor-associated glycoprotein osteopontin (OPN) is discussed as a plasma marker of tumor hypoxia. However, the association of immunohistochemical OPN expression in tumor sections with tumor oxygenation parameters (HF5, median pO 2 ), the hypoxia-related markers hypoxia-inducible factor-1α (HIF-1α) and carbonic anhydrase IX (CAIX), or hemoglobin and systemic vascular endothelial growth factor (VEGF) levels has not been investigated. Methods and Materials: Tumor tissue sections of 34 patients with advanced head-and-neck cancer treated with radiotherapy were assessed by immunochemistry for the expression of OPN, HIF-1α, and CA IX. Relationship of OPN expression with tumor oxygenation parameters (HF5, median pO 2 ), HIF-1α and CA IX expression, hemoglobin and serum VEGF level, and clinical parameters was studied. Results: Bivariate analysis showed a significant correlation of positive OPN staining with low hemoglobin level (p = 0.02), high HIF-1α expression (p = 0.02), and high serum vascular endothelial growth factor level (p = 0.02) for advanced head-and-neck cancer. Furthermore, considering the 31 Stage IV patients, the median pO 2 correlated significantly with the OPN expression (p = 0.02). OPN expression alone had only a small impact on prognosis. However, in a univariate Cox proportional hazard regression model, the expression of either OPN or HIF-1α or CA IX was associated with a 4.1-fold increased risk of death (p = 0.02) compared with negativity of all three markers. Conclusion: Osteopontin expression detected immunohistochemically is associated with oxygenation parameters in advanced head-and-neck cancer. When the results of OPN, HIF-1α, and CA IX immunohistochemistry are combined into a hypoxic profile, a strong and statistically significant impact on overall survival is found

  18. Serum OPN expression for identification of gastric cancer and atrophic gastritis and its influencing factors.

    Science.gov (United States)

    Chen, Tiejun; Sun, Liping; He, Caiyun; Gong, Yuehua; Xu, Qian; Yuan, Yuan

    2014-01-01

    Most studies have found that osteopontin (OPN) expression level is related to the poor prognosis of gastric cancer. However, few studies have examined the relationship between OPN expression and gastric precancerous diseases, and the potential role of OPN in the formation and development of GC. We investigated the relationships between serum OPN levels and the risks of gastric cancer (GC) and its precancerous disease, to explore the diagnostic efficacy of serum OPN level for GC and atrophic gastritis and its influencing factors. A total of 1,452 patients were enrolled, including 609 with mild superficial gastritis (SG), 594 with atrophic gastritis (AG) and 249 with GC. The levels of serum OPN and serum Helicobacter pylori IgG antibody were detected by enzyme-linked immunosorbent assay. Serum OPN levels increased from mild SG (1.99 ± 1.91 ng/ml) to AG (2.37 ± 2.27 ng/ml) to GC (5.94 ± 4.52 ng/ml) (P ≤ 0.002), along with increasing severity of gastric disease. OPN levels were significantly higher in patients with GC compared with the non-cancer population (2.17 ± 2.10, P < 0.0001). Serum OPN level was positively correlated with age and was higher in men than women, but was not correlated with H. pylori infection status. The area under the receiver operating characteristic curve was 0.805, the optimal cutoff was 2.56 ng/ml and the sensitivity and specificity were 74.3% and 71.8%, respectively, for the ability of serum OPN to discriminate GC. Serum OPN expression was closely related to the risks of GC and AG, and it might be a useful marker for the discrimination of GC. OPN level was positively correlated with age and male sex, but was not affected by H. pylori infection, and it was promoted by smoking and drinking, in patients with mild SG.

  19. Osteopontin is a tumor autoantigen in prostate cancer patients

    Science.gov (United States)

    TILLI, TATIANA M.; SILVA, ELOÍSIO A.; MATOS, LÍVIA C.; FAGET, DOUGLAS V.; DIAS, BIANCA F.P.; VASCONCELOS, JULIANA S.P.; YOKOSAKI, YASUYUKI; GIMBA, ETEL R.P.

    2011-01-01

    Anti-tumor antibodies act as biomarkers for the early diagnosis of prostate cancer (PCa). Osteopontin (OPN) is overexpressed in PCa cells and contributes to the progression of the disease. This study aimed to evaluate whether OPN evokes a humoral immune response in PCa patients and whether the reactivity levels of anti-OPN antibodies may be used to better differentiate PCa from benign and healthy donor plasma samples. Plasma samples from biopsy-proven PCa patients (29), benign prostate hyperplasia (BPH) (18) and control healthy donors (HD) (30) were tested by immunoblots using the recombinant human OPN. The frequency of anti-OPN antibodies was significantly higher in PCa (66%) plasma samples as compared to BPH (33%) and HD controls (10%). Anti-OPN antibodies were detected in a high proportion of plasma samples from patients with a Gleason score of less than 6 (57%), prostate-specific antigen levels lower than 10 ng/ml (67%) and pT2 organ-confined disease (70%), suggesting that anti-OPN antibodies may be used as an early serum marker for PCa. To the best of our knowledge, this is the first description of OPN as a tumor autoantigen and one of the most reactive individual autoantigens described thus far. These data support the inclusion of OPN in a multiplex of tumor antigens in order to perform antibody profiling in PCa as well as in other malignancies overexpressing OPN. PMID:22870138

  20. Osteopontin regulates the cross-talk between phosphatidylcholine and cholesterol metabolism in mouse liver.

    Science.gov (United States)

    Nuñez-Garcia, Maitane; Gomez-Santos, Beatriz; Buqué, Xabier; García-Rodriguez, Juan L; Romero, Marta R; Marin, Jose J G; Arteta, Beatriz; García-Monzón, Carmelo; Castaño, Luis; Syn, Wing-Kin; Fresnedo, Olatz; Aspichueta, Patricia

    2017-09-01

    Osteopontin (OPN) is involved in different liver pathologies in which metabolic dysregulation is a hallmark. Here, we investigated whether OPN could alter liver, and more specifically hepatocyte, lipid metabolism and the mechanism involved. In mice, lack of OPN enhanced cholesterol 7α-hydroxylase (CYP7A1) levels and promoted loss of phosphatidylcholine (PC) content in liver; in vivo treatment with recombinant (r)OPN caused opposite effects. rOPN directly decreased CYP7A1 levels through activation of focal adhesion kinase-AKT signaling in hepatocytes. PC content was also decreased in OPN-deficient (OPN-KO) hepatocytes in which de novo FA and PC synthesis was lower, whereas cholesterol (CHOL) synthesis was higher, than in WT hepatocytes. In vivo inhibition of cholesterogenesis normalized liver PC content in OPN-KO mice, demonstrating that OPN regulates the cross-talk between liver CHOL and PC metabolism. Matched liver and serum samples showed a positive correlation between serum OPN levels and liver PC and CHOL concentration in nonobese patients with nonalcoholic fatty liver. In conclusion, OPN regulates CYP7A1 levels and the metabolic fate of liver acetyl-CoA as a result of CHOL and PC metabolism interplay. The results suggest that CYP7A1 is a main axis and that serum OPN could disrupt liver PC and CHOL metabolism, contributing to nonalcoholic fatty liver disease progression in nonobese patients.

  1. Increased osteopontin plasma levels in multiple sclerosis patients correlate with bone-specific markers

    NARCIS (Netherlands)

    Vogt, M.H.J.; ten Kate, J.; Drent, R.J.M.; Polman, C.H.; Hupperts, R.

    2010-01-01

    The pro-inflammatory cytokine osteopontin has been found to be highly expressed in multiple sclerosis lesions and plasma levels are increased during relapses in relapse-onset multiple sclerosis patients. The objective was to determine the relationship between osteopontin plasma and cerebrospinal

  2. Kaempferol regulates OPN-CD44 pathway to inhibit the atherogenesis of apolipoprotein E deficient mice

    Energy Technology Data Exchange (ETDEWEB)

    Xiao, Hong-Bo, E-mail: xhbzhb@yahoo.com [College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128 (China); Lu, Xiang-Yang; Sun, Zhi-Liang [Hunan Agricultural University, Changsha 410128 (China); Zhang, Heng-Bo [Furong District Red Cross Hospital, Changsha 410126 (China)

    2011-12-15

    Recent studies show that osteopontin (OPN) and its receptor cluster of differentiation 44 (CD44) are two pro-inflammatory cytokines contributing to the development of atherosclerosis. The objective of this study was to explore the inhibitory effect of kaempferol, a naturally occurring flavonoid compound, on atherogenesis and the mechanisms involved. The experiments were performed in aorta and plasma from C57BL/6J control and apolipoprotein E-deficient (ApoE{sup -/-}) mice treated or not with kaempferol (50 or 100 mg/kg, intragastrically) for 4 weeks. Kaempferol treatment decreased atherosclerotic lesion area, improved endothelium-dependent vasorelaxation, and increased the maximal relaxation value concomitantly with decrease in the half-maximum effective concentration, plasma OPN level, aortic OPN expression, and aortic CD44 expression in ApoE{sup -/-} mice. In addition, treatment with kaempferol also significantly decreased reactive oxygen species production in mice aorta. The present results suggest that kaempferol regulates OPN-CD44 pathway to inhibit the atherogenesis of ApoE{sup -/-} mice. -- Graphical abstract: Kaempferol regulates OPN-CD44 pathway to inhibit the atherogenesis of ApoE{sup -/-} mice. Highlights: Black-Right-Pointing-Pointer OPN-CD44 pathway plays a critical role in the development of atherosclerosis. Black-Right-Pointing-Pointer We examine lesion area, OPN and CD44 changes after kaempferol treatment. Black-Right-Pointing-Pointer Kaempferol treatment decreased atherosclerotic lesion area in ApoE{sup -/-} mice. Black-Right-Pointing-Pointer Kaempferol treatment decreased aortic OPN and CD44 expressions in ApoE{sup -/-} mice. Black-Right-Pointing-Pointer Kaempferol regulates OPN-CD44 pathway to inhibit the atherogenesis.

  3. Plasma thrombin-cleaved osteopontin elevation after carotid artery stenting in symptomatic ischemic stroke patients

    International Nuclear Information System (INIS)

    Kurata, Mie; Okura, Takafumi; Kumon, Yoshiaki; Tagawa, Masahiko; Watanabe, Hideaki; Miyazaki, Tatsuhiko; Higaki, Jitsuo; Nose, Masato; Nakahara, Toshinori

    2012-01-01

    Atherothrombosis is the primary pathophysiology that underlies ischemic cerebral infarction. Osteopontin (OPN) is produced in atherosclerotic lesions and is cleaved by activated thrombin. We hypothesized that the rupture or damage of an unstable atherosclerotic plaque increases plasma levels of thrombin-cleaved OPN (trOPN). This study included 90 patients who received carotid angioplasty with stenting (CAS), 23 patients with essential hypertension (EHT) and 10 patients who were treated with carotid endarterectomy (CEA). The CAS patient group included 36 patients that had pre- and post-operative blood tests, diffusion-weighted imaging (DWI) using cerebral MRIs and estimated thrombus debris within the protection device. Immunohistochemistry of CEA specimens revealed that trOPN was detected around intra-plaque vessels. The highest tertile of plasma trOPN levels in CAS patients was higher than trOPN levels in EHT patients. Post-operative trOPN levels were significantly higher in symptomatic compared with asymptomatic patients (P=0.003). New ipsilateral DWI-positive patients revealed higher post-operative trOPN levels (P=0.003) and a higher grade of thrombi (P<0.001) than DWI-negative patients. TrOPN may be a novel biomarker that reflects the atherothrombotic status in ischemic stroke. (author)

  4. Link Between GIP and Osteopontin in Adipose Tissue and Insulin Resistance

    DEFF Research Database (Denmark)

    Ahlqvist, Emma; Osmark, Peter; Kuulasmaa, Tiina

    2013-01-01

    Low-grade inflammation in obesity is associated with accumulation of the macrophage-derived cytokine osteopontin (OPN) in adipose tissue and induction of local as well as systemic insulin resistance. Since glucose-dependent insulinotropic polypeptide (GIP) is a strong stimulator of adipogenesis...... and may play a role in the development of obesity, we explored whether GIP directly would stimulate OPN expression in adipose tissue and thereby induce insulin resistance. GIP stimulated OPN protein expression in a dose-dependent fashion in rat primary adipocytes. The level of OPN mRNA was higher...... for transmembrane activity. Carriers of the A allele with a reduced receptor function showed lower adipose tissue OPN mRNA levels and better insulin sensitivity. Together, these data suggest a role for GIP not only as an incretin hormone but also as a trigger of inflammation and insulin resistance in adipose tissue...

  5. Osteopontin is a prognostic biomarker in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Rud, Ane Kongsgaard; Mælandsmo, Gunhild M; Boye, Kjetil; Øijordsbakken, Miriam; Lund-Iversen, Marius; Halvorsen, Ann Rita; Solberg, Steinar K; Berge, Gisle; Helland, Åslaug; Brustugun, Odd Terje

    2013-01-01

    In a previously published report we characterized the expression of the metastasis-associated proteins S100A4, osteopontin (OPN) and ephrin-A1 in a prospectively collected panel of non-small cell lung cancer (NSCLC) tumors. The aim of the present follow-up study was to investigate the prognostic impact of these potential biomarkers in the same patient cohort. In addition, circulating serum levels of OPN were measured and single nucleotide polymorphisms (SNP) in the -443 position of the OPN promoter were analyzed. Associations between immunohistochemical expression of S100A4, OPN and ephrin-A1 and relapse free and overall survival were examined using univariate and multivariate analyses. Serum OPN was measured by ELISA, polymorphisms in the -443 position of the tumor OPN promoter were analyzed by PCR, and associations between OPN levels and promoter polymorphisms and clinicopathological parameters and patient outcome were investigated. High expression of OPN in NSCLC tumors was associated with poor patient outcome, and OPN was a strong, independent prognostic factor for both relapse free and overall survival. Serum OPN levels increased according to tumor pT classification and tumor size, and patients with OPN-expressing tumors had higher serum levels than patients with OPN-negative tumors. S100A4 was a negative prognostic factor in several subgroups of adenocarcinoma patients, but not in the overall patient cohort. There was no association between ephrin-A1 expression and patient outcome. OPN is a promising prognostic biomarker in NSCLC, and should be further explored in the selection of patients for adjuvant treatment following surgical resection

  6. The correlation between osteopontin level and radiation response of malignant gliomas at Cipto Mangunkusumo Hospital

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    Isnaniah Hasan

    2016-12-01

    Full Text Available Osteopontin is an endogenous molecular marker for tumor hypoxia, and hypoxia is one of the factors that determine the aggressiveness of the disease. The purpose of this study is to determine the correlation between osteopontin levels and radiation response in malignant glioma. A retrospective cohort study was conducted on 15 malignant glioma patients who underwent radiation therapy from July 2004 to May 2015 at the RSUPN Dr. Cipto Mangunkusumo Hospital. Osteopontin levels were measured from paraffin-embedded tissue using a commercial ELISA kit. Tumor volume was calculated using computed tomography (CT scan and magnetic resonance imaging (MRI images, based on three-dimensional volume measurements. Tumor response was evaluated by comparing pre- and post-radiation tumor volumes using CT scan and MRI images. The mean osteopontin level was 0.49 ± 0.45 ng/mL and the mean percentage change in tumor volume was 8.59 ± 54.22%, with a 60% enlargement in tumor volume. A progressive disease was found in 26.7% of patients. There was a weak but insignificant negative correlation (r = -0.39, p = 0.146 between the level of osteopontin and radiation response. In contrast, there was a strong but insignificant positive correlation (r = +0.68, p = 0.219 between the level of osteopontin and radiation response in the patient group that used the chemosensitizer temozolamide.

  7. Serum Osteopontin as a Novel Biomarker for Muscle Regeneration in Duchenne Muscular Dystrophy.

    Science.gov (United States)

    Kuraoka, Mutsuki; Kimura, En; Nagata, Tetsuya; Okada, Takashi; Aoki, Yoshitsugu; Tachimori, Hisateru; Yonemoto, Naohiro; Imamura, Michihiro; Takeda, Shin'ichi

    2016-05-01

    Duchenne muscular dystrophy is a lethal X-linked muscle disorder. We have already reported that osteopontin (OPN), an inflammatory cytokine and myogenic factor, is expressed in the early dystrophic phase in canine X-linked muscular dystrophy in Japan, a dystrophic dog model. To further explore the possibility of OPN as a new biomarker for disease activity in Duchenne muscular dystrophy, we monitored serum OPN levels in dystrophic and wild-type dogs at different ages and compared the levels to other serum markers, such as serum creatine kinase, matrix metalloproteinase-9, and tissue inhibitor of metalloproteinase-1. Serum OPN levels in the dystrophic dogs were significantly elevated compared with those in wild-type dogs before and 1 hour after a cesarean section birth and at the age of 3 months. The serum OPN level was significantly correlated with the phenotypic severity of dystrophic dogs at the period corresponding to the onset of muscle weakness, whereas other serum markers including creatine kinase were not. Immunohistologically, OPN was up-regulated in infiltrating macrophages and developmental myosin heavy chain-positive regenerating muscle fibers in the dystrophic dogs, whereas serum OPN was highly elevated. OPN expression was also observed during the synergic muscle regeneration process induced by cardiotoxin injection. In conclusion, OPN is a promising biomarker for muscle regeneration in dystrophic dogs and can be applicable to boys with Duchenne muscular dystrophy. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  8. Interaction of osteopontin with IL-18 in obese individuals: implications for insulin resistance.

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    Rasheed Ahmad

    Full Text Available BACKGROUND/OBJECTIVE: Osteopontin (OPN and IL-18 are known inflammatory mediators and both participate in a wide range of biological processes linked to immunological disorders. Since an interaction between OPN and IL-18 has not been studied in obesity, we investigated whether: (i their levels were simultaneously elevated in obese individuals; (ii OPN was associated with IL-18 in obese individuals and (iii their levels associated with fasting blood glucose (FBG and BMI. SUBJECTS AND METHODS: PBMCs and plasma samples were isolated from 60 individuals including lean as well as overweight and obese individuals. Subcutaneous adipose tissue samples were obtained. OPN and IL-18 were measured by ELISA. OPN and IL-18 mRNA expression was quantified by real time quantitative RT-PCR. RESULTS: Obese individuals exhibited significantly increased circulating OPN levels as compared with lean individuals (obese 2865±101; lean 1681±116 pg/ml; P<0.0001. IL-18 levels were also high in obese individuals (obese 491±39, lean 301±26 pg/ml; P = 0.0009. OPN and IL-18 expression were simultaneously up-regulated (OPN: 5.4-Fold; IL-18: 8.9-Fold; P<0.05 in PBMCs from obese individuals compared to lean group. Adipose tissue from obese individuals had high expression of OPN (7.3-Fold and IL-18 (9.6-Fold. Plasma OPN levels correlated positively with FBG levels (r = 0.32, P = 0.02. Similarly, IL-18 correlated positively with FBG levels (r = 0.406, P = 0.0042. Stepwise multiple regression analysis showed an independent association of BMI with OPN and IL-18. Interestingly, OPN levels increased progressively with an increase in IL-18 levels (r = 0.52, P = 0.0004. We also examined the regulatory role of IL-18 in OPN secretion from PBMCs. Neutralizing anti-IL-18Rα mAb reduced OPN secretion. CONCLUSION: These findings represent the first observation that plasma, PBMC and adipose tissue OPN and IL-18 are simultaneously increased and correlate with each

  9. Increased Obesity-Associated Circulating Levels of the Extracellular Matrix Proteins Osteopontin, Chitinase-3 Like-1 and Tenascin C Are Associated with Colon Cancer.

    Directory of Open Access Journals (Sweden)

    Victoria Catalán

    Full Text Available Excess adipose tissue represents a major risk factor for the development of colon cancer with inflammation and extracellular matrix (ECM remodeling being proposed as plausible mechanisms. The aim of this study was to investigate whether obesity can influence circulating levels of inflammation-related extracellular matrix proteins in patients with colon cancer (CC, promoting a microenvironment favorable for tumor growth.Serum samples obtained from 79 subjects [26 lean (LN and 53 obese (OB] were used in the study. Enrolled subjects were further subclassified according to the established diagnostic protocol for CC (44 without CC and 35 with CC. Anthropometric measurements as well as circulating metabolites and hormones were determined. Circulating concentrations of the ECM proteins osteopontin (OPN, chitinase-3-like protein 1 (YKL-40, tenascin C (TNC and lipocalin-2 (LCN-2 were determined by ELISA.Significant differences in circulating OPN, YKL-40 and TNC concentrations between the experimental groups were observed, being significantly increased due to obesity (P<0.01 and colon cancer (P<0.05. LCN-2 levels were affected by obesity (P<0.05, but no differences were detected regarding the presence or not of CC. A positive association (P<0.05 with different inflammatory markers was also detected.To our knowledge, we herein show for the first time that obese patients with CC exhibit increased circulating levels of OPN, YKL-40 and TNC providing further evidence for the influence of obesity on CC development via ECM proteins, representing promising diagnostic biomarkers or target molecules for therapeutics.

  10. Osteopontin is an endogenous modulator of the constitutively activated phenotype of pulmonary adventitial fibroblasts in hypoxic pulmonary hypertension

    Science.gov (United States)

    Anwar, Adil; Li, Min; Frid, Maria G.; Kumar, Binod; Gerasimovskaya, Evgenia V.; Riddle, Suzette R.; McKeon, B. Alexandre; Thukaram, Roopa; Meyrick, Barbara O.; Fini, Mehdi A.

    2012-01-01

    Increased cell proliferation and migration, of several cell types are key components of vascular remodeling observed in pulmonary hypertension (PH). Our previous data demonstrate that adventitial fibroblasts isolated from pulmonary arteries of chronically hypoxic hypertensive calves (termed PH-Fibs) exhibit a “constitutively activated” phenotype characterized by high proliferative and migratory potential. Osteopontin (OPN) has been shown to promote several cellular activities including growth and migration in cancer cells. We thus tested the hypothesis that elevated OPN expression confers the “activated” highly proproliferative and promigratory/invasive phenotype of PH-Fibs. Our results demonstrate that, both in vivo and ex vivo, PH-Fibs exhibited increased expression of OPN, as well as its cognate receptors, αVβ3 and CD44, compared with control fibroblasts (CO-Fibs). Augmented OPN expression in PH-Fibs corresponded to their high proliferative, migratory, and invasive properties and constitutive activation of ERK1/2 and AKT signaling. OPN silencing via small interfering RNA or sequestering OPN production by specific antibodies led to decreased proliferation, migration, invasion, and attenuated ERK1/2, AKT phosphorylation in PH-Fibs. Furthermore, increasing OPN levels in CO-Fibs via recombinant OPN resulted in significant increases in their proliferative, migratory, and invasive capabilities to the levels resembling those of PH-Fibs. Thus our data suggest OPN as an essential contributor to the activated (highly proliferative, migratory, and proinvasive) phenotype of pulmonary adventitial fibroblasts in hypoxic PH. PMID:22582113

  11. Kaempferol inhibits the production of ROS to modulate OPN-αvβ3 integrin pathway in HUVECs.

    Science.gov (United States)

    Xiao, Hong-Bo; Lu, Xiang-Yang; Liu, Zi-Kui; Luo, Zhi-Feng

    2016-06-01

    In the present study, we tested the hypothesis that aldosterone regulates osteopontin (OPN)-related signaling pathways to promote nuclear factor κB (NF-κB) activation in primary human umbilical vein endothelial cells (HUVECs) and that kaempferol, a flavonoid compound, blocks those changes. Aldosterone induced productions of reactive oxygen species (ROS), OPN, interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) and expression of nicotinamide adenine dinucleotide phosphate-oxidase 4 (Nox4), NF-κB, OPN, alphavbeta3 (αvβ3) integrin, and inhibitor of NF-κB alpha phosphorylation (P-IκBα) in HUVEC. HUVECs were pretreated with kaempferol (0, 1, 3, or 10 μM) for 1 h and exposed to aldosterone (10(-6) M) for 24 h. Kaempferol reduced ROS, OPN, NF-κB, IL-6, and TNF-α levels; Nox4, αvβ3 integrin; and P-IκBα expressions. The effect of aldosterone was also abrogated by spironolactone (10(-6) M). In addition, vitamin C (20 mmol/L) reduced ROS production. Vitamin C and LM609 (10 μg/mL) treatment decreased expressions of OPN, αvβ3 integrin, and NF-κB (P kaempferol may modulate OPN-αvβ3 integrin pathway to inhibit NF-κB activation in HUVECs.

  12. Osteopontin expression in salivary gland carcinomas

    DEFF Research Database (Denmark)

    Bjørndal, Kristine; Larsen, Stine R; Godballe, Christian

    2011-01-01

    J Oral Pathol Med (2010) Background:  In several cancer types, osteopontin (OPN) expression has been correlated with tumor progression and prognosis. Two earlier studies have examined OPN expression in salivary gland carcinomas with contradictory results. Methods:  One hundred and seventy......:  Osteopontin was expressed in all salivary gland carcinomas. Adenoid cystic carcinomas had the highest mean sum score (7.3) and a significantly higher proportion of carcinomas with high OPN sum score than both mucoepidermoid carcinoma and acinic cell carcinoma. Correlation of OPN expression with known...... prognostic factors in salivary gland carcinomas was insignificant. Conclusions:  Salivary gland carcinomas express OPN. The expression does not correlate with known prognostic factors....

  13. Impact of renal failure on the tumor markers of mesothelioma, N-ERC/mesothelin and osteopontin.

    Science.gov (United States)

    Shiomi, Kazu; Shiomi, Satoko; Ishinaga, Yuji; Sakuraba, Motoki; Hagiwara, Yoshiaki; Miyashita, Kazuya; Maeda, Masahiro; Suzuki, Kenji; Takahashi, Kazuhisa; Hino, Okio

    2011-04-01

    Knowledge of the characteristics and effective use of tumour markers for mesothelioma is essential for early-stage diagnosis of mesothelioma. We examined whether renal dysfunction influences blood concentrations of promising new tumour markers, N-ERC/mesothelin (N-ERC) and osteopontin (OPN), to an important degree. Levels of serum N-ERC and plasma OPN in 32 patients with chronic renal dysfunction, 22 of whom were on hemodialysis (CKD group), and 102 healthy volunteers were measured. Serum concentrations of N-ERC and plasma concentrations of OPN in the CKD group were significantly higher than those in volunteers, regardless of diabetes status and age. Blood concentrations of these markers increased as renal function decreased. N-ERC and OPN concentrations are significantly influenced by renal function. Therefore, the extent of renal failure must be considered when inferring the existence of tumours and chemotherapeutic response from the values of these markers in routine practice.

  14. Plasma and tissue osteopontin expression in cutaneous lichen planus and its relation to metabolic syndrome

    International Nuclear Information System (INIS)

    Awad, M.A.I.

    2015-01-01

    Lichen planus (LP) is a chronic inflammatory disease that affects the skin, mucous membranes and appendages. Although its pathogenesis is still unclear, some studies showed that autoreactive cytotoxic T lymphocytes are the effector cells which cause degeneration and destruction of keratinocytes. Osteopontin (OPN) is expressed during inflammation by natural killer cells, activated T cells and macrophages and classified as a T-helper type 1 (Th1) cytokine. Plasma OPN has been reported to be a potential clinical marker for prediction of atherosclerosis. The mean values of plasma and tissue OPN in the lesional skin of LP patients were significantly higher than that in the control group (P Values for both plasma and tissue OPN were < 0.001). Correlating levels of plasma OPN in the LP patients to metabolic syndrome parameters showed a statistically significant correlation with dyslipidemia and diabetes mellitus. In conclusion, levels of plasma and tissue OPN were higher in cutaneous lichen planus patients than controls and plasma OPN could be a marker for cardiovascular risk in these patients

  15. Osteopontin binding to the alpha 4 integrin requires highest affinity integrin conformation, but is independent of post-translational modifications of osteopontin

    DEFF Research Database (Denmark)

    Hui, Tommy; Sørensen, Esben Skipper; Rittling, Susan R.

    2015-01-01

    Osteopontin (OPN) is a ligand for the α4 integrin, but the physiological importance of this binding is not well understood. Here, we have assessed the effect of posttranslational modifications on OPN binding to the α4 integrin on cultured human leukocyte cell lines, and compared OPN interaction...

  16. Schistosome-induced cholangiocyte proliferation and osteopontin secretion correlate with fibrosis and portal hypertension in human and murine schistosomiasis mansoni.

    Science.gov (United States)

    Pereira, Thiago A; Syn, Wing-Kin; Machado, Mariana V; Vidigal, Paula V; Resende, Vivian; Voieta, Izabela; Xie, Guanhua; Otoni, Alba; Souza, Márcia M; Santos, Elisângela T; Chan, Isaac S; Trindade, Guilherme V M; Choi, Steve S; Witek, Rafal P; Pereira, Fausto E; Secor, William E; Andrade, Zilton A; Lambertucci, José Roberto; Diehl, Anna Mae

    2015-11-01

    Schistosomiasis is a major cause of portal hypertension worldwide. It associates with portal fibrosis that develops during chronic infection. The mechanisms by which the pathogen evokes these host responses remain unclear. We evaluated the hypothesis that schistosome eggs release factors that directly stimulate liver cells to produce osteopontin (OPN), a pro-fibrogenic protein that stimulates hepatic stellate cells to become myofibroblasts. We also investigated the utility of OPN as a biomarker of fibrosis and/or severity of portal hypertension. Cultured cholangiocytes, Kupffer cells and hepatic stellate cells were treated with soluble egg antigen (SEA); OPN production was quantified by quantitative reverse transcriptase polymerase chain reaction (qRTPCR) and ELISA; cell proliferation was assessed by BrdU (5-bromo-2'-deoxyuridine). Mice were infected with Schistosoma mansoni for 6 or 16 weeks to cause early or advanced fibrosis. Liver OPN was evaluated by qRTPCR and immunohistochemistry (IHC) and correlated with liver fibrosis and serum OPN. Livers from patients with schistosomiasis mansoni (early fibrosis n=15; advanced fibrosis n=72) or healthy adults (n=22) were immunostained for OPN and fibrosis markers. Results were correlated with plasma OPN levels and splenic vein pressures. SEA-induced cholangiocyte proliferation and OPN secretion (Pportal hypertension severity. © 2015 Authors; published by Portland Press Limited.

  17. Increased amount of phosphorylated proinflammatory osteopontin in rheumatoid arthritis synovia is associated to decreased tartrate-resistant acid phosphatase 5B/5A ratio.

    Directory of Open Access Journals (Sweden)

    Jani Luukkonen

    Full Text Available Osteopontin (OPN is an immunoregulatory protein which production increases in both rheumatoid arthritis (RA and osteoarthritis (OA. Phosphorylated osteopontin (Phospho-OPN is known to increase macrophage and osteoclast activation, this process is controlled by extracellular tartrate-resistant acid phosphatase (TRAcP, also a biomarker for RA. Here, we evaluated the phosphorylation status of OPN in RA and OA synovia, as well as its correlation with TRAcP isoforms.Synovial tissue and fluid were obtained from 24 RA (14 seropositive and 10 seronegative and 24 OA patients. Western blotting was used to analyze the extent of OPN phosphorylation. TRAcP isoforms were measured in synovial fluid using ELISA; immunohistochemistry assessed the distribution of OPN and TRAcP expressing cells in the synovial tissue, especially distinguishing between the TRAcP isoforms.Full-length OPN was more phosphorylated in RA than in OA (p<0.05. The thrombin cleaved C-terminal end of OPN was also more phosphorylated in RA (p<0.05. RA patients had a lower concentration of TRAcP 5B and higher concentration of less active 5A in their synovial fluid compared to OA patients. The TRAcP 5B/5A ratio was decreased in RA and correlated negatively with the amount of phospho-OPN (p<0.05. TRAcP positive cells for both isoforms were found all along the synovial lining; OPN antibody staining was localized in the extracellular matrix.Our data suggests that in RA the synovial fluid contains insufficient amounts of TRAcP 5B which increase levels of the proinflammatory phospho-OPN. This may lead to increased macrophage and osteoclast activation, resulting in the increased local inflammation and bone resorption present in RA joints.

  18. Osteopontin: Relation between Adipose Tissue and Bone Homeostasis

    OpenAIRE

    De Fusco, Carolina; Messina, Antonietta; Monda, Vincenzo; Viggiano, Emanuela; Moscatelli, Fiorenzo; Valenzano, Anna; Esposito, Teresa; Sergio, Chieffi; Cibelli, Giuseppe; Monda, Marcellino; Messina, Giovanni

    2017-01-01

    Osteopontin (OPN) is a multifunctional protein mainly associated with bone metabolism and remodeling. Besides its physiological functions, OPN is implicated in the pathogenesis of a variety of disease states, such as obesity and osteoporosis. Importantly, during the last decades obesity and osteoporosis have become among the main threats to health worldwide. Because OPN is a protein principally expressed in cells with multifaceted effects on bone morphogenesis and remodeling and because it se...

  19. Biological role of site-specific O-glycosylation in cell adhesion activity and phosphorylation of osteopontin.

    Science.gov (United States)

    Oyama, Midori; Kariya, Yoshinobu; Kariya, Yukiko; Matsumoto, Kana; Kanno, Mayumi; Yamaguchi, Yoshiki; Hashimoto, Yasuhiro

    2018-05-09

    Osteopontin (OPN) is an extracellular glycosylated phosphoprotein that promotes cell adhesion by interacting with several integrin receptors. We previously reported that an OPN mutant lacking five O-glycosylation sites (Thr 134 /Thr 138 /Thr 143 /Thr 147 /Thr 152 ) in the threonine/proline-rich region increased cell adhesion activity and phosphorylation compared with the wild type. However, the role of O-glycosylation in cell adhesion activity and phosphorylation of OPN remains to be clarified. Here, we show that site-specific O-glycosylation in the threonine/proline-rich region of OPN affects its cell adhesion activity and phosphorylation independently and/or synergistically. Using site-directed mutagenesis, we found that OPN mutants with substitution sets of Thr 134 /Thr 138 or Thr 143 /Thr 147 /Thr 152 had decreased and increased cell adhesion activity, respectively. In contrast, the introduction of a single mutation into the O-glycosylation sites had no effect on OPN cell adhesion activity. An adhesion assay using function-blocking antibodies against αvβ3 and β1 integrins, as well as αvβ3 integrin-overexpressing A549 cells, revealed that site-specific O-glycosylation affected the association of OPN with the two integrins. Phosphorylation analyses using phos-tag and LC-MS/MS indicated that phosphorylation levels and sites were influenced by the O-glycosylation status, although the number of O-glycosylation sites was not correlated with the phosphorylation level in OPN. Furthermore, a correlation analysis between phosphorylation level and cell adhesion activity in OPN mutants with the site-specific O-glycosylation showed that they were not always correlated. These results provide conclusive evidence of a novel regulatory mechanism of cell adhesion activity and phosphorylation of OPN by site-specific O-glycosylation. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  20. Deletion of the thrombin cleavage domain of osteopontin mediates breast cancer cell adhesion, proteolytic activity, tumorgenicity, and metastasis

    International Nuclear Information System (INIS)

    Beausoleil, Michel S; Schulze, Erika B; Goodale, David; Postenka, Carl O; Allan, Alison L

    2011-01-01

    Osteopontin (OPN) is a secreted phosphoprotein often overexpressed at high levels in the blood and primary tumors of breast cancer patients. OPN contains two integrin-binding sites and a thrombin cleavage domain located in close proximity to each other. To study the role of the thrombin cleavage site of OPN, MDA-MB-468 human breast cancer cells were stably transfected with either wildtype OPN (468-OPN), mutant OPN lacking the thrombin cleavage domain (468-ΔTC) or an empty vector (468-CON) and assessed for in vitro and in vivo functional differences in malignant/metastatic behavior. All three cell lines were found to equivalently express thrombin, tissue factor, CD44, αvβ5 integrin and β1 integrin. Relative to 468-OPN and 468-CON cells, 468-ΔTC cells expressing OPN with a deleted thrombin cleavage domain demonstrated decreased cell adhesion (p < 0.001), decreased mRNA expression of MCAM, maspin and TRAIL (p < 0.01), and increased uPA expression and activity (p < 0.01) in vitro. Furthermore, injection of 468-ΔTC cells into the mammary fat pad of nude mice resulted in decreased primary tumor latency time (p < 0.01) and increased primary tumor growth and lymph node metastatic burden (p < 0.001) compared to 468-OPN and 468-CON cells. The results presented here suggest that expression of thrombin-uncleavable OPN imparts an early tumor formation advantage as well as a metastatic advantage for breast cancer cells, possibly due to increased proteolytic activity and decreased adhesion and apoptosis. Clarification of the mechanisms responsible for these observations and the translation of this knowledge into the clinic could ultimately provide new therapeutic opportunities for combating breast cancer

  1. Association between osteopontin and human abdominal aortic aneurysm.

    Science.gov (United States)

    Golledge, Jonathan; Muller, Juanita; Shephard, Neil; Clancy, Paula; Smallwood, Linda; Moran, Corey; Dear, Anthony E; Palmer, Lyle J; Norman, Paul E

    2007-03-01

    In vitro and animal studies have implicated osteopontin (OPN) in the pathogenesis of aortic aneurysm. The relationship between serum concentration of OPN and variants of the OPN gene with human abdominal aortic aneurysm (AAA) was investigated. OPN genotypes were examined in 4227 subjects in which aortic diameter and clinical risk factors were measured. Serum OPN was measured by ELISA in two cohorts of 665 subjects. The concentration of serum OPN was independently associated with the presence of AAA. Odds ratios (and 95% confidence intervals) for upper compared with lower OPN tertiles in predicting presence of AAA were 2.23 (1.29 to 3.85, P=0.004) for the population cohort and 4.08 (1.67 to 10.00, P=0.002) for the referral cohort after adjusting for other risk factors. In 198 patients with complete follow-up of aortic diameter at 3 years, initial serum OPN predicted AAA growth after adjustment for other risk factors (standardized coefficient 0.24, P=0.001). The concentration of OPN in the aortic wall was greater in patients with small AAAs (30 to 50 mm) than those with aortic occlusive disease alone. There was no association between five single nucleotide polymorphisms or haplotypes of the OPN gene and aortic diameter or AAA expansion. Serum and tissue concentrations of OPN are associated with human AAA. We found no relationship between variation of the OPN gene and AAA. OPN may be a useful biomarker for AAA presence and growth.

  2. Chemokine (C-C motif ligand 20, a potential biomarker for Graves' disease, is regulated by osteopontin.

    Directory of Open Access Journals (Sweden)

    Xiaoli Li

    Full Text Available CONTEXT: Graves' disease (GD is a common autoimmune disease involving the thyroid gland. The altered balance of pro- and anti-inflammatory cytokines plays an important role in the pathogenesis of GD. Chemokine (C-C motif ligand 20 (CCL20 is important for interleukin-17 (IL-17 signal activation and a potent chemoattractant for Th17 cells. Meanwhile, Osteopontin (OPN, a broadly expressed pleiotropic cytokine, has been implicated in GD through inducing Th1-involved response to enhance the production of proinflammatory cytokines and chemokines, but little is known about the role of OPN in regulating CCL20 and IL-17 signaling. OBJECTIVE: This study sought to explore the possibility of CCL20 level as a biomarker for GD, as well as investigate the role of OPN in regulating CCL20 production. METHODS: Fifty untreated GD patients, fifteen euthyroid GD patients, twelve TRAb-negative GD patients and thirty-five healthy control donors were recruited. OPN, CCL20 and other clinical GD diagnosis parameters were measured. CD4+T cells were isolated from peripheral blood mononuclear cells (PBMCs using antibody-coated magnetic beads. Enzyme-linked immune-sorbent assay and quantitative polymerase chain reaction were used to determine CCL20 expression level. RESULTS: We found that the plasma CCL20 level was enhanced in GD patients and decreased in euthyroid and TRAb-negative GD patients. In addition, CCL20 level correlated with GD clinical diagnostic parameters and plasma OPN level. Moreover, we demonstrated that recombinant OPN and plasma from untreated GD patients increased the expression of CCL20 in CD4+T cells, which could be blocked by OPN antibody. Furthermore, we found that the effect of OPN on CCL20 expression was mediated by β3 integrin receptor, IL-17, NF-κB and MAPK pathways. CONCLUSIONS: These results demonstrated that CCL20 might serve as a biomarker for GD and suggested the possible role of OPN in induction of CCL20 expression.

  3. Differential expression of OPN, VEGF-A, and HIF-1α and its clinical significance in hepatocellular carcinoma

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    ZHENG Yan

    2013-01-01

    Full Text Available ObjectiveTo investigate the expression patterns of osteopontin (OPN, vascular endothelial growth factor-A (VEGF-A, and hypoxia-inducible factor-1α(HIF-1α in primary hepatocellular carcinoma (HCC and determine the clinical significance of this differential expression profile. MethodsImmunohistochemical staining of OPN, VEGF-A, and HIF-1α was carried out on primary HCC tissues from 90 patients, HCC-adjacent cirrhosis tissues from 20 of those patients, and normal liver tissues from 15 healthy controls. Correlations between expression levels and HCC clinicopathological characteristics were assessed by Spearman's correlation coefficient. ResultsThe majority of HCC tissues showed positive immunostaining for OPN (69/90, 76.67%, VEGF-A (64/90, 71.11%, and HIF-1α (66/90, 73.33%. OPN- and VEGF-A-positivity were significantly higher than the results from the cirrhosis tissues and normal tissues. HIF-1α-positivity was similar between the HCC and cirrhosis tissues, but both were significantly different from the normal tissues. The differential expressions of OPN, VEGF-A, and HIF-1α were significantly correlated with tumor thrombus, capsular integrity, tumor differentiation and stage, and metastasis (P<0.05. ConclusionHCC tissues overexpress OPN, VEGF-A, and HIF-1α and this differential profile may be related to HCC progression. Future investigations of this triad of factors may provide novel insights into the biological characteristics of HCC and reveal important targets of molecular therapy.

  4. Osteopontin mediates Citrobacter rodentium-induced colonic epithelial cell hyperplasia and attaching-effacing lesions.

    Science.gov (United States)

    Wine, Eytan; Shen-Tu, Grace; Gareau, Mélanie G; Goldberg, Harvey A; Licht, Christoph; Ngan, Bo-Yee; Sorensen, Esben S; Greenaway, James; Sodek, Jaro; Zohar, Ron; Sherman, Philip M

    2010-09-01

    Although osteopontin (OPN) is up-regulated in inflammatory bowel diseases, its role in disease pathogenesis remains controversial. The objective of this study was to determine the role of OPN in host responses to a non-invasive bacterial pathogen, Citrobacter rodentium, which serves as a murine infectious model of colitis. OPN gene knockout and wild-type mice were infected orogastrically with either C. rodentium or Luria-Bertani (LB) broth. Mouse-derived OPN(+/+) and OPN(-/-) fibroblasts were incubated with C. rodentium and attaching-effacing lesions were demonstrated using transmission electron microscopy and immunofluorescence. Colonic expression of OPN was increased by C. rodentium infection of wild-type mice. Furthermore, colonic epithelial cell hyperplasia, the hallmark of C. rodentium infection, was reduced in OPN(-/-) mice, and spleen enlargement by infection was absent in OPN(-/-) mice. Rectal administration of OPN to OPN(-/-) mice restored these effects. There was an 8- to 17-fold reduction in bacterial colonization in OPN(-/-) mice, compared with wild-type mice, which was accompanied by reduced attaching-effacing lesions, both in infected OPN(-/-) mice and OPN(-/-) mouse fibroblasts. Moreover, adhesion pedestals were restored in OPN(-/-) cells complemented with human OPN. Therefore, lack of OPN results in decreased pedestal formation, colonization, and colonic epithelial cell hyperplasia responses to C. rodentium infection, indicating that OPN impacts disease pathogenesis through bacterial attachment and altered host immune responses.

  5. Chromatin organization regulated by EZH2-mediated H3K27me3 is required for OPN-induced migration of bone marrow-derived mesenchymal stem cells.

    Science.gov (United States)

    Liu, Lingling; Luo, Qing; Sun, Jinghui; Ju, Yang; Morita, Yasuyuki; Song, Guanbin

    2018-03-01

    Osteopontin (OPN) is a chemokine-like extracellular matrix-associated protein involved in the migration of bone marrow-derived mesenchymal stem cells (BMSCs). An increasing number of studies have found that chromatin organization may affect cellular migration. However, whether OPN regulates chromatin organization is not understood, nor are the underlying molecular mechanisms. In this study, we investigated the link between chromatin organization and BMSC migration and demonstrated that OPN-mediated BMSC migration leads to elevated levels of heterochromatin marker histone H3 lysine 27 trimethylation (H3K27me3) through the methyltransferase EZH2. The expression of EZH2 reorganizes the chromatin structure of BMSCs. Pharmacological inhibition or depletion of EZH2 blocks BMSC migration. Moreover, using an atomic force microscope (AFM), we found that chromatin decondensation alters the mechanical properties of the nucleus. In addition, inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) signals represses OPN-promoted chromatin condensation and cell migration. Thus, our results identify a mechanism by which ERK1/2 signalling drives specific chromatin modifications in BMSCs, which alters chromatin organization and thereby enables OPN-mediated BMSC migration. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. Dynamic light scattering study of inhibition of nucleation and growth of hydroxyapatite crystals by osteopontin.

    Directory of Open Access Journals (Sweden)

    John R de Bruyn

    Full Text Available We study the effect of isoforms of osteopontin (OPN on the nucleation and growth of crystals from a supersaturated solution of calcium and phosphate ions. Dynamic light scattering is used to monitor the size of the precipitating particles and to provide information about their concentration. At the ion concentrations studied, immediate precipitation was observed in control experiments with no osteopontin in the solution, and the size of the precipitating particles increased steadily with time. The precipitate was identified as hydroxyapatite by X-ray diffraction. Addition of native osteopontin (nOPN extracted from rat bone caused a delay in the onset of precipitation and reduced the number of particles that formed, but the few particles that did form grew to a larger size than in the absence of the protein. Recombinant osteopontin (rOPN, which lacks phosphorylation, caused no delay in initial calcium phosphate precipitation but severely slowed crystal growth, suggesting that rOPN inhibits growth but not nucleation. rOPN treated with protein kinase CK2 to phosphorylate the molecule (p-rOPN produced an effect similar to that of nOPN, but at higher protein concentrations and to a lesser extent. These results suggest that phosphorylations are critical to OPN's ability to inhibit nucleation, whereas the growth of the hydroxyapatite crystals is effectively controlled by the highly acidic OPN polypeptide. This work also demonstrates that dynamic light scattering can be a powerful tool for delineating the mechanism of protein modulation of mineral formation.

  7. Anti-osteopontin monoclonal antibody prevents ovariectomy-induced osteoporosis in mice by promotion of osteoclast apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Bo [International Joint Cancer Institute, The Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433 (China); PLA General Hospital Cancer Center and PLA Cancer Research Institute, PLA Postgraduate School of Medicine, 28 Fuxing Road, Beijing (China); Dai, Jianxin [International Joint Cancer Institute, The Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433 (China); PLA General Hospital Cancer Center and PLA Cancer Research Institute, PLA Postgraduate School of Medicine, 28 Fuxing Road, Beijing (China); National Engineering Research Center for Antibody Medicine and Shanghai Key Lab. of Cell Engineering and Antibody, 399 Libing Road, Shanghai 201203 (China); Wang, Huaqing [International Joint Cancer Institute, The Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433 (China); Wei, Huafeng [International Joint Cancer Institute, The Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433 (China); PLA General Hospital Cancer Center and PLA Cancer Research Institute, PLA Postgraduate School of Medicine, 28 Fuxing Road, Beijing (China); Zhao, Jian [International Joint Cancer Institute, The Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433 (China); National Engineering Research Center for Antibody Medicine and Shanghai Key Lab. of Cell Engineering and Antibody, 399 Libing Road, Shanghai 201203 (China); Guo, Yajun, E-mail: yguo_smmu@163.com [International Joint Cancer Institute, The Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433 (China); PLA General Hospital Cancer Center and PLA Cancer Research Institute, PLA Postgraduate School of Medicine, 28 Fuxing Road, Beijing (China); National Engineering Research Center for Antibody Medicine and Shanghai Key Lab. of Cell Engineering and Antibody, 399 Libing Road, Shanghai 201203 (China); and others

    2014-09-26

    Highlight: • We first report that anti-osteopontin mAb could protect osteoporosis in mice. • Anti-osteopontin mAb could promote the osteoclast apoptosis. • Targeting osteopontin might have therapeutic potentials for osteoporosis. - Abstract: Osteopontin (OPN) is abundant in mineralized tissues and has long been implicated in bone remodeling. However, the therapeutic effect of targeting OPN in bone loss diseases and the underlying molecular mechanism remain largely unknown. Here, we reported that anti-OPN mAb (23C3) could protect against ovariectomy-induced osteoporosis in mice, demonstrated by microcomputed tomography analysis and histopathology evaluation. In vitro assay showed that 23C3 mAb reduced osteoclasts (OCs)-mediated bone resorption through promotion of mature OC apoptosis. Thus, the study has important implications for understanding the role of OPN in OC bone resorption and survival, and OPN antagonists may have therapeutic potential for osteoporosis and other osteopenic diseases.

  8. Anti-osteopontin monoclonal antibody prevents ovariectomy-induced osteoporosis in mice by promotion of osteoclast apoptosis

    International Nuclear Information System (INIS)

    Zhang, Bo; Dai, Jianxin; Wang, Huaqing; Wei, Huafeng; Zhao, Jian; Guo, Yajun

    2014-01-01

    Highlight: • We first report that anti-osteopontin mAb could protect osteoporosis in mice. • Anti-osteopontin mAb could promote the osteoclast apoptosis. • Targeting osteopontin might have therapeutic potentials for osteoporosis. - Abstract: Osteopontin (OPN) is abundant in mineralized tissues and has long been implicated in bone remodeling. However, the therapeutic effect of targeting OPN in bone loss diseases and the underlying molecular mechanism remain largely unknown. Here, we reported that anti-OPN mAb (23C3) could protect against ovariectomy-induced osteoporosis in mice, demonstrated by microcomputed tomography analysis and histopathology evaluation. In vitro assay showed that 23C3 mAb reduced osteoclasts (OCs)-mediated bone resorption through promotion of mature OC apoptosis. Thus, the study has important implications for understanding the role of OPN in OC bone resorption and survival, and OPN antagonists may have therapeutic potential for osteoporosis and other osteopenic diseases

  9. Combined blood and pleural levels of mesothelin and osteopontin for the diagnosis of malignant pleural mesothelioma

    Directory of Open Access Journals (Sweden)

    Wafaa M. Ashour

    2012-07-01

    Conclusion: The performance of serum and pleural mesothelin in diagnosing MPM was improved when combined with plasma and pleural osteopontin (respectively through logistic regression analysis model. This will be a great advance in screening and management of MPM.

  10. Methylglyoxal-bis-guanylhydrazone inhibits osteopontin expression and differentiation in cultured human monocytes.

    Science.gov (United States)

    Jin, Xia; Xu, Hua; McGrath, Michael S

    2018-01-01

    Monocyte activation and polarization play essential roles in many chronic inflammatory diseases. An imbalance of M1 and M2 macrophage activation (pro-inflammatory and alternatively activated, respectively) is believed to be a key aspect in the etiology of these diseases, thus a therapeutic approach that regulates macrophage activation could be of broad clinical relevance. Methylglyoxal-bis-guanylhydrazone (MGBG), a regulator of polyamine metabolism, has recently been shown to be concentrated in monocytes and macrophages, and interfere with HIV integration into the DNA of these cells in vitro. RNA expression analysis of monocytes from HIV+ and control donors with or without MGBG treatment revealed the only gene to be consistently down regulated by MGBG to be osteopontin (OPN). The elevated expression of this pro-inflammatory cytokine and monocyte chemoattractant is associated with various chronic inflammatory diseases. We demonstrate that MGBG is a potent inhibitor of secreted OPN (sOPN) in cultured monocytes with 50% inhibition achieved at 0.1 μM of the drug. Furthermore, inhibition of OPN RNA transcription in monocyte cultures occurs at similar concentrations of the drug. During differentiation of monocytes into macrophages in vitro, monocytes express cell surface CD16 and the cells undergo limited DNA synthesis as measured by uptake of BrdU. MGBG inhibited both activities at similar doses to those regulating OPN expression. In addition, monocyte treatment with MGBG inhibited differentiation into both M1 and M2 classes of macrophages at non-toxic doses. The inhibition of differentiation and anti-OPN effects of MGBG were specific for monocytes in that differentiated macrophages were nearly resistant to MGBG activities. Thus MGBG may have potential therapeutic utility in reducing or normalizing OPN levels and regulating monocyte activation in diseases that involve chronic inflammation.

  11. Dynamic Light Scattering Study of Inhibition of Nucleation and Growth of Hydroxyapatite Crystals by Osteopontin

    Science.gov (United States)

    de Bruyn, John R.; Goiko, Maria; Mozaffari, Maryam; Bator, Daniel; Dauphinee, Ron L.; Liao, Yinyin; Flemming, Roberta L.; Bramble, Michael S.; Hunter, Graeme K.; Goldberg, Harvey A.

    2013-01-01

    We study the effect of isoforms of osteopontin (OPN) on the nucleation and growth of crystals from a supersaturated solution of calcium and phosphate ions. Dynamic light scattering is used to monitor the size of the precipitating particles and to provide information about their concentration. At the ion concentrations studied, immediate precipitation was observed in control experiments with no osteopontin in the solution, and the size of the precipitating particles increased steadily with time. The precipitate was identified as hydroxyapatite by X-ray diffraction. Addition of native osteopontin (nOPN) extracted from rat bone caused a delay in the onset of precipitation and reduced the number of particles that formed, but the few particles that did form grew to a larger size than in the absence of the protein. Recombinant osteopontin (rOPN), which lacks phosphorylation, caused no delay in initial calcium phosphate precipitation but severely slowed crystal growth, suggesting that rOPN inhibits growth but not nucleation. rOPN treated with protein kinase CK2 to phosphorylate the molecule (p-rOPN) produced an effect similar to that of nOPN, but at higher protein concentrations and to a lesser extent. These results suggest that phosphorylations are critical to OPN’s ability to inhibit nucleation, whereas the growth of the hydroxyapatite crystals is effectively controlled by the highly acidic OPN polypeptide. This work also demonstrates that dynamic light scattering can be a powerful tool for delineating the mechanism of protein modulation of mineral formation. PMID:23457612

  12. Interaction of human mesenchymal stem cells with osteopontin coated hydroxyapatite surfaces

    DEFF Research Database (Denmark)

    Jensen, Thomas; Dolatshahi-Pirouz, Alireza; Foss, Morten

    2010-01-01

    In vitro studies of the initial attachment, spreading and motility of human bone mesenchymal stem cells have been carried out on bovine osteopontin (OPN) coated hydroxyapatite (HA) and gold (Au) model surfaces. The adsorption of OPN extracted from bovine milk was monitored by the quartz crystal...

  13. Osteopontin Promotes Cell Migration and Invasion, and Inhibits Apoptosis and Autophagy in Colorectal Cancer by activating the p38 MAPK Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Ren-hong Huang

    2017-04-01

    Full Text Available Background: Osteopontin (OPN is highly expressed in colorectal cancer (CRC and is associated with disease progression in vivo. High levels of OPN have been demonstrated to predict low survival rates in CRC. Autophagy is a process of self-digestion, which is thought to play a significant role in carcinogenesis. However, the mechanisms of OPN's effects on CRC cell autophagy have not been elucidated. Therefore, we aimed to investigate possible mechanisms of OPN's effects on CRC autophagy. Methods: HCT116 cell proliferation, apoptosis, and migration and invasion ability were identified by cell counting k¡t-8 assay, flow cytometry, wound healing assay, and transwell chamber invasion assay, respectively. The ratios of proteins LC3-II/LC3-I, P62, and Atg7 were analyzed by Western-blot. Expressions of Beclin-1, Atg4b, Bnip3, and Vps34, both in transcriptional and translational levels, were analyzed and compared by RT-PCR and Western blot. Immunofluorescence and co-focusing experiments were used to investigate the formation of autophagosomes. Results: The results showed that OPN can promote cell proliferation, migration, and invasion, as well as inhibit cell apoptosis. It was also demonstrated that OPN could inhibit cell autophagy. Further experiments revealed that the inhibitory effect of OPN on autophagy could be reversed by blocking the p38 MAPK pathway in HCT116 cells. Conclusion: OPN is involved in HCT116 cell progression and is capable of inhibiting cell autophagy possibly by activating the p38 MAPK signaling pathway, implying that OPN could be a potential novel molecular therapeutic biomarker in patients with CRC.

  14. Is Osteopontin a Friend or Foe of Cell Apoptosis in Inflammatory Gastrointestinal and Liver Diseases?

    Science.gov (United States)

    Iida, Tomoya; Wagatsuma, Kohei; Hirayama, Daisuke; Nakase, Hiroshi

    2017-12-21

    Osteopontin (OPN) is involved in a variety of biological processes, including bone remodeling, innate immunity, acute and chronic inflammation, and cancer. The expression of OPN occurs in various tissues and cells, including intestinal epithelial cells and immune cells such as macrophages, dendritic cells, and T lymphocytes. OPN plays an important role in the efficient development of T helper 1 immune responses and cell survival by inhibiting apoptosis. The association of OPN with apoptosis has been investigated. In this review, we described the role of OPN in inflammatory gastrointestinal and liver diseases, focusing on the association of OPN with apoptosis. OPN changes its association with apoptosis depending on the type of disease and the phase of disease activity, acting as a promoter or a suppressor of inflammation and inflammatory carcinogenesis. It is essential that the roles of OPN in those diseases are elucidated, and treatments based on its mechanism are developed.

  15. Osteopontin: Relation between Adipose Tissue and Bone Homeostasis

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    Carolina De Fusco

    2017-01-01

    Full Text Available Osteopontin (OPN is a multifunctional protein mainly associated with bone metabolism and remodeling. Besides its physiological functions, OPN is implicated in the pathogenesis of a variety of disease states, such as obesity and osteoporosis. Importantly, during the last decades obesity and osteoporosis have become among the main threats to health worldwide. Because OPN is a protein principally expressed in cells with multifaceted effects on bone morphogenesis and remodeling and because it seems to be one of the most overexpressed genes in the adipose tissue of the obese contributing to osteoporosis, this mini review will highlight recent insights about relation between adipose tissue and bone homeostasis.

  16. Osteopontin: Relation between Adipose Tissue and Bone Homeostasis.

    Science.gov (United States)

    De Fusco, Carolina; Messina, Antonietta; Monda, Vincenzo; Viggiano, Emanuela; Moscatelli, Fiorenzo; Valenzano, Anna; Esposito, Teresa; Sergio, Chieffi; Cibelli, Giuseppe; Monda, Marcellino; Messina, Giovanni

    2017-01-01

    Osteopontin (OPN) is a multifunctional protein mainly associated with bone metabolism and remodeling. Besides its physiological functions, OPN is implicated in the pathogenesis of a variety of disease states, such as obesity and osteoporosis. Importantly, during the last decades obesity and osteoporosis have become among the main threats to health worldwide. Because OPN is a protein principally expressed in cells with multifaceted effects on bone morphogenesis and remodeling and because it seems to be one of the most overexpressed genes in the adipose tissue of the obese contributing to osteoporosis, this mini review will highlight recent insights about relation between adipose tissue and bone homeostasis.

  17. Identification of A Novel Root Resorptive Function of Osteopontin Gene

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    M. Seifi

    2008-12-01

    Full Text Available Objective: Osteopontin (OPN has been proposed to play a role in bone resorption. With regard to bone and cementum/dentin structural and histological similarities, it was hy-pothesized that expression of this gene might be increased in resorptive lacunae during orthodontic tooth movement.Materials and Methods: Fixed Nickel-Titanium closed coil springs (Dentaurum® capa-ble of delivering approximately 60 gf were applied for mesial movement of maxillary left first molars in 26 male 8-week-old Wistar rats. The right maxillary molar served as inter-nal control for each subject. After 21 days, the rats were sacrificed. Tissues from 13 rats were examined by histomorphometric analysis and the scratched material from resorptive lacunae on mesial sides of the roots was used for extracting messenger ribonucleic acid (mRNA in RT-PCR reactions. T-test and Wilcoxon signed-rank test served for statistical analyses.Results: Histomorphometric analysis of histologic sections revealed an increased resorbed area in test group compared to control animals (P<0.001. The integrity of mRNA con-firmed by RT-PCR for housekeeping gene glyceraldehyde 3-phosphate dehydrogenase (GAPDH. Densitometric analysis of OPN mRNA on electrophoresis gel showed an in-crease in background levels of OPN in resorptive lacunae of test group (P<0.001.Conclusion: Data indicates that in the controlled environment of this study, an increase in OPN expression is associated with root resorption induced by orthodontic tooth move-ment.

  18. Osteopontin-enhanced hepatic metastasis of colorectal cancer cells.

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    Jianjin Huang

    Full Text Available Liver metastasis is a major cause of mortality from colorectal cancer (CRC. However, mechanisms underlying this process are largely unknown. Osteopontin (OPN is a secreted phosphorylated glycoprotein that is involved in tumor migration and metastasis. The role of OPN in cancer is currently unclear. In this study, OPN mRNA was examined in tissues from CRC, adjacent normal mucosa, and liver metastatic lesions using quantitative real-time PCR analysis. The protein expression of OPN and its receptors (integrin αv and CD44 v6 was detected by using an immunohistochemical (IHC method. The role of OPN in liver metastasis was studied in established colon cancer Colo-205 and SW-480 cell lines transfected with sense- or antisense-OPN eukaryotic expression plasmids by flow cytometry and cell adhesion assay. Fluorescence redistribution after photobleaching (FRAP was used to study gap functional intercellular communication (GJIC among OPN-transfected cells. It was found that OPN was highly expressed in metastatic hepatic lesions from CRC compared to primary CRC tissue and adjacent normal mucosa. The expression of OPN mRNA in tumor tissues was significantly related with the CRC stages. OPN expression was also detected in normal hepatocytes surrounding CRC metastatic lesions. Two known receptors of OPN, integrin αv and CD44v6 proteins, were strongly expressed in hepatocytes from normal liver. CRC cells with forced OPN expression exhibited increased heterotypic adhesion with endothelial cells and weakened intercellular communication. OPN plays a significant role in CRC metastasis to liver through interaction with its receptors in hepatocytes, decreased homotypic adhesion, and enhanced heterotypic adhesion.

  19. Separation Options for Phosphorylated Osteopontin from Transgenic Microalgae Chlamydomonas reinhardtii

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    Ayswarya Ravi

    2018-02-01

    Full Text Available Correct folding and post-translational modifications are vital for therapeutic proteins to elicit their biological functions. Osteopontin (OPN, a bone regenerative protein present in a range of mammalian cells, is an acidic phosphoprotein with multiple potential phosphorylation sites. In this study, the ability of unicellular microalgae, Chlamydomonas reinhardtii, to produce phosphorylated recombinant OPN in its chloroplast is investigated. This study further explores the impact of phosphorylation and expression from a “plant-like” algae on separation of OPN. Chromatography resins ceramic hydroxyapatite (CHT and Gallium-immobilized metal affinity chromatography (Ga-IMAC were assessed for their binding specificity to phosphoproteins. Non-phosphorylated recombinant OPN expressed in E. coli was used to compare the specificity of interaction of the resins to phosphorylated OPN. We observed that CHT binds OPN by multimodal interactions and was better able to distinguish phosphorylated proteins in the presence of 250 mM NaCl. Ga-IMAC interaction with OPN was not selective to phosphorylation, irrespective of salt, as the resin bound OPN from both algal and bacterial sources. Anion exchange chromatography proved an efficient capture method to partially separate major phosphorylated host cell protein impurities such as Rubisco from OPN.

  20. Absence of bone sialoprotein (BSP) alters profoundly hematopoiesis and upregulates osteopontin.

    Science.gov (United States)

    Granito, Renata Neves; Bouleftour, Wafa; Sabido, Odile; Lescale, Chloé; Thomas, Mireille; Aubin, Jane E; Goodhardt, Michèle; Vico, Laurence; Malaval, Luc

    2015-06-01

    Matrix proteins of the SIBLING family interact with bone cells, extracellular matrix and mineral and are thus in a key position to regulate the microenvironment of the bone tissue, including its hematopoietic component. In this respect, osteopontin (OPN) has been implicated in the hematopoietic stem cell (HSC) niche as negative regulator of the HSC function. We investigated the impact on hematopoietic regulation of the absence of the cognate bone sialoprotein (BSP). BSP knockout (-/-) mice display increased bone marrow cellularity, and an altered commitment of hematopoietic precursors to myeloid lineages, leading in particular to an increased frequency of monocyte/macrophage cells. The B cell pool is increased in -/- bone marrow, and its composition is shifted toward more mature lymphocyte stages. BSP-null mice display a decreased HSC fraction among LSK cells and a higher percentage of more committed progenitors as compared to +/+. The fraction of proliferating LSK progenitors is higher in -/- mice, and after PTH treatment the mutant HSC pool is lower than in +/+. Strikingly, circulating levels of OPN as well as its expression in the bone tissue are much higher in the -/-. Thus, a BSP-null bone microenvironment affects the hematopoietic system both quantitatively and qualitatively, in a manner in part opposite to the OPN knockout, suggesting that the effects might in part reflect the higher OPN expression in the absence of BSP. © 2014 Wiley Periodicals, Inc.

  1. Osteopontin adsorption to Gram-positive cells reduces adhesion forces and attachment to surfaces under flow

    DEFF Research Database (Denmark)

    Kristensen, M F; Zeng, G; Neu, T R

    2017-01-01

    caries or medical device-related infections. It further investigated if OPN's effect on adhesion is caused by blocking the accessibility of glycoconjugates on bacterial surfaces. Bacterial adhesion was determined in a shear-controlled flow cell system in the presence of different concentrations of OPN......The bovine milk protein osteopontin (OPN) may be an efficient means to prevent bacterial adhesion to dental tissues and control biofilm formation. This study sought to determine to what extent OPN impacts adhesion forces and surface attachment of different bacterial strains involved in dental......, and interaction forces of single bacteria were quantified using single-cell force spectroscopy before and after OPN exposure. Moreover, the study investigated OPN's effect on the accessibility of cell surface glycoconjugates through fluorescence lectin-binding analysis. OPN strongly affected bacterial adhesion...

  2. Secreted osteopontin is highly polymerized in human airways and fragmented in asthmatic airway secretions.

    Directory of Open Access Journals (Sweden)

    Mehrdad Arjomandi

    Full Text Available Osteopontin (OPN is a member of the small integrin-binding ligand N-linked glycoprotein (SIBLING family and a cytokine with diverse biologic roles. OPN undergoes extensive post-translational modifications, including polymerization and proteolytic fragmentation, which alters its biologic activity. Recent studies suggest that OPN may contribute to the pathogenesis of asthma.To determine whether secreted OPN (sOPN is polymerized in human airways and whether it is qualitatively different in asthma, we used immunoblotting to examine sOPN in bronchoalveolar lavage (BAL fluid samples from 12 healthy and 21 asthmatic subjects (and in sputum samples from 27 healthy and 21 asthmatic subjects. All asthmatic subjects had mild to moderate asthma and abstained from corticosteroids during the study. Furthermore, we examined the relationship between airway sOPN and cellular inflammation.We found that sOPN in BAL fluid and sputum exists in polymeric, monomeric, and cleaved forms, with most of it in polymeric form. Compared to healthy subjects, asthmatic subjects had proportionately less polymeric sOPN and more monomeric and cleaved sOPN. Polymeric sOPN in BAL fluid was associated with increased alveolar macrophage counts in airways in all subjects.These results suggest that sOPN in human airways (1 undergoes extensive post-translational modification by polymerization and proteolytic fragmentation, (2 is more fragmented and less polymerized in subjects with mild to moderate asthma, and (3 may contribute to recruitment or survival of alveolar macrophages.

  3. [Study on the function of osteopontin in hyperoxia-induced acute lung injury and its mechanism].

    Science.gov (United States)

    Zhang, Xiang-feng; Foda, Hussein D

    2006-06-01

    To examine the role of osteopontin (OPN) in hyperoxia-induced acute lung injury (ALI) and its relationships with matrix metalloproteinases (MMP). Seventy-two OPN gene wild type (OPN(+/+)) mice were divided into normal control group (WN group), hyperoxia for 24 hours group (WO(1) group), hyperoxia for 48 hours group (WO(2) group) and hyperoxia for 72 hours group (WO(3) group) randomly, 18 mice in each group; another seventy-two OPN gene knock-out (OPN(-/-)) mice were also divided into normal control group (DN group), hyperoxia for 24 hours group (DO(1) group), hyperoxia for 48 hours group (DO(2) group) and hyperoxia for 72 hours group (DO(3) group) randomly. The hyperoxia group mice were exposed in sealed cages > 95% oxygen, and their matched background control were put outside of sealed cages and breath room air. Severity of lung injury was assessed and the survival curve was calculated. Cell count and differentials in bronchoalveolar lavage fluid (BALF) in every group were performed, while another 40 OPN(-/-) mice and their matched OPN(+/+) mice were used for survival study. Samples obtained from BALF at the end of the experiment (24, 48 and 72 h) and control animals were used for the measurement of MMP-2, MMP-9 by gelatin zymography, and reverse transcript-polymerase chain reaction (RT-PCR) was used for the semiquantitative assay of mRNA coding for OPN, MMP-2, MMP-9, tissue-inhibitors of metalloproteinase-1, 2 (TIMP-1, TIMP-2). DO(3) group mice developed more severe ALI than WO(3) group mice and the survival times of OPN(-/-) mice were shorter than their matched OPN(+/+) mice (P < 0.01). The total cell count in BALF from DO(3) group mice was higher than WO(3) group mice [(72.2 +/- 22.3) x 10(4)/L, (39.7 +/- 10.4) x 10(4)/L, P < 0.05], the count of polymorphonuclear cells in BALF from DO(3) group mice was almost 8 folds higher than WO(3) group mice [(207.54 +/- 36.45) x 10(3)/L, (25.33 +/- 6.43) x 10(3)/L, P < 0.01]. Gelatin zymography showed that the level of

  4. Requirement of Osteopontin in the migration and protection against Taxol-induced apoptosis via the ATX-LPA axis in SGC7901 cells

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    Huang Zuhu

    2011-03-01

    Full Text Available Abstract Background Autotaxin (ATX possesses lysophospholipase D (lyso PLD activity, which converts lysophosphatidylcholine (LPC into lysophosphatidic acid (LPA. The ATX-LPA signaling axis has been implicated in angiogenesis, chronic inflammation and tumor progression. Osteopontin (OPN is an important chemokine involved in the survival, proliferation, migration, invasion and metastasis of gastric cancer cells. The focus of the present study was to investigate the relationship between the ATX-LPA axis and OPN. Results In comparison with non-treated cells, we found that the ATX-LPA axis up-regulated OPN expression by 1.92-fold in protein levels and 1.3-fold in mRNA levels. The ATX-LPA axis activates LPA2, Akt, ERK and ELK-1 and also protects SGC7901 cells from apoptosis induced by Taxol treatment. Conclusions This study provides the first evidence that expression of OPN induced by ATX-LPA axis is mediated by the activation of Akt and MAPK/ERK pathways through the LPA2 receptor. In addition, OPN is required for the protective effects of ATX-LPA against Taxol-induced apoptosis and ATX-LPA-induced migration of SGC7901 cells.

  5. Harnessing osteopontin and other natural inhibitors to mitigate ectopic calcification of bioprosthetic heart valve material

    Science.gov (United States)

    Ohri, Rachit

    Dystrophic calcification has been the long-standing major cause of bioprosthetic heart valve failure, and has been well studied in terms of the underlying causative mechanisms. Such understanding has yielded several anti-calcification strategies involving biomaterial modification at the preparation stage: chemical alteration, extraction of calcifiable components, or material modification with small-molecule anti-calcific agents. However, newer therapeutic opportunities are offered by the growing illustration of the pathology as a dynamic, actively regulated process involving several gene products, such as osteopontin (OPN), matrix-gla protein (MGP) and glycosaminoglycans (GAGs). Osteopontin, a multi-functional matricellular glycosylated phosphoprotein has emerged as a prime candidate for the role of an in vivo inhibitor of ectopic calcification with two putative mechanisms: crystal poisoning and mineral-dissolution. The full therapeutic realization of its potential necessitates a better understanding of the mechanisms of anti-calcification by osteopontin, as well as appropriate in vivo models in which to evaluate its efficacy, potency and molecular mechanisms. In this work, we pursued the development and characterization of a reliable in vivo model with the OPN-null mouse to simulate the calcification of bioprosthetic valve material, namely glutaraldehyde-fixed bovine pericardium (GFBP) tissue. Subsequently, we used the calcification model to evaluate hypotheses based on the anti-calcific potential of osteopontin. Several modes of administering exogenous OPN to the implant site in OPN-null mice were explored, including soluble injected OPN, OPN covalently immobilized on the biomaterial, and OPN adsorbed onto the biomaterial. An investigation of the structure-function aspects of the anti-calcific ability of OPN was also pursued in the in vivo model. The OPN-null mouse was also used as an in vivo test-bed to evaluate the anti-calcific potential of other biomolecules

  6. The involvement of osteopontin and matrix metalloproteinase- 9 in the migration of endometrial epithelial cells in patients with endometriosis.

    Science.gov (United States)

    Yang, Mei; Jiang, Chunfan; Chen, Hua; Nian, Yan; Bai, Zhimiao; Ha, Chunfang

    2015-08-20

    Endometriosis, which shares certain characteristics with cancers, may cause abnormal expression of proteins involved in cell migration. Endometrial epithelial cells (EECs) are believed to play an important role in endometriotic migration. The aim of this study was to investigate the relationship between the expression of osteopontin (OPN) and matrix metalloproteinase-9 (MMP-9) in endometriotic migration. We performed primary culture of EECs and investigated the expression of OPN and MMP-9 in EECs regulated by 17beta-estradiol (E2). OPN-specific siRNA interference was used to down-regulate OPN and to explore the corresponding change in MMP-9 expression. Real-time RT-PCR, western blot analysis and flow cytometry were used to determine the expression levels of OPN and MMP-9. Gelatin zymography was performed to observe the enzymatic activity of MMP-9 in conditioned media. Transwell and wound scratch assays were performed to investigate the migration ability of EECs. The expression levels of OPN and MMP-9 in normal EECs (NEECs) were inferior to those in EECs from patients with endometriosis (EEECs). The expression levels of OPN and MMP-9 from stage III/IV EEECs and secretory-phase EECs were higher than those of stage I/II EEECs or proliferative-phase EECs. The expression levels of OPN and MMP-9 in EEECs were increased by E2 treatment and remarkably decreased by siRNA interference. Active MMP-9 expression increased with E2 treatment and decreased with siRNA treatment in EEECs compared with the same treatments in NEECs. The migratory abilities of EEECs were enhanced after cells were treated with E2; in contrast, these abilities were reduced by siRNA interference. In NEECs, active MMP-9 and cellular migration abilities were only minimally influenced by E2 and siRNA treatment. The present study suggests that the up-regulation of MMP-9 via activation of OPN induced by estrogen may correlate with the migration of endometrial epithelial cells in patients with endometriosis.

  7. The Role of Osteopontin and Its Gene on Glucocorticoid Response in Myasthenia Gravis

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    Yanchen Xie

    2017-05-01

    Full Text Available Biomarkers that assess treatment response for patients with the autoimmune disorder, myasthenia gravis (MG, have not been evaluated to a significant extent. We hypothesized the pro-inflammatory cytokine, osteopontin (OPN, may be associated with variability of response to glucocorticoids (GCs in patients with MG. A cohort of 250 MG patients treated with standardized protocol of GCs was recruited, and plasma OPN and polymorphisms of its gene, secreted phosphoprotein 1 (SPP1, were evaluated. Mean OPN levels were higher in patients compared to healthy controls. Carriers of rs11728697*T allele (allele definition: one of two or more alternative forms of a gene were more frequent in the poorly GC responsive group compared to the GC responsive group indicating an association of rs11728697*T allele with GC non-responsiveness. One risk haplotype (AGTACT was identified associated with GC non-responsiveness compared with GC responsive MG group. Genetic variations of SPP1 were found associated with the response to GC among MG patients.

  8. Osteopontin attenuates acute gastrointestinal graft-versus-host disease by preventing apoptosis of intestinal epithelial cells

    International Nuclear Information System (INIS)

    Kawakami, Kentaro; Minami, Naoki; Matsuura, Minoru; Iida, Tomoya; Toyonaga, Takahiko; Nagaishi, Kanna; Arimura, Yoshiaki; Fujimiya, Mineko; Uede, Toshimitsu; Nakase, Hiroshi

    2017-01-01

    Background and aims: Acute graft-versus-host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation, which often targets gastrointestinal (GI) tract. Osteopontin (OPN) plays an important physiological role in the efficient development of Th1 immune responses and cell survival by inhibiting apoptosis. The role of OPN in acute GI-GVHD is poorly understood. In the present study, we investigated the role of OPN in donor T cells in the pathogenicity of acute GI-GVHD. Methods: OPN knockout (KO) mice and C57BL/6 (B6) mice were used as donors, and (C57BL/6 × DBA/2) F1 (BDF1) mice were used as allograft recipients. Mice with acute GI-GVHD were divided into three groups: the control group (BDF1→BDF1), B6 group (B6→BDF1), and OPN-KO group (OPN-KO→BDF1). Bone marrow cells and spleen cells from donors were transplanted to lethally irradiated recipients. Clinical GVHD scores were assessed daily. Recipients were euthanized on day 7 after transplantation, and colons and small intestines were collected for various analyses. Results: The clinical GVHD score in the OPN-KO group was significantly increased compared with the B6 and control groups. We observed a difference in the severity of colonic GVHD between the OPN-KO group and B6 group, but not small intestinal-GVHD between these groups. Interferon-γ, Tumor necrosis factor-α, Interleukin-17A, and Interleukin-18 gene expression in the OPN-KO group was differed between the colon and small intestine. Flow cytometric analysis revealed that the fluorescence intensity of splenic and colonic CD8 T cells expressing Fas Ligand was increased in the OPN-KO group compared with the B6 group. Conclusion: We demonstrated that the importance of OPN in T cells in the onset of acute GI-GVHD involves regulating apoptosis of the intestinal cell via the Fas-Fas Ligand pathway. - Highlights: • A lack of osteopontin in donor cells exacerbated clinical gastrointestinal GVHD. • Donor cells lacking

  9. Osteopontin Promotes Invasion, Migration and Epithelial-Mesenchymal Transition of Human Endometrial Carcinoma Cell HEC-1A Through AKT and ERK1/2 Signaling

    OpenAIRE

    Yinghua Li; Yunpeng Xie; Dan Cui; Yanni Ma; Linlin Sui; Chenyang Zhu; Hui Kong; Ying Kong

    2015-01-01

    Background/Aims: Osteopontin (OPN) is an Extracellular Matrix (ECM) molecule and is involved in many physiologic and pathologic processes, including cell adhesion, angiogenesis and tumor metastasis. OPN is a well-known multifunctional factor involved in various aspects of cancer progression, including endometrial cancer. In this study, we examined the significance of OPN in endometrial cancer. Methods: The proliferation, migration and invasion ability of HEC-1A cells were detected by Cell Cou...

  10. Osteopontin Involves Cisplatin Resistance and Poor Prognosis in Oral Squamous Cell Carcinoma

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    Sheng-Dean Luo

    2015-01-01

    Full Text Available Background. Osteopontin (OPN is a multifunctional cytokine involved in cell survival, migration, and adhesion. However, its role in chemosensitivity in locally advanced oral squamous cell carcinoma (OSCC in humans has not yet been investigated. Methods. We enrolled 121 patients with locally advanced stage IVA/B OSCC receiving cisplatin-based IC followed by CCRT from January 1, 2006, through January 1, 2012. Immunohistochemistry was used to assess OPN expression in OSCC patients’ biopsy specimens from paraffin blocks before treatment. In addition, MTT/colony formation assay was used to estimate the influence of OPN in an oral cancer cell line treated with cisplatin. Results. Of the 121 patients, 94 had positive OPN findings and 52 responded to IC followed by CCRT. Positive osteopontin immunostaining also correlated significantly with positive N status/TNM stage/male gender and smoking. Univariate analyses showed that patients whose tumors had a low expression of OPN were more likely to respond to chemotherapy and have a significantly better OS than those whose tumors had a high expression of OPN. Multivariate analysis revealed that prolonged survival was independently predicted for patients with stage IVA disease, negative lymph nodes, and negative expressions of OPN and for those who received chemotherapy with Docetaxel/cisplatin/fluorouracil (TPF. An oral cancer line stimulated with OPN exhibited a dose-dependent resistance to cisplatin treatment. Conversely, endogenous OPN depletion by OPN-mediated shRNA increased sensitivity to cisplatin. Conclusions. A positive expression of OPN predicts a poor response and survival in patients with locally advanced stage IVA/B OSCC treated with cisplatin-based IC followed by CCRT.

  11. Expression patterns of the hypoxia-related genes osteopontin, CA9, erythropoietin, VEGF and HIF-1α in human glioma in vitro and in vivo

    International Nuclear Information System (INIS)

    Said, Harun M.; Hagemann, Carsten; Staab, Adrian; Stojic, Jelena; Kuehnel, Siglinde; Vince, Giles H.; Flentje, Michael; Roosen, Klaus; Vordermark, Dirk

    2007-01-01

    Background and purpose: To identify molecular markers of tumor hypoxia and potential therapeutic targets in glioblastoma (GBM), we investigated the hypoxia-related expression of osteopontin (OPN), carbonic anhydrase 9 (CA9), erythropoietin (EPO), vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) in vitro in human GBM cell lines and in vivo in human tumor samples of GBM, compared to low-grade astrocytoma (LGA). Materials and methods: Expression of the hypoxia-induced genes OPN, CA9, EPO, VEGF and HIF-1α was analyzed in three GBM cell lines, GaMG, U373 and U251, under in vitro hypoxia (1, 6 or 24 h at 5%, 1% or 0.1% O 2 ) and in tumor samples from two patient groups with LGA and GBM (n = 15 each), at the mRNA level (semiquantitative RT-PCR). Selected conditions and representative tumor samples were also evaluated at the protein level by Western blot. Results: OPN and CA9 mRNA was most consistently upregulated in relation to severity and duration of in vitro hypoxia. In tumor samples, mean expression levels (LGA vs. GBM, normalized to mean expression in normal brain) were 1.71 vs. 4.57 (p < 0.001) for OPN, 1.11 vs. 3.35 (p < 0.001) for CA9, 2.79 vs. 5.28 (not significant, n.s.) for Epo, 1.13 vs. 2.0 (p = 0.007) for VEGF and 0.97 vs. 0.97 (n.s.) for HIF-1α. In tumor samples, GBM showed a particularly strong protein expression of OPN. Conclusions: Among a panel of known hypoxia-inducible genes, OPN and CA9 emerge as most consistently induced by in vitro hypoxia in human GBM cell lines and most specifically expressed in patient GBM tumor tissue, rendering these two genes attractive targets for hypoxia-directed treatment approaches

  12. Elevated osteopontin and thrombospondin expression identifies malignant human breast carcinoma but is not indicative of metastatic status

    International Nuclear Information System (INIS)

    Wang-Rodriguez, Jessica; Urquidi, Virginia; Rivard, Amber; Goodison, Steve

    2003-01-01

    Our previous characterization of a human breast tumor metastasis model identified several candidate metastasis genes. The expression of osteopontin (OPN) correlated with the metastatic phenotype, whereas thrombospondin-1 (TSP-1) and tyrosinase-related protein-1 (TYRP-1) correlated with the nonmetastatic phenotype of independent MDA-MB-435 cell lines implanted orthotopically into athymic mice. The aim of the present study was to examine the cellular distribution of these molecules in human breast tissue and to determine whether the relative expression level of these three genes is associated with human breast tumor metastasis. Sixty-eight fresh, frozen specimens including 31 primary infiltrating ductal carcinomas, 22 nodal metastases, 10 fibroadenomas, and five normal breast tissues were evaluated for OPN expression, TSP-1 expression and TYRP-1 expression. Immunohistochemistry was performed to monitor the cellular distribution and to qualitatively assess expression. Quantitative analysis was achieved by enrichment of breast epithelial cells using laser-capture microdissection and subsequent real-time, quantitative PCR. The epithelial components of the breast tissue were the source of OPN and TSP-1 expression, whereas TYRP-1 was present in both the epithelial and stromal components. Both OPN and TSP-1 expression were significantly higher in malignant epithelial sources over normal and benign epithelial sources, but no difference in expression levels was evident between primary tumors with or without metastases, nor between primary and metastatic carcinomas. Elevated expression of OPN and TSP-1 may play a role in the pathogenesis of breast cancer. The multiplex analysis of these molecules may enhance our ability to diagnose and/or prognosticate human breast malignancy

  13. Osteopontin Reduces the Adhesion Force of Dental Bacteria Without Blocking Bacterial Cell Surface Glycoconjugates

    DEFF Research Database (Denmark)

    Kristensen, Mathilde Frost; Zeng, Guanghong; Neu, Thomas R.

    2017-01-01

    . paracasei, and lectins VGA and WGA to S. mitis. Immobilized bacteria were incubated with these lectins in the presence and absence of OPN. For each combination, 12 confocal images were acquired with fixed microscope settings, and average fluorescence intensities were determined. Experiments were performed......The bovine milk protein osteopontin (OPN) has been shown to reduce the adhesion of oral bacteria to saliva-coated surfaces, which reduces biofilm formation and may contribute to caries control. We now quantified the effect of OPN (Lacprodan OPN-10) treatment on the adhesion force of Lactobacillus...... and after OPN treatment. Adhesion energy was found to be reduced by 94% for L. paracasei and 61% for A. naeslundii (pbacteria was screened. Lectins BanLec, ConA, VGA and WGA bound well to A. naeslundii, lectins ABA and HPA to L...

  14. Association of OPN rs11730582 polymorphism with cancer risk: a meta-analysis

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    He LL

    2016-03-01

    Full Text Available Lanlan He,1,* Yong Wang2,* 1Emergency Department, Zhenjiang First People’s Hospital, Zhenjiang, People’s Republic of China; 2Department of Interventional Radiology and Vascular Surgery, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, People’s Republic of China *Both authors contributed equally to this work Purpose: Several molecular epidemiological studies have investigated the association between OPN rs11730582 C>T polymorphism and cancer risk, but the results are inconsistent. Hence, a meta-analysis was conducted to determine the association of this polymorphism with cancer risk. Materials and methods: The related articles were searched in PubMed, Embase, and Chinese National Knowledge Infrastructure databases. Pooled odds ratios and 95% confidence intervals were calculated to evaluate the strength of the associations. A random-effects model or fixed-effects model was employed depending on the heterogeneity. Results: A total of ten case-control studies involving 2,749 cancer cases and 3,398 controls were included in the meta-analysis. In overall analysis, OPN rs11730582 C>T polymorphism was not associated with cancer risk. In a stratified analysis by cancer type, no significant association was found between OPN rs11730582 C>T polymorphism and the risk of glioma, gastric cancer, and other cancers. Conclusion: This meta-analysis suggests that OPN rs11730582 C>T polymorphism is not associated with cancer susceptibility. Keywords: osteopontin, polymorphism, cancer, risk 

  15. Elevated OPN, IP-10, and Neutrophilia in Loop-Mediated Isothermal Amplification Confirmed Tuberculosis Patients

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    Beata Shiratori

    2014-01-01

    Full Text Available Tuberculosis (TB is the second most common cause of death from infectious diseases and results in high socioeconomic losses to many countries. Proper diagnosis is the first step in TB eradication. To develop a rapid, simple, and accurate diagnostic TB test and to characterize the prevalence of Mycobacterium tuberculosis (MTB genotypes and immune profiles of TB patients, a total of 37 TB patients and 30 healthy control (HC from Metro Manila were enrolled. Loop-mediated isothermal amplification (LAMP reliably detected MTB infection. Manila genotype was identified by spoligotyping method in all TB patients. Osteopontin (OPN, interferon-γ-induced protein 10 kDa (IP-10, and neutrophil counts were found to reflect the acute stage of MTB infection. The sensitivity and specificity were 94.6% and 93.3%, respectively, for both OPN and IP-10, and they were 83.8% and 78.6%, respectively, for neutrophils. The combination of OPN, IP-10, neutrophil count, IL-6, IL-8, TNF-α, MCP-1, platelets, galectin-9, and leukocyte count correctly identifies all the HC and 96.3% of TB patients. LAMP method may serve as a rapid, supportive method in addition to time-consuming culture methods. OPN, IP-10, and neutrophil counts are useful in detecting MTB infection and may have utility in monitoring the course of the disease.

  16. Inhibition of Cellular Adhesion by Immunological Targeting of Osteopontin Neoepitopes Generated through Matrix Metalloproteinase and Thrombin Cleavage.

    Science.gov (United States)

    Jürets, Alexander; Le Bras, Marie; Staffler, Günther; Stein, Gesine; Leitner, Lukas; Neuhofer, Angelika; Tardelli, Matteo; Turkof, Edvin; Zeyda, Maximilian; Stulnig, Thomas M

    2016-01-01

    Osteopontin (OPN), a secreted protein involved in inflammatory processes and cancer, induces cell adhesion, migration, and activation of inflammatory pathways in various cell types. Cells bind OPN via integrins at a canonical RGD region in the full length form as well as to a contiguous cryptic site that some have shown is unmasked upon thrombin or matrix metalloproteinase cleavage. Thus, the adhesive capacity of osteopontin is enhanced by proteolytic cleavage that may occur in inflammatory conditions such as obesity, atherosclerosis, rheumatoid arthritis, tumor growth and metastasis. Our aim was to inhibit cellular adhesion to recombinant truncated proteins that correspond to the N-terminal cleavage products of thrombin- or matrix metalloproteinase-cleaved OPN in vitro. We specifically targeted the cryptic integrin binding site with monoclonal antibodies and antisera induced by peptide immunization of mice. HEK 293 cells adhered markedly stronger to truncated OPN proteins than to full length OPN. Without affecting cell binding to the full length form, the raised monoclonal antibodies specifically impeded cellular adhesion to the OPN fragments. Moreover, we show that the peptides used for immunization were able to induce antisera, which impeded adhesion either to all OPN forms, including the full-length form, or selectively to the corresponding truncated recombinant proteins. In conclusion, we developed immunological tools to selectively target functional properties of protease-cleaved OPN forms, which could find applications in treatment and prevention of various inflammatory diseases and cancers.

  17. CD44v10, osteopontin and lymphoma growth retardation by a CD44v10-specific antibody.

    Science.gov (United States)

    Megaptche, Amelie Pajip; Erb, Ulrike; Büchler, Markus Wolfgang; Zöller, Margot

    2014-09-01

    Blockade of CD44 is considered a therapeutic option for the elimination of leukemia-initiating cells. However, the application of anti-panCD44 can be burdened by severe side effects. We determined whether these side effects could be avoided by replacing anti-panCD44 with CD44 variant isoform (CD44v)-specific antibodies in CD44v-positive hematological malignancies using the EL4 thymoma and CD44v10-transfected EL4 (EL4-v10) as models. Subcutaneous growth of EL4 and EL4-v10 was equally well inhibited by the anti-panCD44 and anti-CD44v10 antibodies, respectively. Ex vivo analysis indicated that natural killer cytotoxicity and antibody-dependent cellular cytotoxicity were the main effector mechanisms. Under local inflammation, the efficacy of anti-CD44v10 prolonged the survival time twofold compared with untreated, EL4-v10 tumor-bearing mice, and this was due to inflammation-induced expression of osteopontin (OPN). A high level of OPN in EL4-v10 tumors supported leukocyte recruitment and tumor-infiltrating T-cell activation. Taken together, in hematological malignancies expressing CD44v, anti-panCD44 can be replaced by CD44v-specific antibodies without a loss in efficacy. Furthermore, CD44v10-specific antibodies appear particularly advantageous in cutaneous leukemia therapy, as CD44v10 binding of OPN drives leukocyte recruitment and activation.

  18. Osteopontin attenuates aging-associated phenotypes of hematopoietic stem cells.

    Science.gov (United States)

    Guidi, Novella; Sacma, Mehmet; Ständker, Ludger; Soller, Karin; Marka, Gina; Eiwen, Karina; Weiss, Johannes M; Kirchhoff, Frank; Weil, Tanja; Cancelas, Jose A; Florian, Maria Carolina; Geiger, Hartmut

    2017-04-03

    Upon aging, hematopoietic stem cells (HSCs) undergo changes in function and structure, including skewing to myeloid lineages, lower reconstitution potential and loss of protein polarity. While stem cell intrinsic mechanisms are known to contribute to HSC aging, little is known on whether age-related changes in the bone marrow niche regulate HSC aging. Upon aging, the expression of osteopontin (OPN) in the murine bone marrow stroma is reduced. Exposure of young HSCs to an OPN knockout niche results in a decrease in engraftment, an increase in long-term HSC frequency and loss of stem cell polarity. Exposure of aged HSCs to thrombin-cleaved OPN attenuates aging of old HSCs, resulting in increased engraftment, decreased HSC frequency, increased stem cell polarity and a restored balance of lymphoid and myeloid cells in peripheral blood. Thus, our data suggest a critical role for reduced stroma-derived OPN for HSC aging and identify thrombin-cleaved OPN as a novel niche informed therapeutic approach for ameliorating HSC phenotypes associated with aging. © 2017 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

  19. Immunolocalization of osteopontin in dysplasias and squamous cell carcinomas arising from oral epithelium.

    Science.gov (United States)

    Aravind, Thara; Janardhanan, Mahija; Rakesh, S; Savithri, Vindhya; Unnikrishnan, U G

    2017-01-01

    Early detection of oral squamous cell carcinoma (OSCC) remains one of the most efficient ways to ensure patient survival and improved quality of life. Although specific biomarkers related to OSCC have been investigated, a useful biomarker that assesses the transition potential of potentially malignant lesion to OSCC remains to be found. Osteopontin (OPN) has been recognized as an important factor in tumorigenesis and their expression in OSCC have been investigated earlier. In the present study, evaluation of OPN expression in premalignant and malignant lesions has been carried out to assess their possible role as a biomarker in the early diagnosis and prognosis of OSCC. The objective of this study is to evaluate the role of OPN as a biomarker in the diagnosis and prognosis of OSCC. The study group consisted of archival paraffin-embedded blocks of ten cases each of varying grades of OSCC, oral epithelial dysplasias and epithelial hyperplasias. Sections were subjected to immunohistochemical staining for the biomarker OPN. A positive OPN expression was noticed in epithelial dysplasias and SCC arising from the oral epithelium. A progressive increase in the intensity of staining was seen with increasing grades of dysplasias and a decrease in OPN expression with an increase in grades was observed in OSCC. The expression of OPN in full thickness of epithelium in severe dysplasias, carcinoma in situ, and in the superficial epithelium of OSCC suggest the possibility of considering OPN expression in full epithelial thickness in dysplasias as an indicator for malignant transformation.

  20. Association between promoter polymorphisms of OPN gene and cancer risk: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Liu JW

    2015-12-01

    Full Text Available Jingwei Liu,1–2 Caiyun He,1–2 Quan Yuan,1–2 Zhenning Wang,1–2 Chengzhong Xing,1–2 Yuan Yuan1–2 1Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, 2Key Laboratory of Cancer Etiology and Prevention, China Medical University, Liaoning Provincial Education Department, Shenyang, People’s Republic of China Background: Results of the association between polymorphisms of osteopontin (OPN gene promoter region and risk of cancer were inconclusive. The aim of this meta-analysis was to elucidate whether OPN promoter polymorphisms were associated with cancer risk.Methods: Electronic databases including PubMed, Web of Science, and Chinese National Knowledge Infrastructure were systematically searched. Odd ratios (ORs and their 95% confidential interval (CI were used to assess the strength of association between OPN promoter polymorphisms and cancer risks.Results: Nine studies were finally included in this meta-analysis. For OPN rs17524488 polymorphism, carriers of GG or -/G genotype were significantly associated with increased cancer risk compared with wild-type -/- carriers, respectively (GG vs -/-: OR =1.40, 95% CI =1.03–1.91, P=0.033; -/G vs -/-: OR =1.22, 95% CI =1.07–1.40, P=0.002. Additionally, G allele was significantly associated with increased cancer risk compared with (- allele (OR =1.21, 95% CI =1.04–1.40, P=0.016. However, no significant association was observed of OPN rs11730582 polymorphism and cancer risk (CC vs TT: OR =0.98, 95% CI =0.49–1.97, P=0.964; CT vs TT: OR =0.88, 95% CI =0.54–1.43, P=0.610.Conclusion: Carriers of GG or -/G genotype of OPN promoter rs17524488 (-156-/G polymorphism might be associated with increased risk of cancer compared with wild-type -/- carriers, respectively. However, no significant association was observed between OPN promoter rs11730582 (-443C/T polymorphism and risk of cancer. Keywords: OPN

  1. Immunological Roles of Elevated Plasma Levels of Matricellular Proteins in Japanese Patients with Pulmonary Tuberculosis

    Directory of Open Access Journals (Sweden)

    Beata Shiratori

    2016-12-01

    Full Text Available Elevated matricellular proteins (MCPs, including osteopontin (OPN and galectin-9 (Gal-9, were observed in the plasma of patients with Manila-type tuberculosis (TB previously. Here, we quantified plasma OPN, Gal-9, and soluble CD44 (sCD44 by enzyme-linked immunosorbent assay (ELISA, and another 29 cytokines by Luminex assay in 36 patients with pulmonary TB, six subjects with latent tuberculosis (LTBI, and 19 healthy controls (HCs from Japan for a better understanding of the roles of MCPs in TB. All TB subjects showed positive results of enzyme-linked immunospot assays (ELISPOTs. Spoligotyping showed that 20 out of 36 Mycobacterium tuberculosis (MTB strains belong to the Beijing type. The levels of OPN, Gal-9, and sCD44 were higher in TB (positivity of 61.1%, 66.7%, and 63.9%, respectively than in the HCs. Positive correlations between OPN and Gal-9, between OPN and sCD44, and negative correlation between OPN and ESAT-6-ELISPOT response, between chest X-ray severity score of cavitary TB and ESAT-6-ELISPOT response were observed. Instead of OPN, Gal-9, and sCD44, cytokines G-CSF, GM-CSF, IFN-α, IFN-γ, IL-12p70, and IL-1RA levels were higher in Beijing MTB-infected patients. These findings suggest immunoregulatory, rather than inflammatory, effect of MCPs and can advance the understanding of the roles of MCPs in the context of TB pathology.

  2. Bone toughness at the molecular scale: A model for fracture toughness using crosslinked osteopontin on synthetic and biogenic mineral substrates.

    Science.gov (United States)

    Cavelier, S; Dastjerdi, A K; McKee, M D; Barthelat, F

    2018-05-01

    The most prominent structural components in bone are collagen and mineral. However, bone additionally contains a substantial amount of noncollagenous proteins (most notably of the SIBLING protein family), some of which may act as cohesive/adhesive "binders" for the composite hybrid collagen/mineral scaffolding, whether in the bulk phase of bone, or at its interfaces. One such noncollagenous protein - osteopontin (OPN) - appears to be critical to the deformability and fracture toughness of bone. In the present study, we used a reconstructed synthetic mineral-OPN-mineral interface, and a biogenic (natural tooth dentin) mineral/collagen-OPN-mineral/collagen interface, to measure the fracture toughness of OPN on mineralized substrates. We used this system to test the hypothesis that OPN crosslinking by the enzyme tissue transglutaminase 2 (TG2) that is found in bone enhances interfacial adhesion to increase the fracture toughness of bone. For this, we prepared double-cantilever beam substrates of synthetic pure hydroxyapatite mineral, and of narwhal dentin, and directly apposed them to one another under different intervening OPN/crosslinking conditions, and fracture toughness was tested using a miniaturized loading stage. The work-of-fracture of the OPN interface was measured for different OPN formulations (monomer vs. polymer), crosslinking states, and substrate composition. Noncrosslinked OPN provided negligible adhesion on pure hydroxyapatite, whereas OPN crosslinking (by the chemical crosslinker glutaraldehyde, and TG2 enzyme) provided strong interfacial adhesion for both hydroxyapatite and dentin using monomeric and polymeric OPN. Pre-coating of the substrate beams with monomeric OPN further improved the adhesive performance of the samples, likely by allowing effective binding of this nascent OPN form to mineral/matrix components, with this pre-attachment providing a protein layer for additional crosslinking between the substrates. Copyright © 2018 Elsevier Inc

  3. Quantitative expression of osteopontin in nasal mucosa of patients with allergic rhinitis: effects of pollen exposure and nasal glucocorticoid treatment

    Directory of Open Access Journals (Sweden)

    O'Neil Serena E

    2010-11-01

    Full Text Available Abstract Background Osteopontin (OPN is a multifunctional cytokine that has been primarily investigated in Th1 diseases. Recently, it has also been implicated in Th2-mediated allergic diseases, such as asthma. The expression of OPN in allergic rhinitis (AR is currently unknown, as is the effect of intranasal glucocorticosteroids (GCs on that expression. Methods Subjects with AR were randomised to receive treatment with fluticasone propionate (FP (n = 12 or a placebo (n = 16 over the grass pollen season and nasal biopsies were taken prior to, and during the season. OPN expression in the nasal mucosa was examined with immunohistochemistry. Healthy non-AR controls (n = 5 were used as a comparator. Results OPN expression was detected in epithelial cells, subepithelial infiltrating/inflammatory cells and cells lining the vessels and glands of all subjects. Comparison of the pre- and peak-pollen season biopsy sections in placebo treated patients revealed no increase in OPN expression during the grass pollen season (5.7% vs 6.4%. Treatment with a local glucocorticosteroid did not alter the expression of OPN during pollen exposure (6.2% vs 6.7%. Conclusion OPN has been increasingly associated with the pathogenesis of various Th2-mediated diseases. However, our finding that the OPN expression in the nasal mucosa of AR patients is not significantly affected by allergen exposure and is comparable to that of the healthy controls, suggests that intracellular OPN is not directly involved in the pathogenesis of allergic rhinitis.

  4. Detection of Osteopontin in the pericyst of human hepatic Echinococcus granulosus.

    Science.gov (United States)

    Peng, Xinyu; Li, Jianhui; Wu, Xiangwei; Zhang, Shijie; Niu, Jianhua; Chen, Xiaoping; Yao, Jin; Sun, Hong

    2006-12-01

    It aims at investigating the expression and distribution of the Osteopontin (OPN) in the pericyst of human hepatic Echinococcus granulosus and their related significances. Sixty pericysts excised by "sub-adventitial cystectomy" were studied. OPN was detected in 80% (48/60) of cysts by Western blotting and distributed in the side of "exocyst" layer directing to the parasite, also macrophages were identified in the vicinity of OPN by immunohistochemistry staining. The coexpression of OPN and CD68 was observed by immunofluorescence double labeling and analyzed by Image-Pro Plus 5.1; with special stain techniques, variable degrees of calcium deposits were observed in 80% (48/60) cysts, and the calcium deposits concurrencely found with the OPN expression. The selective distribution of OPN, calcium in the "exocyst" provides a new pathological evidence for the "sub-adventitial cystectomy" we developed. The pericyst of hepatic E. granulosus consists of two detachable layers with different formative mechanisms: the "exocyst" layer directing towards the cyst of parasite was the result of granulomatous reaction; also the results suggest OPN is one regulator in the granulomatous reaction and calcification of "exocyst".

  5. Beclin1-induced autophagy abrogates radioresistance of lung cancer cells by suppressing osteopontin

    International Nuclear Information System (INIS)

    Chang, Seung-Hee; Minai-Tehrani, Arash; Shin, Ji-Young

    2012-01-01

    Osteopontin (OPN) serves as an indicator of resistance to radiotherapy. However, the role of OPN in the development of acquired radioresistance in human lung cancer cells has not yet been fully elucidated. Therefore, the potential importance of OPN as a marker of lung cancer with a potential significant role in the development of radioresistance against repeated radiotherapy has prompted us to define the pathways by which OPN regulates lung cancer cell growth. In addition, autophagy has been reported to play a key role in the radiosensitization of cancer cells. Here, we report that increased OPN expression through induction of nuclear p53 following irradiation was inhibited by exogenous beclin-1 (BECN1). Our results clearly show that BECN1 gene expression led to induction of autophagy and inhibition of cancer cell growth and angiogenesis. Our results suggest that the induction of autophagy abrogated the radioresistance of the cancer cells. Interestingly, we showed that knockdown of OPN by lentivirus-mediated shRNA induced the autophagy of human lung cancer cell. Taken together, these results suggest that OPN and BECN1 can be molecular targets for overcoming radioresistance by controlling autophagy. (author)

  6. Characterization of osteopontin-uranyl interaction: role of multiple phosphorylations

    International Nuclear Information System (INIS)

    Qi, Lei

    2014-01-01

    While some metals are essential for Life, other ones are only toxicants for living organisms, tolerated below well-definite concentrations. This is the case for uranium, a natural element which has no known biological function. It is a low α emitter and its chemical toxicity rather than its radiological toxicity is a subject of concern. Once in the body, this metal reaches the blood and accumulates in the bones under the action of unknown mechanisms. Uranium mainly exists in form of uranyl ion (UO 2 2+ ) in aqueous media and particularly reacts with carboxylates, phenolates and phosphates of the proteins. Previous studies have highlighted that UO 2 2+ modulates the SPP1 expression, a gene which codes for osteopontin (OPN). This highly phosphorylated glycoprotein plays an important role in bone homeostasis. This role and its biochemical properties led us to hypothesize that OPN might be a potential target of UO 2 2+ and involved in its accumulation in bones. A simple and original purification process was optimized to produce very highly purified OPN starting from human and bovine milk. Various biophysical approaches were set up and confirmed that both bovine and human OPN display very high affinity for UO 2 2+ . Moreover, the formation of stable UO 2 -protein complexes originating from structural changes was evidenced. The major role of phosphorylations, both on the OPN's affinity for UO 2 2+ and the stability of the UO 2 -protein complexes, was confirmed. These results demonstrate that OPN presents all the characteristics to be a major UO 2 2+ binding-protein in vitro, and they open new insights in the understanding of the UO 2 2+ mineralization process mechanisms. (author) [fr

  7. Efficacy of dietary phytase supplementation on laying performance and expression of osteopontin and calbindin genes in eggshell gland

    Directory of Open Access Journals (Sweden)

    Divya Shet

    2018-03-01

    Full Text Available This study was conducted to evaluate the effects of different levels of dietary phytase supplementation in the layer feed on egg production performance, egg shell quality and expression of osteopontin (OPN and calbindin (CALB1 genes. Seventy-five White Leghorn layers at 23 weeks of age were randomly divided into 5 groups consisting of a control diet with 0.33% non-phytate phosphorus (NPP and 4 low phosphorus (P diets: 2 diets (T1 and T2 with 0.24% NPP + 250 FTU/kg laboratory produced phytase or commercial phytase and another 2 diets (T3 and T4 with 0.16% NPP + 500 FTU/kg laboratory produced phytase or commercial phytase with complete replacement of inorganic P. The results indicated that there were no significant differences (P > 0.05 in egg production performance and quality of egg during the first 2 months of trial. However, in next 2 months, a significant drop in egg production and feed intake was observed in birds fed diets with low P and 500 FTU/kg supplementation of laboratory produced phytase. Osteopontin gene was up-regulated whereas the CALB1 gene was down regulated in all phytase treatment groups irrespective of the source of phytase. The current data demonstrated that 250 FTU/kg supplementation of laboratory produced phytase with 50% less NPP supplementation and 500 FTU/kg supplementation of commercial phytase even without NPP in diet can maintain the egg production. The up-regulation of OPN and down regulation of CALB1 in egg shell gland in the entire phytase treated group birds irrespective of the source of enzymes is indicative of the changes in P bio-availability at this site. Keywords: Phytase, Layer, Egg production, Gene expression, Egg shell

  8. Post-translational modification of osteopontin: Effects on in vitro hydroxyapatite formation and growth

    International Nuclear Information System (INIS)

    Boskey, Adele L.; Christensen, Brian; Taleb, Hayat; Sørensen, Esben S.

    2012-01-01

    Highlights: ► Thrombin-cleaved fragments of milk-osteopontin effect hydroxyapatite formation differently. ► N- and C-terminal fragments promoted hydroxyapatite formation and growth. ► A central fragment inhibited hydroxyapatite formation and growth. ► Binding to collagen or hydroxyapatite seed crystals modified these effects. -- Abstract: The manuscript tests the hypothesis that posttranslational modification of the SIBLING family of proteins in general and osteopontin in particular modify the abilities of these proteins to regulate in vitro hydroxyapatite (HA) formation. Osteopontin has diverse effects on hydroxyapatite (HA) mineral crystallite formation and growth depending on the extent of phosphorylation. We hypothesized that different regions of full-length OPN would also have distinct effects on the mineralization process. Thrombin fragmentation of milk OPN (mOPN) was used to test this hypothesis. Three fragments were tested in a de novo HA formation assay; an N-terminal fragment (aa 1–147), a central fragment (aa 148–204) denoted SKK-fragment and a C-terminal fragment (aa 205–262). Compared to intact mOPN the C- and N-terminal fragments behaved comparably, promoting HA formation and growth, but the central SKK-fragment acted as a mineralization inhibitor. In a seeded growth experiment all fragments inhibited mineral proliferation, but the SKK-fragment was the most effective inhibitor. These effects, seen in HA-formation and seeded growth assays in a gelatin gel system and in a pH-stat experiment were lost when the protein or fragments were dephosphorylated. Effects of the fully phosphorylated protein and fragments were also altered in the presence of fibrillar collagen. The diverse effects can be explained in terms of the intrinsically disordered nature of OPN and its fragments which enable them to interact with their multiple partners.

  9. Multifunctional role of osteopontin in directing intrafibrillar mineralization of collagen and activation of osteoclasts

    Science.gov (United States)

    Rodriguez, Douglas E.; Thula-Mata, Taili; Toro, Edgardo J.; Yeh, Ya-Wen; Holt, Carl; Holliday, L. Shannon; Gower, Laurie B.

    2013-01-01

    Mineralized collagen composites are of interest because they have the potential to provide a bone-like scaffold that stimulates the natural processes of resorption and remodeling. Working toward this goal, our group has previously shown that the nanostructure of bone can be reproduced using a polymer-induced liquid-precursor (PILP) process, which enables intrafibrillar mineralization of collagen with hydroxyapatite (HA) to be achieved. This prior work used polyaspartic acid (pASP), a simple mimic for acidic non-collagenous proteins (NCPs), to generate nanodroplets/nanoparticles of an amorphous mineral precursor which can infiltrate the interstices of type-I collagen fibrils. In this study we show that osteopontin (OPN) can similarly serve as a process-directing agent for the intrafibrillar mineralization of collagen, even though OPN is generally considered a mineralization inhibitor. We also found that inclusion of OPN in the mineralization process promotes the interaction of mouse marrow-derived osteoclasts with PILP-remineralized bone that was previously demineralized, as measured by actin ring formation. While osteoclast activation occurred when pASP was used as the process-directing agent, using OPN resulted in a dramatic effect on osteoclast activation, presumably because of the inherent arginine-glycine-aspartate acid (RGD) ligands of OPN. By capitalizing on the multifunctionality of OPN, these studies may lead the way to producing biomimetic bone substitutes with the capability of tailorable bioresorption rates. PMID:24140612

  10. Osteopontin protects against hyperoxia-induced lung injury by inhibiting nitric oxide synthases.

    Science.gov (United States)

    Zhang, Xiang-Feng; Liu, Shuang; Zhou, Yu-Jie; Zhu, Guang-Fa; Foda, Hussein D

    2010-04-05

    Exposure of adult mice to more than 95% O(2) produces a lethal injury by 72 hours. Nitric oxide synthase (NOS) is thought to contribute to the pathophysiology of murine hyperoxia-induced acute lung injury (ALI). Osteopontin (OPN) is a phosphorylated glycoprotein produced principally by macrophages. OPN inhibits inducible nitric oxide synthase (iNOS), which generates large amounts of nitric oxide production. However, the relationship between nitric oxide and endogenous OPN in lung tissue during hyperoxia-induced ALI has not yet been elucidated, thus we examined the role that OPN plays in the hyperoxia-induced lung injury and its relationships with NOS. One hundred and forty-four osteopontin knock-out (KO) mice and their matched wild type background control (WT) were exposed in sealed cages > 95% oxygen or room air for 24- 72 hours, and the severity of lung injury was assessed; expression of OPN, endothelial nitric oxide synthase (eNOS) and iNOS mRNA in lung tissues at 24, 48 and 72 hours of hyperoxia were studied by reverse transcription-polymerase chain reaction (RT-PCR); immunohistochemistry (IHC) was performed for the detection of iNOS, eNOS, and OPN protein in lung tissues. OPN KO mice developed more severe acute lung injury at 72 hours of hyperoxia. The wet/dry weight ratio increased to 6.85 +/- 0.66 in the KO mice at 72 hours of hyperoxia as compared to 5.31 +/- 0.92 in the WT group (P < 0.05). iNOS mRNA (48 hours: 1.04 +/- 0.08 vs. 0.63 +/- 0.09, P < 0.01; 72 hours: 0.89 +/- 0.08 vs. 0.72 +/- 0.09, P < 0.05) and eNOS mRNA (48 hours: 0.62 +/- 0.08 vs. 0.43 +/- 0.09, P < 0.05; 72 hours: 0.67 +/- 0.08 vs. 0.45 +/- 0.09, P < 0.05) expression was more significantly increased in OPN KO mice than their matched WT mice when exposed to hyperoxia. IHC study showed higher expression of iNOS (20.54 +/- 3.18 vs. 12.52 +/- 2.46, P < 0.05) and eNOS (19.83 +/- 5.64 vs. 9.45 +/- 3.82, P < 0.05) in lung tissues of OPN KO mice at 72 hours of hyperoxia. OPN can protect against

  11. Silencing of osteopontin promotes the radiosensitivity of breast cancer cells by reducing the expression of hypoxia inducible factor 1 and vascular endothelial growth factor

    Institute of Scientific and Technical Information of China (English)

    YANG Li; ZHAO Wei; ZUO Wen-shu; WEI Ling; SONG Xian-rang; WANG Xing-wu; ZHENG Gang; ZHENG Mei-zhu

    2012-01-01

    Background Osteopontin (OPN) is a secreted phosphoglycoprotein (SSP) that is overexpressed in a variety of tumors and was regarded as a molecular marker of tumors.In this study,we intended to demonstrate the role of OPN in human breast cancer cell line MDA-MB-231.Methods Recombinant plasmid expressing small interfering RNA (siRNA) specific to OPN mRNA was transfected into MDA-MB-231 cells to generate the stable transfected cell line MDA-MB-343,and the empty plasmid tansfected cells (MDA-MB-neg) or wildtype MDA-MB-231 cells were used as control cells respectively.Expression of OPN,hypoxia inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) proteins was analyzed by Western blotting analysis.The radiosensitivity of cells was determined by detecting cell apoptosis,cell proliferation and cell senescence.Results HIF-1 and VEGF proteins in MDA-MB-343 cells were significantly downregulated upon the efficient knockdown of OPN expression under either hypoxia or normoxia environment.Moreover,expression of OPN protein was upregualted upon hypoxic culture.Stable OPN-silencing also decreased cell invasion,increased cell apoptosis and cell senescence,as well as reduced clonogenic survival,resulting in increase radiation tolerance.Conclusions Suppression of OPN gene expression can enhance radiosensitivity and affect cell apoptosis in breast cancer cells.OPN seems to be an attractive target for the improvement of radiotherapy.

  12. Single-walled carbon nanotube based transparent immunosensor for detection of a prostate cancer biomarker osteopontin

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, Abhinav; Hong, Seongkyeol; Singh, Renu [School of Mechanical and Nuclear Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 689-798 (Korea, Republic of); Jang, Jaesung, E-mail: jjang@unist.ac.kr [School of Mechanical and Nuclear Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 689-798 (Korea, Republic of); Department of Biomedical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 689-798 (Korea, Republic of); School of Materials Science and Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 689-798 (Korea, Republic of)

    2015-04-15

    Highlights: • A transparent CNT immunosensor is presented for detection of a prostate cancer biomarker osteopontin. • This immunosensor showed a highly linear and reproducible behavior from 1 pg mL{sup −1} to 1 μg mL{sup −1}. • The limit of detection of the immunosensor was 0.3 pg mL{sup −1}. • This immunosensor demonstrated high selectivity against bovine serum albumin and human serum. - Abstract: Osteopontin (OPN) is involved in almost all steps of cancer development, and it is being investigated as a potential biomarker for a diagnosis and prognosis of prostate cancer. Here, we report a label-free, highly sensitive and transparent immunosensor based on single-walled carbon nanotubes (SWCNTs) for detection of OPN. A high density of −COOH functionalized SWCNTs was deposited between two gold/indium tin oxide electrodes on a glass substrate by dielectrophoresis. Monoclonal antibodies specific to OPN were covalently immobilized on the SWCNTs. Relative resistance change of the immunosensors was measured as the concentration of OPN in phosphate buffer saline (PBS) and human serum was varied from 1 pg mL{sup −1} to 1 μg mL{sup −1} for different channel lengths of 2, 5, and 10 μm, showing a highly linear and reproducible behavior (R{sup 2} > 97%). These immunosensors were also specific to OPN against another test protein, bovine serum albumin, PBS and human serum, showing that a limit of detection for OPN was 0.3 pg mL{sup −1}. This highly sensitive and transparent immunosensor has a great potential as a simple point-of-care test kit for various protein biomarkers.

  13. OpnS, an outer membrane porin of Xenorhabdus nematophila, confers a competitive advantage for growth in the insect host.

    Science.gov (United States)

    van der Hoeven, Ransome; Forst, Steven

    2009-09-01

    The gammaproteobacterium Xenorhabdus nematophila engages in a mutualistic association with an entomopathogenic nematode and also functions as a pathogen toward different insect hosts. We studied the role of the growth-phase-regulated outer membrane protein OpnS in host interactions. OpnS was shown to be a 16-stranded beta-barrel porin. opnS was expressed during growth in insect hemolymph and expression was elevated as the cell density increased. When wild-type and opnS deletion strains were coinjected into insects, the wild-type strain was predominantly recovered from the insect cadaver. Similarly, an opnS-complemented strain outcompeted the DeltaopnS strain. Coinjection of the wild-type and DeltaopnS strains together with uncolonized nematodes into insects resulted in nematode progeny that were almost exclusively colonized with the wild-type strain. Likewise, nematode progeny recovered after coinjection of a mixture of nematodes carrying either the wild-type or DeltaopnS strain were colonized by the wild-type strain. In addition, the DeltaopnS strain displayed a competitive growth defect when grown together with the wild-type strain in insect hemolymph but not in defined culture medium. The DeltaopnS strain displayed increased sensitivity to antimicrobial compounds, suggesting that deletion of OpnS affected the integrity of the outer membrane. These findings show that the OpnS porin confers a competitive advantage for the growth and/or the survival of X. nematophila in the insect host and provides a new model for studying the biological relevance of differential regulation of porins in a natural host environment.

  14. Osteopontin activates the diabetes-associated potassium channel TALK-1 in pancreatic β-cells.

    Directory of Open Access Journals (Sweden)

    Matthew T Dickerson

    Full Text Available Glucose-stimulated insulin secretion (GSIS relies on β-cell Ca2+ influx, which is modulated by the two-pore-domain K+ (K2P channel, TALK-1. A gain-of-function polymorphism in KCNK16, the gene encoding TALK-1, increases risk for developing type-2 diabetes. While TALK-1 serves an important role in modulating GSIS, the regulatory mechanism(s that control β-cell TALK-1 channels are unknown. Therefore, we employed a membrane-specific yeast two-hybrid (MYTH assay to identify TALK-1-interacting proteins in human islets, which will assist in determining signaling modalities that modulate TALK-1 function. Twenty-one proteins from a human islet cDNA library interacted with TALK-1. Some of these interactions increased TALK-1 activity, including intracellular osteopontin (iOPN. Intracellular OPN is highly expressed in β-cells and is upregulated under pre-diabetic conditions to help maintain normal β-cell function; however, the functional role of iOPN in β-cells is poorly understood. We found that iOPN colocalized with TALK-1 in pancreatic sections and coimmunoprecipitated with human islet TALK-1 channels. As human β-cells express two K+ channel-forming variants of TALK-1, regulation of these TALK-1 variants by iOPN was assessed. At physiological voltages iOPN activated TALK-1 transcript variant 3 channels but not TALK-1 transcript variant 2 channels. Activation of TALK-1 channels by iOPN also hyperpolarized resting membrane potential (Vm in HEK293 cells and in primary mouse β-cells. Intracellular OPN was also knocked down in β-cells to test its effect on β-cell TALK-1 channel activity. Reducing β-cell iOPN significantly decreased TALK-1 K+ currents and increased glucose-stimulated Ca2+ influx. Importantly, iOPN did not affect the function of other K2P channels or alter Ca2+ influx into TALK-1 deficient β-cells. These results reveal the first protein interactions with the TALK-1 channel and found that an interaction with iOPN increased

  15. Biological variation and reference intervals for circulating osteopontin, osteoprotegerin, total soluble receptor activator of nuclear factor kappa B ligand and high-sensitivity C-reactive protein

    DEFF Research Database (Denmark)

    Sennels, H P; Jacobsen, Søren; Jensen, T

    2007-01-01

    Objective. Monitoring inflammatory diseases and osteoclastogenesis with osteopontin (OPN), osteoprotegerin (OPG), total soluble receptor activator of nuclear factor kappa B ligand (total sRANKL) and high-sensitivity C-reactive protein (hsCRP) has recently attracted increased interest. The purpose...

  16. Galectin-3, osteopontin and successful aging.

    Science.gov (United States)

    Sanchis-Gomar, Fabian; Santos-Lozano, Alejandro; Pareja-Galeano, Helios; Garatachea, Nuria; Alis, Rafael; Fiuza-Luces, Carmen; Morán, María; Emanuele, Enzo; Lucia, Alejandro

    2016-05-01

    Individuals who reach exceptional longevity (100+ years of age) free of common chronic age diseases (i.e. 'dodgers') arguably represent the paradigm of successful aging in humans. As such, identification of potential biomarkers associated with this phenomenon is of medical interest. We measured serum levels of galectin-3 and osteopontin, both of which have been shown to be linked with major chronic or aging-related disorders in younger populations, in centenarian 'dodgers' (n=81; 40 men; 100-104 years) and healthy controls (n=41; 24 men, 70-80 years). Both biomarkers showed significantly lower values (p<0.001) in the former (galectin-3: 2.4±1.7 vs. 4.8±2.8 ng/mL; osteopontin: 38.1±27.7 vs. 72.6±33.1 μg/mL). Logistic regression analysis identified the combination of these two biomarkers as a significant predictor variable associated with successful aging regardless of sex (p<0.001). The area under the curve (AUC) classified the ability of galectin-3 and osteopontin to predict the likelihood of successful aging as 'fair' (AUC=0.75) and 'good' (AUC=0.80), respectively. Particularly, the combination of the two biomarkers showed good discriminatory power for successful aging (AUC=0.86), with sensitivity=83% and specificity=74%. Lower levels of both galectin-3 and osteopontin are associated with successful aging, representing potential biomarkers of this condition. Our cross-sectional data must be however approached with caution. Further research is necessary to replicate the present preliminary results in other cohorts and to identify the potential use of galectin-3 and osteopontin as potential targets (or at least predictors) in future personalized anti-aging therapies.

  17. Adaptive Regulation of Osteopontin Production by Dendritic Cells Through the Bidirectional Interaction With Mesenchymal Stromal Cells

    Directory of Open Access Journals (Sweden)

    Sara Scutera

    2018-06-01

    Full Text Available Mesenchymal stromal cells (MSCs exert immunosuppressive effects on immune cells including dendritic cells (DCs. However, many details of the bidirectional interaction of MSCs with DCs are still unsolved and information on key molecules by which DCs can modulate MSC functions is limited. Here, we report that osteopontin (OPN, a cytokine involved in homeostatic and pathophysiologic responses, is constitutively expressed by DCs and regulated in the DC/MSC cocultures depending on the activation state of MSCs. Resting MSCs promoted OPN production, whereas the production of OPN was suppressed when MSCs were activated by proinflammatory cytokines (i.e., TNF-α, IL-6, and IL-1β. OPN induction required cell-to-cell contact, mediated at least in part, by β1 integrin (CD29. Conversely, activated MSCs inhibited the release of OPN via the production of soluble factors with a major role played by Prostaglandin E2 (PGE2. Accordingly, pretreatment with indomethacin significantly abrogated the MSC-mediated suppression of OPN while the direct addition of exogenous PGE2 inhibited OPN production by DCs. Furthermore, DC-conditioned medium promoted osteogenic differentiation of MSCs with a concomitant inhibition of adipogenesis. These effects were paralleled by the repression of the adipogenic markers PPARγ, adiponectin, and FABP4, and induction of the osteogenic markers alkaline phosphatase, RUNX2, and of the bone-anabolic chemokine CCL5. Notably, blocking OPN activity with RGD peptides or with an antibody against CD29, one of the OPN receptors, prevented the effects of DC-conditioned medium on MSC differentiation and CCL5 induction. Because MSCs have a key role in maintenance of bone marrow (BM hematopoietic stem cell niche through reciprocal regulation with immune cells, we investigated the possible MSC/DC interaction in human BM by immunohistochemistry. Although DCs (CD1c+ are a small percentage of BM cells, we demonstrated colocalization of CD271+ MSCs with

  18. Osteopontin ablation ameliorates muscular dystrophy by shifting macrophages to a pro-regenerative phenotype

    Science.gov (United States)

    Capote, Joana; Martinez, Leonel; Vetrone, Sylvia; Barton, Elisabeth R.; Sweeney, H. Lee; Miceli, M. Carrie

    2016-01-01

    In the degenerative disease Duchenne muscular dystrophy, inflammatory cells enter muscles in response to repetitive muscle damage. Immune factors are required for muscle regeneration, but chronic inflammation creates a profibrotic milieu that exacerbates disease progression. Osteopontin (OPN) is an immunomodulator highly expressed in dystrophic muscles. Ablation of OPN correlates with reduced fibrosis and improved muscle strength as well as reduced natural killer T (NKT) cell counts. Here, we demonstrate that the improved dystrophic phenotype observed with OPN ablation does not result from reductions in NKT cells. OPN ablation skews macrophage polarization toward a pro-regenerative phenotype by reducing M1 and M2a and increasing M2c subsets. These changes are associated with increased expression of pro-regenerative factors insulin-like growth factor 1, leukemia inhibitory factor, and urokinase-type plasminogen activator. Furthermore, altered macrophage polarization correlated with increases in muscle weight and muscle fiber diameter, resulting in long-term improvements in muscle strength and function in mdx mice. These findings suggest that OPN ablation promotes muscle repair via macrophage secretion of pro-myogenic growth factors. PMID:27091452

  19. Osteopontin binding to lipopolysaccharide lowers tumor necrosis factor-α and prevents early alcohol-induced liver injury in mice

    DEFF Research Database (Denmark)

    Ge, Xiadong; Leung, Tung-Ming; Arriazu, Elena

    2014-01-01

    (Opn−/−), and transgenic mice overexpressing OPN in hepatocytes (OpnHEPTg) were fed either the control or the ethanol Lieber-DeCarli diet. Ethanol increased hepatic, plasma, biliary, and fecal OPN more in OpnHEPTg than in WT mice. Steatosis was less in ethanol-treated OpnHEPTg mice as shown...... by decreased liver-to-body weight ratio, hepatic triglycerides, the steatosis score, oil red-O staining, and lipid peroxidation. There was also less inflammation and liver injury as demonstrated by lower alanine aminotransferase (ALT) activity, hepatocyte ballooning degeneration, LPS levels, the inflammation...

  20. Osteopontin Promotes Invasion, Migration and Epithelial-Mesenchymal Transition of Human Endometrial Carcinoma Cell HEC-1A Through AKT and ERK1/2 Signaling.

    Science.gov (United States)

    Li, Yinghua; Xie, Yunpeng; Cui, Dan; Ma, Yanni; Sui, Linlin; Zhu, Chenyang; Kong, Hui; Kong, Ying

    2015-01-01

    Osteopontin (OPN) is an Extracellular Matrix (ECM) molecule and is involved in many physiologic and pathologic processes, including cell adhesion, angiogenesis and tumor metastasis. OPN is a well-known multifunctional factor involved in various aspects of cancer progression, including endometrial cancer. In this study, we examined the significance of OPN in endometrial cancer. The proliferation, migration and invasion ability of HEC-1A cells were detected by Cell Counting Kit-8 (CCK-8), Wound scratch assay and transwell. Western blots were employed to detect the expression of Matrix metalloproteinase-2 (MMP-2) and epithelial-mesenchymal transition (EMT)-related factors in HEC-1A cells treated with rhOPN. rhOPN promotes cell proliferation, migration and invasion in HEC-1A cells. rhOPN influenced EMT-related factors and MMP-2 expression in HEC-1A cells. rhOPN promoted HEC-1A cells migration, invasion and EMT through protein kinase B (PKB/AKT) and Extracellular regulated protein kinases (ERK1/2) signaling pathway. These results may open up a novel therapeutic strategy for endometrial cancer: namely, rhOPN have important roles in controlling growth of endometrial of cancer cells and suggest a novel target pathway for treatment of this cancer. © 2015 The Author(s) Published by S. Karger AG, Basel.

  1. Osteopontin Promotes Invasion, Migration and Epithelial-Mesenchymal Transition of Human Endometrial Carcinoma Cell HEC-1A Through AKT and ERK1/2 Signaling

    Directory of Open Access Journals (Sweden)

    Yinghua Li

    2015-10-01

    Full Text Available Background/Aims: Osteopontin (OPN is an Extracellular Matrix (ECM molecule and is involved in many physiologic and pathologic processes, including cell adhesion, angiogenesis and tumor metastasis. OPN is a well-known multifunctional factor involved in various aspects of cancer progression, including endometrial cancer. In this study, we examined the significance of OPN in endometrial cancer. Methods: The proliferation, migration and invasion ability of HEC-1A cells were detected by Cell Counting Kit-8 (CCK-8, Wound scratch assay and transwell. Western blots were employed to detect the expression of Matrix metalloproteinase-2 (MMP-2 and epithelial-mesenchymal transition (EMT-related factors in HEC-1A cells treated with rhOPN. Results: rhOPN promotes cell proliferation, migration and invasion in HEC-1A cells. rhOPN influenced EMT-related factors and MMP-2 expression in HEC-1A cells. rhOPN promoted HEC-1A cells migration, invasion and EMT through protein kinase B (PKB/AKT and Extracellular regulated protein kinases (ERK1/2 signaling pathway. Conclusions: These results may open up a novel therapeutic strategy for endometrial cancer: namely, rhOPN have important roles in controlling growth of endometrial of cancer cells and suggest a novel target pathway for treatment of this cancer.

  2. The involvement of osteopontin and matrix metalloproteinase- 9 in the migration of endometrial epithelial cells in patients with endometriosis

    OpenAIRE

    Yang, Mei; Jiang, Chunfan; Chen, Hua; Nian, Yan; Bai, Zhimiao; Ha, Chunfang

    2015-01-01

    Background Endometriosis, which shares certain characteristics with cancers, may cause abnormal expression of proteins involved in cell migration. Endometrial epithelial cells (EECs) are believed to play an important role in endometriotic migration. The aim of this study was to investigate the relationship between the expression of osteopontin (OPN) and matrix metalloproteinase-9 (MMP-9) in endometriotic migration. Methods We performed primary culture of EECs and investigated the expression o...

  3. OSTEOPONTIN, INTERLEUKIN-15 AND DYSFUNCTION OF LEFT VENTRICULAR MYOCARDIUM IN HYPERTENSIVE PATIENTS WITH CHRONIC HEART FAILURE

    Directory of Open Access Journals (Sweden)

    O. M. Kovalyova

    2016-12-01

    Full Text Available Based on a survey of 108 patients with hypertension complicated by chronic heart failure, studied the connection concentration of osteopontin, interleukin-15 inserum and morpho-functional characteristics of the left ventricle of the heart. In patients with CHF osteopontin levels were significantly higher, it revealed a relationship between adverse LV filling state and knots in serum osteopontin, while the level of IL-15 did not show such a relationship. The results indicate the potential value of osteopontin as a biomarker for the diagnosis of CHF.

  4. α-Iso-Cubebene Inhibits PDGF-Induced Vascular Smooth Muscle Cell Proliferation by Suppressing Osteopontin Expression

    Science.gov (United States)

    Jang, Min A.; Lee, Seung Jin; Baek, Seung Eun; Park, So Youn; Choi, Young Whan; Kim, Chi Dae

    2017-01-01

    α-Iso-cubebene (ICB) is a dibenzocyclooctadiene lignin contained in Schisandra chinensis (SC), a well-known medicinal herb that ameliorates cardiovascular symptoms. Thus, we examined the effect of ICB on vascular smooth muscle cell (VSMC) proliferation, a key feature of diverse vascular diseases. When VSMCs primary cultured from rat thoracic aorta were stimulated with PDGF (1–10 ng/ml), cell proliferation and osteopontin (OPN) expression were concomitantly up-regulated, but these effects were attenuated when cells were treated with MPIIIB10, a neutralizing monoclonal antibody for OPN. In aortic tissues exposed to PDGF, sprouting VSMC numbers increased, which was attenuated in tissues from OPN-deficient mice. Furthermore, VSMC proliferation and OPN expression induced by PDGF were attenuated dose-dependently by ICB (10 or 30 μg/ml). Reporter assays conducted using OPN promoter-luciferase constructs showed that the promoter region 538–234 bp of the transcription start site was responsible for transcriptional activity enhancement by PDGF, which was significantly inhibited by ICB. Putative binding sites for AP-1 and C/EBPβ in the indicated promoter region were suggested by TF Search, and increased binding of AP-1 and C/EBPβ in PDGF-treated VSMCs was demonstrated using a ChIP assay. The increased bindings of AP-1 and C/EBPβ into OPN promoter were attenuated by ICB. Moreover, the PDGF-induced expression of OPN was markedly attenuated in VSMCs transfected with siRNA for AP-1 and C/EBPβ. These results indicate that ICB inhibit VSMC proliferation by inhibiting the AP-1 and C/EBPβ signaling pathways and thus downregulating OPN expression. PMID:28114367

  5. OpnS, an Outer Membrane Porin of Xenorhabdus nematophila, Confers a Competitive Advantage for Growth in the Insect Host▿ †

    Science.gov (United States)

    van der Hoeven, Ransome; Forst, Steven

    2009-01-01

    The gammaproteobacterium Xenorhabdus nematophila engages in a mutualistic association with an entomopathogenic nematode and also functions as a pathogen toward different insect hosts. We studied the role of the growth-phase-regulated outer membrane protein OpnS in host interactions. OpnS was shown to be a 16-stranded β-barrel porin. opnS was expressed during growth in insect hemolymph and expression was elevated as the cell density increased. When wild-type and opnS deletion strains were coinjected into insects, the wild-type strain was predominantly recovered from the insect cadaver. Similarly, an opnS-complemented strain outcompeted the ΔopnS strain. Coinjection of the wild-type and ΔopnS strains together with uncolonized nematodes into insects resulted in nematode progeny that were almost exclusively colonized with the wild-type strain. Likewise, nematode progeny recovered after coinjection of a mixture of nematodes carrying either the wild-type or ΔopnS strain were colonized by the wild-type strain. In addition, the ΔopnS strain displayed a competitive growth defect when grown together with the wild-type strain in insect hemolymph but not in defined culture medium. The ΔopnS strain displayed increased sensitivity to antimicrobial compounds, suggesting that deletion of OpnS affected the integrity of the outer membrane. These findings show that the OpnS porin confers a competitive advantage for the growth and/or the survival of X. nematophila in the insect host and provides a new model for studying the biological relevance of differential regulation of porins in a natural host environment. PMID:19465651

  6. Eccentric muscle challenge shows osteopontin polymorphism modulation of muscle damage.

    Science.gov (United States)

    Barfield, Whitney L; Uaesoontrachoon, Kitipong; Wu, Chung-Sheih; Lin, Stephen; Chen, Yue; Wang, Paul C; Kanaan, Yasmine; Bond, Vernon; Hoffman, Eric P

    2014-08-01

    A promoter polymorphism of the osteopontin (OPN) gene (rs28357094) has been associated with multiple inflammatory states, severity of Duchenne muscular dystrophy (DMD) and muscle size in healthy young adults. We sought to define the mechanism of action of the polymorphism, using allele-specific in vitro reporter assays in muscle cells, and a genotype-stratified intervention in healthy controls. In vitro reporter constructs showed the G allele to respond to estrogen treatment, whereas the T allele showed no transcriptional response. Young adult volunteers (n = 187) were enrolled into a baseline study, and subjects with specific rs28357094 genotypes enrolled into an eccentric muscle challenge intervention [n = 3 TT; n = 3 GG/GT (dominant inheritance model)]. Female volunteers carrying the G allele showed significantly greater inflammation and increased muscle volume change as determined by magnetic resonance imaging T1- and T2-weighted images after eccentric challenge, as well as greater decrement in biceps muscle force. Our data suggest a model where the G allele enables enhanced activities of upstream enhancer elements due to loss of Sp1 binding at the polymorphic site. This results in significantly greater expression of the pro-inflammatory OPN cytokine during tissue remodeling in response to challenge in G allele carriers, promoting muscle hypertrophy in normal females, but increased damage in DMD patients. © The Author 2014. Published by Oxford University Press.

  7. Osteopontin, osteocalcin, and osteoprotegerin expression in human tissue affected by cleft lip and palate

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    Smane L.

    2016-01-01

    Full Text Available Cleft lip and palate (CLP is a common congenital anomaly with a complex etiology which has not been elucidated yet. This study investigated whether expression of osteopontin (OPN, osteoprotegerin (OPG, and osteocalcin (OC, which are essential for the normal craniofacial bone remodelling, is not regulated in children with CLP. Alveolar bone tissue samples were obtained from patients with complete bilateral (CB CLP (n = 14 during corrective plastic surgery and unaffected control subjects (n = 9. OPN, OPG, and OC expression was assessed by immunohistochemistry, and data were analyzed with the Mann-Whitney test. OPN expression was observed only sporadically in the alveolar bone of 3 patients, in contrast to the control group (z = −2.962; P < 0.003. The number of OPG-positive bone cells varied from occasional to moderate, in contrast to the control group (z = −2.247; P = 0.025. OC-positive osteocytes were present in moderate to numerous numbers in both patients and controls, with no significant difference between them (z = −1.356; P < 0.175. The prominent expression of OC characteristic for CBCLP affected hard tissue indicates a high potential of bone mineralization. Few OPG-positive osteocytes in the bone tissue implicate the disregulation of osteoclast differentiation, maturation, and activity, but few OPN-containing cells may prove the common disregulation of bone remodelling during cleft morphopathogenesis.

  8. CTX (crosslaps rather than osteopontin is associated with disturbed glucose metabolism in gestational diabetes.

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    Yvonne Winhofer

    Full Text Available OBJECTIVE: Reciprocal interaction between bone and glucose metabolism might play a pivotal role in the development of type 2 diabetes. We recently demonstrated that osteocalcin is increased in women with gestational diabetes (GDM compared to healthy pregnant women and related to enhanced insulin secretion. Here, we aimed to investigate the role of the bone resorption marker CTX and osteopontin (OPN, a key molecule in subclinical inflammation underlying insulin resistance, in gestational diabetes. METHODS: Insulin sensitivity and secretion (derived from OGTT as well as CTX and osteopontin were investigated in 26 GDM and 52 women with normal glucose tolerance during pregnancy [CON] between 24th and 28th gestational weeks; 24 women also underwent postpartum examination. RESULTS: CTX was significantly higher in GDM compared to CON (0.44±0.20 vs.0.28±0.12 ng/ml, p<.0001 and positively correlated with osteocalcin (R = 0.64, p<.0001 and parameters of insulin secretion. Osteopontin plasma concentrations were decreased in GDM compared to CON (28.81±22.12 vs.37.68±19.63 ng/ml, p = 0.04, and did not show any relation to insulin secretion or sensitivity, but were significantly correlated with CRP (R = 0.3, p<0.007 and liver enzymes. Twelve weeks after delivery CTX and OPN were increased compared to pregnancy (both p<.0001 and did not differ between GDM and CON. CONCLUSION: Our findings support the idea of a tight regulation between bone and glucose metabolism, and suggest, that less curbed CTX during pregnancy might be involved in osteocalcin-mediated amelioration of insulin secretion in GDM. On the other hand, osteopontin was unrelated to insulin resistance in GDM, but associated with inflammatory markers and liver enzymes in all women.

  9. Osteopontin expression and its possible functions in the aortic disorders and coronary artery disease A expressão da osteopontina e as suas funções possíveis nas desordens aórticas e doença arterial coronariana

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    Shi-Min Yuan

    2011-06-01

    Full Text Available BACKGROUND: Osteopontin (OPN has been verified to be closely associated with oncogenesis and remodeling processes. But this cytokine was rarely assessed in the presence of aortopathies, especially acute aortic dissection. The aim of the present study was to evaluate the expressions of OPN by way of molecular biological approaches so as to offer a better understanding of the possible mechanisms of the aortopathies. METHODS: Consecutive patients with type A acute aortic dissection (20 patients, aortic aneurysm (nine patients or coronary artery disease (21 patients referred to this hospital for surgical operations were enrolled into this study. Blood samples of the surgical patients after systematic heparinization, and control fast morning blood samples drawn from 21 young healthy volunteers who had no evidence of any healthy problems were investigated for enzyme linked immunosorbent assay (ELISA. The surgical specimens of the aortic tissues collected from the surgical patients during the operations were obtained for quantitative realtime reverse transcription polymerase chain reaction (RT-PCR for OPN mRNA, western blot assay for OPN protein, and for immunohistochemical staining of OPN. Ascending aortic tissues from the autopsies of the healthy individuals dying of accident were obtained as controls of immunohistochemistry. RESULTS: By quantitative RT-PCR, the expressions of OPN mRNA were all upregulated in all three surgical groups. The quantitative results did not reveal any intergroup differences. Western blot assay revealed that OPN was positive with similar intensities of expressions in all three surgical groups. Quantitative western blot analyses of OPN expressions did not show any significance between groups. The OPN expressions by ELISA in the aortic tissue were 3.09311 ± 1.65737, 3.40414 ± 1.15095, and 1.68243 ± 0.31119 pg/mg protein in the aortic dissection, aortic aneurysm, and coronary artery disease groups, respectively. The OPN

  10. Decreased nuclear stiffness via FAK-ERK1/2 signaling is necessary for osteopontin-promoted migration of bone marrow-derived mesenchymal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Lingling, E-mail: liulingling2012@163.com [Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Luo, Qing, E-mail: qing.luo@cqu.edu.cn [Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Sun, Jinghui, E-mail: sunjhemail@163.com [Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Wang, Aoli, E-mail: leaf13332@163.com [Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Shi, Yisong, E-mail: shiyis@cqu.edu.cn [Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China); Ju, Yang, E-mail: ju@mech.nagoya-u.ac.jp [Department of Mechanical Science and Engineering, Nagoya University, Nagoya 464-8603 (Japan); Morita, Yasuyuki, E-mail: morita@mech.nagoya-u.ac.jp [Department of Mechanical Science and Engineering, Nagoya University, Nagoya 464-8603 (Japan); Song, Guanbin, E-mail: song@cqu.edu.cn [Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044 (China)

    2017-06-15

    Migration of bone marrow-derived mesenchymal stem cells (BMSCs) plays an important role in many physiological and pathological settings, including wound healing. During the migration of BMSCs through interstitial tissues, the movement of the nucleus must be coordinated with the cytoskeletal dynamics, which in turn affects the cell migration efficiency. Our previous study indicated that osteopontin (OPN) significantly promotes the migration of rat BMSCs. However, the nuclear behaviors and involved molecular mechanisms in OPN-mediated BMSC migration are largely unclear. In the present study, using an atomic force microscope (AFM), we found that OPN could decrease the nuclear stiffness of BMSCs and reduce the expression of lamin A/C, which is the main determinant of nuclear stiffness. Increased lamin A/C expression attenuates BMSC migration by increasing nuclear stiffness. Decreased lamin A/C expression promotes BMSC migration by decreasing nuclear stiffness. Furthermore, OPN promotes BMSC migration by diminishing lamin A/C expression and decreasing nuclear stiffness via the FAK-ERK1/2 signaling pathway. This study provides strong evidence for the role of nuclear mechanics in BMSC migration as well as new insight into the molecular mechanisms of OPN-promoted BMSC migration. - Highlights: • OPN promotes BMSC migration by decreasing nuclear stiffness. • Lamin A/C knockdown decreases, while its overexpression enhances, the nuclear stiffness of BMSCs. • Lamin A/C overexpression and downregulation affect the migration of BMSCs. • OPN diminishes lamin A/C expression and decreases nuclear stiffness through the activation of the FAK-ERK1/2 signaling pathway. • OPN promotes BMSC migration via the FAK-ERK1/2 signaling pathway.

  11. Decreased nuclear stiffness via FAK-ERK1/2 signaling is necessary for osteopontin-promoted migration of bone marrow-derived mesenchymal stem cells

    International Nuclear Information System (INIS)

    Liu, Lingling; Luo, Qing; Sun, Jinghui; Wang, Aoli; Shi, Yisong; Ju, Yang; Morita, Yasuyuki; Song, Guanbin

    2017-01-01

    Migration of bone marrow-derived mesenchymal stem cells (BMSCs) plays an important role in many physiological and pathological settings, including wound healing. During the migration of BMSCs through interstitial tissues, the movement of the nucleus must be coordinated with the cytoskeletal dynamics, which in turn affects the cell migration efficiency. Our previous study indicated that osteopontin (OPN) significantly promotes the migration of rat BMSCs. However, the nuclear behaviors and involved molecular mechanisms in OPN-mediated BMSC migration are largely unclear. In the present study, using an atomic force microscope (AFM), we found that OPN could decrease the nuclear stiffness of BMSCs and reduce the expression of lamin A/C, which is the main determinant of nuclear stiffness. Increased lamin A/C expression attenuates BMSC migration by increasing nuclear stiffness. Decreased lamin A/C expression promotes BMSC migration by decreasing nuclear stiffness. Furthermore, OPN promotes BMSC migration by diminishing lamin A/C expression and decreasing nuclear stiffness via the FAK-ERK1/2 signaling pathway. This study provides strong evidence for the role of nuclear mechanics in BMSC migration as well as new insight into the molecular mechanisms of OPN-promoted BMSC migration. - Highlights: • OPN promotes BMSC migration by decreasing nuclear stiffness. • Lamin A/C knockdown decreases, while its overexpression enhances, the nuclear stiffness of BMSCs. • Lamin A/C overexpression and downregulation affect the migration of BMSCs. • OPN diminishes lamin A/C expression and decreases nuclear stiffness through the activation of the FAK-ERK1/2 signaling pathway. • OPN promotes BMSC migration via the FAK-ERK1/2 signaling pathway.

  12. Structure, function and nutritional potential of milk osteopontin

    DEFF Research Database (Denmark)

    Christensen, Brian Søndergaard; Sørensen, Esben Skipper

    2016-01-01

    in cancer related events. In this article, we review the differences between milk-derived OPN and OPN derived from transformed cells and compare the structure of OPN from human and bovine milk. Furthermore, current knowledge about the function of OPN in milk and recent findings about the effect of orally...

  13. Osteopontin: A uranium phosphorylated binding-site characterization

    International Nuclear Information System (INIS)

    Safi, Samir; Jeanson, Aurelie; Roques, Jerome; Simoni, Eric; Creff, Gaelle; Qi, Lei; Basset, Christian; Vidaud, Claude; Solari, Pier Lorenzo; Den Auwer, Christophe

    2013-01-01

    Herein, we describe the structural investigation of one possible uranyl binding site inside a non structured protein. This approach couples spectroscopy, thermodynamics, and theoretical calculations (DFT) and studies the interaction of uranyl ions with a phospho-peptide, thus mimicking a possible osteopontin (OPN) hydroxyapatite growth-inhibition site. Although thermodynamical aspects were investigated by using time-resolved laser fluorescence spectroscopy (TRLFS) and isothermal titration calorimetry (ITC), structural characterization was performed by extended X-ray absorption fine structure (EXAFS) at the U L(III)-edge combined with attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy. From the vibrational and fluorescence spectra, several structural models of a UO 2 2+ /peptide complex were developed and subsequently refined by using theoretical calculations to fit the experimental EXAFS obtained. The structural effect of the pH value was also considered under acidic to moderately acidic conditions (pH 1.5-5.5). Most importantly, the uranyl/peptide coordination environment was similar to that of the native protein. (authors)

  14. The association between osteopontin and survival in non-small-cell lung cancer patients: a meta-analysis of 13 cohorts

    Directory of Open Access Journals (Sweden)

    Wang Y

    2015-11-01

    Full Text Available Ying Wang,1,* Jin Yang,1,* Hui Liu,1 Ji-Rui Bi,1 Ying Liu,2 Yan-Yan Chen,2 Ji-Yu Cao,2 You-Jin Lu1 1Department of Respiratory Medicine, the Second Affiliated Hospital of Anhui Medical University, 2Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, People’s Republic of China *These authors contributed equally to this work Abstract: In the last decade, osteopontin (OPN was identified as one of the important proteins that promote the metastasis of tumor. However, the association between OPN overexpression and clinical outcome of non-small-cell lung cancer (NSCLC was unclear. The purpose of this study is to investigate the role of OPN in NSCLC patients. A total of 13 studies are included to explore the relationship between the OPN elevation and the overall survival (OS and disease-free survival (DFS in NSCLC patients. We searched for related articles in PubMed, Web of Science, Google Scholar, and Cochrane Library databases, which were published before January 31, 2015. Hazard ratio (HR, odds ratio (OR, and 95% confidence interval (CI in the high OPN expression group compared with the low OPN expression group were calculated and analyzed. Primary results were summarized by using a fixed-effects model or a random-effects model. The stratified analyses in subgroups were also performed. Thirteen cohort studies, which involved 1,630 patients, were included. Subgroup analyses were performed by area and test method of OPN. We found that OPN was significantly associated with poor OS (HR =2.20, 95% CI 1.71–2.83, P<0.001 and DFS (HR =2.11, 95% CI 1.62–2.74, P<0.001 in NSCLC patients. OPN overexpression tended to be associated with the presence of advanced tumor TNM stage (III and IV (OR =2.57, 95% CI 1.61–4.11, P<0.001. The Egger’s test suggested that there was no publication bias in OS studies (P=0.062 and DFS studies (P=0.740. These data indicate that OPN seems to have a

  15. Osteopontin: A non-invasive parameter of portal hypertension and prognostic marker of cirrhosis.

    Science.gov (United States)

    Bruha, Radan; Jachymova, Marie; Petrtyl, Jaromir; Dvorak, Karel; Lenicek, Martin; Urbanek, Petr; Svestka, Tomislav; Vitek, Libor

    2016-03-28

    To investigate the relationship between osteopontin plasma concentrations and the severity of portal hypertension and to assess osteopontin prognostic value. A cohort of 154 patients with confirmed liver cirrhosis (112 ethylic, 108 men, age 34-72 years) were enrolled in the study. Hepatic venous pressure gradient (HVPG) measurement and laboratory and ultrasound examinations were carried out for all patients. HVPG was measured using a standard catheterization method with the balloon wedge technique. Osteopontin was measured using the enzyme-linked immunosorbent assay (ELISA) method in plasma. Patients were followed up with a specific focus on mortality. The control group consisted of 137 healthy age- and sex- matched individuals. The mean value of HVPG was 16.18 ± 5.6 mmHg. Compared to controls, the plasma levels of osteopontin in cirrhotic patients were significantly higher (P portal hypertension (HVPG above 10 mmHg) at 75% sensitivity and 63% specificity. The mean follow-up of patients was 3.7 ± 2.6 years. The probability of cumulative survival was 39% for patients with HVPG > 10 mmHg and 65% for those with HVPG ≤ 10 mmHg (P = 0.0086, odds ratio (OR), 2.92, 95% confidence interval (CI): 1.09-7.76). Osteopontin showed a similar prognostic value to HVPG. Patients with osteopontin values above 80 ng/mL had significantly lower cumulative survival compared to those with osteopontin ≤ 80 ng/mL (37% vs 56%, P = 0.00035; OR = 2.23, 95%CI: 1.06-4.68). Osteopontin is a non-invasive parameter of portal hypertension that distinguishes patients with clinically significant portal hypertension. It is a strong prognostic factor for survival.

  16. Immobilization of cross linked Col-I–OPN bone matrix protein on aminolysed PCL surfaces enhances initial biocompatibility of human adipogenic mesenchymal stem cells (hADMSC)

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young-Hee; Jyoti, Md. Anirban; Song, Ho-Yeon, E-mail: songmic@sch.ac.kr

    2014-06-01

    In bone tissue engineering surface modification is considered as one of the important ways of fabricating successful biocompatible material. Addition of biologically active functionality on the surfaces has been tried for improving the overall biocompatibility of the system. In this study poly-ε-caprolactone film surfaces have been modified through aminolysis and immobilization process. Collagen type I (COL-I) and osteopontin (OPN), which play an important role in osteogenesis, was immobilized onto PCL films followed by aminolysis treatment using 1,6-hexanediamine. Characterization of animolysed and immobilized surfaces were done by a number techniques using scanning electron microscopy (SEM), FT-IR, XPS, ninhydrin staining, SDS-PAGE and confocal microscopy and compared between the modified and un-modified surfaces. Results of the successive experiments showed that aminolysis treatment was homogeneously achieved which helped to entrap or immobilize Col-I–OPN proteins on surfaces of PCL film. In vitro studies with human adipogenic mesenchymal stem cells (hADMSC) also confirmed the attachment and proliferation of cells was better in modified PCL surfaces than the unmodified surfaces. SEM, confocal microscopy and MTT assay showed a significant increase in cell spreading, attachment and proliferations on the biofunctionalized surfaces compared to the unmodified PCL surfaces at all-time points indicating the success of surface biofunctionalization.

  17. Calcium-phosphate-osteopontin particles for caries control

    DEFF Research Database (Denmark)

    Schlafer, Sebastian

    Oftentimes caries lesions develop in protected sites that are difficult to access by self-performed mechanical tooth cleaning. At present, there is a growing interest in chemical adjuncts to mechanical procedures of oral hygiene that aim at biofilm control rather than biofilm eradication. Calcium......-phosphate-osteopontin particles are a new promising therapeutic approach to caries control. They are designed to bind to dental biofilms and interfere with biofilm build-up, lowering the bacterial burden on the tooth surface without affecting bacterial viability in the oral cavity. Moreover, they dissolve when pH in the biofilm...... drops to 6 or below and release buffering phosphate ions that stabilize biofilm pH above the critical level for enamel dissolution. With that twofold approach, calcium-phosphate-osteopontin particles may make a relevant contribution to clinical caries control....

  18. UV-sensitive photoreceptor protein OPN5 in humans and mice.

    Science.gov (United States)

    Kojima, Daisuke; Mori, Suguru; Torii, Masaki; Wada, Akimori; Morishita, Rika; Fukada, Yoshitaka

    2011-01-01

    A variety of animal species utilize the ultraviolet (UV) component of sunlight as their environmental cues, whereas physiological roles of UV photoreception in mammals, especially in human beings, remain open questions. Here we report that mouse neuropsin (OPN5) encoded by the Opn5 gene exhibited an absorption maximum (λmax) at 380 nm when reconstituted with 11-cis-retinal. Upon UV-light illumination, OPN5 was converted to a blue-absorbing photoproduct (λmax 470 nm), which was stable in the dark and reverted to the UV-absorbing state by the subsequent orange light illumination, indicating its bistable nature. Human OPN5 also had an absorption maximum at 380 nm with spectral properties similar to mouse OPN5, revealing that OPN5 is the first and hitherto unknown human opsin with peak sensitivity in the UV region. OPN5 was capable of activating heterotrimeric G protein Gi in a UV-dependent manner. Immuno-blotting analyses of mouse tissue extracts identified the retina, the brain and, unexpectedly, the outer ears as the major sites of OPN5 expression. In the tissue sections of mice, OPN5 immuno-reactivities were detected in a subset of non-rod/non-cone retinal neurons as well as in the epidermal and muscle cells of the outer ears. Most of these OPN5-immuno-reactivities in mice were co-localized with positive signals for the alpha-subunit of Gi. These results demonstrate the first example of UV photoreceptor in human beings and strongly suggest that OPN5 triggers a UV-sensitive Gi-mediated signaling pathway in the mammalian tissues.

  19. Effect of irinotecan combined with cisplatin on serum CD105, OPN, SCCAg, CEA and T lymphocyte subsets in patients with cervical cancer

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    Xin-Hui Wang

    2017-06-01

    Full Text Available Objective: To study the effect of irinotecan combined with cisplatin on serum CD105, OPN, SCCAg, CEA and T lymphocyte subsets in patients with cervical cancer. Methods: A total of 90 patients with cervical cancer in our hospital from May 2014 to May 2016 were enrolled in this study. The subjects were divided into the control group (n=45 and the treatment group (n=45 randomly. The control group were treated with radiotherapy, the treatment group were treated with irinotecan combined with cisplatin. The two groups were treated for 3 periods. The serum CD105, OPN, SCCAg, CEA levels and peripheral blood CD3 +, CD4 +/CD3 +, CD8 + cells of the two groups before and after treatment were compared. Results: There were no significantly differences of the serum CD105, OPN, SCCAg, CEA levels and peripheral blood CD3 +, CD4 +/ CD3 +, CD8 + cells of the two groups before treatment. The serum CD105, OPN, SCCAg and CEA levels of the two groups after treatment were significantly lower than before treatment, and that of the treatment group were significantly lower than the control group. The peripheral blood CD3 +, CD4 +/CD3 + cells of the two groups after treatment were significantly higher than before treatment, CD8 + cells of the two groups after treatment were significantly lower than before treatment, and that of the treatment group were significantly better than the control group. Conclusion: Irinotecan combined with cisplatin can significantly reduce the serum CD105, OPN, SCCAg, CEA levels, improve peripheral blood CD3 +, CD4 +/CD3 +, CD8 + levels of patients with cervical cancer, and it was worthy clinical application.

  20. Expression of S100A4, ephrin-A1 and osteopontin in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Rud, Ane Kongsgaard; Lund-Iversen, Marius; Berge, Gisle; Brustugun, Odd Terje; Solberg, Steinar K; Mælandsmo, Gunhild M; Boye, Kjetil

    2012-01-01

    The metastasis-promoting protein S100A4 induces expression of ephrin-A1 and osteopontin in osteosarcoma cell lines. The aim of this study was to investigate S100A4-mediated stimulation of ephrin-A1 and osteopontin in non-small cell lung cancer (NSCLC) cell lines, and to characterize the expression of these biomarkers in primary tumor tissue from NSCLC patients. Four NSCLC cell lines were treated with extracellular S100A4, and ephrin-A1 and osteopontin expression was analyzed by real time RT-PCR and Western blotting. Immunohistochemical staining for S100A4, ephrin-A1 and osteopontin was performed on tissue microarrays containing primary tumor samples from a cohort of 217 prospectively recruited NSCLC patients, and associations with clinicopathological parameters were investigated. S100A4 induced ephrin-A1 mRNA and protein expression in adenocarcinoma, but not in squamous carcinoma cell lines, whereas the level of osteopontin was unaffected by S100A4 treatment. In primary tumors, moderate or strong immunoreactivity was observed in 57% of cases for cytoplasmic S100A4, 46% for nuclear S100A4, 86% for ephrin-A1 and 77% for osteopontin. Interestingly, S100A4 expression was associated with ephrin-A1 also in vivo, but there was no association between S100A4 and osteopontin. Expression levels of S100A4 and ephrin-A1 were significantly higher in adenocarcinomas compared to other histological subtypes, and S100A4-positive tumors were smaller and more differentiated than tumors without expression. Our findings suggest that S100A4, ephrin-A1 and osteopontin are involved in the biology of NSCLC, and further investigation of their potential use as biomarkers in NSCLC is warranted

  1. Glucose-Dependent Insulinotropic Polypeptide Stimulates Osteopontin Expression in the Vasculature via Endothelin-1 and CREB

    DEFF Research Database (Denmark)

    Berglund, Lisa M; Lyssenko, Valeriya; Ladenvall, Claes

    2016-01-01

    in individuals with a history of cardiovascular disease (myocardial infarction, stroke) when compared to controls. GIP receptor (GIPR) and OPN mRNA levels are higher in carotid endarterectomies from patients with symptoms (stroke, transient ischemic attacks, amaurosis fugax) than in asymptomatic patients...

  2. Alteration in Oxidative/nitrosative imbalance, histochemical expression of osteopontin and antiurolithiatic efficacy of Xanthium strumarium (L.) in ethylene glycol induced urolithiasis.

    Science.gov (United States)

    Panigrahi, Padma Nibash; Dey, Sahadeb; Sahoo, Monalisa; Choudhary, Shyam Sundar; Mahajan, Sumit

    2016-12-01

    Xanthium strumarium has traditionally been used in the treatment of urolitiasis especially by the rural people in India, but its antiurolithiatic efficacy was not explored scientifically till now. Therefore, the present study was designed to validate the ethnic practice scientifically, and explore the possible antiurolithiatic effect to rationalize its medicinal use. Urolitiasis was induced in hyperoxaluric rat model by giving 0.75% ethylene glycol (EG) for 28days along with 1% ammonium chloride (AC) for first 14days. Antiurolithiatic effect of aqueous-ethanol extract of Xanthium strumarium bur (xanthium) was evaluated based on urine and serum biochemistry, oxidative/nitrosative stress indices, histopathology, kidney calcium and calcium oxalate content and immunohistochemical expression of matrix glycoprotein, osteopontin (OPN). Administration of EG and AC resulted in hyperoxaluria, crystalluria, hypocalciuria, polyurea, raised serum urea, creatinine, erythrocytic lipid peroxidise and nitric oxide, kidney calcium content as well as crystal deposition in kidney section in lithiatic group rats. However, xanthium treatment significantly restored the impairment in above kidney function test as that of standard treatment, cystone. The up-regulation of OPN was also significantly decreased after xanthium treatment. The present findings demonstrate the curative efficacy of xanthium in ethylene glycol induced urolithiasis, possibly mediated through inhibition of various pathways involved in renal calcium oxalate formation, antioxidant property and down regulation of matrix glycoprotein, OPN. Therefore, future studies may be established to evaluate its efficacy and safety for clinical use. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  3. Nuclear osteopontin-c is a prognostic breast cancer marker.

    Science.gov (United States)

    Zduniak, K; Ziolkowski, P; Ahlin, C; Agrawal, A; Agrawal, S; Blomqvist, C; Fjällskog, M-L; Weber, G F

    2015-02-17

    Although Osteopontin has been known as a marker for cancer progression, the elevated production of this cytokine is not specific for cancer. We have identified the splice variant Osteopontin-c as being absent from healthy tissue but associated with about 75% of breast cancer cases. However, in previous studies of Osteopontin-c, follow-up information was not available. Here we have analysed 671 patients, comprising a cohort of 291 paraffin blocks plus a population-based case-control study of 380 arrayed breast tumor tissues. We find that high staining intensity of nuclear Osteopontin-c is strongly associated with mortality in patients with early breast cancer. Cytosolic staining for exon 4, reflective of Osteopontin-a and -b also predicts poor outcome. By contrast, total Osteopontin does not correlate with prognosis. These diverse assessments of Osteopontin also do not correlate with each other, suggesting distinct expression patterns for the variant forms. Consistent with its role in tumor progression, not tumor initiation, Osteopontin-c is not correlated with proliferation markers (Ki-67, cyclin A, cyclin B, cyclin E and cyclin D), neither is it correlated with ER, PR or HER2. The addition of Osteopontin-c immunohistochemistry to standard pathology work-ups may have prognostic benefit in early breast cancer diagnosis.

  4. Purification and characterization of osteopontin from human milk

    DEFF Research Database (Denmark)

    Sørensen, Steen; Justesen, Steen Just; Johnsen, Anders H

    2003-01-01

    biological source is missing. A four-step procedure was used to purify OPN from human milk, based on its crystal growth inhibitory activity, including anion exchange chromatography, the elimination of casein, hydroxyapatite chromatography, and negative affinity chromatography. Purified OPN was further...

  5. Extracellular and Intracellular Mechanisms Mediating Metastatic Activity of Exogenous Osteopontin

    Science.gov (United States)

    Mandelin, Jami; Lin, Emme C. K.; Hu, Dana D.; Knowles, Susan K.; Do, Kim-Anh; Wang, Xuemei; Sage, E. Helene; Smith, Jeffrey W.; Arap, Wadih; Pasqualini, Renata

    2009-01-01

    BACKGROUND Osteopontin affects several steps of the metastatic cascade. Despite direct correlation with metastasis in experimental systems and in patient studies, the extracellular and intracellular basis for these observations remains unsolved. We used human melanoma and sarcoma cell lines to evaluate the effects of soluble osteopontin on metastasis. METHODS Exogenous osteopontin or negative controls, including a site-directed mutant osteopontin, were used in functional assays in vitro, ex vivo, and in vivo designed to test extracellular and intracellular mechanisms involved in experimental metastasis. RESULTS In the extracellular environment, we confirm that soluble osteopontin is required for its pro-metastatic effects; this phenomenon is specific, RGD-dependent, and evident in experimental models of metastasis. In the intracellular environment, osteopontin initially induces rapid Tyr-418 dephosphorylation of c-Src, with decreases in actin stress fibers and increased binding to the vascular endothelium. This heretofore undescribed Tyr dephosphorylation is followed by a tandem c-Src phosphorylation after tumor cell attachment to the metastatic site. CONCLUSION Our results reveal a complex molecular interaction as well as a dual role for osteopontin in metastasis that is dependent on whether tumor cells are in circulation or attached. Such context-dependent functional insights may contribute to anti-metastasis strategies. PMID:19224553

  6. Intranasal administration of vitamin D attenuates blood-brain barrier disruption through endogenous upregulation of osteopontin and activation of CD44/P-gp glycosylation signaling after subarachnoid hemorrhage in rats.

    Science.gov (United States)

    Enkhjargal, Budbazar; McBride, Devin W; Manaenko, Anatol; Reis, Cesar; Sakai, Yasushi; Tang, Jiping; Zhang, John H

    2017-07-01

    In this study, we investigated the role of vitamin D3 (VitD3) on endogenous osteopontin (OPN), a neuroprotective glycoprotein, after subarachnoid hemorrhage (SAH). The endovascular perforation SAH model in Sprague-Dawley rats was used to study the effect of intranasal VitD3 (30 ng/kg) before (Pre-SAH + VitD3) and after (Post-SAH + VitD3) subarachnoid hemorrhage. Vitamin D3 (30, 60, 120 ng/kg/day) increased more than one fold endogenous OPN expression in astrocytes and endothelial cells of rat brain. Vitamin D3 significantly decreased brain edema and Evans blue extravasation. In addition, neurobehavioral scores were significantly higher in Pre-SAH + VitD3, but partly higher in Post-SAH + VitD3, group compared with SAH group. These protective effects of vitamin D3 were completely attenuated by intracerebroventricular injection of transcription inhibitor Actinomycin D and significantly inhibited by small interfering ribonucleic acid (siRNA) for vitamin D receptor and OPN in Pre-SAH + VitD3 rats. OPN expression was significantly higher in Pre-SAH + VitD3 rats, specifically A and C, but not B, isomers were upregulated in the astrocytes, leading to CD44 splicing, and P-gp glycosylation in brain endothelial cells. The results show that intranasal vitamin D3 attenuates blood-brain barrier (BBB) disruption through endogenous upregulation of OPN and subsequent CD44 and P-gp glycosylation signals in brain endothelial cells. Furthermore, this study identifies a novel strategy for the cost-effective management of subarachnoid hemorrhage.

  7. Adsorption and enzymatic cleavage of osteopontin at interfaces with different surface chemistries

    DEFF Research Database (Denmark)

    Malmström, Jenny; Shipovskov, Stepan; Christensen, Brian

    2009-01-01

    (methyl-, carboxylic-, and amine-terminated alkanethiol self-assembled monolayers and bare gold) have been studied utilizing a combination of the quartz crystal microbalance with dissipation and surface plasmon resonance. Full length bovine milk osteopontin was used which is well characterized...... at the polar surfaces with the highest level of hydration being observed at the gold surface. The energy dissipation of these thin films (as measured by the DeltaD/DeltaF value) was altered at the different surface chemistries and interestingly a higher dissipation correlated with a higher density. Thrombin...... with respect to post-translational modifications. Osteopontin adsorbed at all the surfaces formed thin (approximately 2-5 nm) hydrated layers with the highest amount of protein and the highest density layers observed at the hydrophobic surface. Less protein and a higher level of hydration was observed...

  8. Post-translational modification of osteopontin: Effects on in vitro hydroxyapatite formation and growth

    DEFF Research Database (Denmark)

    Boskey, Adele L.; Christensen, Brian Søndergaard; Taleb, Hayat

    2012-01-01

    The manuscript tests the hypothesis that posttranslational modification of the SIBLING family of proteins in general and osteopontin in particular modify the abilities of these proteins to regulate in vitro hydroxyapatite (HA) formation. Osteopontin has diverse effects on hydroxyapatite (HA...

  9. Osteopontin as a marker for response to pegylated interferon Alpha ...

    African Journals Online (AJOL)

    Osteopontin as a marker for response to pegylated interferon Alpha-2b treatment in Chronic HCV Saudi patients. Yousri Mostafa Hussein1,2, Ayman Alhazmi1, Saad Alzahrani3, Ahmad El-Askary1,4,. Abdulrahman Alghamdy5, Eman Bayomy4, Assmaa Selim6, Mohammed Alghamdy1. 1. Medical Laboratories Department ...

  10. Osteopontin splice variants are differential predictors of breast cancer treatment responses.

    Science.gov (United States)

    Zduniak, Krzysztof; Agrawal, Anil; Agrawal, Siddarth; Hossain, Md Monir; Ziolkowski, Piotr; Weber, Georg F

    2016-07-11

    Osteopontin is a marker for breast cancer progression, which in previous studies has also been associated with resistance to certain anti-cancer therapies. It is not known which splice variants may mediate treatment resistance. Here we analyze the association of osteopontin variant expression before treatment, differentiated according to immunohistochemistry with antibodies to exon 4 and to the osteopontin-c splice junction respectively, with the ensuing therapy responses in 119 Polish breast cancer patients who presented between 1995 and 2008. We found from Cox hazard models, logrank test and Wilcoxon test that osteopontin exon 4 was associated with a favorable response to tamoxifen, but a poor response to chemotherapy with CMF (cyclophosphamide, methotrexate, fluorouracil). Osteopontin-c is prognostic, but falls short of being a significant predictor for sensitivity to treatment. The addition of osteopontin splice variant immunohistochemistry to standard pathology work-ups has the potential to aid decision making in breast cancer treatment.

  11. Osteopontin splice variants are differential predictors of breast cancer treatment responses

    International Nuclear Information System (INIS)

    Zduniak, Krzysztof; Agrawal, Anil; Agrawal, Siddarth; Hossain, Md Monir; Ziolkowski, Piotr; Weber, Georg F.

    2016-01-01

    Osteopontin is a marker for breast cancer progression, which in previous studies has also been associated with resistance to certain anti-cancer therapies. It is not known which splice variants may mediate treatment resistance. Here we analyze the association of osteopontin variant expression before treatment, differentiated according to immunohistochemistry with antibodies to exon 4 and to the osteopontin-c splice junction respectively, with the ensuing therapy responses in 119 Polish breast cancer patients who presented between 1995 and 2008. We found from Cox hazard models, logrank test and Wilcoxon test that osteopontin exon 4 was associated with a favorable response to tamoxifen, but a poor response to chemotherapy with CMF (cyclophosphamide, methotrexate, fluorouracil). Osteopontin-c is prognostic, but falls short of being a significant predictor for sensitivity to treatment. The addition of osteopontin splice variant immunohistochemistry to standard pathology work-ups has the potential to aid decision making in breast cancer treatment

  12. Calcium-phosphate-osteopontin particles for caries control

    DEFF Research Database (Denmark)

    Schlafer, Sebastian; Birkedal, Henrik; Olsen, Jakob

    2016-01-01

    Caries is caused by acid production in biofilms on dental surfaces. Preventing caries therefore involves control of microorganisms and/or the acid produced. Here, calcium-phosphate-osteopontin particles are presented as a new approach to caries control. The particles are made by co......-precipitation and designed to bind to bacteria in biofilms, impede biofilm build-up without killing the microflora, and release phosphate ions to buffer bacterial acid production if the pH decreases below 6. Analysis of biofilm formation and pH in a five-species biofilm model for dental caries showed that treatment......H always remained above 5.5. Hence, calcium-phosphate-osteopontin particles show potential for applications in caries control....

  13. Osteopontin splice variants are differential predictors of breast cancer treatment responses

    OpenAIRE

    Zduniak, Krzysztof; Agrawal, Anil; Agrawal, Siddarth; Hossain, Md Monir; Ziolkowski, Piotr; Weber, Georg F.

    2016-01-01

    Background Osteopontin is a marker for breast cancer progression, which in previous studies has also been associated with resistance to certain anti-cancer therapies. It is not known which splice variants may mediate treatment resistance. Methods Here we analyze the association of osteopontin variant expression before treatment, differentiated according to immunohistochemistry with antibodies to exon 4 and to the osteopontin-c splice junction respectively, with the ensuing therapy responses i...

  14. Osteopontin: A novel regulator at the cross roads of inflammation, obesity and diabetes.

    Science.gov (United States)

    Kahles, Florian; Findeisen, Hannes M; Bruemmer, Dennis

    2014-07-01

    Since its first description more than 20 years ago osteopontin has emerged as an active player in many physiological and pathological processes, including biomineralization, tissue remodeling and inflammation. As an extracellular matrix protein and proinflammatory cytokine osteopontin is thought to facilitate the recruitment of monocytes/macrophages and to mediate cytokine secretion in leukocytes. Modulation of immune cell response by osteopontin has been associated with various inflammatory diseases and may play a pivotal role in the development of adipose tissue inflammation and insulin resistance. Here we summarize recent findings on the role of osteopontin in metabolic disorders, particularly focusing on diabetes and obesity.

  15. Structural insights into the osteopontin-aptamer complex y molecular dynamics simulations

    Science.gov (United States)

    La Penna, Giovanni; Chelli, Riccardo

    2018-01-01

    Osteopontin is an intrinsically disordered protein involved in tissue remodeling. As a biomarker for pathological hypertrophy and fibrosis, the protein is targeted by an RNA aptamer. In this work, we model the interactions between osteopontin and its aptamer, including mono- (Na+) and divalent (Mg2+) cations. The molecular dynamics simulations suggest that the presence of divalent cations forces the N-terminus of osteopontin to bind the shell of divalent cations adsorbed over the surface of its RNA aptamer, the latter exposing a high negative charge density. The osteopontin plasticity as a function of the local concentration of Mg is discussed in the frame of the proposed strategies for osteopontin targeting as biomarker and in theranostic.

  16. High Expression of Osteopontin and CD44v6 in Odontogenic Keratocysts

    Directory of Open Access Journals (Sweden)

    Yi-Ping Wang

    2009-04-01

    Conclusion: Binding of OPN to osteoclast cell membrane receptor integrin αv can activate the osteoclasts and increase their osteolytic activity. In addition, binding of OPN to OKC lining epithelial cell membrane receptor CD44v6 can enhance the motility, migration, invasion and spread of lining epithelial cells into the surrounding cancellous bone. Therefore, we suggest that the local aggressive behavior and high osteolytic ability of OKCs in the jawbone can be explained at least partially by high expression of OPN and CD44v6 in lining epithelial cells of OKCs and high expression of integrin αv in osteoclasts.

  17. Osteopontin and systemic lupus erythematosus association: a probable gene-gender interaction.

    Directory of Open Access Journals (Sweden)

    Shizhong Han

    2008-03-01

    Full Text Available Osteopontin (SPP1 is an important bone matrix mediator found to have key roles in inflammation and immunity. SPP1 genetic polymorphisms and increased osteopontin protein levels have been reported to be associated with SLE in small patient collections. The present study evaluates association between SPP1 polymorphisms and SLE in a large cohort of 1141 unrelated SLE patients [707 European-American (EA and 434 African-American (AA], and 2009 unrelated controls (1309 EA and 700 AA. Population-based case-control association analyses were performed. To control for potential population stratification, admixture adjusted logistic regression, genomic control (GC, structured association (STRAT, and principal components analysis (PCA were applied. Combined analysis of 2 ethnic groups, showed the minor allele of 2 SNPs (rs1126616T and rs9138C significantly associated with higher risk of SLE in males (P = 0.0005, OR = 1.73, 95% CI = 1.28-2.33, but not in females. Indeed, significant gene-gender interactions in the 2 SNPs, rs1126772 and rs9138, were detected (P = 0.001 and P = 0.0006, respectively. Further, haplotype analysis identified rs1126616T-rs1126772A-rs9138C which demonstrated significant association with SLE in general (P = 0.02, OR = 1.30, 95%CI 1.08-1.57, especially in males (P = 0.0003, OR = 2.42, 95%CI 1.51-3.89. Subgroup analysis with single SNPs and haplotypes also identified a similar pattern of gender-specific association in AA and EA. GC, STRAT, and PCA results within each group showed consistent associations. Our data suggest SPP1 is associated with SLE, and this association is especially stronger in males. To our knowledge, this report serves as the first association of a specific autosomal gene with human male lupus.

  18. Investigation of the reaction 16O(p,n)16F at Esub(p)=135 MeV

    International Nuclear Information System (INIS)

    Gareev, F.A.; Ershov, S.N.

    1984-01-01

    The 16 O(p,n) 16 F reaction at 135 MeV has been analyzed the framework of the distorted-wave impulse-approximation (DWIA). Both direct and exchange mechanisms of nucleon knock-out are taken into account. Including the n-particle n-hole (n=0, 1, 2) correlations in the wave functions of A=16 nuclei improves the description of experimental data: diminishes the absolute value of the cross sections about twice as compared with the calculations using the simple particle-hole structure models

  19. Bovine milk osteopontin - Targeting bacterial adhesion for biofilm control

    DEFF Research Database (Denmark)

    Kristensen, Mathilde Frost; Meyer, Rikke Louise; Schlafer, Sebastian

    2016-01-01

    Self-performed mechanical tooth cleaning does usually not result in complete biofilm removal, due to the complex oral anatomy and the strong adhesion of the biofilm to the tooth. Therefore, different supportive measures are employed, most of which aim at the chemical eradication of bacteria...... in dental biofilms. As their bactericidal action impacts the entire oral microflora, agents that inhibit biofilm formation without killing bacteria, such as the bovine milk protein osteopontin, have gained increasing attention. Here, we investigate the adhesion of 8 bacterial species associated with dental...... subsp. paracasei, Streptococcus mitis and Streptococcus oralis with 74.0%, 62.4%, 90.0%, 89.6% and 81.5%, respectively, compared to protein-free saliva. All reductions were statistically significant (p

  20. Tumorigenic properties of alternative osteopontin isoforms in mesothelioma

    Energy Technology Data Exchange (ETDEWEB)

    Ivanov, Sergey V., E-mail: Sergey.Ivanov@med.nyu.edu [Thoracic Surgery Laboratory, Cardiothoracic Surgery Department, NYU Langone Medical Center, 462 First Ave., Bellevue Hospital, Room 15N20, NY 10016 (United States); Ivanova, Alla V.; Goparaju, Chandra M.V.; Chen, Yuanbin; Beck, Amanda; Pass, Harvey I. [Thoracic Surgery Laboratory, Cardiothoracic Surgery Department, NYU Langone Medical Center, 462 First Ave., Bellevue Hospital, Room 15N20, NY 10016 (United States)

    2009-05-08

    Osteopontin (SPP1) is an inflammatory cytokine that we previously characterized as a diagnostic marker in patients with asbestos-induced malignant mesothelioma (MM). While SPP1 shows both pro- and anti-tumorigenic biological effects, little is known about the molecular basis of these activities. In this study, we demonstrate that while healthy pleura possesses all three differentially spliced SPP1 isoforms (A-C), in clinical MM specimens isoform A is markedly up-regulated and predominant. To provide a clue to possible functions of the SPP1 isoforms we next performed their functional evaluation via transient expression in MM cell lines. As a result, we report that isoforms A-C demonstrate different activities in cell proliferation, wound closure, and invasion assays. These findings suggest different functions for SPP1 isoforms and underline pro-tumorigenic properties of isoforms A and B.

  1. Statin Treatment Is Associated with Reduction in Serum Levels of Receptor Activator of NF-κB Ligand and Neutrophil Activation in Patients with Severe Carotid Stenosis

    Directory of Open Access Journals (Sweden)

    Sébastien Lenglet

    2014-01-01

    Full Text Available Systemic and intraplaque biomarkers have been widely investigated in clinical cohorts as promising surrogate parameters of cardiovascular vulnerability. In this pilot study, we investigated if systemic and intraplaque levels of calcification biomarkers were affected by treatment with a statin in a cohort of patients with severe carotid stenosis and being asymptomatic for ischemic stroke. Patients on statin therapy had reduced serum osteopontin (OPN, RANKL/osteoprotegerin (OPG ratio, and MMP-9/pro-MMP-9 activity as compared to untreated patients. Statin-treated patients exhibited increased levels of collagen and reduced neutrophil infiltration in downstream portions of carotid plaques as compared to untreated controls. In upstream plaque portions, OPG content was increased in statin-treated patients as compared to controls. Other histological parameters (such as lipid, macrophage, smooth muscle cell, and MMP-9 content as well as RANKL, RANK, and OPG mRNA levels did not differ between the two patient groups. Serum RANKL/OPG ratio positively correlated with serum levels of neutrophilic products, intraplaque neutrophil, and MMP-9 content within downstream portions of carotid plaques. In conclusion, statin treatment was associated with improvement in serum RANKL levels and reduced neutrophil activity both systemically and in atherosclerotic plaques.

  2. Osteopontin deficiency delays inflammatory infiltration and the onset of muscle regeneration in a mouse model of muscle injury

    Directory of Open Access Journals (Sweden)

    Kitipong Uaesoontrachoon

    2013-01-01

    Osteopontin is secreted by skeletal muscle myoblasts and stimulates their proliferation. Expression of osteopontin in skeletal muscle is upregulated in pathological conditions including Duchenne muscular dystrophy, and recent evidence suggests that osteopontin might influence the course of this disease. The current study was undertaken to determine whether osteopontin regulates skeletal muscle regeneration. A whole muscle autografting model of regeneration in osteopontin-null and wild-type mice was used. Osteopontin expression was found to be strongly upregulated in wild-type grafts during the initial degeneration and subsequent early regeneration phases that are observed in this model. Grafted muscle from osteopontin-null mice degenerated more slowly than that of wild-type mice, as determined by histological assessment, fibre diameter and fibre number. The delayed degeneration in osteopontin-null grafts was associated with a delay in neutrophil and macrophage infiltration. Centrally nucleated (regenerating muscle fibres also appeared more slowly in osteopontin-null grafts than in wild-type grafts. These results demonstrate that osteopontin plays a non-redundant role in muscle remodelling following injury.

  3. Associations between the Genetic Polymorphisms of Osteopontin Promoter and Susceptibility to Cancer in Chinese Population: A Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Yulan Liu

    Full Text Available Several studies have been conducted to examine the associations between osteopontin (OPN promoter gene SPP1 polymorphisms with human cancers in Chinese population, but the results remain inconsistent. The aim of this meta-analysis is to clarify the associations between SPP1 polymorphisms and cancer susceptibility.All eligible case-control studies published up to March 2015 were identified by searching PubMed, Web of Science, Embase, and Cochrane Library without language restrictions. Pooled odds ratio (OR and 95% confidence interval (95% CI were calculated using fixed- or random-effect model.A total of 11 case-control studies were included; of those, there were eleven studies (3130 cases and 3828 controls for -443T>C polymorphism, ten studies (3019 cases and 3615 controls for -156G>GG polymorphism, eight studies (2258 cases and 2846 controls for -66T>G polymorphism. Overall, no evidence indicated that the -443 T>C polymorphism was associated with cancer risk (OR = 0.93, 95%CI 0.62-1.38 for dominant model, OR = 1.06, 95%CI 0.73-1.55 for recessive model, OR = 0.88, 95%CI 0.62-1.26 for CT vs TT model, OR = 1.03, 95%CI 0.61-1.73 for CC vs TT model. While, a significantly increase risk was found for -156 G>GG polymorphism (OR = 1.22, 95%CI 1.10-1.35 for dominant model, OR = 1.25, 95%CI 1.10-1.41 for recessive model, OR = 1.18, 95%CI 1.06-1.32 for GGG vs GG model, OR = 1.35, 95%CI 1.09-1.68 for GGGG vs GG model. For -66T>G polymorphism, we found a decrease risk of cancer (OR = 0.84, 95% CI 0.71-0.98 for dominant model, but this result changed (OR = 0.93, 95% CI 0.77-1.12 for dominant model when we excluded a study.This meta-analysis suggests that in Chinese population the -156G>GG polymorphism of SPP1 might be a risk factor for human cancers, while -443T>C mutation is not associated with cancer risk. For -66T>G polymorphism, it may be a protective factor for human cancers.

  4. Melanopsin as a sleep modulator: circadian gating of the direct effects of light on sleep and altered sleep homeostasis in Opn4(-/- mice.

    Directory of Open Access Journals (Sweden)

    Jessica W Tsai

    2009-06-01

    Full Text Available Light influences sleep and alertness either indirectly through a well-characterized circadian pathway or directly through yet poorly understood mechanisms. Melanopsin (Opn4 is a retinal photopigment crucial for conveying nonvisual light information to the brain. Through extensive characterization of sleep and the electrocorticogram (ECoG in melanopsin-deficient (Opn4(-/- mice under various light-dark (LD schedules, we assessed the role of melanopsin in mediating the effects of light on sleep and ECoG activity. In control mice, a light pulse given during the habitual dark period readily induced sleep, whereas a dark pulse given during the habitual light period induced waking with pronounced theta (7-10 Hz and gamma (40-70 Hz activity, the ECoG correlates of alertness. In contrast, light failed to induce sleep in Opn4(-/- mice, and the dark-pulse-induced increase in theta and gamma activity was delayed. A 24-h recording under a LD 1-hratio1-h schedule revealed that the failure to respond to light in Opn4(-/- mice was restricted to the subjective dark period. Light induced c-Fos immunoreactivity in the suprachiasmatic nuclei (SCN and in sleep-active ventrolateral preoptic (VLPO neurons was importantly reduced in Opn4(-/- mice, implicating both sleep-regulatory structures in the melanopsin-mediated effects of light. In addition to these acute light effects, Opn4(-/- mice slept 1 h less during the 12-h light period of a LD 12ratio12 schedule owing to a lengthening of waking bouts. Despite this reduction in sleep time, ECoG delta power, a marker of sleep need, was decreased in Opn4(-/- mice for most of the (subjective dark period. Delta power reached after a 6-h sleep deprivation was similarly reduced in Opn4(-/- mice. In mice, melanopsin's contribution to the direct effects of light on sleep is limited to the dark or active period, suggesting that at this circadian phase, melanopsin compensates for circadian variations in the photo sensitivity of

  5. Regulation of the pro-inflammatory cytokine osteopontin by GIP in adipocytes – A role for the transcription factor NFAT and phosphodiesterase 3B

    International Nuclear Information System (INIS)

    Omar, Bilal; Banke, Elin; Guirguis, Emilia; Aakesson, Lina; Manganiello, Vincent; Lyssenko, Valeriya; Groop, Leif; Gomez, Maria F.; Degerman, Eva

    2012-01-01

    Highlights: ► GIP stimulates lipogenesis and osteopontin expression in primary adipocytes. ► GIP-induced osteopontin expression is NFAT-dependent. ► Osteopontin expression is PDE3-dependent. ► Osteopontin expression is increased in PDE3B KO mice. -- Abstract: The incretin – glucose-dependent insulinotropic polypeptide (GIP) – and the pro-inflammatory cytokine osteopontin are known to have important roles in the regulation of adipose tissue functions. In this work we show that GIP stimulates lipogenesis and osteopontin expression in primary adipocytes. The GIP-induced increase in osteopontin expression was inhibited by the NFAT (the transcription factor nuclear factor of activated T-cells) inhibitor A-285222. Also, the NFAT kinase glycogen synthase kinase (GSK) 3 was upregulated by GIP. To test whether cAMP might be involved in GIP-mediated effects on osteopontin a number of strategies were used. Thus, the β3-adrenergic receptor agonist CL316,243 stimulated osteopontin expression, an effects which was mimicked by OPC3911, a specific inhibitor of phosphodiesterase 3. Furthermore, treatment of phosphodiesterase 3B knock-out mice with CL316,243 resulted in a dramatic upregulation of osteopontin in adipose tissue which was not the case in wild-type mice. In summary, we delineate mechanisms by which GIP stimulates osteopontin in adipocytes. Given the established link between osteopontin and insulin resistance, our data suggest that GIP by stimulating osteopontin expression, also could promote insulin resistance in adipocytes.

  6. Endostatin and osteopontin are elevated in patients with both coronary artery disease and aortic valve calcification

    Directory of Open Access Journals (Sweden)

    Michael Sponder

    2015-12-01

    Conclusions: This is the first study showing an association of ES with AVC in CAD-patients independent from age, BMI and CAD-severity which seems to be of distinct interest when trying to understand the process of heart valve calcification. OPN also correlates with AVC-severity but is mostly dependent on the age of the patients.

  7. Regulation of the pro-inflammatory cytokine osteopontin by GIP in adipocytes - A role for the transcription factor NFAT and phosphodiesterase 3B

    Energy Technology Data Exchange (ETDEWEB)

    Omar, Bilal [Department of Experimental Medical Sciences, Diabetes, Metabolism and Endocrinology, Biomedical Center, Lund University, Lund (Sweden); Banke, Elin, E-mail: elin.banke@med.lu.se [Department of Experimental Medical Sciences, Diabetes, Metabolism and Endocrinology, Biomedical Center, Lund University, Lund (Sweden); Guirguis, Emilia [Cardiovascular Pulmonary Branch, NHLBI, NIH, Bethesda, MD (United States); Aakesson, Lina [Department of Clinical Sciences, Diabetes and Celiac Disease Unit, Clinical Research Centre, Lund University, Malmoe (Sweden); Manganiello, Vincent [Cardiovascular Pulmonary Branch, NHLBI, NIH, Bethesda, MD (United States); Lyssenko, Valeriya; Groop, Leif [Department of Clinical Sciences, Diabetes and Endocrinology, Clinical Research Centre, Lund University, Malmoe (Sweden); Gomez, Maria F. [Department of Clinical Sciences, Vascular ET Coupling, Clinical Research Centre, Lund University, Malmoe (Sweden); Degerman, Eva [Department of Experimental Medical Sciences, Diabetes, Metabolism and Endocrinology, Biomedical Center, Lund University, Lund (Sweden)

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer GIP stimulates lipogenesis and osteopontin expression in primary adipocytes. Black-Right-Pointing-Pointer GIP-induced osteopontin expression is NFAT-dependent. Black-Right-Pointing-Pointer Osteopontin expression is PDE3-dependent. Black-Right-Pointing-Pointer Osteopontin expression is increased in PDE3B KO mice. -- Abstract: The incretin - glucose-dependent insulinotropic polypeptide (GIP) - and the pro-inflammatory cytokine osteopontin are known to have important roles in the regulation of adipose tissue functions. In this work we show that GIP stimulates lipogenesis and osteopontin expression in primary adipocytes. The GIP-induced increase in osteopontin expression was inhibited by the NFAT (the transcription factor nuclear factor of activated T-cells) inhibitor A-285222. Also, the NFAT kinase glycogen synthase kinase (GSK) 3 was upregulated by GIP. To test whether cAMP might be involved in GIP-mediated effects on osteopontin a number of strategies were used. Thus, the {beta}3-adrenergic receptor agonist CL316,243 stimulated osteopontin expression, an effects which was mimicked by OPC3911, a specific inhibitor of phosphodiesterase 3. Furthermore, treatment of phosphodiesterase 3B knock-out mice with CL316,243 resulted in a dramatic upregulation of osteopontin in adipose tissue which was not the case in wild-type mice. In summary, we delineate mechanisms by which GIP stimulates osteopontin in adipocytes. Given the established link between osteopontin and insulin resistance, our data suggest that GIP by stimulating osteopontin expression, also could promote insulin resistance in adipocytes.

  8. Calcium-Phosphate-Osteopontin Particles Reduce Biofilm Formation and pH Drops in in situ-Grown Dental Biofilms

    DEFF Research Database (Denmark)

    Schlafer, Sebastian; Ibsen, Casper Jon Steenberg; Birkedal, Henrik

    2017-01-01

    This 2-period crossover study investigated the effect of calcium-phosphate-osteopontin particles on biofilm formation and pH in 48-h biofilms grown in situ. Bovine milk osteopontin is a highly phosphorylated glycoprotein that has been shown to interfere with bacterial adhesion to salivary......-coated surfaces. Calcium-phosphate-osteopontin particles have been shown to reduce biofilm formation and pH drops in a 5-species laboratory model of dental biofilm without affecting bacterial viability. Here, smooth surface biofilms from 10 individuals were treated ex vivo 6 times/day for 30 min with either...... calcium-phosphate-osteopontin particles or sterile saline. After growth, the amount of biofilm formed was determined by confocal microscopy, and pH drops upon exposure to glucose were monitored using confocal-microscopy-based pH ratiometry. A total of 160 biofilms were analysed. No adverse effects...

  9. VHL genetic alteration in CCRCC does not determine de-regulation of HIF, CAIX, hnRNP A2/B1 and osteopontin.

    LENUS (Irish Health Repository)

    Nyhan, Michelle J

    2012-01-31

    BACKGROUND: von Hippel-Lindau (VHL) tumour suppressor gene inactivation is associated with clear cell renal cell carcinoma (CCRCC) development. The VHL protein (pVHL) has been proposed to regulate the expression of several proteins including Hypoxia Inducible Factor-alpha (HIF-alpha), carbonic anhydrase (CA)IX, heterogeneous nuclear ribonucleoprotein (hnRNP) A2\\/B1 and osteopontin. pVHL has been characterized in vitro, however, clinical studies are limited. We evaluated the impact of VHL genetic alterations on the expression of several pVHL protein targets in paired normal and tumor tissue. METHODS: The VHL gene was sequenced in 23 CCRCC patients and VHL transcript levels were evaluated by real-time RT-PCR. Expression of pVHL\\'s protein targets were determined by Western blotting in 17 paired patient samples. RESULTS: VHL genetic alterations were identified in 43.5% (10\\/23) of CCRCCs. HIF-1alpha, HIF-2alpha and CAIX were up-regulated in 88.2% (15\\/17), 100% (17\\/17) and 88.2% (15\\/17) of tumors respectively and their expression is independent of VHL status. hnRNP A2\\/B1 and osteopontin expression was variable in CCRCCs and had no association with VHL genetic status. CONCLUSION: As expression of these proposed pVHL targets can be achieved independently of VHL mutation (and possibly by hypoxia alone), these data suggests that other pVHL targets may be more crucial in renal carcinogenesis.

  10. Expression and clinical significance of NF-毷B, CTGF and OPN in mononuclear cells in peripheral blood as well as renal tissues in patients with IgA nephropathy

    Directory of Open Access Journals (Sweden)

    Cheng-Luo Hao

    2016-06-01

    Full Text Available Objective: To study the expression and clinical significance of NF-kB, CTGF and OPN in mononuclear cells in peripheral blood as well as renal tissues in patients with IgA nephropathy. Methods: A total of 25 nephropathy patients diagnosed with IgA nephropathy and 25 patients receiving nephrectomy due to trauma or tumor in our hospital were studied. Peripheral blood and kidney tissues were collected to test NF-kB, CTGF, OPN, T-bet, GATA-3, RORγT and Foxp3 expressions. Results: CTGF and OPN percentages in peripheral blood mononuclear cells and kidney tissues of nephropathy patients were higher than those of the control group. NF-kB, CTGF and OPN expressions were significantly higher in M1, E1, S1 group patients’ peripheral blood mononuclear cells and renal tissues than those in M0, E1 and S1 group. T-bet, GATA-3 and RORγT expressions in nephropathy patients’ peripheral blood were significantly higher than those in the control group, and were positively correlated with NF-kB, CTGF and OPN expressions. The expression of Foxp3 was significantly lower than that of control group, and was negatively correlated with NF-kB, CTGF and OPN expressions. Conclusions: The expression of NF-kB, CTGF and OPN in peripheral blood mononuclear cells and renal tissue in patients with IgA nephropathy is abnormally high and can evaluate the prognosis of the disease and the differentiation of CD4+T cells.

  11. Osteopontin and MMP9: Associations with VEGF Expression/Secretion and Angiogenesis in PC3 Prostate Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, Aditi; Zhou, Cindy Q.; Chellaiah, Meenakshi A., E-mail: mchellaiah@umaryland.edu [Department of Oncology and Diagnostic Sciences, Dental School, University of Maryland, Baltimore, MD 21201 (United States)

    2013-05-27

    Osteopontin and MMP9 are implicated in angiogenesis and cancer progression. The objective of this study is to gain insight into the molecular mechanisms underlying angiogenesis, and to elucidate the role of osteopontin in this process. We report here that osteopontin/αvβ3 signaling pathway which involves ERK1/2 phosphorylation regulates the expression of VEGF. An inhibitor to MEK or curcumin significantly suppressed the phosphorylation of ERK1/2 and expression of VEGF. MMP9 knockdown reduces the secretion but not the expression of VEGF. Moreover, MMP9 knockdown increases the release of angiostatin, a key protein that suppresses angiogenesis. Conditioned media from PC3 cells treated with curcumin or MEK inhibitor inhibited tube formation in vitro in human microvascular endothelial cells. Similar inhibitory effect on tube formation was found with conditioned media collected from PC3 cells expressing mutant-osteopontin at integrin-binding site and knockdown of osteopontin or MMP9. We conclude that MMP9 activation is associated with angiogenesis via regulation of secretion of VEGF and angiostatin in PC3 cells. Curcumin is thus a potential drug for cancer treatment because it demonstrated anti-angiogenic and anti-invasive properties.

  12. Calcium-Phosphate-Osteopontin Particles Reduce Biofilm Formation and pH Drops in in situ Grown Dental Biofilms.

    Science.gov (United States)

    Schlafer, Sebastian; Ibsen, Casper J S; Birkedal, Henrik; Nyvad, Bente

    2017-01-01

    This 2-period crossover study investigated the effect of calcium-phosphate-osteopontin particles on biofilm formation and pH in 48-h biofilms grown in situ. Bovine milk osteopontin is a highly phosphorylated glycoprotein that has been shown to interfere with bacterial adhesion to salivary-coated surfaces. Calcium-phosphate-osteopontin particles have been shown to reduce biofilm formation and pH drops in a 5-species laboratory model of dental biofilm without affecting bacterial viability. Here, smooth surface biofilms from 10 individuals were treated ex vivo 6 times/day for 30 min with either calcium-phosphate-osteopontin particles or sterile saline. After growth, the amount of biofilm formed was determined by confocal microscopy, and pH drops upon exposure to glucose were monitored using confocal-microscopy-based pH ratiometry. A total of 160 biofilms were analysed. No adverse effects of repeated ex vivo treatment with calcium-phosphate-osteopontin particles were observed. Particle treatment resulted in a 32% lower amount of biofilm formed (p Biofilm pH was significantly higher upon particle treatment, both shortly after the addition of glucose and after 30 min of incubation with glucose (p biofilms as well as the remineralizing potential of the particles. © 2016 S. Karger AG, Basel.

  13. The Impact of Osteocalcin, Osteoprotegerin and Osteopontin on Arterial Stiffness in Chronic Renal Failure Patients on Hemodialysis

    Directory of Open Access Journals (Sweden)

    Botond Csiky

    2017-12-01

    Full Text Available Background/Aims: This cross-sectional study was designed to assess the relationship between vascular stiffness (VS and bone-related proteins involved in the development of arteriosclerosis in patients on regular hemodialysis (HD. Methods: 68 consecutive patients in stable clinical condition who received regular HD in the FMC Dialysis Center, Pécs were included. VS parameters (carotid-femoral pulse wave velocity – PWV, aortic augmentation index - AIx were determined by applanation tonometry (SphygmoCor, AtCor Medical, Sidney and the routine latoratory test were completed with measurements of osteocalcin (OC, osteopontin (OP and osteoprotegerin (OPG by using commercially available ELISA kits. 35 heathcare workers served as controls. Results: In patients on regular HD PWV markedly increased and there was several-fold elevation in the interrelated bone-specific proteins (OC, OP, OPG. PWV was found to be independently associated only with OC (β:-0.25, p<0.029 and age (r=0.411,p<0.000, but risk factors for arterial calcification had significant impact on OC (systolic blood pressure, hsCRP, BMI, OPG (age, BMI and OP (LDL-cholesterol. Conclusion: Except for OC, our results failed to document direct association of vascular lesion with OP and OPG, therefore their high circulating levels may be an epiphenomenon or they may have counter-regulatory role to attenuate the uremic calcification process.

  14. Listeria monocytogenes alters mast cell phenotype, mediator and osteopontin secretion in a listeriolysin-dependent manner.

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    Catherine E Jobbings

    Full Text Available Whilst mast cells participate in the immune defence against the intracellular bacterium Listeria monocytogenes, there is conflicting evidence regarding the ability of L. monocytogenes to infect mast cells. It is known that the pore-forming toxin listeriolysin (LLO is important for mast cell activation, degranulation and the release of pro-inflammatory cytokines. Mast cells, however, are a potential source of a wide range of cytokines, chemokines and other mediators including osteopontin, which contributes to the clearing of L. monocytogenes infections in vivo, although its source is unknown. We therefore aimed to resolve the controversy of mast cell infection by L. monocytogenes and investigated the extent of mediator release in response to the bacterium. In this paper we show that the infection of bone marrow-derived mast cells by L. monocytogenes is inefficient and LLO-independent. LLO, however, is required for calcium-independent mast cell degranulation as well as for the transient and selective downregulation of cell surface CD117 (c-kit on mast cells. We demonstrate that in addition to the key pro-inflammatory cytokines TNF-α and IL-6, mast cells release a wide range of other mediators in response to L. monocytogenes. Osteopontin, IL-2, IL-4, IL-13 and granulocyte macrophage colony-stimulating factor (GM-CSF, and chemokines including CCL2, CCL3, CCL4 and CCL5 are released in a MyD88-dependent manner. The wide range of mediators released by mast cells in response to L. monocytogenes may play an important role in the recruitment and activation of a variety of immune cells in vivo. The cocktail of mediators, however, is unlikely to skew the immune response to a particular effector response. We propose that mast cells provide a hitherto unreported source of osteopontin, and may provide an important role in co-ordinating the immune response during Listeria infection.

  15. Studerendes mulighed for opnåelse af kompetence til udvikling af professionen i positionen mellem central styring og decentral autonomi

    DEFF Research Database (Denmark)

    Dau, Susanne

    Dette paper bygger på et casestudie af implementeringen af blended læring i to professionsuddannelser ved University College Nord i Danmark. I paperet afdækkes studerendes udfordringer i positionen mellem central styring og decentral autonomi: 1) På den ene side de ydre styringsbetingelser, og...... kompetencemål skal de studerendes opnå selvstyret læring for at kvalificere sig til kommende profession, videreuddannelse, livslang læring og professionsudvikling. Denne kvalificering kan være i risiko for at blive undergravet af den centrale styring. På baggrund heraf undersøges problemstillingen: Hvordan......, praktikken og de studerendes fremtidige professionspraksis. Det anbefales, at der arbejdes både centralt og decentralt med at minimere de studerendes dilemmaposition mellem central styring og autonomi til gavn for samfundet og brugerne af de professionelles ydelser....

  16. Studerende mulighed for opnåelse af kompetence til udvikling af professionen i positionen mellem central styring og decentral autonomi

    DEFF Research Database (Denmark)

    Dau, Susanne

    Dette paper bygger på et casestudie af, hvordan blended læring implementeres i to professionsuddannelser ved University College Nord i Danmark. Denne forskning afslører studerendes udfordringer mellem central styring og decentral autonomi: 1) På den ene side de ydre styringsbetingelser, og kravet...... kompetencemål skal de studerendes opnå selvstyret læring for at kvalificere sig til kommende profession, videreuddannelse, livslang læring og professionsudvikling. Denne kvalificering kan være i risiko for at blive undergravet af den centrale styring. På baggrund heraf undersøges problemstillingen: Hvordan...... studerendes fremtidige professionspraksis. Det anbefales, at der arbejdes både centralt og decentralt med at minimere de studerendes dilemmaposition mellem central styring og autonomi til gavn for samfundet og brugerne af de professionelles ydelser....

  17. Oxymetholone Therapy of Fanconi Anemia Suppresses Osteopontin Transcription and Induces Hematopoietic Stem Cell Cycling

    Directory of Open Access Journals (Sweden)

    Qing-Shuo Zhang

    2015-01-01

    Full Text Available Androgens are widely used for treating Fanconi anemia (FA and other human bone marrow failure syndromes, but their mode of action remains incompletely understood. Aged Fancd2−/− mice were used to assess the therapeutic efficacy of oxymetholone (OXM and its mechanism of action. Eighteen-month-old Fancd2−/− mice recapitulated key human FA phenotypes, including reduced bone marrow cellularity, red cell macrocytosis, and peripheral pancytopenia. As in humans, chronic OXM treatment significantly improved these hematological parameters and stimulated the proliferation of hematopoietic stem and progenitor cells. RNA-Seq analysis implicated downregulation of osteopontin as an important potential mechanism for the drug’s action. Consistent with the increased stem cell proliferation, competitive repopulation assays demonstrated that chronic OXM therapy eventually resulted in stem cell exhaustion. These results expand our knowledge of the regulation of hematopoietic stem cell proliferation and have direct clinical implications for the treatment of bone marrow failure.

  18. Analyzing power for the 16O(p,n)16F (4-, 6.37 MeV) reaction at 134 MeV

    International Nuclear Information System (INIS)

    Madey, R.; Fazely, A.; Anderson, B.D.; Baldwin, A.R.; Kalenda, A.M.; McCarthy, R.J.; Tandy, P.C.; Watson, J.W.; Bertozzi, W.; Buti, T.; Finn, M.; Kovash, M.; Pugh, B.; Foster, C.C.

    1982-01-01

    We measured the analyzing power for the 16 O(p,n) 16 F (4 - , 6.37 MeV) reaction at 134.0 MeV and the differential cross section for the same reaction at 135.2 MeV. The shape of the cross section for the transition to this unnatural parity stretched state is described well by a distorted-wave impulse-approximation calculation using a (πd/sub 5/2/, νp/sub 3/2//sup ts-1/) 4 /sub -/ configuration and the effective interaction derived by Love and Franey from nucleon-nucleon phase shifts. The analyzing power from this calculation reproduces all of the qualitative features of the data and supports the use of the impulse approximation as an excellent starting point for describing the reaction mechanism. Quantitative agreement between the experimental and theoretical analyzing power can be improved by eliminating the imaginary tensor term of this interaction and taking the real part to be that derived by Love from the Sussex matrix elements. The sensitivity of the calculations to the choice of optical potentials and the importance of spin-orbit distortion is explored

  19. Myxovirus resistance, osteopontin and suppressor of cytokine signaling 3 polymorphisms predict hepatitis C virus therapy response in an admixed patient population: comparison with IL28B.

    Science.gov (United States)

    Angelo, Ana Luiza Dias; Cavalcante, Lourianne Nascimento; Abe-Sandes, Kiyoko; Machado, Taísa Bonfim; Lemaire, Denise Carneiro; Malta, Fernanda; Pinho, João Renato; Lyra, Luiz Guilherme Costa; Lyra, Andre Castro

    2013-10-01

    Suppressor of cytokine signaling 3, myxovirus resistance protein and osteopontin gene polymorphisms may influence the therapeutic response in patients with chronic hepatitis C, and an association with IL28 might increase the power to predict sustained virologic response. Our aims were to evaluate the association between myxovirus resistance protein, osteopontin and suppressor of cytokine signaling 3 gene polymorphisms in combination with IL28B and to assess the therapy response in hepatitis C patients treated with pegylated-interferon plus ribavirin. Myxovirus resistance protein, osteopontin, suppressor of cytokine signaling 3 and IL28B polymorphisms were analyzed by PCR-restriction fragment length polymorphism, direct sequencing and real-time PCR. Ancestry was determined using genetic markers. We analyzed 181 individuals, including 52 who were sustained virologic responders. The protective genotype frequencies among the sustained virologic response group were as follows: the G/G suppressor of cytokine signaling 3 (rs4969170) (62.2%); T/T osteopontin (rs2853744) (60%); T/T osteopontin (rs11730582) (64.3%); and the G/T myxovirus resistance protein (rs2071430) genotype (54%). The patients who had ≥3 of the protective genotypes from the myxovirus resistance protein, the suppressor of cytokine signaling 3 and osteopontin had a greater than 90% probability of achieving a sustained response (pC/C IL28B genotype was present in 58.8% of the subjects in this group. The sustained virological response rates increased to 85.7% and 91.7% by analyzing C/C IL28B with the T/T osteopontin genotype at rs11730582 and the G/G suppressor of cytokine signaling 3 genotype, respectively. Genetic ancestry analysis revealed an admixed population. Hepatitis C genotype 1 patients who were responders to interferon-based therapy had a high frequency of multiple protective polymorphisms in the myxovirus resistance protein, osteopontin and suppressor of cytokine signaling 3 genes. The combined

  20. Low-level ultrahigh-frequency and ultrashort-pulse blue laser irradiation enhances osteoblast extracellular calcification by upregulating proliferation and differentiation via transient receptor potential vanilloid 1.

    Science.gov (United States)

    Mikami, Risako; Mizutani, Koji; Aoki, Akira; Tamura, Yukihiko; Aoki, Kazuhiro; Izumi, Yuichi

    2018-04-01

    Low-level laser irradiation (LLLI) exerts various biostimulative effects, including promotion of wound healing and bone formation; however, few studies have examined biostimulation using blue lasers. The purpose of this study was to investigate the effects of low-level ultrahigh-frequency (UHF) and ultrashort-pulse (USP) blue laser irradiation on osteoblasts. The MC3T3-E1 osteoblast cell line was used in this study. Following LLLI with a 405 nm newly developed UHF-USP blue laser (80 MHz, 100 fs), osteoblast proliferation, and alkaline phosphatase (ALP) activity were assessed. In addition, mRNA levels of the osteoblast differentiation markers, runt-related transcription factor 2 (Runx2), osterix (Osx), alkaline phosphatase (Alp), and osteopontin (Opn) was evaluated, and extracellular calcification was quantified. To clarify the involvement of transient receptor potential (TRP) channels in LLLI-induced biostimulation, cells were treated prior to LLLI with capsazepine (CPZ), a selective inhibitor of TRP vanilloid 1 (TRPV1), and subsequent proliferation and ALP activity were measured. LLLI with the 405 nm UHF-USP blue laser significantly enhanced cell proliferation and ALP activity, compared with the non-irradiated control and LLLI using continuous-wave mode, without significant temperature elevation. LLLI promoted osteoblast proliferation in a dose-dependent manner up to 9.4 J/cm 2 and significantly accelerated cell proliferation in in vitro wound healing assay. ALP activity was significantly enhanced at doses up to 5.6 J/cm 2 , and expression of Osx and Alp mRNAs was significantly increased compared to that of the control on days 3 and 7 following LLLI at 5.6 J/cm 2 . The extent of extracellular calcification was also significantly higher as a result of LLLI 3 weeks after the treatment. Measurement of TRPV1 protein expression on 0, 3, and 7 days post-irradiation revealed no differences between the LLLI and control groups; however, promotion of cell

  1. Immunohistochemical localization of integrin alpha V beta 3 and osteopontin suggests that they do not interact during embryo implantation in ruminants

    Directory of Open Access Journals (Sweden)

    MacLaren Leslie A

    2004-04-01

    Full Text Available Abstract Background It has been suggested that trophoblast attachment requires co-expression of integrin alpha V beta 3 and its ligand osteopontin at the fetal-maternal interface. Until now the expression patterns of integrin alpha V beta 3 and osteopontin in the pregnant bovine uterus were unknown. The objectives of this study were to localize integrin alpha V beta 3 and osteopontin in bovine and sheep endometrium during the periimplantation period and to compare the distribution patterns using antibodies that had not yet been tested in sheep. Methods Cell compartments within endometrial tissue sections were scored for immunohistochemical staining intensity and data were analyzed to determine the effects of day of pregnancy or cycle. Results In pregnant bovine endometrium, integrin alpha V beta 3 was detected in luminal epithelium, stroma, myometrium and smooth muscle. A strong band of immunoreactivity was observed in the subepithelial stroma of intercaruncular regions, but there was reduced reactivity in the caruncles and glands. Bovine trophoblast did not express integrin alpha V beta 3 at any stage of pregnancy. In ovine endometrium a different pattern of staining for integrin alpha V beta 3 was observed. Reactivity was not present in the luminal epithelium or trophoblast. There was strong staining of the deep glands and no reactivity in the superficial glands. Osteopontin distribution was similar for sheep and cattle. For both species, apical staining was present on the luminal epithelium and glands and on embryonic tissues. Conclusion In ruminants, integrin alpha V beta 3 and osteopontin do not co-localize at the fetal-maternal interface indicating that these proteins could not interact to facilitate embryo attachment as has been proposed in other species.

  2. Expression analyses of human cleft palate tissue suggest a role for osteopontin and immune related factors in palatal development

    DEFF Research Database (Denmark)

    Jakobsen, L.P.; Borup, R.; Vestergaard, J.

    2009-01-01

    . Moreover, selected differentially expressed genes were analyzed by quantitative RT-PCR, and by immunohistochemical staining of craniofacial tissue from human embryos. Osteopontin (SPP1) and other immune related genes were significantly higher expressed in palate tissue from patients with CLP compared to CP...... and palate (CLP). In order to understand the biological basis in these cleft lip and palate subgroups better we studied the expression profiles in human tissue from patients with CL/P. In each of the CL/P subgroups, samples were obtained from three patients and gene expression analysis was performed...... and immunostaining in palatal shelves against SPP1, chemokine receptor 4 (CXCR4) and serglycin (PRG1) in human embryonic craniofacial tissue were positive, supporting a role for these genes in palatal development. However, gene expression profiles are subject to variations during growth and therefore we recommend...

  3. The secretions of oviduct epithelial cells increase the equine in vitro fertilization rate: are osteopontin, atrial natriuretic peptide A and oviductin involved?

    Directory of Open Access Journals (Sweden)

    Canepa Sylvie

    2009-11-01

    Full Text Available Abstract Background Oviduct epithelial cells (OEC co-culture promotes in vitro fertilization (IVF in human, bovine and porcine species, but no data are available from equine species. Yet, despite numerous attempts, equine IVF rates remain low. Our first aim was to verify a beneficial effect of the OEC on equine IVF. In mammals, oviductal proteins have been shown to interact with gametes and play a role in fertilization. Thus, our second aim was to identify the proteins involved in fertilization in the horse. Methods & results In the first experiment, we co-incubated fresh equine spermatozoa treated with calcium ionophore and in vitro matured equine oocytes with or without porcine OEC. We showed that the presence of OEC increases the IVF rates. In the subsequent experiments, we co-incubated equine gametes with OEC and we showed that the IVF rates were not significantly different between 1 gametes co-incubated with equine vs porcine OEC, 2 intact cumulus-oocyte complexes vs denuded oocytes, 3 OEC previously stimulated with human Chorionic Gonadotropin, Luteinizing Hormone and/or oestradiol vs non stimulated OEC, 4 in vivo vs in vitro matured oocytes. In order to identify the proteins responsible for the positive effect of OEC, we first searched for the presence of the genes encoding oviductin, osteopontin and atrial natriuretic peptide A (ANP A in the equine genome. We showed that the genes coding for osteopontin and ANP A are present. But the one for oviductin either has become a pseudogene during evolution of horse genome or has been not well annotated in horse genome sequence. We then showed that osteopontin and ANP A proteins are present in the equine oviduct using a surface plasmon resonance biosensor, and we analyzed their expression during oestrus cycle by Western blot. Finally, we co-incubated equine gametes with or without purified osteopontin or synthesized ANP A. No significant effect of osteopontin or ANP A was observed, though

  4. Spatial distribution of osteopontin, CD44v6 and podoplanin in the lining epithelium of odontogenic keratocyst, and their biological relevance.

    Science.gov (United States)

    Kechik, Khamisah Awang; Siar, Chong Huat

    2018-02-01

    The odontogenic keratocyst (OKC) remains the most challenging jaw cyst to treat because of its locally-aggressive behaviour and high recurrence potential. Emerging evidence suggests that osteopontin, its receptors CD44v6 and integrin α v , and podoplanin, have a role in the local invasiveness of this cyst. However the spatial distribution characteristics of these pro-invasive markers in the lining epithelium of OKC, and their association with the clinicopathologic parameters of OKC are largely unexplored. This study sought to address these issues in comparison with dentigerous cysts (DCs) and radicular cysts (RCs) and to evaluate their biological relevance. A sample consisting of 20 OKC cases, 10 DCs and 10 RCs was subjected to immunohistochemical staining for osteopontin, CD44v6 and integrin α v , and podoplanin, and semiquantitative analysis was performed. All factors (except integrin α v ) were detected heterogeneously in the constitutive layers of the lining epithelium in all three cyst types. Key observations were significant upregulation of CD44v6 and podoplanin in OKC compared to DCs and RCs, suggesting that these protein molecules may play crucial roles in promoting local invasiveness in OKC (P<0.05). Osteopontin underexpression and distribution patterns were indistinctive among all three cysts indicating its limited role as pro-invasive factor. Clinical parameters showed no significant correlations with all protein factors investigated. Present findings suggest that an osteopontin low CD44v6 high and podoplanin high immunoprofile most probably represent epithelial signatures of OKC and are markers of local invasiveness in this cyst. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Autologous circulating angiogenic cells treated with osteopontin and delivered via a collagen scaffold enhance wound healing in the alloxan-induced diabetic rabbit ear ulcer model.

    Science.gov (United States)

    O'Loughlin, Aonghus; Kulkarni, Mangesh; Vaughan, Erin E; Creane, Michael; Liew, Aaron; Dockery, Peter; Pandit, Abhay; O'Brien, Timothy

    2013-01-01

    Diabetic foot ulceration is the leading cause of amputation in people with diabetes mellitus. Peripheral vascular disease is present in the majority of patients with diabetic foot ulcers. Despite standard treatments there exists a high amputation rate. Circulating angiogenic cells previously known as early endothelial progenitor cells are derived from peripheral blood and support angiogenesis and vasculogenesis, providing a potential topical treatment for non-healing diabetic foot ulcers. A scaffold fabricated from Type 1 collagen facilitates topical cell delivery to a diabetic wound. Osteopontin is a matricellular protein involved in wound healing and increases the angiogenic potential of circulating angiogenic cells. A collagen scaffold seeded with circulating angiogenic cells was developed. Subsequently the effect of autologous circulating angiogenic cells that were seeded in a collagen scaffold and topically delivered to a hyperglycemic cutaneous wound was assessed. The alloxan-induced diabetic rabbit ear ulcer model was used to determine healing in response to the following treatments: collagen seeded with autologous circulating angiogenic cells exposed to osteopontin, collagen seeded with autologous circulating angiogenic cells, collagen alone and untreated wound. Stereology was used to assess angiogenesis in wounds. The cells exposed to osteopontin and seeded on collagen increased percentage wound closure as compared to other groups. Increased angiogenesis was observed with the treatment of collagen and collagen seeded with circulating angiogenic cells. These results demonstrate that topical treatment of full thickness cutaneous ulcers with autologous circulating angiogenic cells increases wound healing. Cells exposed to the matricellular protein osteopontin result in superior wound healing. The wound healing benefit is associated with a more efficient vascular network. This topical therapy provides a potential novel therapy for the treatment of non

  6. Roles of electrostatics and conformation in protein-crystal interactions

    NARCIS (Netherlands)

    Azzopardi, P.V.; O'Young, J.; Lajoie, G.; Karttunen, M.E.J.; Goldberg, H.A.; Hunter, G.K.

    2010-01-01

    In vitro studies have shown that the phosphoprotein osteopontin (OPN) inhibits the nucleation and growth of hydroxyapatite (HA) and other biominerals. In vivo, OPN is believed to prevent the calcification of soft tissues. However, the nature of the interaction between OPN and HA is not understood.

  7. ERC/mesothelin as a marker for chemotherapeutic response in patients with mesothelioma.

    Science.gov (United States)

    Tajima, Ken; Hirama, Michihiro; Shiomi, Kazu; Ishiwata, Toshiji; Yoshioka, Masataka; Iwase, Akihiko; Iwakami, Shinichiro; Yamazaki, Mariko; Toba, Michie; Tobino, Kazunori; Sugano, Koji; Ichikawa, Masako; Hagiwara, Yoshiaki; Takahashi, Kazuhisa; Hino, Okio

    2008-01-01

    It has been recently reported that soluble mesothelin-related protein (SMRP), serum mesothelin, and osteopontin (OPN) are considered as relevant biomarkers for the diagnosis of mesothelioma. The aim of this study was to investigate whether serum N-ERC/mesothelin, an NH3-terminal fragment of mesothelin, and plasma OPN reflect chemotherapeutic effect in patients with mesothelioma. Serum N-ERC/mesothelin and plasma osteopontin were determined with a sandwich enzyme-linked immunosorbent assay (ELISA) system. The average N-ERC ratio, determined by dividing the N-ERC levels following chemotherapy by those prior to chemotherapy, in the partial response (PR) group was significantly lower than that of the stable disease (SD)/progressive disease (PD) group. In contrast, the average OPN ratio, determined by dividing the OPN levels following chemotherapy by those prior to chemotherapy, in the PR group was not statistically different from that of the SD/PD group. N-ERC/mesothelin is considered as relevant in monitoring chemotherapeutic response in patients with mesothelioma.

  8. The increase of plasma galectin-9 in a patient with insulin allergy: a case report

    Directory of Open Access Journals (Sweden)

    Chagan-Yasutan Haorile

    2010-08-01

    Full Text Available Abstract Allergic reaction to insulin is known to be associated with eosinophilia and hyper IgE. Recent report showed that eosinophilia is related with the increased synthesis of galectin-9 (GAL-9 and osteopontin (OPN. Here, we examined plasma levels of GAL-9 and OPN first time in a case of 65-year old patient with insulin allergy. Insulin aspart & insulin aspart 30 mix were given to the patient and an elevation of the eosinophil count (8440/μl, 17.6 fold and a moderate increase of IgE (501 U/ml, reference range: 10-350 U/ml, eotaxin-3 (168 pg/ml, 2 fold, histamine (0.95 ng/ml, 5.3 fold were found 33 days later. The plasma levels of GAL-9 and OPN were 22.5 and 1.7 fold higher than the cut-off point, respectively. After one month cessation of insulin therapy, elevations of the eosinophil count (3,480/μl; 7.3 fold, and OPN (1.4 fold still occurred but the GAL-9 levels became normal. Therefore, we noted the increases of GAL-9 and OPN in plasma for the first time in a patient with insulin allergy and propose that GAL-9 reflects the conditions of allergy more accurately.

  9. Effects of 2-deoxy-D-glucose and quercetin on the expression of osteonectin and osteopontin during the differentiation of irradiated MC3T3-E1 osteoblastic cells

    International Nuclear Information System (INIS)

    Yu, Su Kyung; Koh, Kwang Joon; Kim, Kyoung A

    2008-01-01

    To characterize the effects of 2-deoxy-D-glucose (2-DG) and quercetin (QCT) on gene expression of osteonectin (ON) and osteopontin (OP) in irradiated MC3T3-E1 cells. When MC3T3-E1 osteoblastic cells had reached 70-80% confluence, cultures were transferred to a differentiating medium supplemented with 5 mM 2-DG or 10 μM QCT and then irradiated with 2, 4, 6, and 8 Gy. At various times after irradiation, the cells were analyzed for the expression of bone mineralization genes such as ON and OP. The mRNA expression of both ON and OP was increased according to the culture time in the differentiation medium, and the increase of the genes peaked at 14 days after the differentiation induction. In the case of OP, the increase of mRNA expression was maintained to 28 days after the differentiation, while the mRNA level of ON was reduced to the basal level at the same time. Irradiation adding 2-DG showed a significant peak value in the expression pattern of ON at 4 Gy 7 days after irradiation. Irradiation adding QCT increased the mRNA expression of ON and OP in a dose-dependant manner, but irradiation adding 2-DG did not show any differences between the control and experiments 14 days after irradiation. Irradiation adding QCT increased significantly the expression patterns of ON 21 days after irradiation. The results showed that QCT acted as a radiosensitizer in the gene expression of ON and OP during differentiation of the late stage of irradiated MC3T3-E1 osteoblastic cells in vitro.

  10. T-helper 1 Immune Response in Systemic Lupus Erythematosus ...

    African Journals Online (AJOL)

    ) and osteopontin (OPN) in SLE patients and their correlation with the disease activity. Methods: The study included 24 patients with SLE and 20 age- and sex- matched control subjects. The disease activity was evaluated with the SLE disease ...

  11. Chlamydia trachomatis induces an upregulation of molecular biomarkers podoplanin, Wilms' tumour gene 1, osteopontin and inflammatory cytokines in human mesothelial cells.

    Science.gov (United States)

    De Filippis, Anna; Buommino, Elisabetta; Domenico, Marina Di; Feola, Antonia; Brunetti-Pierri, Raffaella; Rizzo, Antonietta

    2017-05-01

    Chlamydia trachomatis is the most prevalent infection of the genital tract in women worldwide. C. trachomatis has a tendency to cause persistent infection and induce a state of chronic inflammation, which has been reported to play a role in carcinogenesis. We report that persistent C. trachomatis infection increases the expression of inflammatory tumour cytokines and upregulates molecular biomarkers such as podoplanin, Wilms' tumour gene 1 and osteopontin in primary cultures of mesothelial cells (Mes1) and human mesothelioma cells (NCI). Infection experiments showed that Mes1 and NCI supported the growth of C. trachomatisin vitro, and at an m.o.i. of 4, the inclusion-forming units/cell showed many intracellular inclusion bodies after 3 days of infection. However, after 7 days of incubation, increased proliferative and invasive activity was also observed in Mes1 cells, which was more evident after 14 days of incubation. ELISA analysis revealed an increase in vascular endothelial growth factor, IL-6, IL-8, and TNF-α release in Mes1 cells infected for a longer period (14 days). Finally, real-time PCR analysis revealed a strong induction of podoplanin, Wilms' tumour gene 1 and osteopontin gene expression in infected Mes1 cells. The aim of the present study was to investigate the inflammatory response elicited by C. trachomatis persistent infection and the role played by inflammation in cell proliferation, secretion of proinflammatory cytokines and molecular biomarkers of cancer. The results of this study suggest that increased molecular biomarkers of cancer by persistent inflammation from C. trachomatis infection might support cellular transformation, thus increasing the risk of cancer.

  12. Antisense targeting of TGF-β1 augments BMP-induced upregulation of osteopontin, type I collagen and Cbfa1 in human Saos-2 cells

    International Nuclear Information System (INIS)

    Shen, Zhong-Jian; Kook Kim, Sang; Youn Jun, Do; Park, Wan; Ho Kim, Young; Malter, James S.; Jo Moon, Byung

    2007-01-01

    Despite commonalities in signal transduction in osteoblasts from different species, the role of TGF-β1 on bone formation remains elusive. In particular, the role of autocrine TGF-β1 on human osteoblasts is largely unknown. Here we show the effect of TGF-β1 knock-down on the proliferation and differentiation of osteoblasts induced by BMP2. Treatment with antisense TGF-β1 moderately increased the rate of cell proliferation, which was completely reversed by the exogenous addition of TGF-β1. Notably, TGF-β1 blockade significantly enhanced BMP2-induced upregulation of mRNAs encoding osteopontin, type I collagen and Cbfa1, which was suppressed by exogenous TGF-β1. Moreover, TGF-β1 knock-down increased BMP2-induced phosphorylation of Smad1/5 as well as their nuclear import, which paralleled a reduction of inhibitory Smad6. These data suggest autocrine TGF-β1 antagonizes BMP signaling through modulation of inducible Smad6 and the activity of BMP specific Smad1/5

  13. Hypoxia imaging of uterine cervix carcinoma with (18)F-FETNIM PET/CT.

    Science.gov (United States)

    Vercellino, Laetitia; Groheux, David; Thoury, Anne; Delord, Marc; Schlageter, Marie-Hélène; Delpech, Yann; Barré, Emmanuelle; Baruch-Hennequin, Valérie; Tylski, Perrine; Homyrda, Laurence; Walker, Francine; Barranger, Emmanuel; Hindié, Elif

    2012-11-01

    Our aims were to assess the feasibility of imaging hypoxia in cervical carcinoma with (18)F-fluoroerythronitroimidazole ((18)F-FETNIM) and to compare (18)F-FETNIM uptake with metabolic uptake of (18)F-FDG. We included 16 patients with cervical carcinoma. After imaging with FDG, (18)F-FETNIM PET/CT was performed and tumor-to-muscle (T/M) ratio uptake was assessed. (18)F- FETNIM uptake was correlated to FDG uptake and osteopontin (OPN), a marker of hypoxia, and patients' outcomes. All tumors were detected by (18)F-FDG PET. (18)F-FETNIM T/M ratios ranged from 1.3 to 5.4. There was no significant correlation between (18)F-FETNIM and (18)F-FDG uptake. High (18)F-FETNIM uptake (T/M > 3.2) was associated with reduced progression-free survival (log-rank = 0.002) and overall survival (log-rank = 0.02). Osteopontin ranged from 39 to 662 μg/L (median, 102.5 μg/L). Patients with OPN greater than 144 μg/L had reduced progression-free survival compared with those with OPN less than 144 μg/L (log-rank = 0.03). We found no significant correlation between (18)F-FETNIM uptake and OPN blood levels. Our preliminary results showed that a high uptake of (18)F-FETNIM was associated with a worse progression-free and overall survival.

  14. Association of Osteopontin, Neopterin, and Myeloperoxidase With Stroke Risk in Patients With Prior Stroke or Transient Ischemic Attacks

    DEFF Research Database (Denmark)

    Ganz, Peter; Amarenco, Pierre; Goldstein, Larry B

    2017-01-01

    BACKGROUND AND PURPOSE: Established risk factors do not fully identify patients at risk for recurrent stroke. The SPARCL trial (Stroke Prevention by Aggressive Reduction in Cholesterol Levels) evaluated the effect of atorvastatin on stroke risk in patients with a recent stroke or transient ischemic...

  15. MicroRNA array and microarray evaluation of endometrial receptivity in patients with high serum progesterone levels on the day of hCG administration

    Directory of Open Access Journals (Sweden)

    Liu Ping

    2011-03-01

    Full Text Available Abstract Background To determine the effect of higher progesterone (P level on endometrial receptivity. Methods This was a prospective analysis conducted in the Reproductive Medical Center of Peking University Third Hospital. All patients received IVF treatment and canceled embryo transfer in the same cycle and were divided into group 1 (normal P; 7 patients and group 2 (elevated P; 12 patients. Endometrial biopsies were performed 6 days after oocyte retrieval. The global miRNA and mRNA gene expressions in endometrial biopsies were investigated with a V4.0 miRNA probe and 22 K Human Genome Array. Fold ratios were derived to compare gene regulation between the groups. Spp1 and Ang gene expression was selected to verify the array results by RT-PCR and the protein expression of osteopontin and VEGF was determined using an immunohistochemical method. Results There were 4 miRNA (all down-regulated and 22 mRNA (13 up-regulated and 9 down-regulated exhibiting differential expression between the groups on the microRNA and microarray chips. miRNA-451, Spp1, and Ang expression in RT-PCR verified the array results. Osteopontin and VEGF were also shown to have positive expression in the endometrium. Conclusions Data from microRNA and microarray analysis suggests dissimilar endometrial receptivity in patients with high P levels on the day of hCG, and elevated osteopontin and decreased VEGF had poor pregnancy rates.

  16. Biochemical markers of bone turnover in diagnosis of myeloma bone disease.

    Science.gov (United States)

    Dizdar, Omer; Barista, Ibrahim; Kalyoncu, Umut; Karadag, Omer; Hascelik, Gulsen; Cila, Aysenur; Pinar, Asli; Celik, Ismail; Kars, Ayse; Tekuzman, Gulten

    2007-03-01

    This study was designed to explore the value of markers of bone turnover, macrophage inflammatory protein-1alpha (MIP-1alpha), and osteopontin (OPN) in the diagnosis of myeloma bone disease. Twenty-five patients with newly diagnosed and untreated multiple myeloma (MM), and 22 age-, sex-, and bone mineral density-matched control subjects were enrolled. Levels of MIP-1alpha, OPN, carboxy-terminal telopeptide of Type-1 collagen (C-telopeptide or Ctx), deoxypyridinoline (DPD), Type-1 collagen propeptide (T1Pro), and bone-specific alkaline phosphatase (BALP) were assessed in both groups. Twenty-two of the patients had bone involvement documented by skeletal surveys and lumbar spinal magnetic resonance imaging. Levels of serum Ctx, OPN, MIP-1alpha, and urine DPD were significantly higher in MM patients with bone disease than in controls (P<0.01). Serum Ctx levels were elevated in 90.9% of patients with MM and 40.9% of controls (P<0.001). Urine DPD levels were elevated in 90.4% of the patients and 31.8% of the controls (P<0.001). The serum OPN and MIP-1alpha levels of the patients were significantly correlated with beta2-microglobulin and lactate dehydrogenase levels (P<0.05). Our study indicates that Ctx and DPD are sensitive markers of bone disease in MM, and higher than normal values suggest presence of bone disease rather than benign osteoporosis in MM. The utility of OPN and MIP-1alpha needs to be further investigated. Copyright (c) 2006 Wiley-Liss, Inc.

  17. Kaempferol regulates OPN–CD44 pathway to inhibit the atherogenesis of apolipoprotein E deficient mice

    International Nuclear Information System (INIS)

    Xiao, Hong-Bo; Lu, Xiang-Yang; Sun, Zhi-Liang; Zhang, Heng-Bo

    2011-01-01

    Recent studies show that osteopontin (OPN) and its receptor cluster of differentiation 44 (CD44) are two pro-inflammatory cytokines contributing to the development of atherosclerosis. The objective of this study was to explore the inhibitory effect of kaempferol, a naturally occurring flavonoid compound, on atherogenesis and the mechanisms involved. The experiments were performed in aorta and plasma from C57BL/6J control and apolipoprotein E-deficient (ApoE −/− ) mice treated or not with kaempferol (50 or 100 mg/kg, intragastrically) for 4 weeks. Kaempferol treatment decreased atherosclerotic lesion area, improved endothelium-dependent vasorelaxation, and increased the maximal relaxation value concomitantly with decrease in the half-maximum effective concentration, plasma OPN level, aortic OPN expression, and aortic CD44 expression in ApoE −/− mice. In addition, treatment with kaempferol also significantly decreased reactive oxygen species production in mice aorta. The present results suggest that kaempferol regulates OPN–CD44 pathway to inhibit the atherogenesis of ApoE −/− mice. -- Graphical abstract: Kaempferol regulates OPN–CD44 pathway to inhibit the atherogenesis of ApoE −/− mice. Highlights: ► OPN–CD44 pathway plays a critical role in the development of atherosclerosis. ► We examine lesion area, OPN and CD44 changes after kaempferol treatment. ► Kaempferol treatment decreased atherosclerotic lesion area in ApoE −/− mice. ► Kaempferol treatment decreased aortic OPN and CD44 expressions in ApoE −/− mice. ► Kaempferol regulates OPN–CD44 pathway to inhibit the atherogenesis.

  18. Performance of diagnostic biomarkers in predicting liver fibrosis among hepatitis C virus-infected Egyptian children

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    Yasser E Nassef

    2013-11-01

    Full Text Available The aim of the present study was to identify specific markers that mirror liver fibrosis progression as an alternative to biopsy when biopsy is contraindicated, especially in children. After liver biopsies were performed, serum samples from 30 hepatitis C virus (HCV paediatric patients (8-14 years were analysed and compared with samples from 30 healthy subjects. All subjects were tested for the presence of serum anti-HCV antibodies. Direct biomarkers for liver fibrosis, including transforming growth factor-β1, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1, hyaluronic acid (HA, procollagen type III amino-terminal peptide (PIIINP and osteopontin (OPN, were measured. The indirect biomarkers aspartate and alanine aminotransferases, albumin and bilirubin were also tested. The results revealed a significant increase in the serum marker levels in HCV-infected children compared with the healthy group, whereas albumin levels exhibited a significant decrease. Significantly higher levels of PIIINP, TIMP-1, OPN and HA were detected in HCV-infected children with moderate to severe fibrosis compared with children with mild fibrosis (p < 0.05. The diagnostic accuracy of these direct biomarkers, represented by sensitivity, specificity and positive predictive value, emphasises the utility of PIIINP, TIMP-1, OPN and HA as indicators of liver fibrosis among HCV-infected children.

  19. Comparative analysis of gene expression profiles of OPN signalling ...

    Indian Academy of Sciences (India)

    were orally treated with the high-fat emulsion (10 mL/kg) by gavage once a day ... 4 weeks, and drinking water was offered with 10% ethanol. Drinking water ..... detected by Rat Genome 230 2.0 Array and dark grey colour represents RT-PCR.

  20. Melatonin inhibits the migration of human lung adenocarcinoma A549 cell lines involving JNK/MAPK pathway.

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    Qiaoyun Zhou

    Full Text Available OBJECTIVE: Melatonin, an indolamine produced and secreted predominately by the pineal gland, exhibits a variety of physiological functions, possesses antioxidant and antitumor properties. But, the mechanisms for the anti-cancer effects are unknown. The present study explored the effects of melatonin on the migration of human lung adenocarcinoma A549 cells and its mechanism. METHODS: MTT assay was employed to measure the viability of A549 cells treated with different concentrations of melatonin. The effect of melatonin on the migration of A549 cells was analyzed by wound healing assay. Occludin location was observed by immunofluorescence. The expression of occludin, osteopontin (OPN, myosin light chain kinase (MLCK and phosphorylation of myosin light chain (MLC, JNK were detected by western blots. RESULTS: After A549 cells were treated with melatonin, the viability and migration of the cells were inhibited significantly. The relative migration rate of A549 cells treated with melatonin was only about 20% at 24 h. The expression level of OPN, MLCK and phosphorylation of MLC of A549 cells were reduced, while the expression of occludin was conversely elevated, and occludin located on the cell surface was obviously increased. The phosphorylation status of JNK in A549 cells was also reduced when cells were treated by melatonin. CONCLUSIONS: Melatonin significantly inhibits the migration of A549 cells, and this may be associated with the down-regulation of the expression of OPN, MLCK, phosphorylation of MLC, and up-regulation of the expression of occludin involving JNK/MAPK pathway.

  1. Role of the small integrin-binding ligand N-linked glycoprotein (SIBLING), bone sialoprotein (BSP) in bone development and remodeling.

    OpenAIRE

    Malaval, L.; Aubin, J.; Vico, L.

    2009-01-01

    14 pages; International audience; Members of the “small, integrin binding ligand, N-linked glycoprotein” (SIBLING) family, which have both mineral binding and cell binding (integrins) abilities, appear as potent regulators of bone mineralisation and remodeling. Among these, osteopontin (OPN) and bone sialoprotein (BSP) are highly expressed in early bone. Gene knockout of OPN results in increased mineralisation and a resorption defect making mutant mice unable to respond to such challenges as ...

  2. Gingival Crevicular Fluid Turnover Markers in Premenopausal vs Postmenopausal Women receiving Orthodontic Treatment.

    Science.gov (United States)

    Bitra, Anusha; Rani, B Jhansi; Agarkar, Sanket S; Parihar, Anuj S; Vynath, Gopinath P; Grover, Shekhar

    2017-10-01

    Orthodontic treatment is one of the commonly used dental treatments. Orthodontic forces act on the bone by modulating the biomolecules, chiefly the osteoprotegerin (OPG), osteopontin (OPN), receptor activator of nuclear factor kappa-B (RANK), and RANK ligand (RANKL) (OPG ligand). Hormonal changes are known to cause marked alteration in the levels of these biomolecules. Hence, we planned this study to evaluate the response of bone biomarkers in the gingival crevicular fluid (GCF) in postmenopausal women undergoing fixed orthodontic therapy. This study included assessment of 50 subjects who underwent orthodontic treatment from June 2012 to July 2016. All the patients were divided into two study groups with 25 patients in each group: premenopausal group and postmenopausal group. Similar orthodontic wires were used for controlling the forces applied in subjects of both the study groups and their GCF levels of RANKL, and OPN was assessed at baseline and 24 hours after the activation of orthodontic forces. All the results were compiled, assessed, and analyzed by Statistical Package for the Social Sciences software version 16.0. Chi-square test, Student's t-test, and Mann-Whitney U test were used for the assessment of the level of significance. The mean values of RANKL and OPN in the premenopausal and postmenopausal groups were found to be 241.52 and 317.15 pg/μL respectively. The mean values of RANKL at baseline in the premenopausal and postmenopausal groups were found to be 7.15 and 3.84 pg/μL respectively. Nonsignificant results were obtained while comparing mean OPN and RANKL level alteration in between the two study groups. The mean alterations in the GCF levels of bone biomarkers are similar for both premenopausal and postmeno-pausal women. For women with either premenopausal or postmenopausal status, orthodontic treatment appears to be equally safer.

  3. Midkine Increases Diagnostic Yield in AFP Negative and NASH-Related Hepatocellular Carcinoma.

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    Roslyn Vongsuvanh

    Full Text Available Robust biomarkers for population-level hepatocellular carcinoma (HCC surveillance are lacking. We compared serum midkine (MDK, dickkopf-1 (DKK1, osteopontin (OPN and AFP for HCC diagnosis in 86 HCC patients matched to 86 cirrhotics, 86 with chronic liver disease (CLD and 86 healthy controls (HC. Based on the performance of each biomarker, we assessed a separate longitudinal cohort of 28 HCC patients, at and before cancer diagnosis. Serum levels of MDK and OPN were higher in HCC patients compared to cirrhosis, CLD and HC groups. DKK1 was not different between cases and controls. More than half of HCC patients had normal AFP. In this AFP-negative HCC cohort, 59.18% (n = 29/49 had elevated MDK, applying the optimal cut-off of 0.44 ng/ml. Using AFP ≥ 20 IU/ml or MDK ≥ 0.44 ng/ml, a significantly greater number (76.7%; n = 66/86 of HCC cases were detected. The area under the receiver operating curve for MDK was superior to AFP and OPN in NASH-HCC diagnosis. In the longitudinal cohort, MDK was elevated in 15/28 (54% of HCC patients at diagnosis, of whom 67% had elevated MDK 6 months prior.AFP and MDK have a complementary role in HCC detection. MDK increases the diagnostic yield in AFP-negative HCC and has greater diagnostic performance than AFP, OPN and DKK-1 in the diagnosis of NASH-HCC. Additionally, MDK has a promising role in the pre-clinical diagnosis of HCC.

  4. Localization of Microfibrillar-Associated Protein 4 (MFAP4) in Human Tissues

    DEFF Research Database (Denmark)

    Wulf-Johansson, Helle; Lock Johansson, Sofie; Schlosser, Anders

    2013-01-01

    Microfibrillar-associated protein 4 (MFAP4) is located in the extracellular matrix (ECM). We sought to identify tissues with high levels of MFAP4 mRNA and MFAP4 protein expression. Moreover, we aimed to evaluate the significance of MFAP4 as a marker of cardiovascular disease (CVD) and to correlate...... of MFAP4 protein mainly at sites rich in elastic fibers and within blood vessels in all tissues investigated. The AlphaLISA technique was used to determine serum MFAP4 levels in a clinical cohort of 172 patients consisting of 5 matched groups with varying degrees of CVD: 1: patients with ST elevation...... MFAP4 with other known ECM markers, such as fibulin-1, osteoprotegerin (OPG), and osteopontin (OPN). Quantitative real-time PCR demonstrated that MFAP4 mRNA was more highly expressed in the heart, lung, and intestine than in other elastic tissues. Immunohistochemical studies demonstrated high levels...

  5. Imunoidentification of Albumin and Osteopontin in Seminal Plasma of Taurine and Zebuine Bulls/ Imunoidentificação de Albumina e Osteopontina no Plasma Seminal de Reprodutores Taurinos e Zebuínos

    Directory of Open Access Journals (Sweden)

    Rodrigo Costa Mattos

    2002-05-01

    Full Text Available Two dimensional polyacrylamide gel electrophoresis was performed in seminal plasma of seven Bos taurus taurus and seven Bos taurus indicus bulls with high semen freezability, from an artificialinsemination center. In a 8% polyacrylamide gels, three bands of 195, 66 and 55 kDa, present in 100% of the samples in both sub-species, were analyzed by their optical densities. In Bos taurus samples, the opticals densities of 55 kDa band, imunoidentified as osteopontin were superior (pAs proteínas do plasma seminal de 14 reprodutores (7 Bos taurus taurus e 7 Bos taurus indicus, foram analisadas por eletroforese bidimensional, em géis de poliacrilamida a 8%, corados por Comassie Blue. Três bandas protéicas, presentes em 100% das amostras de plasma seminal, foram quantificadas de acordo com a densidade óptica exibida: 195 kDa, pI 6,5-7,5 ; 66 kDa, pI 5,4 e 55 kDa, pI 4,5. As amostras de plasma seminal provenientes de taurinos apresentaram densidades ópticas significativamente superiores (p < 0,05 às dos zebuínos na banda de 55 kDa, que foi imunoidentificada como osteopontina. As demais proteínas analisadas não apresentaram variações significativas entre as subespécies. A banda protéica de 66 kDa, foi imunoidentificada como albumina. Nas amostras provenientes de taurinos, as densidades ópticas das três bandas protéicas quantificadas não evidenciaram variação significativa entre os reprodutores. Entretanto, nos zebuínos, as densidades ópticas da albumina apresentaram diferenças significativas entre os touros (p < 0,05.

  6. Hypoxia induced expression of endogenous markers in vitro is highly influenced by pH

    DEFF Research Database (Denmark)

    Sørensen, Brita Singers; Alsner, Jan; Overgaard, Jens

    2007-01-01

    BACKGROUND: Genes such as carbonic anhydrase IX (Ca9), glucose transporter 1 (Glut1), lactate dehydrogenase A (LDH-A), osteopontin (OPN) and lysyl oxidase (LOX) have been suggested as hypoxic markers, but inconsistent results suggest that factors other than oxygen influence their expression...

  7. Attachment of a Genetically Engineered Antibody to a Carbon Nanotube Transistor for Detection of Prostate Cancer Biomarkers

    Science.gov (United States)

    Lerner, Mitchell; Dailey, Jennifer; Goldsmith, Brett; Robinson, Matthew; Johnson, A. T. Charlie

    2011-03-01

    We have developed a novel detection method for osteopontin (OPN) by attaching an engineered single chain variable fragment (scFv) protein with high binding affinity for OPN to a carbon nanotube transistor. Osteopontin is a potential new biomarker for prostate cancer; its presence in humans is already associated with several forms of cancer, arthritis, osteoporosis and stress. Prostate cancer is the most commonly diagnosed cancer and second leading cause of cancer deaths among American men and as such represents a major public health issue. Detection of early-stage cancer often results in successful treatment, with long term disease-free survival in 60-90% of patients. Electronic transport measurements are used to detect the presence of OPN in solution at clinically relevant concentrations.

  8. Aggravation of Allergic Airway Inflammation by Cigarette Smoke in Mice Is CD44-Dependent.

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    Smitha Kumar

    Full Text Available Although epidemiological studies reveal that cigarette smoke (CS facilitates the development and exacerbation of allergic asthma, these studies offer limited information on the mechanisms involved. The transmembrane glycoprotein CD44 is involved in cell adhesion and acts as a receptor for hyaluronic acid and osteopontin. We aimed to investigate the role of CD44 in a murine model of CS-facilitated allergic airway inflammation.Wild type (WT and CD44 knock-out (KO mice were exposed simultaneously to house dust mite (HDM extract and CS. Inflammatory cells, hyaluronic acid (HA and osteopontin (OPN levels were measured in bronchoalveolar lavage fluid (BALF. Proinflammatory mediators, goblet cell metaplasia and peribronchial eosinophilia were assessed in lung tissue. T-helper (Th 1, Th2 and Th17 cytokine production was evaluated in mediastinal lymph node cultures.In WT mice, combined HDM/CS exposure increased the number of inflammatory cells and the levels of HA and OPN in BALF and Th2 cytokine production in mediastinal lymph nodes compared to control groups exposed to phosphate buffered saline (PBS/CS, HDM/Air or PBS/Air. Furthermore, HDM/CS exposure significantly increased goblet cell metaplasia, peribronchial eosinophilia and inflammatory mediators in the lung. CD44 KO mice exposed to HDM/CS had significantly fewer inflammatory cells in BALF, an attenuated Th2 cytokine production, as well as decreased goblet cells and peribronchial eosinophils compared to WT mice. In contrast, the levels of inflammatory mediators were similar or higher than in WT mice.We demonstrate for the first time that the aggravation of pulmonary inflammation upon combined exposure to allergen and an environmental pollutant is CD44-dependent. Data from this murine model of concomitant exposure to CS and HDM might be of importance for smoking allergic asthmatics.

  9. Involvement of proinflammatory S100A9/A8 in the atherocalcinosis of aortic valves

    Directory of Open Access Journals (Sweden)

    R. А. Moskalenko

    2017-04-01

    Full Text Available According to the results of the Euro-Heart Survey on Vascular Heart Disease the most common pathology is nonrheumatic aortic stenosis, it is also called as calcific aortic valve stenosis (CAVS, as in its pathogenesis the process of biomineralization of valve cusps and ring plays the main role. The aim of the work is the immunohistochemical study of mineralized tissue of aortic heart valves, which are affected by atherocalcinosis. Materials and methods. 30 samples of mineralized aortic valves (I group and 10 samples of aortic valve without evidence of biomineralization (II group -– control were studied. Immunohistochemical study of expression of collagen (Collagen I, CD68, myeloperoxidase (MPO, calgranulin A (S100A8, calgranulin B (S100A9, caspase 3 (Casp 3 and osteopontin (OPN was conducted in AV tissue of both groups. Results. In CAV tissues the fibrillar component (collagen I growths was found, but the quantitative and qualitative compositions of CD68+ circulating inflammatory cells are not significantly different from the control group. CAVs contain much more MPO+ -cells (p <0.001 in comparison to the group of AVs without biomineralization. Our data show a significant increase of the S100A9 and OPN expression in the mineralized tissue of AVs (p < 0.01. Also, a higher expression level of Casp3 and MPO was found in CAVs (p < 0.05. Comparing the first and the second groups of AVs connection between the expression of S100A8 was not determined. Conclusion. High Casp 3 expression confirms the increased level of cell elimination in the CAVs tissue, which is obviously connected with the impact of high local concentrations of S100A9. These facts can contribute to the development of pathological biomineralization of AV. Since osteopontin inhibits the hydroxyapatite formation by binding to the surface of the crystals, its hyperproduction is a counteracting factor against biomineralization in AV tissue.

  10. Evaluation of two endometriosis models by transplantation of human endometrial tissue fragments and human endometrial mesenchymal cells

    Directory of Open Access Journals (Sweden)

    Mina Jafarabadi

    2017-08-01

    Full Text Available Background: The animal models of endometriosis could be a valuable alternative tool for clarifying the etiology of endometriosis. Objective: In this study two endometriosis models at the morphological and molecular levels was evaluated and compared. Materials and Methods: The human endometrial tissues were cut into small fragments then they were randomly considered for transplantation into γ irradiated mice as model A; or they were isolated and cultured up to fourth passages. 2×106 cultured stromal cells were transplanted into γ irradiated mice subcutaneously as model B. twenty days later the ectopic tissues in both models were studied morphologically by Periodic acid-Schiff and hematoxylin and eosin staining. The expression of osteopontin (OPN and matrix metalloproteinase 2 (MMP2 genes were also assessed using real time RT-PCR. 17-β estradiol levels of mice sera were compared before and after transplantation. Results: The endometrial like glands and stromal cells were formed in the implanted subcutaneous tissue of both endometriosis models. The gland sections per cubic millimeter, the expression of OPN and MMP2 genes and the level of 17-β estradiol were higher in model B than model A (p=0.03. Conclusion: Our observation demonstrated that endometrial mesenchymal stromal cells showed more efficiency to establish endometriosis model than human endometrial tissue fragments.

  11. Effects of the micro-nano surface topography of titanium alloy on the biological responses of osteoblast.

    Science.gov (United States)

    Yin, Chengcheng; Zhang, Yanjing; Cai, Qing; Li, Baosheng; Yang, Hua; Wang, Heling; Qi, Hua; Zhou, Yanmin; Meng, Weiyan

    2017-03-01

    In clinical applications, osseointegration is essential for the long-term stability of dental implants. Inspired by the hierarchical structure of natural bone, we applied the electrochemical etching (EC) technique to form a micro-nano structure on a titanium alloy (Ti6Al4V) substrate, called EC surface. Sand blasting and acid etching (SLA) and machined (M) methods were employed to generate micro and smooth textures, respectively, as the control groups. The surface topographies of the three substrates were characterized using scanning electron microscopy (SEM). Then, human osteoblast-like cells (MG63) were cultured on substrates, and adhesion, proliferation, morphology, alkaline phosphatase activity (ALP), and gene expression levels of Runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), osteopontin (OPN), and type I collagen (COLIA 1) were analyzed. MG63 cells cultured on the EC Ti alloy substrates displayed better cell adhesion, significant proliferation, and a higher production level of ALP, gene expressions of RUNX2, OCN, OPN and COLIA 1 (p < 0.01 or p < 0.05) compared with those of SLA and M substrates. These results indicate that the micro-nano structure fabricated by electrochemical etching method is beneficial for the biological functions of MG63 cells and may be a promising candidate in dental implants. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 757-769, 2017. © 2016 Wiley Periodicals, Inc.

  12. In Vitro Dialysis of Cytokine-Rich Plasma With High and Medium Cut-Off Membranes Reduces Its Procalcific Activity.

    Science.gov (United States)

    Willy, Kevin; Hulko, Michael; Storr, Markus; Speidel, Rose; Gauss, Julia; Schindler, Ralf; Zickler, Daniel

    2017-09-01

    Recently developed high-flux (HF) dialysis membranes with extended permeability provide better clearance of middle-sized molecules such as interleukins (ILs). Whether this modulation of inflammation influences the procalcific effects of septic plasma on vascular smooth muscle cells (VSMCs) is not known. To assess the effects of high cut-off (HCO) and medium cut-off (MCO) membranes on microinflammation and in vitro vascular calcification we developed a miniature dialysis model. Plasma samples from lipopolysaccharide-spiked blood were dialyzed with HF, HCO, and MCO membranes in an in vitro miniature dialysis model. Afterwards, IL-6 concentrations were determined in dialysate and plasma. Calcifying VSMCs were incubated with dialyzed plasma samples and vascular calcification was assessed. Osteopontin (OPN) and matrix Gla protein (MGP) were measured in VSMC supernatants. IL-6 plasma concentrations were markedly lower with HCO and MCO dialysis. VSMC calcification was significantly lower after incubation with MCO- and HCO-serum compared to HF plasma. MGP and OPN levels in supernatants were significantly lower in the MCO but not in the HCO group compared to HF. In vitro dialysis of cytokine-enriched plasma samples with MCO and HCO membranes reduces IL-6 levels. The induction of vascular calcification by cytokine-enriched plasma is reduced after HCO and MCO dialysis. © 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  13. Comparison of biological characteristics of mesenchymal stem cells grown on two different titanium implant surfaces

    International Nuclear Information System (INIS)

    Wang Chengyue; Zhao Baohong; Ai Hongjun; Wang Yiwei

    2008-01-01

    This study examined the biological characteristics of mesenchymal stem cells (MSCs) grown on sand-blasted, large-grit, acid-etched (SLA) surface and hydroxyapatite (HA) coating on the SLA (HA/SLA) surface of titanium dental implants. The HA/SLA surfaces of titanium dental implants were formed by the ion beam assisted deposition (IBAD) method. Rabbit bone marrow derived mesenchymal stem cells cultured in vitro were seeded onto the surface of SLA and HA/SLA; the growth states of MSCs on the two samples were observed by a scanning electron microscope; the proliferation index, alkaline phosphatase (ALP) activity, osteocalcin (OCN) content of MSCs and mRNA relative expression level of osteopontin (opn) were compared between two groups. MSCs were found to be easier to adhere to the HA/SLA surface compared to the SLA surface. At the same time, the ALP activity and the OCN content of MSCs grown on the HA/SLA surface were obviously higher, and the relative expression level of opn mRNA was 4.78 times higher than that on the SLA surface. The HA coating formed by the IBAD method on the SLA surface of titanium dental implants significantly improves proliferation and well-differentiated osteoblastic phenotype of MSCs, which indicates a promising method for the surface modification of titanium dental implants

  14. Roles of electrostatics and conformation in protein-crystal interactions.

    Directory of Open Access Journals (Sweden)

    Paul V Azzopardi

    2010-02-01

    Full Text Available In vitro studies have shown that the phosphoprotein osteopontin (OPN inhibits the nucleation and growth of hydroxyapatite (HA and other biominerals. In vivo, OPN is believed to prevent the calcification of soft tissues. However, the nature of the interaction between OPN and HA is not understood. In the computational part of the present study, we used molecular dynamics simulations to predict the adsorption of 19 peptides, each 16 amino acids long and collectively covering the entire sequence of OPN, to the {100} face of HA. This analysis showed that there is an inverse relationship between predicted strength of adsorption and peptide isoelectric point (P<0.0001. Analysis of the OPN sequence by PONDR (Predictor of Naturally Disordered Regions indicated that OPN sequences predicted to adsorb well to HA are highly disordered. In the experimental part of the study, we synthesized phosphorylated and non-phosphorylated peptides corresponding to OPN sequences 65-80 (pSHDHMDDDDDDDDDGD and 220-235 (pSHEpSTEQSDAIDpSAEK. In agreement with the PONDR analysis, these were shown by circular dichroism spectroscopy to be largely disordered. A constant-composition/seeded growth assay was used to assess the HA-inhibiting potencies of the synthetic peptides. The phosphorylated versions of OPN65-80 (IC(50 = 1.93 microg/ml and OPN220-235 (IC(50 = 1.48 microg/ml are potent inhibitors of HA growth, as is the nonphosphorylated version of OPN65-80 (IC(50 = 2.97 microg/ml; the nonphosphorylated version of OPN220-235 has no measurable inhibitory activity. These findings suggest that the adsorption of acidic proteins to Ca2+-rich crystal faces of biominerals is governed by electrostatics and is facilitated by conformational flexibility of the polypeptide chain.

  15. Candidate biomarkers for the diagnosis and prognosis of drug-induced liver injury: An international collaborative effort.

    Science.gov (United States)

    Church, Rachel J; Kullak-Ublick, Gerd A; Aubrecht, Jiri; Bonkovsky, Herbert L; Chalasani, Naga; Fontana, Robert J; Goepfert, Jens C; Hackman, Frances; King, Nicholas M P; Kirby, Simon; Kirby, Patrick; Marcinak, John; Ormarsdottir, Sif; Schomaker, Shelli J; Schuppe-Koistinen, Ina; Wolenski, Francis; Arber, Nadir; Merz, Michael; Sauer, John-Michael; Andrade, Raul J; van Bömmel, Florian; Poynard, Thierry; Watkins, Paul B

    2018-01-22

    Current blood biomarkers are suboptimal in detecting drug-induced liver injury (DILI) and predicting its outcome. We sought to characterize the natural variabilty and performance characteristics of fourteen promising DILI biomarker candidates. Serum or plasma from multiple cohorts of healthy volunteers (n=192 and =81), subjects who safely took potentially hepatotoxic drugs without adverse effects (n=55 and =92) and DILI patients (n=98, =28, and =143) were assayed for microRNA-122 (miR-122), glutamate dehydrogenase (GLDH), total keratin 18 (K18), caspase cleaved K18 (ccK18), glutathione S-transferase alpha (GSTα), alpha fetoprotein (AFP), arginase-1 (ARG1), osteopontin (OPN), sorbitol dehydrogenase (SDH), fatty acid binding protein (FABP1), cadherin-5 (CDH5), macrophage colony stimulating factor receptor (MCSFR), paraoxonase 1 (PON1, normalized to prothrombin protein), and leucocyte cell-derived chemotaxin-2 (LECT2). Most candidate biomarkers were significantly altered in DILI cases compared to healthy volunteers. GLDH correlated more closely with gold standard alanine aminotransferase (ALT) than miR-122 and there was a surprisingly wide inter- and intra-individual variability of miR-122 levels among the healthy volunteers. Serum K18, OPN, and MCSFR levels were most strongly associated with liver-related death or transplant within 6 months of DILI-onset. Prediction of prognosis among DILI patients using Model for End-stage Liver Disease (MELD) was improved by incorporation of K18 and MCSFR levels. GLDH appears to be more useful than miR-122 in identifying DILI patients. K18, OPN and MCSFR are promising candidates for prediction of prognosis during an acute DILI event. Serial assessment of these biomarkers in large prospective studies will help further delineate their role in DILI diagnosis and management. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

  16. Differences in otosclerotic and normal human stapedial osteoblast properties are normalized by alendronate in vitro.

    Science.gov (United States)

    Gronowicz, Gloria; Richardson, Yvonne L; Flynn, John; Kveton, John; Eisen, Marc; Leonard, Gerald; Aronow, Michael; Rodner, Craig; Parham, Kourosh

    2014-10-01

    Identify and compare phenotypic properties of osteoblasts from patients with otosclerosis (OSO), normal bones (HOB), and normal stapes (NSO) to determine a possible cause for OSO hypermineralization and assess any effects of the bisphosphonate, alendronate. OSO (n = 11), NSO (n = 4), and HOB (n = 13) cultures were assayed for proliferation, adhesion, mineralization, and gene expression with and without 10(-10)M-10(-8)M alendronate. Academic hospital. Cultures were matched for age, sex, and passage number. Cell attachment and proliferation + alendronate were determined by Coulter counting cells and assaying tritiated thymidine uptake, respectively. At 7, 14, and 21 days of culture + alendronate, calcium content and gene expression by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were determined. OSO had significantly more cells adhere but less proliferation than NSO or HOB. Calcification was significantly increased in OSO compared to HOB and NSO. NSO and HOB had similar cell adhesion and proliferation rates. A dose-dependent effect of alendronate on OSO adhesion, proliferation, and mineralization was found, resulting in levels equal to NSO and HOB. All cultures expressed osteoblast-specific genes such as RUNX2, alkaline phosphatase, type I collagen, and osteocalcin. However, osteopontin was dramatically reduced, 9.4-fold at 14 days, in OSO compared to NSO. Receptor activator of nuclear factor κB ligand/osteoprotegerin (RANKL/OPG), important in bone resorption, was elevated in OSO with decreased levels of OPG levels. Alendronate had little effect on gene expression in HOB but in OSO increased osteopontin levels and decreased RANKL/OPG. OSO cultures displayed properties of hypermineralization due to decreased osteopontin (OPN) and also had increased RANKL/OPG, which were normalized by alendronate. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

  17. Genetic Polymorphisms of Osteopontin in Association with ...

    African Journals Online (AJOL)

    2323. ISSN: 1596-5996 (print); 1596-9827 (electronic) ... Revised accepted: 5 November 2015. Abstract. Purpose: To determine the association of ..... Brenner D, Labreuche J, Touboul PJ, Schmidt-Petersen. K, Poirier O, Perret C, Schonfelder J, ...

  18. Osteopontin Prevents Monocyte Recirculation and Apoptosis

    OpenAIRE

    Burdo, Tricia H.; Wood, Malcolm R.; Fox, Howard S.

    2007-01-01

    Cells of the monocyte/macrophage lineage have been shown to be the principal targets for productive HIV-1 replication within the central nervous system. In addition, HIV-1-associated dementia (HAD) has been shown to correlate with macrophage abundance in the brain. While increased entry of monocytes into the brain is thought to initiate this process, mechanisms that prevent macrophage egress from the brain and means that prevent macrophage death may also contribute to cell accumulation. We hy...

  19. Hypoxia-Inducible Factor-1α (HIF-1α) Expression on Endothelial Cells in Juvenile Nasopharyngeal Angiofibroma: A Review of 70 cases and Tissue Microarray Analysis.

    Science.gov (United States)

    Song, Xiaole; Yang, Chenhe; Zhang, Huankang; Wang, Jingjing; Sun, Xicai; Hu, Li; Liu, Zhuofu; Wang, Dehui

    2018-06-01

    To examine the expression of hypoxia-inducible factor-1α (HIF-1α) and its related molecules (cellular repressor of E1A-stimulated genes [CREG], osteopontin [OPN], proto-oncogene tyrosine-protein kinase Src [c-Src], and vascular endothelial growth factor [VEGF]) in juvenile nasopharyngeal angiofibroma (JNA) and explore the correlation between clinical prognosis and HIF-1α expression. The study performed a retrospective review of the clinical records of patients with JNA treated between 2003 and 2007. Specimens were analyzed by immunohistochemistry for HIF-1α, CREG, OPN, c-Src, and VEGF expression, and microvessel density (MVD) was assessed by tissue microarray. The correlation between expression levels and clinicopathological features including age, tumor stage, intraoperative blood loss, and recurrence was analyzed. HIF-1α, CREG, OPN, c-Src, and VEGF were upregulated in endothelial cells (ECs) of patients with JNA, and strong correlations in the expression of these molecules were observed. HIF-1α expression was higher in young patients ( P = .032) and in recurrent cases ( P = .01). Survival analysis showed that low HIF-1α levels in ECs predicted longer time to recurrence (log rank test P = .006). Receiver operating characteristic curve analysis showed that HIF-1α was a prognostic factor for recurrence (area under the curve = 0.690, P = .019). No correlation was found between the expression of molecules and Radkowski stage or intraoperative blood loss. In cases of JNA treated surgically, HIF-1α expression in ECs is a useful prognostic factor for tumor recurrence.

  20. Evaluation of uterine cervix cancer hypoxia by PET with {sup 18}F-F.E.T.N.I.M.. Relation with squamous cell carcinoma (S.C.C.) and osteopontin tumoral markers; Evaluation de l'hypoxie du cancer du col uterin par la TEP au {sup 18}F-FETNIM. Relation avec les marqueurs tumoraux SCC et osteopontine

    Energy Technology Data Exchange (ETDEWEB)

    Barre, E.; Schlageter, M.H.; Groheux, D.; Vercellino, L.; Lussato, D.; Thoury, A.; Hennequin, V.; Hindie, E.; Barranger, E.; Moretti, J.L. [CHU Saint-Louis-Lariboisiere, universite Paris-7, IMDCT, 75 - Paris (France)

    2010-07-01

    Purpose: to evaluate the imaging feasibility of hypoxia of cervical squamous cell carcinoma by PET with {sup 18}F-F.E.T.N.I.M. (Iason). to compare the {sup 18}F-F.E.T.N.I.M. uptake to the metabolic uptake in {sup 18}F-F.D.G. and to study their relationship with the squamous cell carcinoma, tumoral marker and osteoponin, circulating tracer of hypoxia. Conclusions: the F.E.T.N.I.M. uptake by the tumor is always of lower level than the {sup 18}F-F.D.G. uptake. By using the ratio Tumor/Muscle, these preliminary results do not enlighten any correlation between the circulating hypoxia tracer and the tumor uptake of {sup 18}F-F.E.T.N.I.M.. (N.C.)

  1. Proximal renal tubular injury in rats sub-chronically exposed to low fluoride concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Cárdenas-González, Mariana C.; Del Razo, Luz M. [Departmento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), México, D. F., México (Mexico); Barrera-Chimal, Jonatan [Unidad de Fisiología Molecular, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México and Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México, D. F., México (Mexico); Jacobo-Estrada, Tania [Departmento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), México, D. F., México (Mexico); López-Bayghen, Esther [Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), México, D. F., México (Mexico); and others

    2013-11-01

    Fluoride is usually found in groundwater at a very wide range of concentration between 0.5 and 25 ppm. At present, few studies have assessed the renal effects of fluoride at environmentally relevant concentrations. Furthermore, most of these studies have used insensitive and nonspecific biomarkers of kidney injury. The aim of this study was to use early and sensitive biomarkers to evaluate kidney injury after fluoride exposure to environmentally relevant concentrations. Recently weaned male Wistar rats were exposed to low (15 ppm) and high (50 ppm) fluoride concentrations in drinking water for a period of 40 days. At the end of the exposure period, kidney injury biomarkers were measured in urine and renal mRNA expression levels were assessed by real time RT-PCR. Our results showed that the urinary kidney injury molecule (Kim-1), clusterin (Clu), osteopontin (OPN) and heat shock protein 72 excretion rate significantly increased in the group exposed to the high fluoride concentration. Accordingly, fluoride exposure increased renal Kim-1, Clu and OPN mRNA expression levels. Moreover, there was a significant dose-dependent increase in urinary β-2-microglobulin and cystatin-C excretion rate. Additionally, a tendency towards a dose dependent increase of tubular damage in the histopathological light microscopy findings confirmed the preferential impact of fluoride on the tubular structure. All of these changes occurred at early stages in which, the renal function was not altered. In conclusion using early and sensitive biomarkers of kidney injury, we were able to found proximal tubular alterations in rats sub-chronically exposed to fluoride. - Highlights: • Exposure to low concentrations of fluoride induced proximal tubular injury • Increase in urinary Kim-1, Clu, OPN and Hsp72 in 50 ppm fluoride-exposed group • Increase in urinary B2M and CysC in 15 and 50 ppm fluoride-exposed groups • Fluoride exposure increased renal Kim, Clu and OPN mRNA expression levels.

  2. Patients with Ankylosing Spondylitis and Low Disease Activity because of Anti-TNF-Alpha Therapy Have Higher TRAIL Levels Than Controls: A Potential Compensatory Effect

    Directory of Open Access Journals (Sweden)

    Fernanda Genre

    2014-01-01

    Full Text Available Objective. TRAIL is a potential biomarker of cardiovascular (CV disease. Ankylosing spondylitis (AS is a chronic inflammatory disease associated with metabolic syndrome (MeS and accelerated atherosclerosis. We assessed whether disease activity, systemic inflammation, and MeS features were associated with circulating TRAIL levels in AS patients undergoing TNF-α antagonist infliximab therapy and if infliximab infusion modified TRAIL levels. Methods. We measured TRAIL serum levels in 30 nondiabetic AS patients without CV disease undergoing anti-TNF-α therapy, immediately before and after an infliximab infusion, and in 48 matched controls. Correlations of TRAIL levels with disease activity, systemic inflammation and MeS features, adipokines, and biomarkers of endothelial activation were evaluated. Changes in TRAIL levels following anti-TNF-α infusion were analyzed. Results. TRAIL levels were higher in AS patients than controls. TRAIL levels displayed an inverse correlation with total and LDL cholesterol. We observed an inverse correlation with QUICKI and a marginal association with HOMA-IR. We also found an inverse correlation with resistin and a marginal association with apelin and OPN. Anti-TNF-α infusion did not change TRAIL levels after 120′. Conclusion. Elevated TRAIL levels in AS patients may be the result of a compensatory mechanism to reduce CV risk in these patients.

  3. Rationel antibiotikabehandling kan opnås ved audit og undervisning

    DEFF Research Database (Denmark)

    Bjerrum, Lars; Gahrn-Hansen, Bente; Kolmos, Hans Jørn

    2011-01-01

    doctors and patients in primary care led to a considerable decrease in antibiotic prescribing. Teaching of hospital doctors, combined with a restriction in the choice of antibiotics, resulted in a decrease in multidrug-resistant strains. A concerted effort is needed to curb the growing resistance problem.......A prerequisite for rational antibiotic treatment is the suspicion that the disease is caused by bacteria and that treatment will reduce symptoms and complications. In primary health care most infections are caused by bacteria. The European project HAPPY AUDIT found that an intervention targeting...

  4. Fra offer til kriger - at opnå et liv i balance

    DEFF Research Database (Denmark)

    Østergaard, Lars Jørgen; Rodkjær, Lotte Ørneborg; Laursen, Tinne

    2015-01-01

    “Find din indre kriger og kom ud af din tilværelse som et sygdomsramt offer.” Det er en del af budskabet til en gruppe HIV-patienter fra et alternativt behandlingsforløb med indianeren, Hawk. Forløbet er kommet i stand på Skejby Sygehus, som samtidig har undersøgt den mentale effekt. Dokumentarfi......“Find din indre kriger og kom ud af din tilværelse som et sygdomsramt offer.” Det er en del af budskabet til en gruppe HIV-patienter fra et alternativt behandlingsforløb med indianeren, Hawk. Forløbet er kommet i stand på Skejby Sygehus, som samtidig har undersøgt den mentale effekt...

  5. Rationel antibiotikabehandling kan opnås ved audit og undervisning

    DEFF Research Database (Denmark)

    Bjerrum, Lars; Gahrn-Hansen, Bente; Kolmos, Hans Jørn

    2011-01-01

    A prerequisite for rational antibiotic treatment is the suspicion that the disease is caused by bacteria and that treatment will reduce symptoms and complications. In primary health care most infections are caused by bacteria. The European project HAPPY AUDIT found that an intervention targeting...

  6. Intense inflammation and nerve damage in early multiple sclerosis subsides at older age: a reflection by cerebrospinal fluid biomarkers.

    Directory of Open Access Journals (Sweden)

    Mohsen Khademi

    Full Text Available Inflammatory mediators have crucial roles in leukocyte recruitment and subsequent central nervous system (CNS neuroinflammation. The extent of neuronal injury and axonal loss are associated with the degree of CNS inflammation and determine physical disability in multiple sclerosis (MS. The aim of this study was to explore possible associations between a panel of selected cerebrospinal fluid biomarkers and robust clinical and demographic parameters in a large cohort of patients with MS and controls (n = 1066 using data-driven multivariate analysis. Levels of matrix metalloproteinase 9 (MMP9, chemokine (C-X-C motif ligand 13 (CXCL13, osteopontin (OPN and neurofilament-light chain (NFL were measured by ELISA in 548 subjects comprising different MS subtypes (relapsing-remitting, secondary progressive and primary progressive, clinically isolated syndrome and persons with other neurological diseases with or without signs of inflammation/infection. Principal component analyses and orthogonal partial least squares methods were used for unsupervised and supervised interrogation of the data. Models were validated using data from a further 518 subjects in which one or more of the four selected markers were measured. There was a significant association between increased patient age and lower levels of CXCL13, MMP9 and NFL. CXCL13 levels correlated well with MMP9 in the younger age groups, but less so in older patients, and after approximately 54 years of age the levels of CXCL13 and MMP9 were consistently low. CXCL13 and MMP9 levels also correlated well with both NFL and OPN in younger patients. We demonstrate a strong effect of age on both inflammatory and neurodegenerative biomarkers in a large cohort of MS patients. The findings support an early use of adequate immunomodulatory disease modifying drugs, especially in younger patients, and may provide a biological explanation for the relative inefficacy of such treatments in older patients at later

  7. Lathe leveler

    Energy Technology Data Exchange (ETDEWEB)

    Lovelady, III, Michael W.J.

    2018-03-06

    A lathe leveler for centering a cutting tool in relation to a cylindrical work piece includes a first leveling arm having a first contact point disposed adjacent a distal end of the first leveling arm, a second leveling arm having a second contact point disposed adjacent a distal end of the second leveling arm, a leveling gage, and a leveling plate having a cutting tool receiving surface positioned parallel to a horizontal axis of the leveling gage and on a same plane as a midpoint of the first contact point and the second contact point. The leveling arms and leveling plate are dimensioned and configured such that the cutting tool receiving surface is centered in relation to the work piece when the first and second contact points are in contact with one of the inner surface and outer surface of the cylindrical work piece and the leveling gage is centered.

  8. MEPE, a new gene expressed in bone marrow and tumors causing osteomalacia.

    Science.gov (United States)

    Rowe, P S; de Zoysa, P A; Dong, R; Wang, H R; White, K E; Econs, M J; Oudet, C L

    2000-07-01

    Oncogenic hypophosphatemic osteomalacia (OHO) is characterized by a renal phosphate leak, hypophosphatemia, low-serum calcitriol (1,25-vitamin-D3), and abnormalities in skeletal mineralization. Resection of OHO tumors results in remission of the symptoms, and there is evidence that a circulating phosphaturic factor plays a role in the bone disease. This paper describes the characterization and cloning of a gene that is a candidate for the tumor-secreted phosphaturic factor. This new gene has been named MEPE (matrix extracellular phosphoglycoprotein) and has major similarities to a group of bone-tooth mineral matrix phospho-glycoproteins (osteopontin (OPN; HGMW-approved symbol SPP1), dentin sialo phosphoprotein (DSPP), dentin matrix protein 1 (DMP1), bone sialoprotein II (IBSP), and bone morphogenetic proteins (BMP). All the proteins including MEPE contain RGD sequence motifs that are proposed to be essential for integrin-receptor interactions. Of further interest is the finding that MEPE, OPN, DSPP, DMP1, IBSP, and BMP3 all map to a defined region in chromosome 4q. Refined mapping localizes MEPE to 4q21.1 between ESTs D4S2785 (WI-6336) and D4S2844 (WI-3770). MEPE is 525 residues in length with a short N-terminal signal peptide. High-level expression of MEPE mRNA occurred in all four OHO tumors screened. Three of 11 non-OHO tumors screened contained trace levels of MEPE expression (detected only after RT-PCR and Southern 32P analysis). Normal tissue expression was found in bone marrow and brain with very-low-level expression found in lung, kidney, and human placenta. Evidence is also presented for the tumor secretion of clusterin (HGMW-approved symbol CLU) and its possible role as a cytotoxic factor in one of the OHO patients described.

  9. Cortisol level

    Science.gov (United States)

    ... enable JavaScript. The cortisol blood test measures the level of cortisol in the blood. Cortisol is a ... in the morning. This is important, because cortisol level varies throughout the day. You may be asked ...

  10. Triglyceride level

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003493.htm Triglyceride level To use the sharing features on this page, please enable JavaScript. The triglyceride level is a blood test to measure the amount ...

  11. Adhesion and internalization differences of COM nanocrystals on Vero cells before and after cell damage

    Energy Technology Data Exchange (ETDEWEB)

    Gan, Qiong-Zhi; Sun, Xin-Yuan; Ouyang, Jian-Ming, E-mail: toyjm@jnu.edu.cn

    2016-02-01

    The adhesion and internalization between African green monkey kidney epithelial (Vero) cells (before and after oxidative damage by hydrogen peroxide) and calcium oxalate monohydrate (COM) nanocrystals (97 ± 35 nm) were investigated so as to discuss the molecular and cellular mechanism of kidney stone formation. Scanning electron microscope (SEM) was used to observe the Vero–COM nanocrystal adhesion; the nanocrystal-cell adhesion was evaluated by measuring the content of malonaldehyde (MDA), the activity of superoxide dismutase (SOD), the expression level of cell surface osteopontin (OPN) and the change of Zeta potential. Confocal microscopy and flow cytometry were used for the observation and quantitative analysis of crystal internalization. In the process of adhesion, the cell viability and the SOD activity declined, the MDA content, Zeta potential, and the OPN expression level increased. The adhesive capacity of injured Vero was obviously stronger than normal cells; in addition the injured cells promoted the aggregation of COM nanocrystals. The capacity of normal cells to internalize crystals was obviously stronger than that of injured cells. Cell injury increased adhesive sites on cell surface, thereby facilitating the aggregation of COM nanocrystals and their attachment, which results in enhanced risk of calcium oxalate stone formation. - Graphical abstract: The adhesion and internalization differences between Vero cells before and after oxidative damage and calcium oxalate monohydrate nanocrystals were comparatively studied. - Highlights: • Adhesion capacity of injured Vero cells was stronger than normal cells. • Internalization capacity of injured Vero cells was weaker than normal cells. • Injured cells promoted the aggregation of COM nanocrystals. • COM adhesion could aggravate cell injury in both normal and injured cells.

  12. Level 1 - level 2 interface

    International Nuclear Information System (INIS)

    Boneham, P.

    2003-01-01

    The Plant Damage States (PDS) are the starting point for the level 2 analysis. A PDS is group of core damage sequences that are expected to have similar severe accident progressions. In this paper an overview of Level 1/Level 2 interface, example PDS parameters, example PDS definitions using codes and example Bridge Tree are presented. PDS frequency calculation (identification of sequences for each PDS in level 1,split some CD sequences which have different level 2 progressions), code calculations providing support for grouping decisions and timings as well as PDS frequencies and definitions input to level 2 are also discussed

  13. Level densities

    International Nuclear Information System (INIS)

    Ignatyuk, A.V.

    1998-01-01

    For any applications of the statistical theory of nuclear reactions it is very important to obtain the parameters of the level density description from the reliable experimental data. The cumulative numbers of low-lying levels and the average spacings between neutron resonances are usually used as such data. The level density parameters fitted to such data are compiled in the RIPL Starter File for the tree models most frequently used in practical calculations: i) For the Gilber-Cameron model the parameters of the Beijing group, based on a rather recent compilations of the neutron resonance and low-lying level densities and included into the beijing-gc.dat file, are chosen as recommended. As alternative versions the parameters provided by other groups are given into the files: jaeri-gc.dat, bombay-gc.dat, obninsk-gc.dat. Additionally the iljinov-gc.dat, and mengoni-gc.dat files include sets of the level density parameters that take into account the damping of shell effects at high energies. ii) For the backed-shifted Fermi gas model the beijing-bs.dat file is selected as the recommended one. Alternative parameters of the Obninsk group are given in the obninsk-bs.dat file and those of Bombay in bombay-bs.dat. iii) For the generalized superfluid model the Obninsk group parameters included into the obninsk-bcs.dat file are chosen as recommended ones and the beijing-bcs.dat file is included as an alternative set of parameters. iv) For the microscopic approach to the level densities the files are: obninsk-micro.for -FORTRAN 77 source for the microscopical statistical level density code developed in Obninsk by Ignatyuk and coworkers, moller-levels.gz - Moeller single-particle level and ground state deformation data base, moller-levels.for -retrieval code for Moeller single-particle level scheme. (author)

  14. Soluble guanylate cyclase stimulation prevents fibrotic tissue remodeling and improves survival in salt-sensitive Dahl rats.

    Directory of Open Access Journals (Sweden)

    Sandra Geschka

    Full Text Available A direct pharmacological stimulation of soluble guanylate cyclase (sGC is an emerging therapeutic approach to the management of various cardiovascular disorders associated with endothelial dysfunction. Novel sGC stimulators, including riociguat (BAY 63-2521, have a dual mode of action: They sensitize sGC to endogenously produced nitric oxide (NO and also directly stimulate sGC independently of NO. Little is known about their effects on tissue remodeling and degeneration and survival in experimental malignant hypertension.Mortality, hemodynamics and biomarkers of tissue remodeling and degeneration were assessed in Dahl salt-sensitive rats maintained on a high salt diet and treated with riociguat (3 or 10 mg/kg/d for 14 weeks. Riociguat markedly attenuated systemic hypertension, improved systolic heart function and increased survival from 33% to 85%. Histological examination of the heart and kidneys revealed that riociguat significantly ameliorated fibrotic tissue remodeling and degeneration. Correspondingly, mRNA expression of the pro-fibrotic biomarkers osteopontin (OPN, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1 and plasminogen activator inhibitor-1 (PAI-1 in the myocardium and the renal cortex was attenuated by riociguat. In addition, riociguat reduced plasma and urinary levels of OPN, TIMP-1, and PAI-1.Stimulation of sGC by riociguat markedly improves survival and attenuates systemic hypertension and systolic dysfunction, as well as fibrotic tissue remodeling in the myocardium and the renal cortex in a rodent model of pressure and volume overload. These findings suggest a therapeutic potential of sGC stimulators in diseases associated with impaired cardiovascular and renal functions.

  15. The Src inhibitor dasatinib accelerates the differentiation of human bone marrow-derived mesenchymal stromal cells into osteoblasts

    International Nuclear Information System (INIS)

    Id Boufker, Hichame; Lagneaux, Laurence; Najar, Mehdi; Piccart, Martine; Ghanem, Ghanem; Body, Jean-Jacques; Journé, Fabrice

    2010-01-01

    The proto-oncogene Src is an important non-receptor protein tyrosine kinase involved in signaling pathways that control cell adhesion, growth, migration and differentiation. It negatively regulates osteoblast activity, and, as such, its inhibition is a potential means to prevent bone loss. Dasatinib is a new dual Src/Bcr-Abl tyrosine kinase inhibitor initially developed for the treatment of chronic myeloid leukemia. It has also shown promising results in preclinical studies in various solid tumors. However, its effects on the differentiation of human osteoblasts have never been examined. We evaluated the effects of dasatinib on bone marrow-derived mesenchymal stromal cells (MSC) differentiation into osteoblasts, in the presence or absence of a mixture of dexamethasone, ascorbic acid and β-glycerophosphate (DAG) for up to 21 days. The differentiation kinetics was assessed by evaluating mineralization of the extracellular matrix, alkaline phosphatase (ALP) activity, and expression of osteoblastic markers (receptor activator of nuclear factor kappa B ligand [RANKL], bone sialoprotein [BSP], osteopontin [OPN]). Dasatinib significantly increased the activity of ALP and the level of calcium deposition in MSC cultured with DAG after, respectively, 7 and 14 days; it upregulated the expression of BSP and OPN genes independently of DAG; and it markedly downregulated the expression of RANKL gene and protein (decrease in RANKL/OPG ratio), the key factor that stimulates osteoclast differentiation and activity. Our results suggest a dual role for dasatinib in both (i) stimulating osteoblast differentiation leading to a direct increase in bone formation, and (ii) downregulating RANKL synthesis by osteoblasts leading to an indirect inhibition of osteoclastogenesis. Thus, dasatinib is a potentially interesting candidate drug for the treatment of osteolysis through its dual effect on bone metabolism

  16. Erhuang Formula ameliorates renal damage in adenine-induced chronic renal failure rats via inhibiting inflammatory and fibrotic responses.

    Science.gov (United States)

    Zhang, Chun-Yan; Zhu, Jian-Yong; Ye, Ying; Zhang, Miao; Zhang, Li-Jun; Wang, Su-Juan; Song, Ya-Nan; Zhang, Hong

    2017-11-01

    The present study aimed to evaluate the protective effects of Erhuang Formula (EHF) and explore its pharmacological mechanisms on adenine-induced chronic renal failure (CRF). The compounds in EHF were analyzed by HPLC/MS. Adenine-induced CRF rats were administrated by EHF. The effects were evaluated by renal function examination and histology staining. Immunostaining of some proteins related cell adhesion was performedin renal tissues, including E-cadherin, β-catenin, fibronectin and laminin. The qRT-PCR was carried out determination of gene expression related inflammation and fibrosis including NF-κB, TNF-α, TGF-β1, α-SMA and osteopontin (OPN). Ten compounds in EHF were identified including liquiritigenin, farnesene, vaccarin, pachymic acid, cycloastragenol, astilbin, 3,5,6,7,8,3',4'-heptemthoxyflavone, physcion, emodin and curzerene. Abnormal renal function and histology had significant improvements by EHF treatment. The protein expression of β-catenin, fibronectin and laminin were significantly increased and the protein expression of E-cadherin significantly decreased in CRF groups. However, these protein expressions were restored to normal levels in EHF group. Furthermore, low expression of PPARγ and high expression of NF-κB, TNF-α, TGF-β1, α-SMA and OPN were substantially restored by EHF treatment in a dose-dependent manner. EHF ameliorated renal damage in adenine-induced CRF rats, and the mechanisms might involve in the inhibition of inflammatory and fibrotic responses and the regulation of PPARγ, NF-κB and TGF-β signaling pathways. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  17. Cooperation of phosphates and carboxylates controls calcium oxalate crystallization in ultrafiltered urine.

    Science.gov (United States)

    Grohe, Bernd; Chan, Brian P H; Sørensen, Esben S; Lajoie, Gilles; Goldberg, Harvey A; Hunter, Graeme K

    2011-10-01

    Osteopontin (OPN) is one of a group of proteins found in urine that are believed to limit the formation of kidney stones. In the present study, we investigate the roles of phosphate and carboxylate groups in the OPN-mediated modulation of calcium oxalate (CaOx), the principal mineral phase found in kidney stones. To this end, crystallization was induced by addition of CaOx solution to ultrafiltered human urine containing either human kidney OPN (kOPN; 7 consecutive carboxylates, 8 phosphates) or synthesized peptides corresponding to residues 65-80 (pSHDHMDDDDDDDDDGD; pOPAR) or 220-235 (pSHEpSTEQSDAIDpSAEK; P3) of rat bone OPN. Sequence 65-80 was also synthesized without the phosphate group (OPAR). Effects on calcium oxalate monohydrate (COM) and dihydrate (COD) formation were studied by scanning electron microscopy. We found that controls form large, partly intergrown COM platelets; COD was never observed. Adding any of the polyelectrolytes was sufficient to prevent intergrowth of COM platelets entirely, inhibiting formation of these platelets strongly, and inducing formation of the COD phase. Strongest effects on COM formation were found for pOPAR and OPAR followed by kOPN and then P3, showing that acidity and hydrophilicity are crucial in polyelectrolyte-affected COM crystallization. At higher concentrations, OPAR also inhibited COD formation, while P3, kOPN and, in particular, pOPAR promoted COD, a difference explainable by the variations of carboxylate and phosphate groups present in the molecules. Thus, we conclude that carboxylate groups play a primary role in inhibiting COM formation, but phosphate and carboxylate groups are both important in initiating and promoting COD formation.

  18. Translating golden retriever muscular dystrophy microarray findings to novel biomarkers for cardiac/skeletal muscle function in Duchenne muscular dystrophy.

    Science.gov (United States)

    Galindo, Cristi L; Soslow, Jonathan H; Brinkmeyer-Langford, Candice L; Gupte, Manisha; Smith, Holly M; Sengsayadeth, Seng; Sawyer, Douglas B; Benson, D Woodrow; Kornegay, Joe N; Markham, Larry W

    2016-04-01

    In Duchenne muscular dystrophy (DMD), abnormal cardiac function is typically preceded by a decade of skeletal muscle disease. Molecular reasons for differences in onset and progression of these muscle groups are unknown. Human biomarkers are lacking. We analyzed cardiac and skeletal muscle microarrays from normal and golden retriever muscular dystrophy (GRMD) dogs (ages 6, 12, or 47+ mo) to gain insight into muscle dysfunction and to identify putative DMD biomarkers. These biomarkers were then measured using human DMD blood samples. We identified GRMD candidate genes that might contribute to the disparity between cardiac and skeletal muscle disease, focusing on brain-derived neurotropic factor (BDNF) and osteopontin (OPN/SPP1, hereafter indicated as SPP1). BDNF was elevated in cardiac muscle of younger GRMD but was unaltered in skeletal muscle, while SPP1 was increased only in GRMD skeletal muscle. In human DMD, circulating levels of BDNF were inversely correlated with ventricular function and fibrosis, while SPP1 levels correlated with skeletal muscle function. These results highlight gene expression patterns that could account for differences in cardiac and skeletal disease in GRMD. Most notably, animal model-derived data were translated to DMD and support use of BDNF and SPP1 as biomarkers for cardiac and skeletal muscle involvement, respectively.

  19. Effect of the Copaifera langsdorffii Desf. Leaf Extract on the Ethylene Glycol-Induced Nephrolithiasis in Rats

    Directory of Open Access Journals (Sweden)

    Rejane Barbosa de Oliveira

    2013-01-01

    Full Text Available The potential of the Copaifera langsdorffii leaves extract to prevent stone formation was analyzed by means of an ethylene glycol (EG animal model of nephrolithiasis and an in vitro crystallization assay. Different doses of the C. langsdorffii leaves extract were administered to rats treated with EG. Urine biochemical parameters were quantified. CaOx deposits count and analysis of osteopontin expression were conducted on kidneys fixed in formalin. The in vitro assay was performed by turbidimetry. Phytochemical analyses of the extract were accomplished by HPLC-UV-DAD, and several compounds were isolated. C. langsdorffii leaf extract was able to avoid stone formation. The number of deposits was 50.30±31.29 at the higher extract dose, compared to the value of 179.5±45.96 achieved with the EG control. Significantly lower oxalate levels and OPN expression and increased citrate levels were observed after extract administration. In the in vitro assay, the extract diluted the formed crystals. Phytochemical analyses showed that the extract is rich in phenolic compounds that are capable of preventing stone formation. Thus, on the basis of our results, we suggest that the C. langsdorffii leaf extract has potential application in the prevention of kidney stone formation.

  20. [Effects of ADAM28 on biological functions of human dental pulp stem cells].

    Science.gov (United States)

    Zhao, Zheng; Liu, Hong-chen; E, Ling-ling; Wang, Yi; Wang, Dong-sheng

    2010-06-01

    To investigate the effects of a disintegrin and metalloproteinase 28 (ADAM28) on proliferation, differentiation and apoptosis of human dental pulp stem cells (HDPSCs) and the possible mechanism. Firstly, HDPSCs were isolated and cultured in vitro and identified. ADAM28 eukaryotic expression plasmid was constructed via gene rebuilt technique and transfected into HDPSCs. Then MTT chromatometry, enzyme dynamics and flow cytometry (FCM) techniques were performed to detect the effects of ADAM28 on biological characteristics of HDPSCs. Immunocytochemical and image analysis techniques were used to determine the influence of ADAM28 on HDPSCs expressing dentin sialophosphoprotein (DSPP), bone sialoprotein (BSP) and osteopontin (OPN). Statistical significance was assessed by the Student-Newman-Keuls (SNK) test with SPSS 13.0 software package. ADAM28 eukaryotic plasmid was constructed and transfected into HDPSCs for 48 hours successfully. In ADAM28 eukaryotic plasmid group, proliferation activity and index of HDPSCs were lower than those of pcDNA3.1(+) group and untransfected group significantly.Alkaline phosphatase (ALP) secretion level and percentage of apoptotic cells went up remarkly. Significant difference was detected between eukaryotic plasmid group and other groups (P<0.05). The expression level of DSPP in HDPSCs elevated significantly (P<0.05). ADAM28 could inhibit HDPSCs proliferation, promote ALP secretion activity and DSPP expression in HDPSCs and induce HDPSCs apoptosis significantly.

  1. Interleukin-1beta-induced release of matrix proteins into culture media causes inhibition of mineralization of nodules formed by periodontal ligament cells in vitro.

    Science.gov (United States)

    Chien, H H; Lin, W L; Cho, M I

    1999-05-01

    The mechanism by which interleukin-1beta (IL-1) inhibits the formation of mineralized tissue nodules by periodontal ligament (PDL) cells in vitro was investigated through the processes of morphological analysis, immunoprecipitation, and Northern blot analysis. PDL cells were obtained from a 2-day-old coagulum in tooth socket and cultured in Dulbecco's Modified Eagle Medium (DMEM) containing 10% fetal bone serum (FBS) and antibiotics. Confluent cells were grown for up to 3 weeks in the presence of ascorbic acid (AA), beta-glycerophosphate (GP), and dexamethasone (Dex), or IL-1. PDL cells cultured in the presence of GP and AA did not differentiate, but those treated with Dex, GP, and AA (Dex group) underwent differentiation, showing four stages (confluent, multilayer, nodule, and mineralization) of disparate morphological characteristics. In contrast, the cells treated with IL-1, Dex, GP, and AA (IL-1 group) did form multilayers but failed to form mineralized nodules. Electron microscopy demonstrated that the Dex-induced mineralized nodules contain multilayers of fibroblastic cells, numerous collagen fibrils, and dense globular as well as fused electron dense patches that are associated with numerous apatite crystals. The nodule-like structures in the IL-1 group were also comprised of multilayered fibroblastic cells, but they contained only a small number of collagen fibrils, and no dense globular or fused patches. Von Kossa staining confirmed the presence of numerous mineralized nodules in the Dex group and their scarceness in the IL-1 group. Northern blot analysis of IL-1-treated cells, however, revealed the presence of mRNAs for type I collagen (Col I), secreted protein, acidic and rich in cysteine (SPARC), osteopontin (OPN), alkaline phosphatase (ALP), bone sialoprotein (BSP), and osteocalcin (OC), whose expression patterns and levels were comparable to those of the Dex group. Immunoprecipitation analysis of OPN and BSP in the cell/matrix layers and the culture

  2. Modulation of Calcium Oxalate Crystallization by Proteins and Small Molecules Investigated by In Situ Atomic Force Microscopy

    Science.gov (United States)

    Qiu, R.; Orme, C.; Cody, A. M.; Wierzbicki, A.; Hoyer, J.; Nancollas, G.; de Yoreo, J.

    2002-12-01

    Understanding the physical mechanisms by which biological inhibitors control nucleation and growth of inorganic crystals is a major focus of biomineral research. Calcium oxalate monohydrate (COM), which plays a functional role in plant physiology, is also a source of pathogenesis in humans where it causes kidney stone disease. Although a great deal of research has been carried out on the modulation COM by proteins and small molecules, the basic mechanism has not yet been understood. However, because the proteins that play a role in COM growth have been identified and sequenced, COM provides an excellent model system for research into biomineral growth. In this study, in situ atomic force microscopy (AFM) was used to monitor the COM surface under controlled growth conditions both from pure solutions and those doped with citrate and osteopontin (OPN) in order to determine their effects on surface morphology and growth dynamics at the molecular level. As with other solution-grown crystals such as calcite, COM grows on complex dislocation hillocks. In pure solution, while growth on the (010) face is isotropic, hillocks on the (-101) face exhibit anisotropic step kinetics. Steps of [-10-1] and orientation are clearly delineated with the [-10-1] being the fast growing direction. When citrate is added to the solution, both growth rate and morphology are drastically changed on (-101) face, especially along the [-10-1] direction. This results in isotropic disc-shaped hillocks a shape that is then reflected in the macroscopic growth habit. In contrast, no large growth changes were observed on the (010) facet. At the same time, molecular modeling predicts an excellent fit of the citrate ion into the (-101) plane and a poor fit to the (010) face. Here we propose a model that reconciles the step-specific interactions implied by the AFM results with the face-specific predictions of the calculations. Finally, we present the results of doping with aspartic acid as well as OPN, an

  3. Prostate Cancer Progression and Serum Sibling (Small Integrin Binding N-Linked Glycoprotein) Levels

    Science.gov (United States)

    2008-10-01

    4302. Respondents should be aware that notwithstanding any other provision of law , no person shall be subject to any penalty for failing to comply...SIBLING proteins, bone sialoprotein, and osteopontin. Biochem Biophys Res Commun 2001;280:460–465. [PubMed: 11162539] 27. Tompa P, Szasz C, Buday L

  4. The role of osteopontin in children with systemic inflammatory ...

    African Journals Online (AJOL)

    involvement in the acute inflammatory diseases and its possible role as a marker differentiating ... or nonsteroidal anti-inflammatory drugs. Sample collection .... interactions with several integrins, also it mediates .... inflammatory bowel disease.

  5. The role of osteopontin in children with systemic inflammatory ...

    African Journals Online (AJOL)

    Introduction: Sepsis is a leading cause of morbidity and mortality in critically ill children despite the use of modern antibiotics and resuscitation therapies. Sepsis must be distinguished from non-infection systemic inflammatory response syndrome (SIRS) induced by agents such as trauma and ischemia causing extensive ...

  6. Effects of hydroxyapatite nanostructure on channel surface of porcine acellular dermal matrix scaffold on cell viability and osteogenic differentiation of human periodontal ligament stem cells

    Directory of Open Access Journals (Sweden)

    Ge S

    2013-05-01

    Full Text Available Shaohua Ge,1 Ning Zhao,1 Lu Wang,1 Hong Liu,2 Pishan Yang11Shandong Provincial Key Laboratory of Oral Biomedicine, Department of Periodontology, Shandong University; 2State Key Laboratory of Crystal Materials, Center of Bio and Micro/Nano Functional Materials, Shandong University, Jinan, People's Republic of ChinaAbstract: A new nanostructured hydroxyapatite-coated porcine acellular dermal matrix (HAp-PADM was fabricated by a biomimetic mineralization method. Human periodontal ligament stem cells were seeded on HAp-PADM and the effects of this scaffold on cell shape, cytoskeleton organization, cell viability, and osteogenic differentiation were examined. Periodontal ligament stem cells cultured on HAp-PADM exhibited different cell shape when compared with those on pure PADM. Moreover, HAp-PADM promoted cell viability and alkaline phosphatase activity significantly. Based on quantitative real-time polymerase chain reaction, the expression of bone-related markers runt-related transcription factor 2 (Runx2, osteopontin (OPN, and osteocalcin (OCN upregulated in the HAp-PADM scaffold. The enhancement of osteogenic differentiation of periodontal ligament stem cells on the HAp-PADM scaffold was proposed based on the research results. The results of this study highlight the micro-nano, two-level, three-dimensional HAp-PADM composite as a promising scaffold for periodontal tissue engineering.Keywords: hydroxyapatite, scaffold, nanostructure, proliferation, differentiation, tissue engineering

  7. Evaluation of 3D-Printed Polycaprolactone Scaffolds Coated with Freeze-Dried Platelet-Rich Plasma for Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Junda Li

    2017-07-01

    Full Text Available Three-dimensional printing is one of the most promising techniques for the manufacturing of scaffolds for bone tissue engineering. However, a pure scaffold is limited by its biological properties. Platelet-rich plasma (PRP has been shown to have the potential to improve the osteogenic effect. In this study, we improved the biological properties of scaffolds by coating 3D-printed polycaprolactone (PCL scaffolds with freeze-dried and traditionally prepared PRP, and we evaluated these scaffolds through in vitro and in vivo experiments. In vitro, we evaluated the interaction between dental pulp stem cells (DPSCs and the scaffolds by measuring cell proliferation, alkaline phosphatase (ALP activity, and osteogenic differentiation. The results showed that freeze-dried PRP significantly enhanced ALP activity and the mRNA expression levels of osteogenic genes (ALP, RUNX2 (runt-related gene-2, OCN (osteocalcin, OPN (osteopontin of DPSCs (p < 0.05. In vivo, 5 mm calvarial defects were created, and the PRP-PCL scaffolds were implanted. The data showed that compared with traditional PRP-PCL scaffolds or bare PCL scaffolds, the freeze-dried PRP-PCL scaffolds induced significantly greater bone formation (p < 0.05. All these data suggest that coating 3D-printed PCL scaffolds with freeze-dried PRP can promote greater osteogenic differentiation of DPSCs and induce more bone formation, which may have great potential in future clinical applications.

  8. Sustained release of melatonin from TiO2 nanotubes for modulating osteogenic differentiation of mesenchymal stem cells in vitro.

    Science.gov (United States)

    Lai, Min; Jin, Ziyang; Tang, Qiang; Lu, Min

    2017-10-01

    To control the sustained release of melatonin and modulate the osteogenic differentiation of mesenchymal stem cells (MSCs), melatonin was firstly loaded onto TiO 2 nanotubes by direct dropping method, and then a multilayered film was coated by a spin-assisted layer-by-layer technique, which was composed of chitosan (Chi) and gelatin (Gel). Successful fabrication was characterized by field emission scanning electron microscopy, atomic force microscope, X-ray photoelectron spectroscopy and contact angle measurement, respectively. The efficient sustained release of melatonin was measured by UV-visible-spectrophotometer. After 2 days of culture, well-spread morphology was observed in MSCs grown on the Chi/Gel multilayer-coated melatonin-loaded TiO 2 nanotube substrates as compared to different groups. After 4, 7, 14 and 21 days of culture, the multilayered-coated melatonin-loaded TiO 2 nanotube substrates increased cell proliferation, increased alkaline phosphatase (ALP) and mineralization, increased expression of mRNA levels for runt-related transcription factor 2 (Runx2), ALP, osteopontin (OPN) and osteocalcin (OC), indicative of osteoblastic differentiation. These results demonstrated that Chi/Gel multilayer-coated melatonin-loaded TiO 2 nanotube substrates promoted cell adhesion, spreading, proliferation and differentiation and could provide an alternative fabrication method for titanium-based implants to enhance the osteointegration between bone tissues and implant surfaces.

  9. Physical Activity Increases the Total Number of Bone-Marrow-Derived Mesenchymal Stem Cells, Enhances Their Osteogenic Potential, and Inhibits Their Adipogenic Properties

    Directory of Open Access Journals (Sweden)

    Monika Marędziak

    2015-01-01

    Full Text Available Aging and sedentary lifestyle are common nowadays and are associated with the increasing number of chronic diseases. Thus, physical activity is recommended as one of three healthy behavior factors that play a crucial role in health prophylaxis. In the present study, we were interested whether physical activity influences the number and potential of bone-marrow-derived mesenchymal stem cells BMMSCs. In this study, four-week-old male C57Bl/6 mice were trained on a treadmill at progressive speeds over a 5-week period. Comparisons made between exercised (EX and sedentary animal groups revealed (i significantly higher number of MSCs in EX animals, (ii elevated alkaline phosphatase (ALP activity, (iii increased level of osteopontin (OPN and osteocalcin (OCL, and (iv reduced marrow cavity fat. The results obtained support the thesis that EX may play a substantial role in the regeneration of mesenchymal tissues. Therefore, EX may represent a novel, nonpharmacological strategy of slowing down age-related decline of the musculoskeletal functions.

  10. Effect of S-1 chemotherapy and FP chemotherapy on prognosis, imaging characteristics and serum marker levels after operation for gastric carcinoma

    Directory of Open Access Journals (Sweden)

    Qing-Hao Gong

    2016-09-01

    Full Text Available Objective: To analyze the effect of S-1 chemotherapy and FP chemotherapy on prognosis, imaging characteristics and serum marker levels after operation for gastric carcinoma. Methods: A total of 68 patients with gastric cancer who underwent radical surgery were included in the study and divided into observation group and control group patients (n=34 according to random number table. Control group received FP chemotherapy, observation group received S-1 chemotherapy, and then differences in serum tumor markers, illnessrelated factors, nutrition indexes and T cell immune function values were compared between two groups. Results: After observation group received systematic chemotherapy, serum tumor markers such as MMP-9, MMP-2, MG7-Ag, TSGF, CA72-4, CA19-9, TP and DpD as well as illness-related factors such as DKK1, MK, Leptin, Exosome and OPN were all lower than those of control group (P<0.05; nutrition and cellular immune function indexes such as TP, ALB, PA, CD4+ T and CD4+ T/ CD8+ T values were higher than those of control group and CD8+ T value was lower than that of control group (P<0.05. Conclusions: S-1 chemotherapy after operation for gastric carcinoma can inhibit the tumor activity and optimize patients’ overall condition, and it has positive clinical significance.

  11. A dual-reservoir remote loading water target system for 18F and 13N production with direct in-target liquid level sensing

    International Nuclear Information System (INIS)

    Ferrieri, R.A.; Alexoff, D.L.; Schlyer, D.J.; Wolf, A.P.

    1991-01-01

    This report describes our universal water target loading system that serves both [ 18 F] and [ 13 N] production targets, and a radionuclide delivery system that is specific for [ 18 F] fluoride. The system was designed and fabricated around the operation of a single pneumatic syringe dispenser that accesses one of two reservoirs filled with [ 18 O] enriched water for [ 18 F] fluoride production from the 18 O(p,n) 18 F reaction and natural abundance water for [ 13 N] nitrate/nitrite production from the 16 O(p,α) 13 N reaction and loads one of two targets depending on the radionuclide desired. The system offers several novel features for reliable radionuclide production. First, there exists an in-target probe for direct liquid level sensing using the conductivity response of water. In addition, transfer of [ 18 F] fluoride to the Hot Lab is completely decoupled from the irradiated water through the actions of a resin/recovery system which is located in the cyclotron vault, thus maintaining transfer line integrity. This feature also provides a mechanism for vault-containment of long-lived contaminants generated through target activation and leaching into the water

  12. Journal of Genetics | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    Abstract. To explore the relevance of OPN signalling pathway to the occurrence and development of nonalcoholic fatty liver disease (NAFLD), liver cirrhosis (LC), hepatic cancer (HC) and acute hepatic failure (AHF) at transcriptional level, Rat Genome 230 2.0 Array was used to detect expression profiles of OPN signalling ...

  13. Fedmekirurgi er mere effektiv end medicinsk behandling til opnåelse af remission af type 2-diabetes

    DEFF Research Database (Denmark)

    Klein, Mads; Rosenberg, Jacob; Gögenur, Ismail

    2013-01-01

    Observational studies have shown that bariatric surgery can lead to remission of diabetes mellitus type 2 (DMII), but randomized controlled trials have been lacking. Recently, randomized controlled trials comparing bariatric surgery with optimal medical treatment in patients suffering from poorly...... controlled DMII, have been performed. These trials show that bariatric surgery in general, and the malabsorptive procedures in particular, are more effective than medical treatment in achieving remission of DMII. These procedures should therefore be considered in the treatment of patients with DMII...

  14. Sea level change

    Digital Repository Service at National Institute of Oceanography (India)

    Church, J.A.; Clark, P.U.; Cazenave, A.; Gregory, J.M.; Jevrejeva, S.; Levermann, A.; Merrifield, M.A.; Milne, G.A.; Nerem, R.S.; Nunn, P.D.; Payne, A.J.; Pfeffer, W.T.; Stammer, D.; Unnikrishnan, A.S.

    This chapter considers changes in global mean sea level, regional sea level, sea level extremes, and waves. Confidence in projections of global mean sea level rise has increased since the Fourth Assessment Report (AR4) because of the improved...

  15. Osteogenic gene expression of murine osteoblastic (MC3T3-E1) cells under cyclic tension

    International Nuclear Information System (INIS)

    Kao, C T; Chen, C C; Cheong, U-I; Liu, S L; Huang, T H

    2014-01-01

    Low-level laser therapy (LLLT) can promote cell proliferation. The remodeling ability of the tension side of orthodontic teeth affects post-orthodontic stability. The purpose of the present study was to investigate the osteogenic effects of LLLT on osteoblast-like cells treated with a simulated tension system that provides a mechanical tension regimen. Murine osteoblastic (MC3T3-E1) cells were cultured in a Flexcell strain unit with programmed loads of 12% elongation at a frequency of 0.5 Hz for 24 and 48 h. The cultured cells were treated with a low-level diode laser using powers of 5 J and 10 J. The proliferation of MC3T3-E1 cells was determined using the Alamar Blue assay. The expression of osteogenic genes (type I collagen (Col-1), osteopontin (OPN), osteocalcin (OC), osteoprotegerin (OPG), receptor activator of nuclear factor kappa B ligand (RANKL), bone morphologic protein (BMP-2), and bone morphologic protein (BMP-4)) in MC3T3-E1 cells was analyzed using reverse transcription polymerase chain reaction (RT-PCR). The data were analyzed using one-way analysis of variance. The proliferation rate of tension-cultured MC3T3-E1 cells under 5 J and 10 J LLLT increased compared with that of the control group (p < 0.05). Prominent mineralization of the MC3T3-E1 cells was visible using a von Kossa stain in the 5 J LLLT group. Osteogenic genes (Col-1, OC, OPG and BMP-2) were significantly expressed in the MC3T3-E1 cells treated with 5 J and 10 J LLLT (p < 0.05). LLLT in tension-cultured MC3T3-E1 cells showed synergistic osteogenic effects, including increases in cell proliferation and Col-1, OPN, OC, OPG and BMP-2 gene expression. LLLT might be beneficial for bone remodeling on the tension side of orthodontics. (paper)

  16. Isoform-specific regulation of osteogenic factors by polypeptide N-Acetylgalactosaminyltransferases 1 and 4

    International Nuclear Information System (INIS)

    Tang, Juan; Zheng, Hanxi; Chen, Ling; Gao, Shangshang; Shi, Xiaorui; Liu, Jingjing; Xu, Lan

    2017-01-01

    The family of UDP-GalNAc polypeptide: N-Acetylgalactosaminlytransfersases (ppGalNAcTs) catalyzes the initial step of O-linked protein glycosylation. Mucin-type O-glycoproteins are abundant in the bone and may play an important role in osteogenesis. Herein, we examined the effects of ppGalNAc-T isoforms on osteogenesis of MC3T3-E1 pre-osteoblasts. We found that ppGalNAc-T1 and -T4 isoforms were highly expressed during osteogenesis of MC3T3-E1 and their knockdown by short hairpin RNA (shRNA) decreased osteoblast formation and bone mineralization. Knockdown of ppGalNAc-T1 or -T4 decreased mRNA and protein levels of bone sialoprotein (BSP). Knockdown of ppGalNAc-T1decreased mRNA levels of osteocalcin (OC), osteoprotegerin (OPG). Knockdown ofppGalNAc-T4 isoform decreased mRNA levels of OC, OPG and vitamin D receptor (VDR). While knockdown of T1 or T4 isoforms did not change the expression of osteopontin (OPN), COLLI, receptor activator for nuclear factor-κB ligand (RANKL) and transforming growth factor-β (TGF-β). Our results demonstrated that the ppGalNAc-T4 was highly expressed in MC3T3-E1 cells during osteogenesis for the first time. We also found that ppGalNAc-T1 and -T4 affected the expression of different osteogenic factors, suggesting distinct roles ppGalNAc-T isoformsplay in regulating osteogenesis in vitro. - Highlights: • ppGalNAc-T1 and T4 are highly expressed during MC3T3 cell osteogenesis. • Knockdown of ppGalNAc-T1 and -T4 decreases osteogenic differentiation and mineralization. • Expression of osteogenic factors are differentially affected by decreased ppGalNAc-T1 and -T4 expression.

  17. Gene expression analysis after receptor tyrosine kinase activation reveals new potential melanoma proteins

    International Nuclear Information System (INIS)

    Teutschbein, Janka; Haydn, Johannes M; Samans, Birgit; Krause, Michael; Eilers, Martin; Schartl, Manfred; Meierjohann, Svenja

    2010-01-01

    Melanoma is an aggressive tumor with increasing incidence. To develop accurate prognostic markers and targeted therapies, changes leading to malignant transformation of melanocytes need to be understood. In the Xiphophorus melanoma model system, a mutated version of the EGF receptor Xmrk (Xiphophorus melanoma receptor kinase) triggers melanomagenesis. Cellular events downstream of Xmrk, such as the activation of Akt, Ras, B-Raf or Stat5, were also shown to play a role in human melanomagenesis. This makes the elucidation of Xmrk downstream targets a useful method for identifying processes involved in melanoma formation. Here, we analyzed Xmrk-induced gene expression using a microarray approach. Several highly expressed genes were confirmed by realtime PCR, and pathways responsible for their induction were revealed using small molecule inhibitors. The expression of these genes was also monitored in human melanoma cell lines, and the target gene FOSL1 was knocked down by siRNA. Proliferation and migration of siRNA-treated melanoma cell lines were then investigated. Genes with the strongest upregulation after receptor activation were FOS-like antigen 1 (Fosl1), early growth response 1 (Egr1), osteopontin (Opn), insulin-like growth factor binding protein 3 (Igfbp3), dual-specificity phosphatase 4 (Dusp4), and tumor-associated antigen L6 (Taal6). Interestingly, most genes were blocked in presence of a SRC kinase inhibitor. Importantly, we found that FOSL1, OPN, IGFBP3, DUSP4, and TAAL6 also exhibited increased expression levels in human melanoma cell lines compared to human melanocytes. Knockdown of FOSL1 in human melanoma cell lines reduced their proliferation and migration. Altogether, the data show that the receptor tyrosine kinase Xmrk is a useful tool in the identification of target genes that are commonly expressed in Xmrk-transgenic melanocytes and melanoma cell lines. The identified molecules constitute new possible molecular players in melanoma development

  18. Hypoxia induced expression of endogenous markers in vitro is highly influenced by pH

    International Nuclear Information System (INIS)

    Sorensen, Brita Singers; Alsner, Jan; Overgaard, Jens; Horsman, Michael R.

    2007-01-01

    Background: Genes such as carbonic anhydrase IX (Ca9), glucose transporter 1 (Glut1), lactate dehydrogenase A (LDH-A), osteopontin (OPN) and lysyl oxidase (LOX) have been suggested as hypoxic markers, but inconsistent results suggest that factors other than oxygen influence their expression. The current study is a detailed investigation using a range of pH values from 6.3 to 7.5 in two human cell lines to establish the pH dependency of hypoxia induced gene expression. Methods: Human tumour cell lines (uterine cervix squamous cell carcinoma (SiHa) and pharyngeal squamous cell carcinoma [FaDu DD ]) were used. Hypoxia was induced by gassing cells in airtight chambers with various oxygen concentrations (21%, 1%, 0.1%, 0.01% and 0%) for up to 24 h. The media were titrated to a range of pH values (7.5, 7.0, 6.7, 6.5 and 6.3). Gene expression was determined by real-time PCR. Results: In both SiHa and FaDu DD cells Ca9 and LOX reached the highest level of expression at 1% oxygen. In FaDu DD cells, a pH of 6.5 had a medium suppression effect on the hypoxia induced expression of Ca9. pH 6.3 resulted in severe suppression of expression for Ca9 and LOX in both SiHa and FaDu DD . Glut1 and LDH-A had a similar expression pattern to each other, with a maximum expression at 0.01% oxygen, in both cell lines. For these genes pH 6.5 and 6.3 changed the expression pattern in SiHa cells. OPN was up regulated at low oxygen in SiHa cells, but was not induced by hypoxia in FaDu DD cells. Conclusion: As tumour hypoxia occurs in a deprived microenvironment, other environmental factors, for example low pH, might interact with the effect of low oxygen concentration on gene expression. This study shows that pH in two cell lines has a profound influence on the oxygen dependent induction of certain endogenous hypoxic markers

  19. Gene expression analysis after receptor tyrosine kinase activation reveals new potential melanoma proteins

    Directory of Open Access Journals (Sweden)

    Krause Michael

    2010-07-01

    Full Text Available Abstract Background Melanoma is an aggressive tumor with increasing incidence. To develop accurate prognostic markers and targeted therapies, changes leading to malignant transformation of melanocytes need to be understood. In the Xiphophorus melanoma model system, a mutated version of the EGF receptor Xmrk (Xiphophorus melanoma receptor kinase triggers melanomagenesis. Cellular events downstream of Xmrk, such as the activation of Akt, Ras, B-Raf or Stat5, were also shown to play a role in human melanomagenesis. This makes the elucidation of Xmrk downstream targets a useful method for identifying processes involved in melanoma formation. Methods Here, we analyzed Xmrk-induced gene expression using a microarray approach. Several highly expressed genes were confirmed by realtime PCR, and pathways responsible for their induction were revealed using small molecule inhibitors. The expression of these genes was also monitored in human melanoma cell lines, and the target gene FOSL1 was knocked down by siRNA. Proliferation and migration of siRNA-treated melanoma cell lines were then investigated. Results Genes with the strongest upregulation after receptor activation were FOS-like antigen 1 (Fosl1, early growth response 1 (Egr1, osteopontin (Opn, insulin-like growth factor binding protein 3 (Igfbp3, dual-specificity phosphatase 4 (Dusp4, and tumor-associated antigen L6 (Taal6. Interestingly, most genes were blocked in presence of a SRC kinase inhibitor. Importantly, we found that FOSL1, OPN, IGFBP3, DUSP4, and TAAL6 also exhibited increased expression levels in human melanoma cell lines compared to human melanocytes. Knockdown of FOSL1 in human melanoma cell lines reduced their proliferation and migration. Conclusion Altogether, the data show that the receptor tyrosine kinase Xmrk is a useful tool in the identification of target genes that are commonly expressed in Xmrk-transgenic melanocytes and melanoma cell lines. The identified molecules constitute

  20. Guidance levels, achievable doses and expectation levels

    International Nuclear Information System (INIS)

    Li, Lianbo; Meng, Bing

    2002-01-01

    The National Radiological Protection Board (NRPB), the International Atomic Energy Agency (IAEA) and the Commission of the European Communities (CEC) published their guidance levels and reference doses for typical X-ray examination and nuclear medicine in their documents in 1993, 1994 and 1996 respectively. From then on, the concept of guidance levels or reference doses have been applied to different examinations in the field of radiology and proved to be effective for reduction of patient doses. But the guidance levels or reference doses are likely to have some shortcomings and can do little to make further reduction of patient dose in the radiology departments where patient dose are already below them. For this reason, the National Radiological Protection Board (NRPB) proposed a concept named achievable doses which are based on the mean dose observed for a selected sample of radiology departments. This paper will review and discuss the concept of guidance levels and achievable doses, and propose a new concept referred to as Expectation Levels that will encourage the radiology departments where patient dose are already below the guidance levels to keep patient dose as low as reasonably achievable. Some examples of the expectation levels based on the data published by a few countries are also illustrated in this paper

  1. Readability versus Leveling.

    Science.gov (United States)

    Fry, Edward

    2002-01-01

    Shows some similarities and differences between readability formulas and leveling procedures and reports some current large-scale uses of readability formulas. Presents a dictionary definition of readability and leveling, and a history and background of readability and leveling. Discusses what goes into determining readability and leveling scores.…

  2. Biological roles of the O-methyl phosphoramidate capsule modification in Campylobacter jejuni.

    Directory of Open Access Journals (Sweden)

    Lieke B van Alphen

    Full Text Available Campylobacter jejuni is a major cause of bacterial gastroenteritis worldwide, and the capsular polysaccharide (CPS of this organism is required for persistence and disease. C. jejuni produces over 47 different capsular structures, including a unique O-methyl phosphoramidate (MeOPN modification present on most C. jejuni isolates. Although the MeOPN structure is rare in nature it has structural similarity to some synthetic pesticides. In this study, we have demonstrated, by whole genome comparisons and high resolution magic angle spinning NMR, that MeOPN modifications are common to several Campylobacter species. Using MeOPN biosynthesis and transferase mutants generated in C. jejuni strain 81-176, we observed that loss of MeOPN from the cell surface correlated with increased invasion of Caco-2 epithelial cells and reduced resistance to killing by human serum. In C. jejuni, the observed serum mediated killing was determined to result primarily from activation of the classical complement pathway. The C. jejuni MeOPN transferase mutant showed similar levels of colonization relative to the wild-type in chickens, but showed a five-fold drop in colonization when co-infected with the wild-type in piglets. In Galleria mellonella waxmoth larvae, the MeOPN transferase mutant was able to kill the insects at wild-type levels. Furthermore, injection of the larvae with MeOPN-linked monosaccharides or CPS purified from the wild-type strain did not result in larval killing, indicating that MeOPN does not have inherent insecticidal activity.

  3. Data analysis at Level-1 Trigger level

    CERN Document Server

    Wittmann, Johannes; Aradi, Gregor; Bergauer, Herbert; Jeitler, Manfred; Wulz, Claudia; Apanasevich, Leonard; Winer, Brian; Puigh, Darren Michael

    2017-01-01

    With ever increasing luminosity at the LHC, optimum online data selection is getting more and more important. While in the case of some experiments (LHCb and ALICE) this task is being completely transferred to computer farms, the others - ATLAS and CMS - will not be able to do this in the medium-term future for technological, detector-related reasons. Therefore, these experiments pursue the complementary approach of migrating more and more of the offline and High-Level Trigger intelligence into the trigger electronics. This paper illustrates how the Level-1 Trigger of the CMS experiment and in particular its concluding stage, the Global Trigger, take up this challenge.

  4. Low magnesium level

    Science.gov (United States)

    Low magnesium level is a condition in which the amount of magnesium in the blood is lower than normal. The medical ... that convert or use energy ( metabolism ). When the level of magnesium in the body drops below normal, ...

  5. Fibroblast growth factor-2 induces osteogenic differentiation through a Runx2 activation in vascular smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Nakahara, Takehiro; Sato, Hiroko; Shimizu, Takehisa; Tanaka, Toru; Matsui, Hiroki; Kawai-Kowase, Keiko; Sato, Mahito; Iso, Tatsuya; Arai, Masashi [Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, 3-39-15 Showa-machi, Maebashi, Gunma 371-8511 (Japan); Kurabayashi, Masahiko, E-mail: mkuraba@med.gunma-u.ac.jp [Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, 3-39-15 Showa-machi, Maebashi, Gunma 371-8511 (Japan)

    2010-04-02

    Expression of bone-associated proteins and osteoblastic transcription factor Runx2 in arterial cells has been implicated in the development of vascular calcification. However, the signaling upstream of the Runx2-mediated activation of osteoblastic program in vascular smooth muscle cells (VSMC) is poorly understood. We examined the effects of fibroblast growth factor-2 (FGF-2), an important regulator of bone formation, on osteoblastic differentiation of VSMC. Stimulation of cultured rat aortic SMC (RASMC) with FGF-2 induced the expression of the osteoblastic markers osteopontin (OPN) and osteocalcin. Luciferase assays showed that FGF-2 induced osteocyte-specific element (OSE)-dependent transcription. Downregulation of Runx2 by siRNA repressed the basal and FGF-2-stimulated expression of the OPN gene in RASMC. FGF-2 produced hydrogen peroxide in RASMC, as evaluated by fluorescent probe. Induction of OPN expression by FGF-2 was inhibited not only by PD98059 (MEK1 inhibitor) and PP1 (c-Src inhibitor), but also by an antioxidant, N-acetyl cysteine. Nuclear extracts from FGF-2-treated RASMC exhibited increased DNA-binding of Runx2 to its target sequence. Immunohistochemistry of human coronary atherectomy specimens and calcified aortic tissues showed that expression of FGF receptor-1 and Runx2 was colocalized. In conclusion, these results suggest that FGF-2 plays a role in inducing osteoblastic differentiation of VSMC by activating Runx2 through mitogen-activated protein kinase (MAPK)-dependent- and oxidative stress-sensitive-signaling pathways.

  6. Beyond level planarity

    NARCIS (Netherlands)

    Angelini, P.; Da Lozzo, G.; Di Battista, G.; Frati, F.; Patrignani, M.; Rutter, I.; Hu, Y.; Nöllenburg, M.

    2016-01-01

    In this paper we settle the computational complexity of two open problems related to the extension of the notion of level planarity to surfaces different from the plane. Namely, we show that the problems of testing the existence of a level embedding of a level graph on the surface of the rolling

  7. Liquid metal level measurement

    International Nuclear Information System (INIS)

    Hale, J.C.; Leyland, K.S.

    1982-01-01

    A liquid metal level indicator is described which can be used to measure, in a stainless steel tank, the level of a nuclear reactor coolant such as sodium. The instrument, which is based on the eddy current induction effect, gives readings over substantially the full depth of the tank and indicates the sense of change of level. (U.K.)

  8. A novel chimeric peptide binds MC3T3‑E1 cells to titanium and enhances their proliferation and differentiation.

    Science.gov (United States)

    Wang, Dan; Liao, Xiaofu; Qin, Xu; Shi, Wei; Zhou, Bin

    2013-05-01

    Previous studies have demonstrated that the modification of the titanium (Ti) surface of an implant with RGD (Arg‑Gly‑Asp) promotes the activity of osteoblasts. A novel Ti‑binding peptide, minTBP‑1, and a chimeric peptide, minTBP‑1‑PRGDN, have been synthesized to assist the fixing of RGD to Ti. In our previous study, minTBP‑1‑PRGDN demonstrated favorable affinity for Ti surfaces and facilitated the adhesion of MC3T3‑E1 cells. The aim of the present study was to evaluate the effect of this chimeric peptide on the proliferation and differentiation of MC3T3‑E1 cells. For this purpose, MC3T3‑E1 cells were cultured and differentiation was induced on Ti discs precoated with minTBP‑1‑PRGDN, minTBP‑1 or PRGDN. The MC3T3‑E1 cells on the minTBP‑1‑PRGDN‑precoated Ti disc were observed to exhibit the highest cell number after 24 h and alkaline phosphatase levels in all groups increased in a time‑dependent manner. In addition, marked expression of osteogenic marker genes [osteopontin (OPN) and osteocalcin (OC)] was detected on minTBP‑1‑PRGDN/Ti at day 14. Mineralized deposits on minTBP‑1‑PRGDN/Ti presented the maximal average area and the highest number of deposits was observed on PRGDN/Ti. The present study indicates that minTBP‑1‑PRGDN may enhance and accelerate the activities of MC3T3‑E1 cells on Ti, however, its role in vivo must be determined by further studies.

  9. Evaluation of the osteo-inductive potential of hollow three-dimensional magnesium-strontium substitutes for the bone grafting application

    Energy Technology Data Exchange (ETDEWEB)

    Li, Mei [State Key Laboratory for Mechanical Behavior of Materials, Xi' an Jiaotong University, Xi' an 710049 (China); Department of Orthopedics, Guangdong Key Lab of Orthopaedic Technology and Implant Materials, Guangzhou General Hospital of Guangzhou military command, Guangzhou 510010 (China); Yang, Xuan [Guangzhou University of Chinese Medicine, Guangzhou 510405 (China); Wang, Weidan [Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016 (China); Zhang, Yu [Department of Orthopedics, Guangdong Key Lab of Orthopaedic Technology and Implant Materials, Guangzhou General Hospital of Guangzhou military command, Guangzhou 510010 (China); Wan, Peng, E-mail: pwan@imr.ac.cn [Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016 (China); Yang, Ke [Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016 (China); Han, Yong, E-mail: yonghan@mail.xjtu.edu.cn [State Key Laboratory for Mechanical Behavior of Materials, Xi' an Jiaotong University, Xi' an 710049 (China)

    2017-04-01

    Regeneration of bone defects is a clinical challenge that usually necessitates bone grafting materials. Limited bone supply and donor site morbidity limited the application of autografting, and improved biomaterials are needed to match the performance of autografts. Osteoinductive materials would be the perfect candidates for achieving this task. Strontium (Sr) is known to encourage bone formation and also prevent osteoporosis. Such twin requirements have motivated researchers to develop Sr-substituted biomaterials for orthopedic applications. The present study demonstrated a new concept of developing biodegradable and hollow three-dimensional magnesium-strontium (Mg−Sr) devices for grafting with their clinical demands. The microstructure and performance of Mg−Sr devices, in vitro degradation and biological properties including in vitro cytocompatibility and osteoinductivity were investigated. The results showed that our Mg−Sr devices exhibited good cytocompatibility and osteogenic effect. To further investigate the underlying mechanisms, RT-PCR and Western Blotting assays were taken to analyze the expression level of osteogenesis-related genes and proteins, respectively. The results showed that our Mg−Sr devices could both up-regulate the genes and proteins expression of the transcription factors of Runt-related transcription factor 2 (RUNX2) and Osterix (OSX), as well as alkaline phosphatase (ALP), Osteopontin (OPN), Collagen I (COL I) and Osteocalcin (OCN) significantly. Taken together, our innovation presented in this work demonstrated that the hollow three-dimensional Mg−Sr substitutes had excellent biocompatibility and osteogenesis and could be potential candidates for bone grafting for future orthopedic applications. - Highlights: • Novel biodegradable Mg−Sr bone substitutes with the hollow and marginal design was fabricated • The Mg−Sr substitutes exhibited excellent cyto-compatibility and osteo-inductivity effects • The osteo

  10. Surface modification of TiO{sub 2} nanotubes with osteogenic growth peptide to enhance osteoblast differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Lai, Min, E-mail: minlai@jsnu.edu.cn [School of Life Science, Jiangsu Normal University, Xuzhou, Jiangsu 221116 (China); Jin, Ziyang [School of Life Science, Jiangsu Normal University, Xuzhou, Jiangsu 221116 (China); Su, Zhiguo [Department of Pharmacy, The Affiliated hospital of Qingdao University, Qingdao, Shandong 266555 (China)

    2017-04-01

    To investigate the influence of surface-biofunctionalized substrates on osteoblast behavior, a layer of aligned TiO{sub 2} nanotubes with a diameter of around 70 nm was fabricated on titanium surface by anodization, and then osteogenic growth peptide (OGP) was conjugated onto TiO{sub 2} nanotubes through the intermediate layer of polydopamine. The morphology, composition and wettability of different surfaces were characterized by field-emission scanning electron microscopy (FE-SEM), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS) and contact angle measurements, respectively. The effects of OGP-modified TiO{sub 2} nanotube substrates on the morphology, proliferation and differentiation of osteoblasts were examined in vitro. Immunofluorescence staining revealed that the OGP-functionalized TiO{sub 2} nanotubes were favorable for cell spreading. However, there was no significant difference in cell proliferation observed among the different groups. Cells grown onto OGP-functionalized TiO{sub 2} nanotubes showed significantly higher (p < 0.05 or p < 0.01) levels of alkaline phosphatase (ALP) and mineralization after 4, 7 and 14 days of culture, respectively. Cells grown on OGP-functionalized TiO{sub 2} nanotubes had significantly higher (p < 0.05 or p < 0.01) expression of osteogenic-related genes including runt related transcription factor 2 (Runx2), ALP, collagen type I (Col I), osteopontin (OPN) and osteocalcin (OC) after 14 days of culture. These data suggest that surface functionalization of TiO{sub 2} nanotubes with OGP was beneficial for cell spreading and differentiation. This study provides a novel platform for the development and fabrication of titanium-based implants that enhance the propensity for osseointegration between the native tissue and implant interface. - Highlights: • The OGP functionalized TiO{sub 2} nanotube substrates were successfully fabricated through a direct and effective method. • The OGP functionalized substrates

  11. Study of hMSC proliferation and differentiation on Mg and Mg–Sr containing biphasic β-tricalcium phosphate and amorphous calcium phosphate ceramics

    International Nuclear Information System (INIS)

    Singh, Satish S.; Roy, Abhijit; Lee, Boeun; Kumta, Prashant N.

    2016-01-01

    Biphasic mixtures of either Mg"2"+ or combined Mg"2"+ and Sr"2"+ cation substituted β-tricalcium phosphate (β-TCP) and amorphous calcium phosphate (ACP) were prepared using a low temperature chemical phosphatizing and hydrolysis reaction approach. Scaffolds prepared using the cation substituted calcium phosphates were capable of supporting similar levels of human mesenchymal stem cell proliferation in comparison to commercially available β-TCP. The concentrations of Mg"2"+, Sr"2"+, and PO_4"3"− released from these scaffolds were also within the ranges desired from previous reports to support both hMSC proliferation and osteogenic differentiation. Interestingly, hMSCs cultured directly on scaffolds prepared with only Mg"2"+ substituted β-TCP were capable of supporting statistically significantly increased alkaline phosphatase activity, osteopontin, and osteoprotegerin expression in comparison to all compositions containing both Mg"2"+ and Sr"2"+, and commercially available β-TCP. hMSCs cultured in the presence of scaffold extracts also exhibited similar trends in the expression of osteogenic markers as was observed during direct culture. Therefore, it was concluded that the enhanced differentiation observed was due to the release of bioactive ions rather than the surface microstructure. The role of these ions on transforming growth factor-β and bone morphogenic protein signaling was also evaluated using a PCR array. It was concluded that the release of these ions may support enhanced differentiation through SMAD dependent TGF-β and BMP signaling. - Highlights: • Synthesis of Mg and Mg-Sr containing biphasic beta tricalcium phosphate ceramics • Magnesium substitution influences ALP activity compared to strontium content. • Solution extract plays a more dominant role on hMSC differentiation. • Direct and indirect Mg and Mg-Sr TCP culture show similar OPG and OPN expression.

  12. Study of hMSC proliferation and differentiation on Mg and Mg–Sr containing biphasic β-tricalcium phosphate and amorphous calcium phosphate ceramics

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Satish S., E-mail: sss42@pitt.edu [Department of Chemical & Petroleum Engineering, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Roy, Abhijit, E-mail: abr20@pitt.edu [Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Lee, Boeun [Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Kumta, Prashant N., E-mail: pkumta@pitt.edu [Department of Chemical & Petroleum Engineering, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Center for Craniofacial Regeneration, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Department of Mechanical Engineering and Materials Science, University of Pittsburgh, PA 15261 (United States)

    2016-07-01

    Biphasic mixtures of either Mg{sup 2+} or combined Mg{sup 2+} and Sr{sup 2+} cation substituted β-tricalcium phosphate (β-TCP) and amorphous calcium phosphate (ACP) were prepared using a low temperature chemical phosphatizing and hydrolysis reaction approach. Scaffolds prepared using the cation substituted calcium phosphates were capable of supporting similar levels of human mesenchymal stem cell proliferation in comparison to commercially available β-TCP. The concentrations of Mg{sup 2+}, Sr{sup 2+}, and PO{sub 4}{sup 3−} released from these scaffolds were also within the ranges desired from previous reports to support both hMSC proliferation and osteogenic differentiation. Interestingly, hMSCs cultured directly on scaffolds prepared with only Mg{sup 2+} substituted β-TCP were capable of supporting statistically significantly increased alkaline phosphatase activity, osteopontin, and osteoprotegerin expression in comparison to all compositions containing both Mg{sup 2+} and Sr{sup 2+}, and commercially available β-TCP. hMSCs cultured in the presence of scaffold extracts also exhibited similar trends in the expression of osteogenic markers as was observed during direct culture. Therefore, it was concluded that the enhanced differentiation observed was due to the release of bioactive ions rather than the surface microstructure. The role of these ions on transforming growth factor-β and bone morphogenic protein signaling was also evaluated using a PCR array. It was concluded that the release of these ions may support enhanced differentiation through SMAD dependent TGF-β and BMP signaling. - Highlights: • Synthesis of Mg and Mg-Sr containing biphasic beta tricalcium phosphate ceramics • Magnesium substitution influences ALP activity compared to strontium content. • Solution extract plays a more dominant role on hMSC differentiation. • Direct and indirect Mg and Mg-Sr TCP culture show similar OPG and OPN expression.

  13. Precision contact level gauge

    International Nuclear Information System (INIS)

    Krejci, M.; Pilat, M.; Stulik, P.

    1977-01-01

    Equipment was developed measuring the heavy water level in the TR-0 reactor core within an accuracy of several hundredths of a millimeter in a range of around 3.5 m and at a temperature of up to 90 degC. The equipment uses a vibrating needle contact as a high sensitivity level gauge and a servomechanical system with a motion screw carrying the gauge for monitoring and measuring the level in the desired range. The advantage of the unique level gauge consists in that that the transducer converts the measured level position to an electric signal, ie., pulse width, with high sensitivity and without hysteresis. (Kr)

  14. High-level verification

    CERN Document Server

    Lerner, Sorin; Kundu, Sudipta

    2011-01-01

    Given the growing size and heterogeneity of Systems on Chip (SOC), the design process from initial specification to chip fabrication has become increasingly complex. This growing complexity provides incentive for designers to use high-level languages such as C, SystemC, and SystemVerilog for system-level design. While a major goal of these high-level languages is to enable verification at a higher level of abstraction, allowing early exploration of system-level designs, the focus so far for validation purposes has been on traditional testing techniques such as random testing and scenario-based

  15. Multi-Level Model

    Directory of Open Access Journals (Sweden)

    Constanta Nicoleta BODEA

    2008-01-01

    Full Text Available Is an original paper, which contains a hierarchical model with three levels, for determining the linearized non-homogeneous and homogeneous credibility premiums at company level, at sector level and at contract level, founded on the relevant covariance relations between the risk premium, the observations and the weighted averages. We give a rather explicit description of the input data for the multi- level hierarchical model used, only to show that in practical situations, there will always be enough data to apply credibility theory to a real insurance portfolio.

  16. Sea level report

    International Nuclear Information System (INIS)

    Schwartz, M.L.

    1979-01-01

    Study of Cenozoic Era sea levels shows a continual lowering of sea level through the Tertiary Period. This overall drop in sea level accompanied the Pleistocene Epoch glacio-eustatic fluctuations. The considerable change of Pleistocene Epoch sea level is most directly attributable to the glacio-eustatic factor, with a time span of 10 5 years and an amplitude or range of approximately 200 m. The lowering of sea level since the end of the Cretaceous Period is attributed to subsidence and mid-ocean ridges. The maximum rate for sea level change is 4 cm/y. At present, mean sea level is rising at about 3 to 4 mm/y. Glacio-eustacy and tectono-eustacy are the parameters for predicting sea level changes in the next 1 my. Glacio-eustatic sea level changes may be projected on the basis of the Milankovitch Theory. Predictions about tectono-eustatic sea level changes, however, involve predictions about future tectonic activity and are therefore somewhat difficult to make. Coastal erosion and sedimentation are affected by changes in sea level. Erosion rates for soft sediments may be as much as 50 m/y. The maximum sedimentation accumulation rate is 20 m/100 y

  17. System level ESD protection

    CERN Document Server

    Vashchenko, Vladislav

    2014-01-01

    This book addresses key aspects of analog integrated circuits and systems design related to system level electrostatic discharge (ESD) protection.  It is an invaluable reference for anyone developing systems-on-chip (SoC) and systems-on-package (SoP), integrated with system-level ESD protection. The book focuses on both the design of semiconductor integrated circuit (IC) components with embedded, on-chip system level protection and IC-system co-design. The readers will be enabled to bring the system level ESD protection solutions to the level of integrated circuits, thereby reducing or completely eliminating the need for additional, discrete components on the printed circuit board (PCB) and meeting system-level ESD requirements. The authors take a systematic approach, based on IC-system ESD protection co-design. A detailed description of the available IC-level ESD testing methods is provided, together with a discussion of the correlation between IC-level and system-level ESD testing methods. The IC-level ESD...

  18. Gamma spectrometry; level schemes

    International Nuclear Information System (INIS)

    Blachot, J.; Bocquet, J.P.; Monnand, E.; Schussler, F.

    1977-01-01

    The research presented dealt with: a new beta emitter, isomer of 131 Sn; the 136 I levels fed through the radioactive decay of 136 Te (20.9s); the A=145 chain (β decay of Ba, La and Ce, and level schemes for 145 La, 145 Ce, 145 Pr); the A=47 chain (La and Ce, β decay, and the level schemes of 147 Ce and 147 Pr) [fr

  19. Nuclear Level Densities

    International Nuclear Information System (INIS)

    Grimes, S.M.

    2005-01-01

    Recent research in the area of nuclear level densities is reviewed. The current interest in nuclear astrophysics and in structure of nuclei off of the line of stability has led to the development of radioactive beam facilities with larger machines currently being planned. Nuclear level densities for the systems used to produce the radioactive beams influence substantially the production rates of these beams. The modification of level-density parameters near the drip lines would also affect nucleosynthesis rates and abundances

  20. Levels of safety

    International Nuclear Information System (INIS)

    Povyakalo, A.A.

    1996-01-01

    When speaking about danger of catastrophe, it is the first level of danger. Its absence is the first level of safety. When speaking about danger of danger of catastrophe, it is the second level of danger. Its absence is the second level of safety. The paper proposes the way to formalize these ideas and use formal models to construct the states-and-event scale for a given object. The proposed approach can be applied to objects of different nature. The states-and-events scale may be used for transformation of initial objectives state-and-transitions graph to reduce bad classes of states

  1. Tiltmeter leveling mechanism

    Science.gov (United States)

    Hunter, Steven L.; Boro, Carl O.; Farris, Alvis

    2002-01-01

    A tiltmeter device having a pair of orthogonally disposed tilt sensors that are levelable within an inner housing containing the sensors. An outer housing can be rotated to level at least one of the sensor pair while the inner housing can be rotated to level the other sensor of the pair. The sensors are typically rotated up to about plus or minus 100 degrees. The device is effective for measuring tilts in a wide range of angles of inclination of wells and can be employed to level a platform containing a third sensor.

  2. Standard Industry Fare Level

    Data.gov (United States)

    Department of Transportation — Standard Industry Fare Level was establish after airline deregulation to serve as the standard against which a statutory zone of operating expense reasonableness was...

  3. PEP liquid level system

    International Nuclear Information System (INIS)

    Lauritzen, T.; Sah, R.C.

    1981-03-01

    A liquid level system has been installed in the accelerator housing of the PEP storage ring. This instrument spans the entire 2.2 km circumference of the PEP project, and over one hundred readouts provide reference elevations which are used for the accurate alignment of accelerator components. The liquid level has proven to be extremely precise (+-0.10 mm) and quick to use, and it has contributed to the accurate alignment of PEP before beam turn-on. Since the liquid level readouts are rigidly attached to the accelerator housing, the liquid level has been a convenient means to monitor the settling of the accelerator housing

  4. Reference handbook: Level detectors

    International Nuclear Information System (INIS)

    1990-01-01

    The purpose of this handbook is to provide Rocky Flats personnel with the information necessary to understand level measurement and detection. Upon completion of this handbook you should be able to do the following: List three reasons for measuring level. Describe the basic operating principles of the sight glass. Demonstrate proper techniques for reading a sight glass. Describe the basic operating principles of a float level detector. Describe the basic operating principles of a bubbler level indicating system. Explain the differences between a wet and dry reference leg indicating system, and describe how each functions. This handbook is designed for use by experienced Rocky Flats operators to reinforce and improve their current knowledge level, and by entry-level operators to ensure that they possess a minimum level of fundamental knowledge. Level Detectors is applicable to many job classifications and can be used as a reference for classroom work or for self-study. Although this reference handbook is by no means all-encompassing, you will gain enough information about this subject area to assist you in contributing to the safe operation of Rocky Flats Plant

  5. Authentication Assurance Levels

    International Nuclear Information System (INIS)

    Kouzes, Richard T.; Cash, James R.; Devaney, David M.; Geelhood, Bruce D.; Hansen, Randy R.; Melton, Ronald B.; Pitts, W. Karl

    2002-01-01

    This Common Criteria approach has been applied to create a definition of Authentication Assurance Levels that can quantify the level of assurance reached for a system subject to a set of authentication procedures. The arms-control authentication application of the Common Criteria expands on more typical information security evaluations in that it must contend with information barriers and preclude sophisticated intentional subversion attempts.

  6. Raised IL-6 Levels

    African Journals Online (AJOL)

    user

    Cardiovascular Associated Complications in HIV. Positive Zambians before ... compare plasma levels of IL-6 in HIV positive and. HIV negative .... cancer. Results from this study showed that IL-6 levels in. HIV positive ART naive individuals were significantly higher than in the HIV positive individuals on ART. Our findings ...

  7. Low level waste repositories

    International Nuclear Information System (INIS)

    Hill, P.R.H.; Wilson, M.A.

    1983-11-01

    Factors in selecting a site for low-level radioactive waste disposal are discussed. South Australia has used a former tailings dam in a remote, arid location as a llw repository. There are also low-level waste disposal procedures at the Olympic Dam copper/uranium project

  8. Definition of Virtual Levels.

    Science.gov (United States)

    Shore, Bruce W.

    1979-01-01

    Presents an examination of graphical displays of solutions to time-dependent Schrodinger equation modeling a laser-excited three-level atom. It suggests that an energy level may be regarded as virtual when it is detuned from resonance by more than two Rabi frequencies. (Author/HM)

  9. Levels of Literary Meaning

    DEFF Research Database (Denmark)

    Klausen, Søren Harnow

    2017-01-01

    I argue that intentionalist theories of meaning and interpretation, like those of Hirsch and Juhl, have been insufficiently attentive to the different levels of authorial intention that are operative in literary works. By countenancing intentions on different levels – ranging from simple semantic...

  10. Arctic Sea Level Reconstruction

    DEFF Research Database (Denmark)

    Svendsen, Peter Limkilde

    Reconstruction of historical Arctic sea level is very difficult due to the limited coverage and quality of tide gauge and altimetry data in the area. This thesis addresses many of these issues, and discusses strategies to help achieve a stable and plausible reconstruction of Arctic sea level from...... 1950 to today.The primary record of historical sea level, on the order of several decades to a few centuries, is tide gauges. Tide gauge records from around the world are collected in the Permanent Service for Mean Sea Level (PSMSL) database, and includes data along the Arctic coasts. A reasonable...... amount of data is available along the Norwegian and Russian coasts since 1950, and most published research on Arctic sea level extends cautiously from these areas. Very little tide gauge data is available elsewhere in the Arctic, and records of a length of several decades,as generally recommended for sea...

  11. Contemporary Arctic Sea Level

    Science.gov (United States)

    Cazenave, A. A.

    2017-12-01

    During recent decades, the Arctic region has warmed at a rate about twice the rest of the globe. Sea ice melting is increasing and the Greenland ice sheet is losing mass at an accelerated rate. Arctic warming, decrease in the sea ice cover and fresh water input to the Arctic ocean may eventually impact the Arctic sea level. In this presentation, we review our current knowledge of contemporary Arctic sea level changes. Until the beginning of the 1990s, Arctic sea level variations were essentially deduced from tide gauges located along the Russian and Norwegian coastlines. Since then, high inclination satellite altimetry missions have allowed measuring sea level over a large portion of the Arctic Ocean (up to 80 degree north). Measuring sea level in the Arctic by satellite altimetry is challenging because the presence of sea ice cover limits the full capacity of this technique. However adapted processing of raw altimetric measurements significantly increases the number of valid data, hence the data coverage, from which regional sea level variations can be extracted. Over the altimetry era, positive trend patterns are observed over the Beaufort Gyre and along the east coast of Greenland, while negative trends are reported along the Siberian shelf. On average over the Arctic region covered by satellite altimetry, the rate of sea level rise since 1992 is slightly less than the global mea sea level rate (of about 3 mm per year). On the other hand, the interannual variability is quite significant. Space gravimetry data from the GRACE mission and ocean reanalyses provide information on the mass and steric contributions to sea level, hence on the sea level budget. Budget studies show that regional sea level trends over the Beaufort Gyre and along the eastern coast of Greenland, are essentially due to salinity changes. However, in terms of regional average, the net steric component contributes little to the observed sea level trend. The sea level budget in the Arctic

  12. Re-expression of pro-fibrotic, embryonic preserved mediators in irradiated arterial vessels of the head and neck region

    Energy Technology Data Exchange (ETDEWEB)

    Moebius, Patrick; Preidl, Raimund H.M.; Weber, Manuel; Neukam, Friedrich W.; Wehrhan, Falk [Friedrich-Alexander-Universitaet Erlangen-Nuernberg (FAU), Department of Oral and Maxillofacial Surgery, University Hospital of Erlangen, Erlangen (Germany); Amann, Kerstin [Friedrich-Alexander-Universitaet Erlangen-Nuernberg (FAU), Department of Nephropathology, Institute of Pathology, University Hospital of Erlangen, Erlangen (Germany)

    2017-11-15

    Surgical treatment of head and neck malignancies frequently includes microvascular free tissue transfer. Preoperative radiotherapy increases postoperative fibrosis-related complications up to transplant loss. Fibrogenesis is associated with re-expression of embryonic preserved tissue developmental mediators: osteopontin (OPN), regulated by sex-determining region Y-box 9 (Sox9), and homeobox A9 (HoxA9) play important roles in pathologic tissue remodeling and are upregulated in atherosclerotic vascular lesions; dickkopf-1 (DKK1) inhibits pro-fibrotic and atherogenic Wnt signaling. We evaluated the influence of irradiation on expression of these mediators in arteries of the head and neck region. DKK1, HoxA9, OPN, and Sox9 expression was examined immunohistochemically in 24 irradiated and 24 nonirradiated arteries of the lower head and neck region. The ratio of positive cells to total cell number (labeling index) in the investigated vessel walls was assessed semiquantitatively. DKK1 expression was significantly decreased, whereas HoxA9, OPN, and Sox9 expression were significantly increased in irradiated compared to nonirradiated arterial vessels. Preoperative radiotherapy induces re-expression of embryonic preserved mediators in arterial vessels and may thus contribute to enhanced activation of pro-fibrotic downstream signaling leading to media hypertrophy and intima degeneration comparable to fibrotic development steps in atherosclerosis. These histopathological changes may be promoted by HoxA9-, OPN-, and Sox9-related inflammation and vascular remodeling, supported by downregulation of anti-fibrotic DKK1. Future pharmaceutical strategies targeting these vessel alterations, e. g., bisphosphonates, might reduce postoperative complications in free tissue transfer. (orig.) [German] Die operative Behandlung von Tumoren im Kopf- und Halsbereich umfasst den Transfer mikrovaskulaerer Gewebetransplantate. Praeoperative Bestrahlung verursacht eine erhoehte Inzidenz

  13. Nuclear level density

    International Nuclear Information System (INIS)

    Cardoso Junior, J.L.

    1982-10-01

    Experimental data show that the number of nuclear states increases rapidly with increasing excitation energy. The properties of highly excited nuclei are important for many nuclear reactions, mainly those that go via processes of the compound nucleus type. In this case, it is sufficient to know the statistical properties of the nuclear levels. First of them is the function of nuclear levels density. Several theoretical models which describe the level density are presented. The statistical mechanics and a quantum mechanics formalisms as well as semi-empirical results are analysed and discussed. (Author) [pt

  14. Measuring Your Fitness Level

    Science.gov (United States)

    ... online calculator. If you'd rather do the math yourself, divide your weight in pounds by your ... Human Services recommends one of the following activity levels for adult fitness and health benefits: 150 minutes ...

  15. Three Levels of Semiosis

    DEFF Research Database (Denmark)

    Alrøe, Hugo Fjelsted

    2016-01-01

    This paper presents a second-order semiotic framework for ontological levels, which is based on the structure of semiosis in a more fundamental way than other existing approaches to semiotic levels. Building on the key semiotic concept of representation, three levels are posited: (1) non- or proto......-semiotic processes, without representation, such as physical or causal processes, (2) semiotic processes, with representation, such as the processes of life and cognition, and (3) second-order semiotic processes, with representation of representation, such as self-conscious and self-reflexive communicative processes....... This semiotic framework for ontological levels is compared with recent discussions of different ontological kinds of kinds such as indifferent and interactive kinds. This leads to the distinction between not two, but three kinds of kinds: indifferent, adaptive and reflexive kinds, of which the last two hitherto...

  16. Water Level Station History

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Images contain station history information for 175 stations in the National Water Level Observation Network (NWLON). The NWLON is a network of long-term,...

  17. Projecting future sea level

    Science.gov (United States)

    Cayan, Daniel R.; Bromirski, Peter; Hayhoe, Katharine; Tyree, Mary; Dettinger, Mike; Flick, Reinhard

    2006-01-01

    California’s coastal observations and global model projections indicate that California’s open coast and estuaries will experience increasing sea levels over the next century. Sea level rise has affected much of the coast of California, including the Southern California coast, the Central California open coast, and the San Francisco Bay and upper estuary. These trends, quantified from a small set of California tide gages, have ranged from 10–20 centimeters (cm) (3.9–7.9 inches) per century, quite similar to that estimated for global mean sea level. So far, there is little evidence that the rate of rise has accelerated, and the rate of rise at California tide gages has actually flattened since 1980, but projections suggest substantial sea level rise may occur over the next century. Climate change simulations project a substantial rate of global sea level rise over the next century due to thermal expansion as the oceans warm and runoff from melting land-based snow and ice accelerates. Sea level rise projected from the models increases with the amount of warming. Relative to sea levels in 2000, by the 2070–2099 period, sea level rise projections range from 11–54 cm (4.3–21 in) for simulations following the lower (B1) greenhouse gas (GHG) emissions scenario, from 14–61 cm (5.5–24 in) for the middle-upper (A2) emission scenario, and from 17–72 cm (6.7–28 in) for the highest (A1fi) scenario. In addition to relatively steady secular trends, sea levels along the California coast undergo shorter period variability above or below predicted tide levels and changes associated with long-term trends. These variations are caused by weather events and by seasonal to decadal climate fluctuations over the Pacific Ocean that in turn affect the Pacific coast. Highest coastal sea levels have occurred when winter storms and Pacific climate disturbances, such as El Niño, have coincided with high astronomical tides. This study considers a range of projected future

  18. High potassium level

    Science.gov (United States)

    ... level is very high, or if you have danger signs, such as changes in an ECG . Emergency ... Seifter JL. Potassium disorders. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine . 25th ed. Philadelphia, PA: ...

  19. Technology Readiness Level Guidebook

    Science.gov (United States)

    2017-09-01

    This guidebook provides the necessary information for conducting a Technology Readiness Level (TRL) Assessment. TRL Assessments are a tool for determining the maturity of technologies and identifying next steps in the research process. This guidebook...

  20. Low potassium level

    Science.gov (United States)

    ... treat and prevent low level of potassium. These foods include: Avocados Baked potato Bananas Bran Carrots Cooked lean beef Milk Oranges Peanut butter Peas and beans Salmon Seaweed Spinach Tomatoes Wheat germ

  1. Low level waste disposal

    International Nuclear Information System (INIS)

    Barthoux, A.

    1985-01-01

    Final disposal of low level wastes has been carried out for 15 years on the shallow land disposal of the Manche in the north west of France. Final participant in the nuclear energy cycle, ANDRA has set up a new waste management system from the production center (organization of the waste collection) to the disposal site including the setting up of a transport network, the development of assessment, additional conditioning, interim storage, the management of the disposal center, records of the location and characteristics of the disposed wastes, site selection surveys for future disposals and a public information Department. 80 000 waste packages representing a volume of 20 000 m 3 are thus managed and disposed of each year on the shallow land disposal. The disposal of low level wastes is carried out according to their category and activity level: - in tumuli for very low level wastes, - in monoliths, a concrete structure, of the packaging does not provide enough protection against radioactivity [fr

  2. Lead levels - blood

    Science.gov (United States)

    Blood lead levels ... is used to screen people at risk for lead poisoning. This may include industrial workers and children ... also used to measure how well treatment for lead poisoning is working. Lead is common in the ...

  3. Lake Level Reconstructions

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Records of past lake levels, mostly related to changes in moisture balance (evaporation-precipitation). Parameter keywords describe what was measured in this data...

  4. Liquid level controller

    International Nuclear Information System (INIS)

    Mangus, J.D.; Redding, A.H.

    1975-01-01

    A system for maintaining two distinct sodium levels within the shell of a heat exchanger having a plurality of J-shaped modular tube bundles each enclosed in a separate shell which extends from a common base portion. A lower liquid level is maintained in the base portion and an upper liquid level is maintained in the shell enwrapping the long stem of the J-shaped tube bundles by utilizing standpipes with a notch at the lower end which decreases in open area the distance from the end of the stand pipe increases and a supply of inert gas fed at a constant rate to produce liquid levels, which will remain generally constant as the flow of liquid through the vessel varies

  5. Fission level densities

    International Nuclear Information System (INIS)

    Maslov, V.M.

    1998-01-01

    Fission level densities (or fissioning nucleus level densities at fission saddle deformations) are required for statistical model calculations of actinide fission cross sections. Back-shifted Fermi-Gas Model, Constant Temperature Model and Generalized Superfluid Model (GSM) are widely used for the description of level densities at stable deformations. These models provide approximately identical level density description at excitations close to the neutron binding energy. It is at low excitation energies that they are discrepant, while this energy region is crucial for fission cross section calculations. A drawback of back-shifted Fermi gas model and traditional constant temperature model approaches is that it is difficult to include in a consistent way pair correlations, collective effects and shell effects. Pair, shell and collective properties of nucleus do not reduce just to the renormalization of level density parameter a, but influence the energy dependence of level densities. These effects turn out to be important because they seem to depend upon deformation of either equilibrium or saddle-point. These effects are easily introduced within GSM approach. Fission barriers are another key ingredients involved in the fission cross section calculations. Fission level density and barrier parameters are strongly interdependent. This is the reason for including fission barrier parameters along with the fission level densities in the Starter File. The recommended file is maslov.dat - fission barrier parameters. Recent version of actinide fission barrier data obtained in Obninsk (obninsk.dat) should only be considered as a guide for selection of initial parameters. These data are included in the Starter File, together with the fission barrier parameters recommended by CNDC (beijing.dat), for completeness. (author)

  6. Changing Sea Levels

    Science.gov (United States)

    Pugh, David

    2004-04-01

    Flooding of coastal communities is one of the major causes of environmental disasters world-wide. This textbook explains how sea levels are affected by astronomical tides, weather effects, ocean circulation and climate trends. Based on courses taught by the author in the U.K. and the U.S., it is aimed at undergraduate students at all levels, with non-basic mathematics being confined to Appendices and a website http://publishing.cambridge.org/resources/0521532183/.

  7. Float level indicator

    International Nuclear Information System (INIS)

    Grishchuk, M.Kh.; Laptev, A.G.; Pashkov, V.A.

    1980-01-01

    Specially developed level indicator is suggested with differential to-transformer converter of the float motion, operating in line with a movable electronic block, intended for indicating the level of the dissociating nitrogen tetroxide liquid phase. On the basis of the indicator elements the device is realized to measure the time of calibrated volume fillino. in by liquid nitrogen tetroxide in steady state operation of the experimental bench-marks [ru

  8. Contemporary sea level rise.

    Science.gov (United States)

    Cazenave, Anny; Llovel, William

    2010-01-01

    Measuring sea level change and understanding its causes has considerably improved in the recent years, essentially because new in situ and remote sensing observations have become available. Here we report on most recent results on contemporary sea level rise. We first present sea level observations from tide gauges over the twentieth century and from satellite altimetry since the early 1990s. We next discuss the most recent progress made in quantifying the processes causing sea level change on timescales ranging from years to decades, i.e., thermal expansion of the oceans, land ice mass loss, and land water-storage change. We show that for the 1993-2007 time span, the sum of climate-related contributions (2.85 +/- 0.35 mm year(-1)) is only slightly less than altimetry-based sea level rise (3.3 +/- 0.4 mm year(-1)): approximately 30% of the observed rate of rise is due to ocean thermal expansion and approximately 55% results from land ice melt. Recent acceleration in glacier melting and ice mass loss from the ice sheets increases the latter contribution up to 80% for the past five years. We also review the main causes of regional variability in sea level trends: The dominant contribution results from nonuniform changes in ocean thermal expansion.

  9. Water level indicator

    International Nuclear Information System (INIS)

    Murase, Michio; Araki, Hidefumi.

    1996-01-01

    A difference of pressure between a standard pressure conduit in communication with a gas phase of a reactor pressure vessel and a water level pressure conduit in communication with a liquid phase of the pressure vessel is detected by a pressure difference gage. A communication pipe and a standard level vessel are disposed between the pressure vessel and the standard pressure conduit, and a standard liquid surface on the side of the standard pressure conduit is formed in the standard level vessel. A gas releaser is disposed to the gas phase portion of the standard level vessel. The gas releaser equipment is constituted by a porous material, a permeation membrane and a gas exhaustion hole. The gas phase of the standard level vessel is divided by a partition plate into a first gas phase being in contact with a connection portion with the communication pipe and a second gas phase in contact with the gas releaser. A gas flow channel hole and a condensate descending hole are disposed to the partition plate. Since incondensible gases accumulated to the standard level vessel are effectively exhausted, the incondensible gases are prevented from being dissolved into liquid. (I.N.)

  10. Re-expression of pro-fibrotic, embryonic preserved mediators in irradiated arterial vessels of the head and neck region.

    Science.gov (United States)

    Möbius, Patrick; Preidl, Raimund H M; Weber, Manuel; Amann, Kerstin; Neukam, Friedrich W; Wehrhan, Falk

    2017-11-01

    Surgical treatment of head and neck malignancies frequently includes microvascular free tissue transfer. Preoperative radiotherapy increases postoperative fibrosis-related complications up to transplant loss. Fibrogenesis is associated with re-expression of embryonic preserved tissue developmental mediators: osteopontin (OPN), regulated by sex-determining region Y‑box 9 (Sox9), and homeobox A9 (HoxA9) play important roles in pathologic tissue remodeling and are upregulated in atherosclerotic vascular lesions; dickkopf-1 (DKK1) inhibits pro-fibrotic and atherogenic Wnt signaling. We evaluated the influence of irradiation on expression of these mediators in arteries of the head and neck region. DKK1, HoxA9, OPN, and Sox9 expression was examined immunohistochemically in 24 irradiated and 24 nonirradiated arteries of the lower head and neck region. The ratio of positive cells to total cell number (labeling index) in the investigated vessel walls was assessed semiquantitatively. DKK1 expression was significantly decreased, whereas HoxA9, OPN, and Sox9 expression were significantly increased in irradiated compared to nonirradiated arterial vessels. Preoperative radiotherapy induces re-expression of embryonic preserved mediators in arterial vessels and may thus contribute to enhanced activation of pro-fibrotic downstream signaling leading to media hypertrophy and intima degeneration comparable to fibrotic development steps in atherosclerosis. These histopathological changes may be promoted by HoxA9-, OPN-, and Sox9-related inflammation and vascular remodeling, supported by downregulation of anti-fibrotic DKK1. Future pharmaceutical strategies targeting these vessel alterations, e. g., bisphosphonates, might reduce postoperative complications in free tissue transfer.

  11. Effect of triiodothyronine on the maxilla and masseter muscles of the rat stomatognathic system

    Directory of Open Access Journals (Sweden)

    M.V. Mariúba

    2011-07-01

    Full Text Available The maxilla and masseter muscles are components of the stomatognathic system involved in chewing, which is frequently affected by physical forces such as gravity, and by dental, orthodontic and orthopedic procedures. Thyroid hormones (TH are known to regulate the expression of genes that control bone mass and the oxidative properties of muscles; however, little is known about the effects of TH on the stomatognathic system. This study investigated this issue by evaluating: i osteoprotegerin (OPG and osteopontine (OPN mRNA expression in the maxilla and ii myoglobin (Mb mRNA and protein expression, as well as fiber composition of the masseter. Male Wistar rats (~250 g were divided into thyroidectomized (Tx and sham-operated (SO groups (N = 24/group treated with T3 or saline (0.9% for 15 days. Thyroidectomy increased OPG (~40% and OPN (~75% mRNA expression, while T3 treatment reduced OPG (~40% and OPN (~75% in Tx, and both (~50% in SO rats. Masseter Mb mRNA expression and fiber type composition remained unchanged, despite the induction of hypo- and hyperthyroidism. However, Mb content was decreased in Tx rats even after T3 treatment. Since OPG and OPN are key proteins involved in the osteoclastogenesis inhibition and bone mineralization, respectively, and that Mb functions as a muscle store of O2 allowing muscles to be more resistant to fatigue, the present data indicate that TH also interfere with maxilla remodeling and the oxidative properties of the masseter, influencing the function of the stomatognathic system, which may require attention during dental, orthodontic and orthopedic procedures in patients with thyroid diseases.

  12. A mammalian melanopsin in the retina of a fresh water turtle, the red-eared slider (Trachemys scripta elegans).

    Science.gov (United States)

    Dearworth, James R; Selvarajah, Brian P; Kalman, Ross A; Lanzone, Andrew J; Goch, Abraham M; Boyd, Alison B; Goldberg, Laura A; Cooper, Lori J

    2011-01-28

    A mammalian-like melanopsin (Opn4m) has been found in all major vertebrate classes except reptile. Since the pupillary light reflex (PLR) of the fresh water turtle takes between 5 and 10 min to achieve maximum constriction, and since photosensitive retinal ganglion cells (ipRGCs) in mammals use Opn4m to control their slow sustained pupil responses, we hypothesized that a Opn4m homolog exists in the retina of the turtle. To identify its presence, retinal tissue was dissected from seven turtles, and total RNA extracted. Reverse transcriptase-polymerase chain reactions (RT-PCRs) were carried out to amplify gene sequences using primers targeting the highly conserved core region of Opn4m, and PCR products were analyzed by gel electrophoresis and sequenced. Sequences derived from a 1004-bp PCR product were compared to those stored in GenBank by the basic local alignment search tool (BLAST) algorithm and returned significant matches to several Opn4ms from other vertebrates including chicken. Quantitative real-time PCR (qPCR) was also carried out to compare expression levels of Opn4m in different tissues. The normalized expression level of Opn4m in the retina was higher in comparison to other tissue types: iris, liver, lung, and skeletal muscle. The results suggest that Opn4m exists in the retina of the turtle and provides a possible explanation for the presence of a slow PLR. The turtle is likely to be a useful model for further understanding the photoreceptive mechanisms in the retina which control the dynamics of the PLR. Copyright © 2010 Elsevier Ltd. All rights reserved.

  13. Transmutations across hierarchical levels

    International Nuclear Information System (INIS)

    O'Neill, R.V.

    1977-01-01

    The development of large-scale ecological models depends implicitly on a concept known as hierarchy theory which views biological systems in a series of hierarchical levels (i.e., organism, population, trophic level, ecosystem). The theory states that an explanation of a biological phenomenon is provided when it is shown to be the consequence of the activities of the system's components, which are themselves systems in the next lower level of the hierarchy. Thus, the behavior of a population is explained by the behavior of the organisms in the population. The initial step in any modeling project is, therefore, to identify the system components and the interactions between them. A series of examples of transmutations in aquatic and terrestrial ecosystems are presented to show how and why changes occur. The types of changes are summarized and possible implications of transmutation for hierarchy theory, for the modeler, and for the ecological theoretician are discussed

  14. Optimal Levels of Embeddedness

    DEFF Research Database (Denmark)

    Andersen, Kristina Vaarst

    Co-location of industry professionals often leads to development of collaboration networks, and multiple studies have emphasized the benefits of embedded collaboration. Due to higher levels of trust, embedded collaboration reduces transaction costs and facilitates ready knowledge exchanged. Other...... on regional level data on co-location of knowledge workers, workplaces, and cultural amenities. Two papers build on individual level data from the Danish film industry. The first paper analyses why the importance of co-location differs between groups of knowledge workers and aim to explain centralization...... in localized collaboration networks is so essential, it affects location choices. The second paper challenges the proposition of embeddedness as an absolute term through an analysis of costs and benefits of embeddedness in an industry network. The results show that the association between embeddedness...

  15. Caribbean Sea Level Network

    Science.gov (United States)

    von Hillebrandt-Andrade, C.; Crespo Jones, H.

    2012-12-01

    Over the past 500 years almost 100 tsunamis have been observed in the Caribbean and Western Atlantic, with at least 3510 people having lost their lives to this hazard since 1842. Furthermore, with the dramatic increase in population and infrastructure along the Caribbean coasts, today, millions of coastal residents, workers and visitors are vulnerable to tsunamis. The UNESCO IOC Intergovernmental Coordination Group for Tsunamis and other Coastal Hazards for the Caribbean and Adjacent Regions (CARIBE EWS) was established in 2005 to coordinate and advance the regional tsunami warning system. The CARIBE EWS focuses on four areas/working groups: (1) Monitoring and Warning, (2) Hazard and Risk Assessment, (3) Communication and (4) Education, Preparedness and Readiness. The sea level monitoring component is under Working Group 1. Although in the current system, it's the seismic data and information that generate the initial tsunami bulletins, it is the data from deep ocean buoys (DARTS) and the coastal sea level gauges that are critical for the actual detection and forecasting of tsunamis impact. Despite multiple efforts and investments in the installation of sea level stations in the region, in 2004 there were only a handful of sea level stations operational in the region (Puerto Rico, US Virgin Islands, Bermuda, Bahamas). Over the past 5 years there has been a steady increase in the number of stations operating in the Caribbean region. As of mid 2012 there were 7 DARTS and 37 coastal gauges with additional ones being installed or funded. In order to reach the goal of 100 operational coastal sea level stations in the Caribbean, the CARIBE EWS recognizes also the importance of maintaining the current stations. For this, a trained workforce in the region for the installation, operation and data analysis and quality control is considered to be critical. Since 2008, three training courses have been offered to the sea level station operators and data analysts. Other

  16. Seismic Level 2 PSA

    International Nuclear Information System (INIS)

    Dirksen, Gerben; Pellissetti, Manuel; Duncan-Whiteman, Paul

    2014-01-01

    For most external events, the calculation of the core damage frequency (CDF) in Level 1 PSA is sufficient to be able to show that the contribution of the event to the plant risk is negligible. However, it is not sufficient to compare the CDF due to the external event to the total plant CDF; instead the Level 1 PSA result for the event should be compared to the large early release frequency (LERF), or alternatively arguments should be given why the CDF from the external event will not contribute mostly to LERF. For seismic events in particular, it can often not be easily excluded that sequences leading to core damage would not also result in LERF. Since the confinement function is one of the most essential functions for Level 2 PSA, special care must be taken of the containment penetrations. For example systems with containment penetrations that are normally closed during operation or are designed to withstand more than the maximum containment pressure are normally screened out in the Level 2 PSA for the containment isolation function, however the possibility of LOCA in such systems due to an earthquake may nevertheless lead to containment bypass. Additionally, the functionality of passive features may be compromised in case of a beyond design earthquake. In the present paper, we present crucial ingredients of a methodology for a Level 2 seismic PSA. This methodology consists of the following steps: Extension of the seismic equipment list (SEL) to include Level 2 PSA relevant systems (e.g. containment isolation system, features for core melt stabilization, hydrogen mitigation systems), Determination of the systems within the existing SEL with increased demands in case of severe accidents, Determination of essential components for which a dedicated fragility analysis needs to be performed. (author)

  17. Street level society

    DEFF Research Database (Denmark)

    Vinum, Christine; Nissen, Morten

    2006-01-01

    This paper aims to reflect on research findings from different empirical studies of social work with young drug users and socially excluded young people in Copenhagen. In the paper we account for historical changes in social policy and interventions into young people's drug taking in Copenhagen......, and partly from the decentralizing and specializing efforts characteristic of the Danish welfare state and its institutions. We discuss a general turn towards street level interventions to address the problems of social exclusion, as well as different attempts to create what we term street level heterotopias...

  18. Level width broadening effect

    International Nuclear Information System (INIS)

    Zhang Jingshang

    2003-01-01

    In file-6 for double-differential cross sections, the level width broadening effect should be taken into account properly due to Heisenberg' uncertainty. Besides level width broadening effect, the energy resolution in the measurements is also needed in fitting measurement procedure. In general, the traditional normal Gaussian expansion is employed. However, to do so in this way the energy balance could not be held. For this reason, the deformed Gaussian expansion functions with exponential form for both the single energy point and continuous spectrum are introduced, with which the normalization and energy balance conditions could be held exactly in the analytical form. (author)

  19. Middle Level Learning.

    Science.gov (United States)

    Wyman, Richard M., Jr.; Young, Katherine A.; Sliger, Bruce; Kafi, Patricia; Singer, Alan; Lamme, Linda Leonard

    1998-01-01

    Presents five brief articles related to middle-level learning. The articles are, "Using Children's Diaries to Teach the Oregon Trail"; "Living the Geography of Joseph and Temperance Brown"; "The ABCs of Small Grant Acquisition for Social Studies"; "Isomo Loruko: The Yoruba Naming Ceremony"; and "Child…

  20. New level of structure

    International Nuclear Information System (INIS)

    Greenberg, O.W.

    1985-01-01

    In the standard model of matter, ther are five stages of compositeness- molecules, atoms, nuclei, nucleons, and quarks and leptons-but we are beginning to see regularities at the fifth layer that may point to a deeper, sixth level of structure

  1. Reliability and code level

    NARCIS (Netherlands)

    Kasperski, M.; Geurts, C.P.W.

    2005-01-01

    The paper describes the work of the IAWE Working Group WBG - Reliability and Code Level, one of the International Codification Working Groups set up at ICWE10 in Copenhagen. The following topics are covered: sources of uncertainties in the design wind load, appropriate design target values for the

  2. Organotin levels in seafood

    NARCIS (Netherlands)

    Belfroid, A.C.; Purperhart, M.; Ariese, F.

    2000-01-01

    Tolerable average residue levels (TARL) for tributylin (TBT) in seafood products were calculated based on the tolerable daily intake (TDI) of TBT and the seafood consumption of the average consumer in various countries. Data from the literature show that these TARLs in seafood are exceeded in one or

  3. 55Co level properties

    International Nuclear Information System (INIS)

    Lodin, G.; Nilsson, L.; Erlandsson, B.; Lyttkens, J.

    1975-01-01

    The decay pf low-lying levels in 55 Co has been studied by means of the 54 Fe(d,nγ) 55 Co reaction. Neutron energies were determined by time-of-flight techniques using a pulsed incident beam and a large liquid scintillator. Gamma rays in coincidence with neutrons were detected by a Ge(Li)spectrometer, Three levels at 4720.8+-0.6, 4747.1+-0.6 and 5172.4+-0.6 keV were strongly populated. The 4720 and 5172 keV levels have earlier been identified as the isobaric analogues of the 55 Fe ground state and first excited state. On the basis of a comparison of the present results with previous particle-transfer reaction studies it is suggested that the ground state analogue is split into the 4720 and 4747 keV levels. A study of excitation functions of 54 Fe(d,n)transitions at incident deuteron energies between 5.0 and 6.0 MeV show that the spectroscopic strengths obtained from (d,n) experiments in this mass region at these energies depend strongly on the incident energy. (Auth.)

  4. Implementing Modular A Levels.

    Science.gov (United States)

    Holding, Gordon

    This document, which is designed for curriculum managers at British further education (FE) colleges, presents basic information on the implementation and perceived benefits of the General Certificate of Education (GCE) modular A (Advanced) levels. The information was synthesized from a survey of 12 FE colleges that introduced the modular A levels…

  5. Levels of valence

    Directory of Open Access Journals (Sweden)

    Vera eShuman

    2013-05-01

    Full Text Available The distinction between the positive and the negative is fundamental in our emotional life. In appraisal theories, in particular in the component process model of emotion (Scherer, 1984, 2010, qualitatively different types of valence are proposed based on appraisals of (unpleasantness, goal obstructiveness/conduciveness, low or high power, self- (incongruence, and moral badness/goodness. This multifaceted conceptualization of valence is highly compatible with the frequent observation of mixed feelings in real life. However, it seems to contradict the one-dimensional conceptualization of valence often encountered in psychological theories, and the notion of valence as a common currency used to explain choice behavior. Here, we propose a framework to integrate the seemingly disparate conceptualizations of multifaceted valence and one-dimensional valence by suggesting that valence should be conceived at different levels, micro and macro. Micro-valences correspond to qualitatively different types of evaluations, potentially resulting in mixed feelings, whereas one-dimensional macro-valence corresponds to an integrative common currency to compare alternatives for choices. We propose that conceptualizing levels of valence may focus research attention on the mechanisms that relate valence at one level (micro to valence at another level (macro, leading to new hypotheses and addressing various concerns that have been raised about the valence concept, such as the valence-emotion relation.

  6. Levels of Valence

    Science.gov (United States)

    Shuman, Vera; Sander, David; Scherer, Klaus R.

    2013-01-01

    The distinction between the positive and the negative is fundamental in our emotional life. In appraisal theories, in particular in the component process model of emotion (Scherer, 1984, 2010), qualitatively different types of valence are proposed based on appraisals of (un)pleasantness, goal obstructiveness/conduciveness, low or high power, self-(in)congruence, and moral badness/goodness. This multifaceted conceptualization of valence is highly compatible with the frequent observation of mixed feelings in real life. However, it seems to contradict the one-dimensional conceptualization of valence often encountered in psychological theories, and the notion of valence as a common currency used to explain choice behavior. Here, we propose a framework to integrate the seemingly disparate conceptualizations of multifaceted valence and one-dimensional valence by suggesting that valence should be conceived at different levels, micro and macro. Micro-valences correspond to qualitatively different types of evaluations, potentially resulting in mixed feelings, whereas one-dimensional macro-valence corresponds to an integrative “common currency” to compare alternatives for choices. We propose that conceptualizing levels of valence may focus research attention on the mechanisms that relate valence at one level (micro) to valence at another level (macro), leading to new hypotheses, and addressing various concerns that have been raised about the valence concept, such as the valence-emotion relation. PMID:23717292

  7. Higher-level Innovization

    DEFF Research Database (Denmark)

    Bandaru, Sunith; Tutum, Cem Celal; Deb, Kalyanmoy

    2011-01-01

    we introduce the higher-level innovization task through an application of a manufacturing process simulation for the Friction Stir Welding (FSW) process where commonalities among two different Pareto-optimal fronts are analyzed. Multiple design rules are simultaneously deciphered from each front...

  8. Guideline level-3 PSA

    International Nuclear Information System (INIS)

    Roelofsen, P.M.; Van der Steen, J.

    1993-09-01

    For several applications of radioactive materials calculations must be executed to determine the radiation risk for the population. A guideline for the risk calculation method of two main sources: nuclear power plants, and other intended and unintended activities with radioactive materials, is given. The standards, recommendations and regulations in this report concern mainly the analysis of the radiological (external) consequences of nuclear power plant accidents, classified as level-3 PSA (Probabilistic Safety Analysis). Level-3 PSA falls within the scales 5-7 of the International Nuclear Event Scale (INES). The standards, etc., focus on the risks for groups of people and the so-called maximum individual risk. In chapter two the standards and regulations are formulated for each part of level-3 PSA: the source term spectrum, atmospheric distribution and deposition, exposure to radiation doses and calculation of radiation doses, dose-response relationships, measures to reduce the effect of radiation doses, design basis accidents, and finally uncertainty analysis. In chapter four, modelled descriptions are given of the standards and regulations, which could or should be used in a calculation program in case of level-3 PSA. In chapter three the practical execution of a probabilistic consequences analysis, the collection of input data and the presentation of the results are dealt with. 2 figs., 14 tabs., 64 refs

  9. General Algorithm (High level)

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. General Algorithm (High level). Iteratively. Use Tightness Property to remove points of P1,..,Pi. Use random sampling to get a Random Sample (of enough points) from the next largest cluster, Pi+1. Use the Random Sampling Procedure to approximate ci+1 using the ...

  10. Liquid level detector

    International Nuclear Information System (INIS)

    Dean, A.P.; Pendleton, J.R.

    1982-01-01

    A device is described for locating the level of the liquid metal in a sodium cooled nuclear reactor by using a movable probe equipped to signal a phase change with null on arrival at the interface between two conductively differing media. (U.K.)

  11. Low-level effects

    International Nuclear Information System (INIS)

    Devine, R.T.; Chaput, R.L.

    1987-01-01

    Risk assignments can be made to given practices involving exposure to radiation, because sufficient data are available for the effects of high-dose, low-LET radiation and because sufficient exists in the methods of extrapolation to low doses and low dose rates. The confidence in the extrapolations is based on the fact that the risk is not expected to be overestimated, using the assumptions made (as opposed to the possibility that the extrapolations represent an accurate estimate of the risk). These risk estimates have been applied to the selection of permissible exposure levels, to show that various amounts of radiation involve no greater risk to the worker than the risk expected in another industry that is generally considered safe. The setting of standards for protection from exposure to low levels of ionizing radiation is made by expert committees at the national and international levels who weigh social factors as well as scientific factors. Data on low-level effects may be applied when assigning a ''probability of causation'' to a certain exposure of radiation. This has become a prominent method for arriving at an equitable award for damages caused by such exposure. The generation of these tables requires as many (if not more) social and political considerations as does the setting up of protection criteria. It is impossible to extract a purely scientific conclusion solely from the protection standards and other legal decisions. Sufficient information exists on low-LET radiation that safety standards for exposure can be rationally (if not scientifically) agreed upon

  12. Low-level radiation

    International Nuclear Information System (INIS)

    Myers, D.K.

    1982-05-01

    It is known that the normal incidence of cancer in human populations is increased by exposure to moderately high doses of ionizing radiation. At background radiation levels or at radiation levels which are 100 times greater, the potential health risks are considered to be directly proportional to the total accumulated dose of radiation. Some of the uncertainties associated with this assumption and with the accepted risk estimates have been critically reviewed in this document. The general scientific consensus at present suggests that the accepted risk estimates may exaggerate the actual risk of low levels of sparsely ionizing radiations (beta-, gamma- or X-rays) somewhat but are unlikely to overestimate the actual risks of densely ionizing radiations (fast neutrons, alpha-particles). At the maximum permissible levels of exposure for radiation workers in nuclear power stations, the potential health hazards in terms of life expectancy would be comparable to those encountered in transportation and public utilities or in the construction industry. At the average radiation exposures received by these workers in practice, the potential health hazards are similar to those associated with safe categories of industries. Uranium mining remains a relativly hazardous occupation. In terms of absolute numbers, the genetic hazards, which are less well established, are thought to be smaller than the carcinogenic hazards of radiation when only the first generation is considered but to be of the same order of magnitude as the carcinogenic hazards when the total number of induced genetic disorders is summed over all generations

  13. Levels of Literacy.

    Science.gov (United States)

    Nettle, Keith

    Democracy in western countries now depends on literacy at every level: censuses by which governments can plan for the future; elections which are the cornerstone of democratic choice; local meetings which have agendas and minutes--the whole apparatus of social living is organized and recorded through literacy. This paper is concerned with how…

  14. Identification of platform levels

    DEFF Research Database (Denmark)

    Mortensen, Niels Henrik

    2005-01-01

    reduction, ability to launch a wider product portfolio without increasing resources and reduction of complexity within the whole company. To support the multiple product development process, platform based product development has in many companies such as Philips, VW, Ford etc. proven to be a very effective...... product development in one step and therefore the objective of this paper is to identify levels of platform based product development. The structure of this paper is as follows. First the applied terminology for platforms will be briefly explained and then characteristics between single and multi product...... development will be examined. Based on the identification of the above characteristics five platform levels are described. The research presented in this paper is a result of MSc, Ph.D projects at the Technical University of Denmark and consultancy projects within the organisation of Institute of Product...

  15. Tree-level formalism

    International Nuclear Information System (INIS)

    Brandhuber, Andreas; Spence, Bill; Travaglini, Gabriele

    2011-01-01

    We review two novel techniques used to calculate tree-level scattering amplitudes efficiently: MHV diagrams, and on-shell recursion relations. For the MHV diagrams, we consider applications to tree-level amplitudes and focus in particular on the N=4 supersymmetric formulation. We also briefly describe the derivation of loop amplitudes using MHV diagrams. For the recursion relations, after presenting their general proof, we discuss several applications to massless theories with and without supersymmetry, to theories with massive particles, and to graviton amplitudes in general relativity. This article is an invited review for a special issue of Journal of Physics A: Mathematical and Theoretical devoted to 'Scattering amplitudes in gauge theories'. (review)

  16. High level nuclear wastes

    International Nuclear Information System (INIS)

    Lopez Perez, B.

    1987-01-01

    The transformations involved in the nuclear fuels during the burn-up at the power nuclear reactors for burn-up levels of 33.000 MWd/th are considered. Graphs and data on the radioactivity variation with the cooling time and heat power of the irradiated fuel are presented. Likewise, the cycle of the fuel in light water reactors is presented and the alternatives for the nuclear waste management are discussed. A brief description of the management of the spent fuel as a high level nuclear waste is shown, explaining the reprocessing and giving data about the fission products and their radioactivities, which must be considered on the vitrification processes. On the final storage of the nuclear waste into depth geological burials, both alternatives are coincident. The countries supporting the reprocessing are indicated and the Spanish programm defined in the Plan Energetico Nacional (PEN) is shortly reviewed. (author) 8 figs., 4 tabs

  17. Acceptable noise level

    DEFF Research Database (Denmark)

    Olsen, Steen Østergaard; Nielsen, Lars Holme; Lantz, Johannes

    2012-01-01

    The acceptable noise level (ANL) is used to quantify the amount of background noise that subjects can accept while listening to speech, and is suggested for prediction of individual hearing-aid use. The aim of this study was to assess the repeatability of the ANL measured in normal-hearing subjects...... using running Danish and non-semantic speech materials as stimuli and modulated speech-spectrum and multi-talker babble noises as competing stimuli....

  18. Service Level Status

    CERN Multimedia

    Lopienski, S

    2007-01-01

    Nowadays, IT departments provide, and people use, computing services of an increasingly heterogeneous nature. There is thus a growing need for a status display that groups these different services and reports status and availability in a uniform way. The Service Level Status (SLS) system addresses these needs by providing a web-based display that dynamically shows availability, basic information and statistics about various IT services, as well as the dependencies between them.

  19. Liquid Level Sensing System

    Science.gov (United States)

    Korman, Valentin (Inventor); Wiley, John T. (Inventor); Duffell, Amanda G. (Inventor)

    2014-01-01

    A liquid level sensing system includes waveguides disposed in a liquid and distributed along a path with a gap between adjacent waveguides. A source introduces electromagnetic energy into the waveguides at a first end of the path. A portion of the electromagnetic energy exits the waveguides at a second end of the path. A detector measures the portion of the electromagnetic energy exiting the second end of the path.

  20. Level up Book Club

    Science.gov (United States)

    LaGarde, Jennifer; Winner, Matthew C.

    2012-01-01

    Like all great ideas, Level Up Book Club grew out of a genuine need, the spontaneous firing of a few brain sparks, and the kind of luck that comes from being "in the right place at the right time." By mid-June 2011 the authors were already "bona fide" wonder twins--two educators who, although they'd never met, had stumbled upon each other through…

  1. Current level detector

    International Nuclear Information System (INIS)

    Kerns, C.R.

    1977-01-01

    A device is provided for detecting the current level of a dc signal. It includes an even harmonic modulator to which a reference ac signal is applied. The unknown dc signal acts on the reference ac signal so that the output of the modulator includes an even harmonic whose amplitude is proportional to the unknown dc current. The device may be used to provide overcurrent protection for proportional wire chambers

  2. Acceptable noise level

    DEFF Research Database (Denmark)

    Olsen, Steen Østergaard; Nielsen, Lars Holme; Lantz, Johannes

    2012-01-01

    The acceptable noise level (ANL) is used to quantify the amount of background noise that subjects can accept while listening to speech, and is suggested for prediction of individual hearing-aid use. The aim of this study was to assess the repeatability of the ANL measured in normal-hearing subjec...... using running Danish and non-semantic speech materials as stimuli and modulated speech-spectrum and multi-talker babble noises as competing stimuli....

  3. Multi-level spondylolysis.

    Science.gov (United States)

    Hersh, David S; Kim, Yong H; Razi, Afshin

    2011-01-01

    The incidence of isthmic spondylolysis is approximately 3% to 6% in the general population. Spondylolytic defects involving multiple vertebral levels, on the other hand, are extremely rare. Only a handful of reports have examined the outcomes of surgical treatment of multi-level spondylolysis. Here, we present one case of bilateral pars defects at L3, L4, and L5. The patient, a 46-year-old female, presented with lower back pain radiating into the left lower extremity. Radiographs and CT scans of the lumbar spine revealed bilateral pars defects at L3-L5. The patient underwent lumbar discectomy and interbody fusion of L4-S1 as well as direct repair of the pars defect at L3. There were no postoperative complications, and by seven months the patient had improved clinically. While previous reports describe the use of either direct repair or fusion in the treatment of spondylolysis, we are unaware of reports describing the use of both techniques at adjacent levels.

  4. ENRAF gauge reference level calculations

    Energy Technology Data Exchange (ETDEWEB)

    Huber, J.H., Fluor Daniel Hanford

    1997-02-06

    This document describes the method for calculating reference levels for Enraf Series 854 Level Detectors as installed in the tank farms. The reference level calculation for each installed level gauge is contained herein.

  5. Insignificant levels of dose

    International Nuclear Information System (INIS)

    Webb, G.A.M.; McLean, A.S.

    1977-01-01

    The procedures recommended by the International Commission on Radiological Protection (ICRP) for making decisions concerning controllable sources of radiation exposure of the public include 'justification' and 'optimisation'. The tool recommended by the ICRP for reaching these decisions is collective dose or dose commitment supplemented by consideration of doses to individuals. In both these considerations the practical problem arises of whether very small doses to large numbers of people should contribute to the final decision-making process. It may be that at levels of dose which are small increments on natural background, the relationship between dose and effect is linear even though the slope may be close to zero. If so, collective dose is a meaningful concept and the calculation of total detriment for the purpose of justification could legitimately include all doses. In the calculation of collective doses for the purpose of optimisation, which involves decisions on how much money or resource should be allocated to dose reduction, it is necessary to appraise radiation detriment realistically. At low levels of dose to the individual such as those small by comparison with variations in natural background within the UK, the risk to the individual is such that his well-being will not be significantly changed by the presence or absence of the radiation dose. These small doses, which are well below the point at which an individual attaches significance, should not carry a societal significance. Societal acceptance of risk is analysed with a view to assessing a level of possible risk, and hence dose, below which resources should not in general be diverted to secure further reduction. A formulation for collective dose commitment is proposed incorporating a cut-off to exclude insignificant doses. The implications of this formulation in practical situations are discussed

  6. ALICE High Level Trigger

    CERN Multimedia

    Alt, T

    2013-01-01

    The ALICE High Level Trigger (HLT) is a computing farm designed and build for the real-time, online processing of the raw data produced by the ALICE detectors. Events are fully reconstructed from the raw data, analyzed and compressed. The analysis summary together with the compressed data and a trigger decision is sent to the DAQ. In addition the reconstruction of the events allows for on-line monitoring of physical observables and this information is provided to the Data Quality Monitor (DQM). The HLT can process event rates of up to 2 kHz for proton-proton and 200 Hz for Pb-Pb central collisions.

  7. Global physical activity levels

    DEFF Research Database (Denmark)

    Hallal, Pedro C; Andersen, Lars Bo; Bull, Fiona C

    2012-01-01

    To implement effective non-communicable disease prevention programmes, policy makers need data for physical activity levels and trends. In this report, we describe physical activity levels worldwide with data for adults (15 years or older) from 122 countries and for adolescents (13-15-years......-income countries. The proportion of 13-15-year-olds doing fewer than 60 min of physical activity of moderate to vigorous intensity per day is 80·3% (80·1-80·5); boys are more active than are girls. Continued improvement in monitoring of physical activity would help to guide development of policies and programmes......-old) from 105 countries. Worldwide, 31·1% (95% CI 30·9-31·2) of adults are physically inactive, with proportions ranging from 17·0% (16·8-17·2) in southeast Asia to about 43% in the Americas and the eastern Mediterranean. Inactivity rises with age, is higher in women than in men, and is increased in high...

  8. Water level detection pipeline

    International Nuclear Information System (INIS)

    Koshikawa, Yukinobu; Imanishi, Masatoshi; Niizato, Masaru; Takagi, Masahiro

    1998-01-01

    In the present invention, water levels of a feedwater heater and a drain tank in a nuclear power plant are detected at high accuracy. Detection pipeline headers connected to the upper and lower portions of a feedwater heater or a drain tank are connected with each other. The connection line is branched at appropriate two positions and an upper detection pipeline and a lower detection pipeline are connected thereto, and a gauge entrance valve is disposed to each of the detection pipelines. A diaphragm of a pressure difference generator is connected to a flange formed to the end portion. When detecting the change of water level in the feedwater heater or the drain tank as a change of pressure difference, gauge entrance valves on the exit side of the upper and lower detection pipelines are connected by a connection pipe. The gauge entrance valve is closed, a tube is connected to the lower detection pipe to inject water to the diaphragm of the pressure difference generator passing through the connection pipe thereby enabling to calibrate the pressure difference generator. The accuracy of the calibration of instruments is improved and workability thereof upon flange maintenance is also improved. (I.S.)

  9. LHC Report: Level best

    CERN Multimedia

    Mike Lamont for the LHC team

    2012-01-01

    The LHCb experiment is special: there is a limit to the number of the events the detector can handle per bunch crossing. Consequently the maximum luminosity provided in 2012 has been around 4 x1032 cm-2s-1 (compared to the maximum of 7.7 x1033 cm-2s-1 seen by ATLAS and CMS). Nonetheless LHCb still wants to integrate as much luminosity as possible.    To meet LHCb's requirements a luminosity leveling technique is used. A machine setup is chosen that would give a peak luminosity well above the required maximum if the beams are collided head-on at LHCb's interaction point. This peak luminosity is then reduced to the required maximum by moving the two beams transversely apart at the interaction point. As the beam current goes down during a fill, the beams can be moved together in small increments to keep the collision rate constant throughout the fill. In practice, when the LHC goes into collisions in LHCb, the initial luminosity is safely below LHCb's demanded le...

  10. Monitoring Your Blood Sugar Level

    Science.gov (United States)

    ... and NutritionHealth Insurance: Understanding What It CoversHigh Homocysteine Level: How It Affects Your Blood VesselsUnderstanding Your Medical ... Health Resources Healthcare Management Monitoring Your Blood Sugar Level Monitoring Your Blood Sugar Level Share Print What ...

  11. The Role of Osteopontin in the Malignancy of Human Breast Carcinoma

    Science.gov (United States)

    1999-07-01

    1997; Yebra et al., 1996). 1990). Probes for human proteinase and uPAR genes The finding that human breast epithelial cells up- included: MMP-9 (92...680 -Senger DR and Perruzzi CA. (1996). Biochim. Biaphys. 69D.Adta., 1314, 13-24. Yebra M, Parry GCN, Str6mblad S, Mackman N,Shanmugamn V

  12. Identification of a macromolecular crystal growth inhibitor in human urine as osteopontin

    DEFF Research Database (Denmark)

    Sørensen, Steen; Justesen, S J; Johnsen, A H

    1995-01-01

    , an unidentified protein rich in uronic acid, and uropontin have all been described as possessing such activity. We have recently isolated an unknown inhibitor of calcium oxalate crystal growth that co-eluted with trypsin inhibitor in several separation steps, which suggested its identity. The aim of the present......Macromolecules occurring in human urine inhibit the growth and/or aggregation of calcium oxalate crystals and may prevent the formation of kidney stones. Attention has focused particularly on proteins, as these seem to be most responsible for the inhibitory activity; three proteins, nephrocalcin...... study was to outline a simple procedure for isolating and identifying this inhibitor. Purification was done as follows: precipitation of the major proteins (albumin and uromucoid) with trichloroacetic acid, followed by anion exchange chromatography, hydroxyapatite chromatography, anion exchange...

  13. Heparin-immobilized hydroxyapatite nanoparticles as a lactoferrin delivery system for improving osteogenic differentiation of adipose-derived stem cells

    International Nuclear Information System (INIS)

    Kim, Sung Eun; Yun, Young-Pil; Kim, Hak-Jun; Lee, Deok-Won; Shim, Kyu-Sik; Jeon, Daniel I; Rhee, Jin-Kyu; Park, Kyeongsoon

    2016-01-01

    The aim of this study is to fabricate lactoferrin (LF)-carrying hydroxyapatite nanoparticles (HAp NPs) to enhance osteogenic differentiation of rabbit adipose-derived stem cells (rADSCs). HAp NPs were modified with heparin-dopamine (Hep-DOPA) (Hep-HAp) and further immobilized with LF (LF/Hep-HAp). Heparin immobilization on HAp NPs prevented aggregation of HAp NPs in aqueous solution and prolonged the release of LF from LF/Hep-HAp NPs. In vitro studies of rADSCs have demonstrated that LF-Hep/HAp NPs significantly increase alkaline phosphatase (ALP) activity, calcium deposition, and both mRNA expression of osteocalcin (OCN) and osteopontin (OPN) in comparison with HAp and Hep-HAp NPs. These results suggest that LF/Hep-HAp NPs can effectively induce osteogenic differentiation of rADSCs. (paper)

  14. Fasting and nonfasting lipid levels

    DEFF Research Database (Denmark)

    Langsted, Anne; Freiberg, Jacob J; Nordestgaard, Børge G

    2008-01-01

    Lipid profiles are usually measured after fasting. We tested the hypotheses that these levels change only minimally in response to normal food intake and that nonfasting levels predict cardiovascular events.......Lipid profiles are usually measured after fasting. We tested the hypotheses that these levels change only minimally in response to normal food intake and that nonfasting levels predict cardiovascular events....

  15. Science Curriculum Guide, Level 4.

    Science.gov (United States)

    Newark School District, DE.

    The fourth of four levels in a K-12 science curriculum is outlined. In Level 4 (grades 9-12), science areas include earth science, biology, chemistry, and physics. Six major themes provide the basis for study in all levels (K-12). These are: Change, Continuity, Diversity, Interaction, Limitation, and Organization. In Level 4, all six themes are…

  16. Emotion-driven level generation

    OpenAIRE

    Togelius, Julian; Yannakakis, Georgios N.

    2016-01-01

    This chapter examines the relationship between emotions and level generation. Grounded in the experience-driven procedural content generation framework we focus on levels and introduce a taxonomy of approaches for emotion-driven level generation. We then review four characteristic level generators of our earlier work that exemplify each one of the approaches introduced. We conclude the chapter with our vision on the future of emotion-driven level generation.

  17. Localization of microfibrillar-associated protein 4 (MFAP4 in human tissues: clinical evaluation of serum MFAP4 and its association with various cardiovascular conditions.

    Directory of Open Access Journals (Sweden)

    Helle Wulf-Johansson

    Full Text Available Microfibrillar-associated protein 4 (MFAP4 is located in the extracellular matrix (ECM. We sought to identify tissues with high levels of MFAP4 mRNA and MFAP4 protein expression. Moreover, we aimed to evaluate the significance of MFAP4 as a marker of cardiovascular disease (CVD and to correlate MFAP4 with other known ECM markers, such as fibulin-1, osteoprotegerin (OPG, and osteopontin (OPN. Quantitative real-time PCR demonstrated that MFAP4 mRNA was more highly expressed in the heart, lung, and intestine than in other elastic tissues. Immunohistochemical studies demonstrated high levels of MFAP4 protein mainly at sites rich in elastic fibers and within blood vessels in all tissues investigated. The AlphaLISA technique was used to determine serum MFAP4 levels in a clinical cohort of 172 patients consisting of 5 matched groups with varying degrees of CVD: 1: patients with ST elevation myocardial infarction (STEMI, 2: patients with non-STEMI, 3: patients destined for vascular surgery because of various atherosclerotic diseases (stable atherosclerotic disease, 4: apparently healthy individuals with documented coronary artery calcification (CAC-positive, and 5: apparently healthy individuals without signs of coronary artery calcification (CAC-negative. Serum MFAP4 levels were significantly lower in patients with stable atherosclerotic disease than CAC-negative individuals (p<0.05. Furthermore, lower serum MFAP4 levels were present in patients with stable atherosclerotic disease compared with STEMI and non-STEMI patients (p<0.05. In patients with stable atherosclerotic disease, positive correlations between MFAP4 and both fibulin-1 (ρ = 0.50; p = 0.0244 and OPG (ρ = 0.62; p = 0.0014 were found. Together, these results indicate that MFAP4 is mainly located in elastic fibers and is highly expressed in blood vessels. The present study suggests that serum MFAP4 varies in groups of patients with different cardiovascular conditions

  18. WE-E-BRE-05: Ensemble of Graphical Models for Predicting Radiation Pneumontis Risk

    Energy Technology Data Exchange (ETDEWEB)

    Lee, S; Ybarra, N; Jeyaseelan, K; El Naqa, I [McGill University, Montreal, Quebec (Canada); Faria, S; Kopek, N [Montreal General Hospital, Montreal, Quebec (Canada)

    2014-06-15

    Purpose: We propose a prior knowledge-based approach to construct an interaction graph of biological and dosimetric radiation pneumontis (RP) covariates for the purpose of developing a RP risk classifier. Methods: We recruited 59 NSCLC patients who received curative radiotherapy with minimum 6 month follow-up. 16 RP events was observed (CTCAE grade ≥2). Blood serum was collected from every patient before (pre-RT) and during RT (mid-RT). From each sample the concentration of the following five candidate biomarkers were taken as covariates: alpha-2-macroglobulin (α2M), angiotensin converting enzyme (ACE), transforming growth factor β (TGF-β), interleukin-6 (IL-6), and osteopontin (OPN). Dose-volumetric parameters were also included as covariates. The number of biological and dosimetric covariates was reduced by a variable selection scheme implemented by L1-regularized logistic regression (LASSO). Posterior probability distribution of interaction graphs between the selected variables was estimated from the data under the literature-based prior knowledge to weight more heavily the graphs that contain the expected associations. A graph ensemble was formed by averaging the most probable graphs weighted by their posterior, creating a Bayesian Network (BN)-based RP risk classifier. Results: The LASSO selected the following 7 RP covariates: (1) pre-RT concentration level of α2M, (2) α2M level mid- RT/pre-RT, (3) pre-RT IL6 level, (4) IL6 level mid-RT/pre-RT, (5) ACE mid-RT/pre-RT, (6) PTV volume, and (7) mean lung dose (MLD). The ensemble BN model achieved the maximum sensitivity/specificity of 81%/84% and outperformed univariate dosimetric predictors as shown by larger AUC values (0.78∼0.81) compared with MLD (0.61), V20 (0.65) and V30 (0.70). The ensembles obtained by incorporating the prior knowledge improved classification performance for the ensemble size 5∼50. Conclusion: We demonstrated a probabilistic ensemble method to detect robust associations between

  19. Level density of 57Co

    International Nuclear Information System (INIS)

    Mishra, V.; Boukharouba, N.; Brient, C.E.; Grimes, S.M.; Pedroni, R.S.

    1994-01-01

    Levels in 57 Co have been studied in the region of resolved levels (E 57 Fe(p,n) 57 Co neutron spectrum with resolution ΔE∼5 keV. Seventeen previously unknown levels are located. Level density parameters in the continuum region are deduced from thick target measurements of the same reaction and additional level density information is deduced from Ericson fluctuation studies of the reaction 56 Fe(p,n) 56 Co. A set of level density parameters is found which describes the level density of 57 Co at energies up to 14 MeV. Efforts to obtain level density information from the 56 Fe(d,n) 57 Co reaction were unsuccessful, but estimates of the fraction of the deuteron absorption cross section corresponding to compound nucleus formation are obtained

  20. Reactor water level control device

    International Nuclear Information System (INIS)

    Hiramatsu, Yohei.

    1980-01-01

    Purpose: To increase the rapid response of the waterlevel control converting a reactor water level signal into a non-linear type, when the water level is near to a set value, to stabilize the water level reducting correlatively the reactor water level variation signal to stabilize greatly from the set value, and increasing the variation signal. Constitution: A main vapor flow quality transmitter detects the vapor flow generated in a reactor and introduced into a turbine. A feed water flow transmitter detects the quantity of a feed water flow from the turbine to the reactor, this detected value is sent to an addition operating apparatus. On the other hand, the power signal of the reactor water level transmitter is sent to the addition operating apparatus through a non-linear water level signal converter. The addition operation apparatus generates a signal for requesting the feed water flow quantity from both signals. Upon this occasion, the reactor water level signal converter makes small the reactor water level variation when the reactor level is close the set value, and when the water level deviates greatly from the set value, the reactor water level variation is made large thereby to improve the rapid response of the reactor coater level control. (Yoshino, Y.)

  1. Specified assurance level sampling procedure

    International Nuclear Information System (INIS)

    Willner, O.

    1980-11-01

    In the nuclear industry design specifications for certain quality characteristics require that the final product be inspected by a sampling plan which can demonstrate product conformance to stated assurance levels. The Specified Assurance Level (SAL) Sampling Procedure has been developed to permit the direct selection of attribute sampling plans which can meet commonly used assurance levels. The SAL procedure contains sampling plans which yield the minimum sample size at stated assurance levels. The SAL procedure also provides sampling plans with acceptance numbers ranging from 0 to 10, thus, making available to the user a wide choice of plans all designed to comply with a stated assurance level

  2. Digital Levelling in Subterranean Spaces

    Directory of Open Access Journals (Sweden)

    Tomáš Jiřikovský

    2007-06-01

    Full Text Available For precision levelling works are now more often used digital levels and code-scale staffs. Advantages in (and problems with their application to the regular line-levelling are well known and described. However, when using the digital levelling for measurements in specific local geodetic networks, monitoring networks and inside of buildings and underground spaces, new problems appear with the signalisation of the observed points, readability of the code (non-uniform illumination, temperature changes etc. The article informs about the application of two types of digital levels (Sokkia SDL-2, Trimble Zeiss DiNi 12T in the experimental subterranean levelling network for the basement settlement monitoring of a ten-floor building; the solution of marking of the points, field calibration and the system calibration of digital levels.

  3. Liquid level measurement in high level nuclear waste slurries

    International Nuclear Information System (INIS)

    Weeks, G.E.; Heckendorn, F.M.; Postles, R.L.

    1990-01-01

    Accurate liquid level measurement has been a difficult problem to solve for the Defense Waste Processing Facility (DWPF). The nuclear waste sludge tends to plug or degrade most commercially available liquid-level measurement sensors. A liquid-level measurement system that meets demanding accuracy requirements for the DWPF has been developed. The system uses a pneumatic 1:1 pressure repeater as a sensor and a computerized error correction system. 2 figs

  4. Proteasome Activators, PA28α and PA28β, Govern Development of Microvascular Injury in Diabetic Nephropathy and Retinopathy

    Directory of Open Access Journals (Sweden)

    Saeed Yadranji Aghdam

    2016-01-01

    Full Text Available Diabetic nephropathy (DN and diabetic retinopathy (DR are major complications of type 1 and type 2 diabetes. DN and DR are mainly caused by injury to the perivascular supporting cells, the mesangial cells within the glomerulus, and the pericytes in the retina. The genes and molecular mechanisms predisposing retinal and glomerular pericytes to diabetic injury are poorly characterized. In this study, the genetic deletion of proteasome activator genes, PA28α and PA28β genes, protected the diabetic mice in the experimental STZ-induced diabetes model against renal injury and retinal microvascular injury and prolonged their survival compared with wild type STZ diabetic mice. The improved wellbeing and reduced renal damage was associated with diminished expression of Osteopontin (OPN and Monocyte Chemoattractant Protein-1 (MCP-1 in the glomeruli of STZ-injected PA28α/PA28β double knockout (Pa28αβDKO mice and also in cultured mesangial cells and retinal pericytes isolated from Pa28αβDKO mice that were grown in high glucose. The mesangial PA28-mediated expression of OPN under high glucose conditions was suppressed by peptides capable of inhibiting the binding of PA28 to the 20S proteasome. Collectively, our findings demonstrate that diabetic hyperglycemia promotes PA28-mediated alteration of proteasome activity in vulnerable perivascular cells resulting in microvascular injury and development of DN and DR.

  5. Effects of “Danzhi Decoction” on Chronic Pelvic Pain, Hemodynamics, and Proinflammatory Factors in the Murine Model of Sequelae of Pelvic Inflammatory Disease

    Directory of Open Access Journals (Sweden)

    Xiaoling Bu

    2015-01-01

    Full Text Available Objective. To evaluate the effect of Danzhi decoction (DZD on chronic pelvic pain (CPP, hemodynamics, and proinflammatory factors of sequelae of pelvic inflammatory diseases (SPID in murine model. Methods. SPID mice were randomly treated with high-dose DZD, mid-dose DZD, low-dose DZD, aspirin, and vehicle for 3 estrous circles. The Mouse Grimace Scale (MGS was performed to evaluate CPP; blood flows of the upper genital tract, pelvic wall, and mesentery were used to assess hemodynamics in SPID mice; expressions of vascular endothelial growth factor (VEGF, angiopoietin-2 (Ang-2, and osteopontin (OPN were measured by Western blot and immunochemistry. Results. Treatment with dose-dependent DZD significantly decreased the MGS scores, accelerated blood flows of the pelvis, and reduced expressions of VEGF, Ang-2, and OPN in the upper genital tract. Conclusions and Discussions. DZD was effective in relieving CPP and improving hemodynamics of the pelvic blood-stasis microenvironment in SPID mice. There was a relationship between CPP and the pelvic blood-stasis microenvironment. Furthermore, DZD might play a positive role in the anti-inflammatory process.

  6. Osteogenic capability of autologous rabbit adipose-derived stromal cells in repairing calvarial defects.

    Science.gov (United States)

    Cheng, Shao-Wen; Lin, Zhong-Qin; Wang, Wei; Zhang, Wei; Kou, Dong-Quan; Ying, Xiao-Zhou; Chen, Qing-Yu; Shen, Yue; Cheng, Xiao-Jie; Peng, Lei; Lv, Chuan-Zhu

    2011-01-01

    To evaluate the in vitro and in vivo osteogenic capability of adipose-derived stromal cells (ASCs). ASCs were isolated from New Zealand white rabbits and determined by alkaline phosphatase (ALP) staining, von Kossa staining and alizarin red staining. Some specific markers of osteogenic differentiation, including ALP, osteocalcin (OCN), osteopontin (OPN) were examined by reverse transcription-polymerase chain reaction (RT-PCR). In vivo, demineralized bone matrix (DBM)-ASCs composites were implanted into the rabbit calvarial defects created at each side of the longitudinal midline. After 6 weeks, histologic properties of the transplants were analyzed. ASCs were successfully induced into osteogenesis. ALP staining, von Kossa staining and alizarin red staining showed positive results. The expressions of ALP, OCN and OPN were detected in ASCs after cultivation in osteogenic medium. Extensive new bone was observed in the defects transplanted with DBM-ASCs composites. ASCs have the potential to differentiate into osteogenic lineage and DBM-ASCs constructs are a promising method for regeneration in bone defects.

  7. Osteogenic capability of autologous rabbit adipose-derived stromal cells in repairing calvarial defects

    Directory of Open Access Journals (Sweden)

    CHENG Shao-wen

    2012-02-01

    Full Text Available 【Abstract】Objective: To evaluate the in vitro and in vivo osteogenic capability of adipose-derived stromal cells (ASCs. Methods: ASCs were isolated from New Zealand white rabbits and determined by alkaline phosphatase (ALP staining, von Kossa staining and alizarin red staining. Some specific markers of osteogenic differentiation, including ALP, osteocalcin (OCN, osteopontin (OPN were examined by reverse transcription-polymerase chain reaction (RT-PCR. In vivo, demineralized bone matrix (DBM-ASCs composites were implanted into the rabbit calvarial defects created at each side of the longitudinal midline. After 6 weeks, histologic properties of the transplants were analyzed. Results: ASCs were successfully induced into osteogenesis. ALP staining, von Kossa staining and alizarin red staining showed positive results. The expressions of ALP, OCN and OPN were detected in ASCs after cultivation in osteogenic medium. Extensive new bone was observed in the defects transplanted with DBM-ASCs composites. Conclusion: ASCs have the potential to differentiate into osteogenic lineage and DBM-ASCs constructs are a promising method for regeneration in bone defects. Key words: Adipose tissue; Bone regeneration; Osteogenesis

  8. Si-Wu-tang extract stimulates bone formation through PI3K/Akt/NF-κB signaling pathways in osteoblasts.

    Science.gov (United States)

    Wu, Chi-Ming; Chen, Po-Chun; Li, Te-Mao; Fong, Yi-Chin; Tang, Chih-Hsin

    2013-10-24

    Si-Wu-Tang (SWT), a Traditional Chinese Medicine (TCM) formula, is widely used for the treatment of gynopathies diseases such as menstrual discomfort, climacteric syndrome, dysmenorrhea, and other estrogen-related diseases. Recent studies have shown that SWT can treat primary dysmenorrhea, have anti-pruritic anti-inflammatory effects, and protect against radiation-induced bone marrow damage in an animal model. It has been reported that anti-inflammatory and anti-oxidant agents have the potential to treat osteoporosis by increasing bone formation and/or suppressing bone resorption. However, the effect of SWT on bone cell function has not yet been reported. Alkaline phosphatase (ALP), bone morphogenetic proteins (BMP)-2, and osteopontin (OPN) mRNA expression was analyzed by qPCR. The mechanism of action of SWT extract was investigated using western blotting. The in vivo anti-osteoporotic effect of SWT extract was assessed in ovariectomized mice. Here, we report that SWT increases ALP, BMP-2, and OPN expression as well as bone mineralization. In addition, we show that the PI3K, Akt, and NF-κB signaling pathways may be involved in the SWT-mediated increase in gene expression and bone mineralization. Notably, treatment of mice with SWT extract prevented bone loss induced by ovariectomy in vivo. SWT may be used to stimulate bone formation for the treatment of osteoporosis.

  9. Hyaluronan and Stone Disease

    Science.gov (United States)

    Asselman, Marino

    2008-09-01

    Kidney stones cannot be formed as long as crystals are passed in the urine. However, when crystals are retained it becomes possible for them to aggregate and form a stone. Crystals are expected to be formed not earlier than the distal tubules and collecting ducts. Studies both in vitro and in vivo demonstrate that calcium oxalate monohydrate crystals do not adhere to intact distal epithelium, but only when the epithelium is proliferating or regenerating, so that it possesses dedifferentiated cells expressing hyaluronan, osteopontin (OPN) and their mutual receptor CD44 at the apical cell membrane. The polysaccharide hyaluronan is an excellent crystal binding molecule because of its negative ionic charge. We hypothesized that the risk for crystal retention in the human kidney would be increased when tubular cells express hyaluronan at their apical cell membrane. Two different patient categories in which nephrocalcinosis frequently occurs were studied to test this hypothesis (preterm neonates and kidney transplant patients). Hyaluronan (and OPN) expression at the luminal membrane of tubular cells indeed was observed, which preceded subsequent retention of crystals in the distal tubules. Tubular nephrocalcinosis has been reported to be associated with decline of renal function and thus further studies to extend our knowledge of the mechanisms of retention and accumulation of crystals in the kidney are warranted. Ultimately, this may allow the design of new strategies for the prevention and treatment of both nephrocalcinosis and nephrolithiasis in patients.

  10. The Osteogenic Properties of Multipotent Mesenchymal Stromal Cells in Cultures on TiO2 Sol-Gel-Derived Biomaterial

    Directory of Open Access Journals (Sweden)

    Krzysztof Marycz

    2015-01-01

    Full Text Available The biocompatibility of the bone implants is a crucial factor determining the successful tissue regeneration. The aim of this work was to compare cellular behavior and osteogenic properties of rat adipose-derived multipotent stromal cells (ASCs and bone marrow multipotent stromal cells (BMSCs cultured on metallic substrate covered with TiO2 sol-gel-derived nanolayer. The morphology, proliferation rate, and osteogenic differentiation potential of both ASCs and BMSCs propagated on the biomaterials were examined. The potential for osteogenic differentiation of ASCs and BMSCs was determined based on the presence of specific markers of osteogenesis, that is, alkaline phosphatase (ALP, osteopontin (OPN, and osteocalcin (OCL. Additionally, the concentration of calcium and phosphorus in extracellular matrix was determined using energy-dispersive X-ray spectroscopy (SEM-EDX. Obtained results showed that TiO2 layer influenced proliferation activity of ASCs, which manifested by shortening of population doubling time and increase of OPN secretion. However, characteristic features of cells morphology and growth pattern of cultures prompted us to conclude that ultrathin TiO2 layer might also enhance osteodifferentiation of BMSCs. Therefore in our opinion, both populations of MSCs should be used for biological evaluation of biomaterials compatibility, such results may enhance the area of investigations related to regenerative medicine.

  11. The role of the SIBLING, Bone Sialoprotein in skeletal biology - Contribution of mouse experimental genetics.

    Science.gov (United States)

    Bouleftour, Wafa; Juignet, Laura; Bouet, Guenaelle; Granito, Renata Neves; Vanden-Bossche, Arnaud; Laroche, Norbert; Aubin, Jane E; Lafage-Proust, Marie-Hélène; Vico, Laurence; Malaval, Luc

    2016-01-01

    Bone Sialoprotein (BSP) is a member of the "Small Integrin-Binding Ligand N-linked Glycoproteins" (SIBLING) extracellular matrix protein family of mineralized tissues. BSP has been less studied than other SIBLING proteins such as Osteopontin (OPN), which is coexpressed with it in several skeletal cell types. Here we review the contribution of genetically engineered mice (BSP gene knockout and overexpression) to the understanding of the role of BSP in the bone organ. The studies made so far highlight the role of BSP in skeletal mineralization, as well as its importance for proper osteoblast and osteoclast differentiation and activity, most prominently in primary/repair bone. The absence of BSP also affects the local environment of the bone tissue, in particular hematopoiesis and vascularization. Interestingly, lack of BSP induces an overexpression of OPN, and the cognate protein could be responsible for some aspects of the BSP gene knockout skeletal phenotype, while replacing BSP for some of its functions. Such interplay between the partly overlapping functions of SIBLING proteins, as well as the network of cross-regulations in which they are involved should now be the focus of further work. Copyright © 2016 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

  12. 'Level-level correlation and absorption in nuclear reactions'

    International Nuclear Information System (INIS)

    Hussein, M.S.

    Level-level correlation (LLC) in nuclear reactions is discussed in general and it is shown that in the presence of LLC, N sub(μ) = Σ/g μa/ 2 > divided by gamma μ T tilde, where T tilde is the average absorption in the eigen channels [pt

  13. Comments About a Chameleon Theory: Level I/Level II.

    Science.gov (United States)

    Horn, John; Stankov, Lazar

    1982-01-01

    Jensen's ideas about two levels of intellectual abilities are criticized as being oversimplified. More than two levels of intellectual abilities and relationships between variables reflecting more than racial and socioeconomic status (SES) differences are suggested, arguing that Jensen's statements about race and SES differences are not properly…

  14. Low-level waste management

    International Nuclear Information System (INIS)

    Levin, G.B.

    1980-01-01

    An overview of the current situation in the United States and a look to the future of low-level waste management are presented. Current problems and challenges are discussed, such as: the need of additional disposal sites in the future; risks and costs involved in transport of low-level wastes; reduction of low-level waste volume through smelting, incineration, and storage for wastes containing nuclides with short half lives; development of a national policy for the management of low-level waste, and its implementation through a sensible system of regulations. Establishing a success with low-level waste management should provide the momentum and public confidence needed to continue on and to resolve the technical and politically more difficult low-level waste problems

  15. ClC-3 Promotes Osteogenic Differentiation in MC3T3-E1 Cell After Dynamic Compression.

    Science.gov (United States)

    Wang, Dawei; Wang, Hao; Gao, Feng; Wang, Kun; Dong, Fusheng

    2017-06-01

    ClC-3 chloride channel has been proved to have a relationship with the expression of osteogenic markers during osteogenesis, persistent static compression can upregulate the expression of ClC-3 and regulate osteodifferentiation in osteoblasts. However, there was no study about the relationship between the expression of ClC-3 and osteodifferentiation after dynamic compression. In this study, we applied dynamic compression on MC3T3-E1 cells to detect the expression of ClC-3, runt-related transcription factor 2 (Runx2), bone morphogenic protein-2 (BMP-2), osteopontin (OPN), nuclear-associated antigen Ki67 (Ki67), and proliferating cell nuclear antigen (PCNA) in biopress system, then we investigated the expression of these genes after dynamic compression with Chlorotoxin (specific ClC-3 chloride channel inhibitor) added. Under transmission electron microscopy, there were more cell surface protrusions, rough surfaced endoplasmic reticulum, mitochondria, Golgi apparatus, abundant glycogen, and lysosomes scattered in the cytoplasm in MC3T3-E1 cells after dynamic compression. The nucleolus was more obvious. We found that ClC-3 was significantly up-regulated after dynamic compression. The compressive force also up-regulated Runx2, BMP-2, and OPN after dynamic compression for 2, 4 and 8 h. The proliferation gene Ki67 and PCNA did not show significantly change after dynamic compression for 8 h. Chlorotoxin did not change the expression of ClC-3 but reduced the expression of Runx2, BMP-2, and OPN after dynamic compression compared with the group without Cltx added. The data from the current study suggested that ClC-3 may promotes osteogenic differentiation in MC3T3-E1 cell after dynamic compression. J. Cell. Biochem. 118: 1606-1613, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  16. Skeletal development of mice lacking bone sialoprotein (BSP--impairment of long bone growth and progressive establishment of high trabecular bone mass.

    Directory of Open Access Journals (Sweden)

    Wafa Bouleftour

    Full Text Available Adult Ibsp-knockout mice (BSP-/- display shorter stature, lower bone turnover and higher trabecular bone mass than wild type, the latter resulting from impaired bone resorption. Unexpectedly, BSP knockout also affects reproductive behavior, as female mice do not construct a proper "nest" for their offsprings. Multiple crossing experiments nonetheless indicated that the shorter stature and lower weight of BSP-/- mice, since birth and throughout life, as well as their shorter femur and tibia bones are independent of the genotype of the mothers, and thus reflect genetic inheritance. In BSP-/- newborns, µCT analysis revealed a delay in membranous primary ossification, with wider cranial sutures, as well as thinner femoral cortical bone and lower tissue mineral density, reflected in lower expression of bone formation markers. However, trabecular bone volume and osteoclast parameters of long bones do not differ between genotypes. Three weeks after birth, osteoclast number and surface drop in the mutants, concomitant with trabecular bone accumulation. The growth plates present a thinner hypertrophic zone in newborns with lower whole bone expression of IGF-1 and higher IHH in 6 days old BSP-/- mice. At 3 weeks the proliferating zone is thinner and the hypertrophic zone thicker in BSP-/- than in BSP+/+ mice of either sex, maybe reflecting a combination of lower chondrocyte proliferation and impaired cartilage resorption. Six days old BSP-/- mice display lower osteoblast marker expression but higher MEPE and higher osteopontin(Opn/Runx2 ratio. Serum Opn is higher in mutants at day 6 and in adults. Thus, lack of BSP alters long bone growth and membranous/cortical primary bone formation and mineralization. Endochondral development is however normal in mutant mice and the accumulation of trabecular bone observed in adults develops progressively in the weeks following birth. Compensatory high Opn may allow normal endochondral development in BSP-/- mice

  17. Protective effect of ellagic acid on healing alveolar bone after tooth extraction in rat--a histological and immunohistochemical study.

    Science.gov (United States)

    Al-Obaidi, Mazen M Jamil; Al-Bayaty, Fouad Hussain; Al Batran, Rami; Hassandarvish, Pouya; Rouhollahi, Elham

    2014-09-01

    This study has attempted to evaluate the effects of ellagic acid (EA) on alveolar bone healing after tooth extraction in rats. Twenty-four Sprague Dawley (SD) male rats (200-250g) were selected and were anaesthetised for the extraction of upper left incisor. Then, the rats were divided into two groups, comprising 12 rats each; the first group has been considered as a control group and was given only normal saline, whereas, the second group (treated group) was intragastrically administrated with EA daily once, for 28 days. Then three rats from each group had been selected on 7th, 14th, 21st, and 28th days to dissect their maxilla tissue either for histological observation and homogenisation purposes. The tissues fixed, decalcified and embedded in paraffin. Serial sections of 5μm thickness were prepared and stained with haematoxylin and eosin (H&E) for the histological study. Similar sections were taken for immunohistochemical analysis to assess osteocalcin (OSC) and osteopontin (OPN). Furthermore, Malondialdehyde (MDA) and superoxide dismutase (SOD) were measured in homogenated gingival maxilla tissue of rat by commercial kit. Based on the histological analysis we have identified that, EA treatment has induced earlier trabecular bone deposition in the treated group, resulting in more organised bone matrix on the 14th, 21st, and 28th days after tooth extraction, as against the control group. In comparison to control group, the positive labelling of OSC and OPN of the treated group have been highly expressed in the alveolar socket on 14th, and 21st days, which has indicated a the possibility of formation of new bone trabeculae at the beginning of the mineralisation process, after tooth extraction. In the EA treatment group, lipid per-oxidation (MDA) was significantly decreased (Phealing process in teeth socket of rats. Furthermore, the EA treated group showed a stronger positive immunolabelling for OSC and OPN, when compared with the control group. Copyright © 2014

  18. Culture at the Country Level

    OpenAIRE

    Maseland, R.K.J.; Hoorn, A.A.J. van; Herk, H. van; Torelli, C.J.

    2017-01-01

    This chapter introduces and critically discusses the idea of measuring the culture of countries and cross-national differences therein. We start by elaborating the theoretical foundations for studying culture at the country level. We highlight the use of countries or nations as a unit of analysis and pay special attention to the way in which a group-level construct such as culture has implications at lower levels of analysis, affecting the values and beliefs of individuals. After briefly trac...

  19. Nucleonic level control in industries

    International Nuclear Information System (INIS)

    Eapen, A.C.; Rao, S.S.; Nair, R.S.

    1979-01-01

    The paper elicits the particular advantages of nucleonic level control methods in certain applications. The technique used is described briefly. Normal radioactive sources used and their selection for any application based on their characteristic emissions is explained. Level controller developed by the Bhabha Atomic Research Centre, Bombay, is described including details regarding electronic circuitry and the radiation detector used. Its application in zinc powder plant to measure powder level in a hopper is described. Some of the typical applications of gamma-ray level controllers are mentioned. (auth.)

  20. Effects on bone metabolism markers and arterial stiffness by switching to rivaroxaban from warfarin in patients with atrial fibrillation.

    Science.gov (United States)

    Namba, Sayaka; Yamaoka-Tojo, Minako; Kakizaki, Ryota; Nemoto, Teruyoshi; Fujiyoshi, Kazuhiro; Hashikata, Takehiro; Kitasato, Lisa; Hashimoto, Takuya; Kameda, Ryo; Meguro, Kentaro; Shimohama, Takao; Tojo, Taiki; Ako, Junya

    2017-08-01

    In recent years, direct oral anticoagulants (DOACs) of dabigatran, rivaroxaban, apixaban, edoxaban, which are all alternatives to warfarin, have been released. The use of DOACs is becoming more widespread in the clinical management of thrombotic stroke risk in patients with atrial fibrillation (AF). In large-scale clinical trials of each drug, DOACs were reported to inhibit intracranial hemorrhage, stroke, and death compared to warfarin. Warfarin is an endogenous vitamin K antagonist; therefore, patients who are taking warfarin must be prohibited from taking vitamin K. Vitamin K is an essential cofactor required for the ɤ-carboxylation of vitamin K-dependent proteins including coagulation factors, osteocalcin (OC), matrix Gla protein (MGP), and the growth arrest-specific 6 (GAS6). OC is a key factor for bone matrix formation. MGP is a local inhibitor of soft tissue calcification in the vessel wall. GAS6 prevents the apoptosis of vascular smooth muscle cells. Therefore, decrease of blood vitamin K levels may cause osteoporosis, vascular calcification, and the inhibition of vessels angiogenesis. This study aimed to evaluate the effects of changing from warfarin to rivaroxaban on bone mineral metabolism, vascular calcification, and vascular endothelial dysfunction. We studied 21 consecutive patients with persistent or chronic AF, who were treated with warfarin at least for 12 months. Warfarin administration was changed to rivaroxaban (10 or 15 mg/day) in all patients. Osteopontin (OPN), bone alkaline phosphatase (BAP), and under-carboxylated osteocalcin (ucOC) were measured. Pulse wave velocity (PWV) and augmentation index (AI) were also measured as atherosclerosis assessments. All measurements were done before and six months after the rivaroxaban treatment. There was a significant increase in serum level of BAP compared to baseline (12.5 ± 4.6 to 13.4 ± 4.1 U/L, P warfarin in patients with atrial fibrillation was associated with an increase of bone

  1. On 165Ho level scheme

    International Nuclear Information System (INIS)

    Ardisson, Claire; Ardisson, Gerard.

    1976-01-01

    A 165 Ho level scheme was constructed which led to the interpretation of sixty γ rays belonging to the decay of 165 Dy. A new 702.9keV level was identified to be the 5/2 - member of the 1/2 ) 7541{ Nilsson orbit. )] [fr

  2. Background noise levels in Europe

    OpenAIRE

    Gjestland, Truls

    2008-01-01

    - This report gives a brief overview of typical background noise levels in Europe, and suggests a procedure for the prediction of background noise levels based on population density. A proposal for the production of background noise maps for Europe is included.

  3. Sea Level Rise Data Discovery

    Science.gov (United States)

    Quach, N.; Huang, T.; Boening, C.; Gill, K. M.

    2016-12-01

    Research related to sea level rise crosses multiple disciplines from sea ice to land hydrology. The NASA Sea Level Change Portal (SLCP) is a one-stop source for current sea level change information and data, including interactive tools for accessing and viewing regional data, a virtual dashboard of sea level indicators, and ongoing updates through a suite of editorial products that include content articles, graphics, videos, and animations. The architecture behind the SLCP makes it possible to integrate web content and data relevant to sea level change that are archived across various data centers as well as new data generated by sea level change principal investigators. The Extensible Data Gateway Environment (EDGE) is incorporated into the SLCP architecture to provide a unified platform for web content and science data discovery. EDGE is a data integration platform designed to facilitate high-performance geospatial data discovery and access with the ability to support multi-metadata standard specifications. EDGE has the capability to retrieve data from one or more sources and package the resulting sets into a single response to the requestor. With this unified endpoint, the Data Analysis Tool that is available on the SLCP can retrieve dataset and granule level metadata as well as perform geospatial search on the data. This talk focuses on the architecture that makes it possible to seamlessly integrate and enable discovery of disparate data relevant to sea level rise.

  4. Sea level and climate variations

    NARCIS (Netherlands)

    Oerlemans, J.

    1985-01-01

    Review paper, ESA Symposium on Application of Satellite Data to Climate Modelling. Alpbach (Austria) Sea level is an essential component of the climate system, on which many human activities in the coastal zone depend. Climate variations leading to changes in relative sea level are

  5. Enhanced Waste Tank Level Model

    Energy Technology Data Exchange (ETDEWEB)

    Duignan, M.R.

    1999-06-24

    'With the increased sensitivity of waste-level measurements in the H-Area Tanks and with periods of isolation, when no mass transfer occurred for certain tanks, waste-level changes have been recorded with are unexplained.'

  6. Evaluations of average level spacings

    International Nuclear Information System (INIS)

    Liou, H.I.

    1980-01-01

    The average level spacing for highly excited nuclei is a key parameter in cross section formulas based on statistical nuclear models, and also plays an important role in determining many physics quantities. Various methods to evaluate average level spacings are reviewed. Because of the finite experimental resolution, to detect a complete sequence of levels without mixing other parities is extremely difficult, if not totally impossible. Most methods derive the average level spacings by applying a fit, with different degrees of generality, to the truncated Porter-Thomas distribution for reduced neutron widths. A method that tests both distributions of level widths and positions is discussed extensivey with an example of 168 Er data. 19 figures, 2 tables

  7. Noise levels in Damascus city

    International Nuclear Information System (INIS)

    Al-Oudat, M.; Maslmani, Y.

    2004-01-01

    Outdoor noise levels were measured at 22 sites in Damascus city. Sound level meter model NC-10 with a 20-140 dBA selectable range was used in the current investigation. At each site noise data were collected from 7 to 21 o'clock. The results showed that the noise levels were higher than WHO (World Health Organization) standard by 5-24.7 dB, 10-16 dB, 10-11 dB and 12-17 dB in residential, commercial, Commercial-industrial, and Heavy traffic streets respectively. Indoor and outdoor noise levels in some hospitals were higher than WHO standard by 15-28 dB and 19-23 dB respectively. The study showed that the authorities administration must take necessary procedures to reduce the noise levels in residential regions and in the regions surrounding the hospitals. (author)

  8. The CDF level-3 trigger

    International Nuclear Information System (INIS)

    Devlin, T.

    1993-01-01

    The Collider Detector at Fermilab (CDF) has been operating at the Tevatron and collecting data on proton-antiproton interactions with collision rates above 250,000 Hz. Three levels of filtering select events for data logging at a rate of about 4 Hz. The Level 3 trigger provides most of the capabilities of the offline production programs for event reconstruction and physics analysis. The type of physics triggers, application of cuts, and combinations of logical requirements for event selection are controlled at run time by a trigger table using a syntax fully integrated with the Level 1 and Level 2 hardware triggers. The level 3 software operates in 48 RISC/UNIX processors (over 1000 mips) served by four 20-MByte/sec data buses for input, output and control. The system architecture, debugging, code validation, error reporting, analysis capabilities and performance will be described

  9. Relationships between the school-level and classroom-level ...

    African Journals Online (AJOL)

    education; school-level environment; science education; South Africa. Introduction .... instrument to the primary school students (N = 1,077) of 31 distance-education primary school teachers ..... Centre for Curriculum, Transfer and Technology.

  10. The Barbados Sea Level Record

    Science.gov (United States)

    Fairbanks, R. G.; Mortlock, R. A.; Abdul, N. A.; Wright, J. D.; Cao, L.; Mey, J. L.

    2013-12-01

    Additional offshore drill cores, nearly 100 new radiometric dates, and more than 1000 kilometers of Multibeam mapping greatly enhance the Barbados Sea Level record. Extensive Multibeam mapping around the entire island covers approximately 2650 km2 of the sea bottom and now integrates the offshore reef topography and Barbados Sea Level Record with the unparalleled onshore core collection, digital elevation maps, and Pleistocene sea level record spanning the past one million years. The reef crest coral, Acropora palmata, remains the stalwart indicator of sea level for many reasons that are validated by our redundant sea level records and redundant dating via Th/U and Pa/U analyses. Microanalysis and densitometry studies better explain why Acropora palmata is so well preserved in the Pleistocene reef records and therefore why it is the species of choice for sea level reconstructions and radiometric dating. New drill cores into reefs that formed during Marine Isotope Stage 3 lead us to a model of diagenesis that allows us to better prospect for unaltered coral samples in older reefs that may be suitable for Th/U dating. Equally important, our diagenesis model reinforces our rigorous sample quality criteria in a more quantitative manner. The Barbados Sea Level record has a sampling resolution of better than 100 years throughout much of the last deglaciation showing unprecedented detail in redundant drill cores. The Melt Water Pulses (MWP1A and MWP1B) are well resolved and the intervening interval that includes the Younger Dryas reveals sea level changes in new detail that are consistent with the terrestrial records of ice margins (see Abdul et al., this section). More than 100 paired Th/U and radiocarbon ages place the Barbados Sea Level Record unambiguously on the radiocarbon time scale for direct comparisons with the terrestrial records of ice margin changes.

  11. Optimum Safety Levels for Breakwaters

    DEFF Research Database (Denmark)

    Burcharth, H. F.; Sørensen, John Dalsgaard

    2005-01-01

    Optimum design safety levels for rock and cube armoured rubble mound breakwaters without superstructure are investigated by numerical simulations on the basis of minimization of the total costs over the service life of the structure, taking into account typical uncertainties related to wave...... statistics and structure response. The study comprises the influence of interest rate, service lifetime, downtime costs and damage accumulation. Design limit states and safety classes for breakwaters are discussed. The results indicate that optimum safety levels are somewhat higher than the safety levels...

  12. Farmers as Employers. Numeracy. Level 1. Level 2. Level 3. Support Materials for Agricultural Training.

    Science.gov (United States)

    Batman, Kangan; Tully, Chris

    This publication contains the three numeracy units of the three levels of Support Materials for Agricultural Training (SMAT) in the area of farmers as employers: Level 1 (starting), 2 (continuing), and 3 (completing). The units are designed to help the learner improve his or her numeracy skills needed to deal with employment of agriculture…

  13. Farm Management and Leadership. Numeracy. Level 1. Level 2. Level 3. Support Materials for Agricultural Training.

    Science.gov (United States)

    Batman, Kangan; Gadd, Nick; Lucas, Michele

    This publication contains the three numeracy units of the three levels of Support Materials for Agricultural Training (SMAT) in farm management and leadership: Level 1 (starting), 2 (continuing), and 3 (completing). The units are designed to help the learner improve his or her numeracy skills needed to deal with farm management. SMAT materials can…

  14. Occupational Health and Safety. Level 1. Level 2. Level 3. Support Materials for Agricultural Training.

    Science.gov (United States)

    Batman, Kangan; Gadd, Nick; Lucas, Michele

    This publication contains the three communication skills units of the three levels of Support Materials for Agricultural Training (SMAT) in the area of occupational health and safety: Level 1 (starting), 2 (continuing), and 3 (completing). The units are designed to help the learner improve his or her written and spoken communication skills needed…

  15. Occupational Health and Safety. Numeracy. Level 1. Level 2. Level 3. Support Materials for Agricultural Training.

    Science.gov (United States)

    Batman, Kangan; Tully, Chris

    This publication contains the three numeracy units of the three levels of Support Materials for Agricultural Training (SMAT) in the area of occupational health and safety: Level 1 (starting), 2 (continuing), and 3 (completing). The units are designed to help the learner improve his or her numeracy skills needed to deal with occupational safety and…

  16. Farmers as Employers. Level 1. Level 2. Level 3. Support Materials for Agricultural Training.

    Science.gov (United States)

    Batman, Kangan; Gadd, Nick; Lucas, Michele

    This publication contains the three communication skills units of the three levels of Support Materials for Agricultural Training (SMAT) in the area of farmers as employers: Level 1 (starting), 2 (continuing), and 3 (completing). The units are designed to help the learner improve his or her written and spoken communication and numeracy skills…

  17. Agricultural Production. Level 1. Level 2. Level 3. Support Materials for Agricultural Training.

    Science.gov (United States)

    Batman, Kangan; Gadd, Nick; Lucas, Michele

    This publication contains the three communication skills units of the three levels of Support Materials for Agricultural Training (SMAT) in agricultural production: Level 1 (starting), 2 (continuing), and 3 (completing). The units are designed to help the learner improve his or her written and spoken communication skills needed to deal with…

  18. Agricultural Production. Numeracy. Level 1. Level 2. Level 3. Support Materials for Agricultural Training.

    Science.gov (United States)

    Batman, Kangan; Tully, Chris

    This publication contains the three numeracy units of the three levels of Support Materials for Agricultural Training (SMAT) in agricultural production: Level 1 (starting), 2 (continuing), and 3 (completing). The units are designed to help the learner improve his or her numeracy skills needed to deal with agricultural production. SMAT materials…

  19. Farm Management and Leadership. Level 1. Level 2. Level 3. Support Materials for Agricultural Training.

    Science.gov (United States)

    Batman, Kangan; Gadd, Nick; Lucas, Michele

    This publication contains the three communication skills units of the three levels of Support Materials for Agricultural Training (SMAT) in farm management and leadership: Level 1 (starting), 2 (continuing), and 3 (completing). The units are designed to help the learner with the reading, writing, and spoken communication skills needed to deal with…

  20. Acceptance criteria for deposition of low-level and intermediate-level radiation levels radioactive wastes

    International Nuclear Information System (INIS)

    2002-09-01

    This norm establishes the criteria for acceptance low and intermediate radiation level for safe deposition in repositories, for assuring the protection of workers, population and environment against the hazardous effects of the ionizing radiations. The criteria of this norm applies to the low and intermediate radiation levels

  1. Level best : drilling seasonal load leveling business case : final report

    International Nuclear Information System (INIS)

    2005-10-01

    Drilling and seismic costs in Western Canada are as much as 35 per cent higher during winter months. Favourable commodity pricing has prompted aggressive expansion of drilling programs in the Western Canada Sedimentary Basin (WCSB), and capacity is becoming a significant issue. Many operators are turning to load leveling in order to secure rigs and crew availability. However, many operators still adhere to the traditional view that drilling of oil and gas wells is best accomplished during the winter. The purpose of the project discussed in this paper was to develop and present a business case for greater seasonal load leveling in the WCSB and spreading it more evenly throughout the year. Using calendar year quarters, publicly available data for a 5 year period from 2000-2004 for drilling activity, safety, weather, and environmental restrictions were examined. A list of candidate fields with high levels of activity and a good representation of well depths was selected. Well cost and rig data from 14 different companies was used. A variety of industry participants, drilling contractors, load leveling technology suppliers and provincial agencies were consulted to supplement well cost analyses. The financial impacts of load leveling were examined. Benefits included lower well costs; advanced production; avoided rig construction; reduced incident rates; and reduced turnover. While the focus of the business case for load leveling was based on hard cost data, many indirect benefits were identified, including First Nations sustainability and greater job security and comfort for workers. Various policies and incentives that encouraged load leveling in British Columbia and Alberta were reviewed. 57 figs

  2. Serum protein profiles predict coronary artery disease in symptomatic patients referred for coronary angiography

    Directory of Open Access Journals (Sweden)

    LaFramboise William A

    2012-12-01

    revascularization. Osteopontin (14 times and resistin (10 times were most frequently represented among these diagnostic signatures. The most efficacious protein signature in validation studies comprised osteopontin (OPN, resistin, matrix metalloproteinase 7 (MMP7 and interferon γ (IFNγ as a four-marker panel while the addition of either CRP or adiponectin (ACRP-30 yielded comparable results in five protein signatures. Conclusions Proteins in the serum of CAD patients predominantly reflected (1 a positive acute phase, inflammatory response and (2 alterations in lipid metabolism, transport, peroxidation and accumulation. There were surprisingly few indicators of growth factor activation or extracellular matrix remodeling in the serum of CAD patients except for elevated OPN. These data suggest that many symptomatic patients without significant CAD could be identified by a targeted multiplex serum protein test without cardiac catheterization thereby eliminating exposure to ionizing radiation and decreasing the economic burden of angiographic testing for these patients.

  3. Atomic-level computer simulation

    International Nuclear Information System (INIS)

    Adams, J.B.; Rockett, Angus; Kieffer, John; Xu Wei; Nomura, Miki; Kilian, K.A.; Richards, D.F.; Ramprasad, R.

    1994-01-01

    This paper provides a broad overview of the methods of atomic-level computer simulation. It discusses methods of modelling atomic bonding, and computer simulation methods such as energy minimization, molecular dynamics, Monte Carlo, and lattice Monte Carlo. ((orig.))

  4. High-level-waste immobilization

    International Nuclear Information System (INIS)

    Crandall, J.L.

    1982-01-01

    Analysis of risks, environmental effects, process feasibility, and costs for disposal of immobilized high-level wastes in geologic repositories indicates that the disposal system safety has a low sensitivity to the choice of the waste disposal form

  5. MOVES regional level sensitivity analysis

    Science.gov (United States)

    2012-01-01

    The MOVES Regional Level Sensitivity Analysis was conducted to increase understanding of the operations of the MOVES Model in regional emissions analysis and to highlight the following: : the relative sensitivity of selected MOVES Model input paramet...

  6. Association in Level 2 Fusion

    National Research Council Canada - National Science Library

    Kokar, Mieczyslaw M; Matheus, Christopher J; Letkowski, Jerzy A; Baclawski, Kenneth; Kogut, Paul

    2004-01-01

    ... system, this cannot be said about the number of possible relations, which can grow exponentially. To alleviate the problems of computational complexity in Level 2 processing, the authors of this paper have suggested the use of ontologies...

  7. Processing TES Level-2 Data

    Science.gov (United States)

    Poosti, Sassaneh; Akopyan, Sirvard; Sakurai, Regina; Yun, Hyejung; Saha, Pranjit; Strickland, Irina; Croft, Kevin; Smith, Weldon; Hoffman, Rodney; Koffend, John; hide

    2006-01-01

    TES Level 2 Subsystem is a set of computer programs that performs functions complementary to those of the program summarized in the immediately preceding article. TES Level-2 data pertain to retrieved species (or temperature) profiles, and errors thereof. Geolocation, quality, and other data (e.g., surface characteristics for nadir observations) are also included. The subsystem processes gridded meteorological information and extracts parameters that can be interpolated to the appropriate latitude, longitude, and pressure level based on the date and time. Radiances are simulated using the aforementioned meteorological information for initial guesses, and spectroscopic-parameter tables are generated. At each step of the retrieval, a nonlinear-least-squares- solving routine is run over multiple iterations, retrieving a subset of atmospheric constituents, and error analysis is performed. Scientific TES Level-2 data products are written in a format known as Hierarchical Data Format Earth Observing System 5 (HDF-EOS 5) for public distribution.

  8. Intermediate Levels of Visual Processing

    National Research Council Canada - National Science Library

    Nakayama, Ken

    1998-01-01

    ...) surface representation, here we have shown that there is an intermediate level of visual processing, between the analysis of the image and higher order representations related to specific objects; (2...

  9. Nuclear systems of level measurement

    International Nuclear Information System (INIS)

    Lara, A.J.; Cabrera, M.J.

    1992-01-01

    In the industry there are processes in which is necessary to maintain the products level controlled which are handled for their transformation. The majority of such processes and by the operation conditions, they do not admit measure systems of level of invasive type then the application of nuclear techniques for level measurement results a big aid in these cases, since all the system installation is situated beyond frontiers of vessels that contain the product for measuring. In the Department of Nuclear Technology Applications of Mexican Petroleum Institute was developed a level measurement system by gamma rays transmission which operates in the Low Density Polyethylene plant of Petrochemical Complex Escolin at Poza Rica, Veracruz, Mexico. (Author)

  10. The controlled release of simvastatin from TiO{sub 2} nanotubes to promote osteoblast differentiation and inhibit osteoclast resorption

    Energy Technology Data Exchange (ETDEWEB)

    Lai, Min, E-mail: minlai@jsnu.edu.cn [School of Life Science, Jiangsu Normal University, Xuzhou, Jiangsu 221116 (China); Jin, Ziyang; Yang, Xinyi; Wang, Huaying [School of Life Science, Jiangsu Normal University, Xuzhou, Jiangsu 221116 (China); Xu, Kui [Biomedical Engineering Center, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211 (China)

    2017-02-28

    Highlights: • The TiO{sub 2} nanotube substrates filled with simvastatin were successfully coated using chitosan/gelatin multilayers. • The bio-functionalized substrates display controlled release of simvastatin in a sustained manner. • The bio-functionalized substrates have great potential for improving osteoblast differentiation. • The bio-functionalized substrates effectively inhibit osteoclast differentiation. - Abstract: The aim of this study was to fabricate a novel drug-releasing bioactive platform that has excellent potential for improving osteoblast differentiation and inhibiting osteoclast resorption. TiO{sub 2} nanotubes (TNTs) with an outer diameter of around 70 nm were prepared by an anodization method. TNTs were filled with simvastatin (SV) and then coated using chitosan/gelatin multilayers (TNT-SV-LBL). The successful fabrication of TNT-SV-LBL substrates was confirmed by field emission scanning electron microscopy (FE-SEM), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS) and contact angle measurement, respectively. The in vitro release behavior of simvastatin from TNT-SV-LBL substrates showed a sustained release as compared to the uncoated group. Osteoblasts adhering to TNT-SV-LBL substrates attached well and displayed significantly higher (p < 0.01) cell viability compared with the other substrates. More importantly, osteoblasts grown on TNT-SV-LBL substrates displayed a statistically significant (p < 0.01 or p < 0.05) increase in protein production levels of alkaline phosphatase (ALP), osteocalcin (OC) and mRNA expression of runt related transcription factor 2 (Runx2), ALP, collagen type I (Col I), osteopontin (OPN), OC and osteoprotegerin (OPG) compared to the other groups after 4, 7 and 14 days of culture, respectively. Additionally, multinuclear osteoclastic differentiation of RAW264.7 cells grown on TNT-SV-LBL substrates was inhibited as confirmed by tartrate-resistant acid phosphatase (TRAP) analysis. These

  11. Levels of radioactivity in Qatar

    International Nuclear Information System (INIS)

    Al-Thani, A.A.; Abdul-Majid, S.; Mohammed, K.

    1995-01-01

    The levels of natural and man-made radioactivity in soil and seabed were measured in Qatar to assess radiation exposure levels and to evaluate any radioactive contamination that may have reached the country from fallout or due to the Chernobyl accident radioactivity release. Qatar peninsula is located on the Arabian Gulf, 4500 km from Chernobyl, and has an area of ∼11,600 km 2 and a population of ∼600,000

  12. Level structure in 123Xe

    International Nuclear Information System (INIS)

    Luukko, A.; Hattula, J.; Helppi, H.; Knuuttila, O.

    1980-09-01

    The level structure of 123 Xe has been studied with 122 Te( 3 He,2n) and 123 Te( 3 He,3n) reactions using in-beam γ-ray spectroscopic methods. Band-like level structures based on the unique-parity hsub(11/2) neutron state and different low-j states are observed. The isomeric state proposed earlier is established at 185.4 keV with a half-life of 5.6+-0.3 μs, and a new spin assignment of 7/2 - is proposed for this level. A triaxial-rotor-model calculation has been performed to interprete the negative-parity level system. Because of the 7/2 - state, we do not obtain a consistent description of the negative-parity states with the triaxial rotor model, unlike the heavier odd-A Xe nuclei. On the other hand, the positive-parity level structures are interpreted in terms of the core-quasiparticle model supposing a vibrational core. This indicates different core shapes for the positive- and negative-parity level systems. (author)

  13. Intermittent sea-level acceleration

    Science.gov (United States)

    Olivieri, M.; Spada, G.

    2013-10-01

    Using instrumental observations from the Permanent Service for Mean Sea Level (PSMSL), we provide a new assessment of the global sea-level acceleration for the last ~ 2 centuries (1820-2010). Our results, obtained by a stack of tide gauge time series, confirm the existence of a global sea-level acceleration (GSLA) and, coherently with independent assessments so far, they point to a value close to 0.01 mm/yr2. However, differently from previous studies, we discuss how change points or abrupt inflections in individual sea-level time series have contributed to the GSLA. Our analysis, based on methods borrowed from econometrics, suggests the existence of two distinct driving mechanisms for the GSLA, both involving a minority of tide gauges globally. The first effectively implies a gradual increase in the rate of sea-level rise at individual tide gauges, while the second is manifest through a sequence of catastrophic variations of the sea-level trend. These occurred intermittently since the end of the 19th century and became more frequent during the last four decades.

  14. Serum gonadotropins levels in childhood

    International Nuclear Information System (INIS)

    Hertogh, R. De; Vankrieken, L.; Wolter, R.; Vliet, G. Van

    1989-01-01

    The complex changes in serum LH and FSH levels from infancy to adulthood are diversely evaluated by radioimmunoassays or bioassays. The relative lack of sensitivity and specificity of radioimmunoassay, using polyclonal antibodies, could possibly be overcome by new immunoradiometric assays, using specific antibodies to LH and FSH. Significant differences were indeed observed between radioimmunoassays and immunoradiometric assays. During the prepubertal period, LH levels, measured by the immunoradiometric assays, were below the sensitivity of the method in the majority of the samples. LH levels were, however, well detectable when measured with radioimmunoassay, showing the heterogeneity of circulating LH structures. At the onset of puberty, LH levels increased at least 3 to 4 times in both sexes, when measured with immunoradiometric assays, whereas their increase was only 20 to 60% with the radioimmunoassays. FSH levels remained well detectable in the prepubertal period whether measured by immunoradiometric or radioimmunoassays. At pubertal onset, FSH increase in both sexes was more important in the immunoradiometric assays. The results obtained with immunoradiometric assays give a better insight into the quantitative and qualitative function of the gonadotropes during childhood. The almost complete absence of LH during the prepubertal period and the steep increase at the onset of puberty better reflects the reported data obtained with bioassays. The persistance of significant levels of FSH in the prepubertal ages, and the lesser increase at the onset of puberty, when compared with LH, illustrates that the individual regulation of LH and FSH secretion vary over time and is influenced by developmental factors. (author)

  15. Reactor water level control device

    International Nuclear Information System (INIS)

    Utagawa, Kazuyuki.

    1993-01-01

    A device of the present invention can effectively control fluctuation of a reactor water level upon power change by reactor core flow rate control operation. That is, (1) a feedback control section calculates a feedwater flow rate control amount based on a deviation between a set value of a reactor water level and a reactor water level signal. (2) a feed forward control section forecasts steam flow rate change based on a reactor core flow rate signal or a signal determining the reactor core flow rate, to calculate a feedwater flow rate control amount which off sets the steam flow rate change. Then, the sum of the output signal from the process (1) and the output signal from the process (2) is determined as a final feedwater flow rate control signal. With such procedures, it is possible to forecast the steam flow rate change accompanying the reactor core flow rate control operation, thereby enabling to conduct preceding feedwater flow rate control operation which off sets the reactor water level fluctuation based on the steam flow rate change. Further, a reactor water level deviated from the forecast can be controlled by feedback control. Accordingly, reactor water level fluctuation upon power exchange due to the reactor core flow rate control operation can rapidly be suppressed. (I.S.)

  16. Low-level toxicity of chemicals: No acceptable levels?

    Directory of Open Access Journals (Sweden)

    Bruce P Lanphear

    2017-12-01

    Full Text Available Over the past 3 decades, in a series of studies on some of the most extensively studied toxic chemicals and pollutants, scientists have found that the amount of toxic chemical linked with the development of a disease or death-which is central to determining "safe" or "hazardous" levels-is proportionately greater at the lowest dose or levels of exposure. These results, which are contrary to the way the United States Environmental Protection Agency (EPA and other regulatory agencies assess the risk of chemicals, indicate that we have underestimated the impact of toxic chemicals on death and disease. If widely disseminated chemicals and pollutants-like radon, lead, airborne particles, asbestos, tobacco, and benzene-do not exhibit a threshold and are proportionately more toxic at the lowest levels of exposure, we will need to achieve near-zero exposures to protect public health.

  17. Promoting system-level learning from project-level lessons

    International Nuclear Information System (INIS)

    Jong, Amos A. de; Runhaar, Hens A.C.; Runhaar, Piety R.; Kolhoff, Arend J.; Driessen, Peter P.J.

    2012-01-01

    A growing number of low and middle income nations (LMCs) have adopted some sort of system for environmental impact assessment (EIA). However, generally many of these EIA systems are characterised by a low performance in terms of timely information dissemination, monitoring and enforcement after licencing. Donor actors (such as the World Bank) have attempted to contribute to a higher performance of EIA systems in LMCs by intervening at two levels: the project level (e.g. by providing scoping advice or EIS quality review) and the system level (e.g. by advising on EIA legislation or by capacity building). The aims of these interventions are environmental protection in concrete cases and enforcing the institutionalisation of environmental protection, respectively. Learning by actors involved is an important condition for realising these aims. A relatively underexplored form of learning concerns learning at EIA system-level via project level donor interventions. This ‘indirect’ learning potentially results in system changes that better fit the specific context(s) and hence contribute to higher performances. Our exploratory research in Ghana and the Maldives shows that thus far, ‘indirect’ learning only occurs incidentally and that donors play a modest role in promoting it. Barriers to indirect learning are related to the institutional context rather than to individual characteristics. Moreover, ‘indirect’ learning seems to flourish best in large projects where donors achieved a position of influence that they can use to evoke reflection upon system malfunctions. In order to enhance learning at all levels donors should thereby present the outcomes of the intervention elaborately (i.e. discuss the outcomes with a large audience), include practical suggestions about post-EIS activities such as monitoring procedures and enforcement options and stimulate the use of their advisory reports to generate organisational memory and ensure a better information

  18. Promoting system-level learning from project-level lessons

    Energy Technology Data Exchange (ETDEWEB)

    Jong, Amos A. de, E-mail: amosdejong@gmail.com [Innovation Management, Utrecht (Netherlands); Runhaar, Hens A.C., E-mail: h.a.c.runhaar@uu.nl [Section of Environmental Governance, Utrecht University, Utrecht (Netherlands); Runhaar, Piety R., E-mail: piety.runhaar@wur.nl [Organisational Psychology and Human Resource Development, University of Twente, Enschede (Netherlands); Kolhoff, Arend J., E-mail: Akolhoff@eia.nl [The Netherlands Commission for Environmental Assessment, Utrecht (Netherlands); Driessen, Peter P.J., E-mail: p.driessen@geo.uu.nl [Department of Innovation and Environment Sciences, Utrecht University, Utrecht (Netherlands)

    2012-02-15

    A growing number of low and middle income nations (LMCs) have adopted some sort of system for environmental impact assessment (EIA). However, generally many of these EIA systems are characterised by a low performance in terms of timely information dissemination, monitoring and enforcement after licencing. Donor actors (such as the World Bank) have attempted to contribute to a higher performance of EIA systems in LMCs by intervening at two levels: the project level (e.g. by providing scoping advice or EIS quality review) and the system level (e.g. by advising on EIA legislation or by capacity building). The aims of these interventions are environmental protection in concrete cases and enforcing the institutionalisation of environmental protection, respectively. Learning by actors involved is an important condition for realising these aims. A relatively underexplored form of learning concerns learning at EIA system-level via project level donor interventions. This 'indirect' learning potentially results in system changes that better fit the specific context(s) and hence contribute to higher performances. Our exploratory research in Ghana and the Maldives shows that thus far, 'indirect' learning only occurs incidentally and that donors play a modest role in promoting it. Barriers to indirect learning are related to the institutional context rather than to individual characteristics. Moreover, 'indirect' learning seems to flourish best in large projects where donors achieved a position of influence that they can use to evoke reflection upon system malfunctions. In order to enhance learning at all levels donors should thereby present the outcomes of the intervention elaborately (i.e. discuss the outcomes with a large audience), include practical suggestions about post-EIS activities such as monitoring procedures and enforcement options and stimulate the use of their advisory reports to generate organisational memory and ensure a better

  19. State level operations and interaction with facility level systems

    International Nuclear Information System (INIS)

    Bellinger, J.

    1989-01-01

    The role of the State System of Accounting for and Control of Nuclear Materials at the State level, particularly the role of the National Authority, in ensuring that both national and international safeguards objectives are met is discussed. The legislative basis for the National Authority is examined. The activities of Australia's National Authority - the Australian Safeguards Office - are described

  20. Level densities in nuclear physics

    International Nuclear Information System (INIS)

    Beckerman, M.

    1978-01-01

    In the independent-particle model nucleons move independently in a central potential. There is a well-defined set of single- particle orbitals, each nucleon occupies one of these orbitals subject to Fermi statistics, and the total energy of the nucleus is equal to the sum of the energies of the individual nucleons. The basic question is the range of validity of this Fermi gas description and, in particular, the roles of the residual interactions and collective modes. A detailed examination of experimental level densities in light-mass system is given to provide some insight into these questions. Level densities over the first 10 MeV or so in excitation energy as deduced from neutron and proton resonances data and from spectra of low-lying bound levels are discussed. To exhibit some of the salient features of these data comparisons to independent-particle (shell) model calculations are presented. Shell structure is predicted to manifest itself through discontinuities in the single-particle level density at the Fermi energy and through variatons in the occupancy of the valence orbitals. These predictions are examined through combinatorial calculations performed with the Grover [Phys. Rev., 157, 832(1967), 185 1303(1969)] odometer method. Before the discussion of the experimenta results, statistical mechanical level densities for spherical nuclei are reviewed. After consideration of deformed nuclei, the conclusions resulting from this work are drawn. 7 figures, 3 tables

  1. Space elevator systems level analysis

    Energy Technology Data Exchange (ETDEWEB)

    Laubscher, B. E. (Bryan E.)

    2004-01-01

    The Space Elevator (SE) represents a major paradigm shift in space access. It involves new, untried technologies in most of its subsystems. Thus the successful construction of the SE requires a significant amount of development, This in turn implies a high level of risk for the SE. This paper will present a systems level analysis of the SE by subdividing its components into their subsystems to determine their level of technological maturity. such a high-risk endeavor is to follow a disciplined approach to the challenges. A systems level analysis informs this process and is the guide to where resources should be applied in the development processes. It is an efficient path that, if followed, minimizes the overall risk of the system's development. systems level analysis is that the overall system is divided naturally into its subsystems, and those subsystems are further subdivided as appropriate for the analysis. By dealing with the complex system in layers, the parameter space of decisions is kept manageable. Moreover, A rational way to manage One key aspect of a resources are not expended capriciously; rather, resources are put toward the biggest challenges and most promising solutions. This overall graded approach is a proven road to success. The analysis includes topics such as nanotube technology, deployment scenario, power beaming technology, ground-based hardware and operations, ribbon maintenance and repair and climber technology.

  2. Nuclear level mixing resonance spectroscopy

    International Nuclear Information System (INIS)

    Coussement, R.; Put, P.; Scheveneels, G.; Hardeman, F.

    1985-01-01

    The existent methods for measuring quadrupole interactions are not suited to nuclei with lifetimes in the micro-seconds to minutes region. AD/NQR, a possible candidate in this lifetime gap, has not yet succeeded in overcoming its predicted difficulties. A new resonant method, recently developed and based on the principles of level mixing (cfr atomic spectroscopy) covers this less accessible lifetime range. Many other kinds of resonances can be described according to the level mixing formalism. The particular example of NMR as a level mixing resonance (LMR) is discussed. The underlying theory of LMR and its important consequences, leading to some interesting features of the method, is briefly formulated. Two successfully performed measurements demonstrate the feasibility and the predicted characteristics of this new promising method. (orig.)

  3. Low-level Radioactivity Measurements

    International Nuclear Information System (INIS)

    Churtgen, C.

    2007-01-01

    The low-level radioactivity measurements service performs measurements of alpha or beta emitters on various types of low-radioactivity samples (biological and environmental) from internal and external clients. to maintain and develop techniques concerning the measurement of low-level radioactivity of alpha and beta emitting radionuclides in environmental or biological samples; to measure these samples by means of low-background counters (liquid scintillators, proportional counters, ZnS counters and alpha-spectrometers); to support and advise the nuclear and non-nuclear industry on problems of radioactive contamination or low level radioactivity measurements; to maintain the quality assurance system according to the ISO17025 standard for which we obtained the Beltest accreditation in 1998; to assess the internal dose from occupational intakes of radionuclides for workers of the nuclear industry;

  4. High Level Radioactive Waste Management

    International Nuclear Information System (INIS)

    1991-01-01

    The proceedings of the second annual international conference on High Level Radioactive Waste Management, held on April 28--May 3, 1991, Las Vegas, Nevada, provides information on the current technical issue related to international high level radioactive waste management activities and how they relate to society as a whole. Besides discussing such technical topics as the best form of the waste, the integrity of storage containers, design and construction of a repository, the broader social aspects of these issues are explored in papers on such subjects as conformance to regulations, transportation safety, and public education. By providing this wider perspective of high level radioactive waste management, it becomes apparent that the various disciplines involved in this field are interrelated and that they should work to integrate their waste management activities. Individual records are processed separately for the data bases

  5. High-level Petri Nets

    DEFF Research Database (Denmark)

    various journals and collections. As a result, much of this knowledge is not readily available to people who may be interested in using high-level nets. Within the Petri net community this problem has been discussed many times, and as an outcome this book has been compiled. The book contains reprints...... of some of the most important papers on the application and theory of high-level Petri nets. In this way it makes the relevant literature more available. It is our hope that the book will be a useful source of information and that, e.g., it can be used in the organization of Petri net courses. To make......High-level Petri nets are now widely used in both theoretical analysis and practical modelling of concurrent systems. The main reason for the success of this class of net models is that they make it possible to obtain much more succinct and manageable descriptions than can be obtained by means...

  6. Low-level Radioactivity Measurements

    International Nuclear Information System (INIS)

    Hurtgen, C.

    2002-01-01

    The objectives of the research performed in the area of low-level radioactivity measurements are (1) to maintain and develop techniques for the measurement of low-level environmental and biological samples, (2) to measure these samples by means of low-background counters (liquid scintillators, proportional counters, ZnS counters, alpha spectrometry), (3) to support and advise the nuclear and non-nuclear industry on problems of radioactive contamination and low-level radioactivity measurements; (4) to maintain and improve the quality assurance system according to the ISO17025 standard; and (5) to assess the internal dose from occupational intakes of radionuclides of workers of the nuclear industry. Progress and achievements in these areas in 2001 are reported

  7. Integrated at the neighbourhood level

    DEFF Research Database (Denmark)

    Putri, Prathiwi Widyatmi

    2017-01-01

    Cities in the Global South are generally vast due to urban sprawl. They are characterised by a varying level of density, and enclaves of informal settlements. Within this context, this article addresses the limits of large-scale and centralised water systems. It seeks to understand, qualitatively......-spatial characteristics of local communities can be accommodated. Smaller-scale development intervention also means stimulating creativity in planning and policy-making processes to address water-infrastructure needs at local levels and opens possibilities for integrating water-infrastructures with public space....... Such a decentralised approach matters to improve the overall socio-spatial quality of a neighbourhood, however it requires, in parallel, new institutional mechanisms to provide a coherent water and environmental management system at the urban level. This article argues for a synergy of two axes: the water sector...

  8. Low-level Radioactivity Measurements

    International Nuclear Information System (INIS)

    Hurtgen, C.

    2001-01-01

    The objectives of the research performed in the area of low-level radioactivity measurements are (1) to maintain and develop techniques for the measurement of low-level environmental and biological samples, (2) to measure these samples by means of low-background counters (liquid scintillators, proportional counters, ZnS counters, alpha spectrometry), (3) to support and advice the nuclear and non-nuclear industry in matters concerning radioactive contamination and/or low-level radioactivity measurements; (4) to maintain the quality assurance system according to the EN45001/ISO17025 standard; and (5) to assess the internal dose from occupational intakes of radionuclides of workers of the nuclear industry. Progress and achievements in these areas in 2000 are reported

  9. Modeling Multi-Level Systems

    CERN Document Server

    Iordache, Octavian

    2011-01-01

    This book is devoted to modeling of multi-level complex systems, a challenging domain for engineers, researchers and entrepreneurs, confronted with the transition from learning and adaptability to evolvability and autonomy for technologies, devices and problem solving methods. Chapter 1 introduces the multi-scale and multi-level systems and highlights their presence in different domains of science and technology. Methodologies as, random systems, non-Archimedean analysis, category theory and specific techniques as model categorification and integrative closure, are presented in chapter 2. Chapters 3 and 4 describe polystochastic models, PSM, and their developments. Categorical formulation of integrative closure offers the general PSM framework which serves as a flexible guideline for a large variety of multi-level modeling problems. Focusing on chemical engineering, pharmaceutical and environmental case studies, the chapters 5 to 8 analyze mixing, turbulent dispersion and entropy production for multi-scale sy...

  10. Deafness and motor abilities level

    Directory of Open Access Journals (Sweden)

    A Zwierzchowska

    2008-09-01

    Full Text Available The audition injury hinders some motor motions and the organised coordination at the higher level and may be a cause of disturbances and disorder in some motor abilities adoption. It was assumed that deafness including its aetiology and injury mechanism may significantly influence the motor development of human being. The study aimed in checking if the deafness, as a result of various unfavourable factors, determines the motor development of children and youngsters. Consequently the dependency between qualitative features i.e.: signed motor level and aetiology, audition injury mechanism and the deafness degree was examined. The mechanism and aetiology of hearing correlated with the motor abilities displayed statistically significant dependencies in few motor trials only. Revealed correlations regarded mostly the coordination trials excluding the flexibility one. Statistically significant dependencies between the audition diminution and the motor abilities level were not found.

  11. Is sea-level rising?

    Digital Repository Service at National Institute of Oceanography (India)

    Unnikrishnan, A.S.

    correction in the estimation of trends obtained for tide gauge records. The altimeter data permits to prepare spatial maps of sea-level rise trends. We present a map prepared for the Indian Ocean (Figure 4) north of 10oS , which shows a fairly uniform... drawn information from research papers published by the author and report of the IPCC AR5 WG1 Chapter 13: Sea Level Changes, in which the author has served as a ‘Lead Author’. Figure1 is prepared using data from the University of Colorado. Nerem, R...

  12. Levels of Outsourcing and Offshoring

    DEFF Research Database (Denmark)

    Madsen, Erik Skov; Slepniov, Dmitrij

    2011-01-01

    The purpose of this paper is to examine the evolution of offshoring and outsourcing over time and highlight strategic considerations underpinning this process in companies. On the basis of four case studies of Danish and German industrial companies, this paper develops a holistic framework...... conceptualizing various levels of outsourcing and offshoring as well as factors driving the transition between these levels. The framework adds to better understanding of the process and challenges the linear nature of it and suggests that ‘backsourcing’ and repatriation of activities should receive more...

  13. Colloids related to low level and intermediate level waste

    International Nuclear Information System (INIS)

    Ramsay, J.D.F.; Russell, P.J.; Avery, R.G.

    1991-01-01

    A comprehensive research investigation has been undertaken to improve the understanding of the potential role of colloids in the context of disposal and storage of low level and intermediate level waste immobilized in cement. Several topics have been investigated which include: (a) the study of the formation and characteristics of colloids in cement leachates; (b) the effects of the near-field aqueous chemistry on the characteristics of colloids in repository environments; (c) colloid sorption behaviour; (d) interactions of near-field materials with leachates; (e) characteristics of near-field materials in EC repository simulation tests; and (f) colloid migration behaviour. These experimental investigations should provide data and a basis for the development of transport models and leaching mechanisms, and thus relate directly to the part of the Task 3 programme concerned with migration and retention of radionuclides in the near field. 114 Figs.; 39 Tabs.; 12 Refs

  14. High-Level Radioactive Waste.

    Science.gov (United States)

    Hayden, Howard C.

    1995-01-01

    Presents a method to calculate the amount of high-level radioactive waste by taking into consideration the following factors: the fission process that yields the waste, identification of the waste, the energy required to run a 1-GWe plant for one year, and the uranium mass required to produce that energy. Briefly discusses waste disposal and…

  15. Beyond macrocognition : The transaction level

    NARCIS (Netherlands)

    Schraagen, J.M.C.

    2017-01-01

    The purpose of this paper is to respond to a number of developments in the past 15 years in the areas of NDM and macrocognition. In my view, these developments necessitate the definition of a new systems level, extending and modifying Newell’s (1990) "bands of cognition". I will argue that what has

  16. Cultural Understanding: Spanish Level 1.

    Science.gov (United States)

    Scott, Reid

    The teacher's attention is focused on selected elements of Spanish culture which may be taught integrally with instructional materials found in the first-year Spanish texts "Entender y Hablar", "La Familia Fernandez", and "A-LM Spanish, Level One". Items are cross-referenced for 42 cultural concepts ranging from nicknames to streets, roads, and…

  17. Level Design as Model Transformation

    NARCIS (Netherlands)

    Dormans, Joris

    2011-01-01

    This paper frames the process of designing a level in a game as a series of model transformations. The transformations correspond to the application of particular design principles, such as the use of locks and keys to transform a linear mission into a branching space. It shows that by using rewrite

  18. Biocards and Level of Abstraction

    DEFF Research Database (Denmark)

    Lenau, Torben Anker; Keshwani, Sonal; Chakrabarti, Amaresh

    2015-01-01

    Biocards are formal descriptions of biological phenomena and their underlying functional principles. They are used in bioinspired design to document search results and to communicate the findings for use in the further design process. The present study explored the effect of abstraction level used...

  19. Time orientation and construal level

    NARCIS (Netherlands)

    Beek, van Jannette; Handgraaf, Michel J.J.; Antonides, Gerrit

    2017-01-01

    Eating and exercising behaviour are both characterized by immediate and future consequences. Consequently, consideration of these consequences (i.e. time orientation) predicts eating and exercising behaviour. We investigate whether construal level acts as an underlying mechanism of these

  20. Engineering at the Elementary Level

    Science.gov (United States)

    McGrew, Cheryl

    2012-01-01

    Can engineering technology be taught at the elementary level? Designing and building trebuchets, catapults, solar cars, and mousetrap vehicles in a west central Florida elementary class was considered very unusual in recent years. After a review of current research on failing schools and poor curriculum, the author wondered what her school could…

  1. Energy levels of 56Mn

    DEFF Research Database (Denmark)

    Van Assche, P. H. M.; Baader, H. A.; Koch, H. R.

    1971-01-01

    The low-energy spectrum of the 55Mn(n,γ)56 Mn reaction has been studied with a γ-diffraction spectrometer. These data allowed the construction of a level scheme for 56Mn with two previously unobserved doublets. High-energy γ-transitions to the low-energy states have been measured for different...

  2. Transportable type neutron level indicators

    International Nuclear Information System (INIS)

    Khatskevich, M.V.; Kalinin, O.V.; Moskovkin, V.N.; Molchanov, A.V.; Bobkov, A.D.; Rabotnov, Yu.A.

    1979-01-01

    Some peculiarities of designing level neutron converters (LNC) for portable indicators or level neutron relays are considered. The effect of the LNC geometry and other factors on measurement errors has been studied. Calibration results of the LNC with a neutron reflector and without it are presented. It is shown that the problem of level monitoring with the help of portable indicators can be solved practically for any volume, provided two LNC modifications with reflectors are available: the NPU-G modification with horizontal location of a counter for large volumes and the NPU-V with vertical location of a counter for lesser volumes. A possibility of perfecting LNC performances by shielding the counter with thermal neutron absorbers has been studied. The design of the NPU-V modification for the NIUP-2 level indicator is described. It is intended for tubes and cylinders 30-100 mm in diameter. Measurements carried out on different steel and aluminium vessels with a diameter ranging from 300 to 100 mm and a wall thickness of up to 16 mm with the help of the NPU-V and NPU-G modifications proved the efficiency of the LNC to control a variety of products (kerosine, gasoline, oils, acids, alkalis) [ru

  3. Visualizing attitudes towards service levels

    NARCIS (Netherlands)

    K.Y. Lam (Kar Yin); M. van de Velden (Michel); Ph.H.B.F. Franses (Philip Hans)

    2011-01-01

    textabstractTo assess the attitudes with respect to the quality of banks’ service levels, we use survey data amongst more than 250 Chief Financial Officers (CFOs) of a range of Netherlands-based companies. These companies range from small to very large (including multinationals as Philips and Shell)

  4. Selfishness Level of Strategic Games

    NARCIS (Netherlands)

    Apt, K.R.; Schäfer, G.

    2014-01-01

    We introduce a new measure of the discrepancy in strategic games between the social welfare in a Nash equilibrium and in a social optimum, that we call selfishness level. It is the smallest fraction of the social welfare that needs to be offered to each player to achieve that a social optimum is

  5. Logical Entity Level Sentiment Analysis

    DEFF Research Database (Denmark)

    Petersen, Niklas Christoffer; Villadsen, Jørgen

    2017-01-01

    We present a formal logical approach using a combinatory categorial grammar for entity level sentiment analysis that utilizes machine learning techniques for efficient syntactical tagging and performs a deep structural analysis of the syntactical properties of texts in order to yield precise resu...

  6. RPython high-level synthesis

    Science.gov (United States)

    Cieszewski, Radoslaw; Linczuk, Maciej

    2016-09-01

    The development of FPGA technology and the increasing complexity of applications in recent decades have forced compilers to move to higher abstraction levels. Compilers interprets an algorithmic description of a desired behavior written in High-Level Languages (HLLs) and translate it to Hardware Description Languages (HDLs). This paper presents a RPython based High-Level synthesis (HLS) compiler. The compiler get the configuration parameters and map RPython program to VHDL. Then, VHDL code can be used to program FPGA chips. In comparison of other technologies usage, FPGAs have the potential to achieve far greater performance than software as a result of omitting the fetch-decode-execute operations of General Purpose Processors (GPUs), and introduce more parallel computation. This can be exploited by utilizing many resources at the same time. Creating parallel algorithms computed with FPGAs in pure HDL is difficult and time consuming. Implementation time can be greatly reduced with High-Level Synthesis compiler. This article describes design methodologies and tools, implementation and first results of created VHDL backend for RPython compiler.

  7. Middle Level Learning Number 47

    Science.gov (United States)

    Lapham, Steven S.; Hanes, Peter; Turner, Thomas N.; Clabough, Jeremiah C.; Cole, William

    2013-01-01

    This issue's "Middle Level Learning" section presents two articles. The first is "Harriet Tubman: Emancipate Yourself!" (by Steven S. Lapham and Peter Hanes). "Argo," which won the 2012 Oscar for best picture, was about a daring escape of six U.S. diplomats from Iran during the 1979 hostage crisis. Now imagine the…

  8. Legitimizing differentiated flood protection levels

    NARCIS (Netherlands)

    Thomas, Hartmann; Spit, Tejo

    2016-01-01

    The European flood risk management plan is a new instrument introduced by the Floods Directive. It introduces a spatial turn and a scenario approach in flood risk management, ultimately leading to differentiated flood protection levels on a catchment basis. This challenges the traditional sources of

  9. Reduction of parathyoid hormone levels

    DEFF Research Database (Denmark)

    2011-01-01

    A method of acutely reducing the plasma level of PTH of a patient having an elevated PTH comprising the administration of a pharmaceutical composition comprising a GLP-2, or a variant, an analogue, or derivative of GLP-2 having the ability to bind and activate a GLP-2 receptor such as GLP-2 1-34...

  10. High-level radioactive wastes

    International Nuclear Information System (INIS)

    Grissom, M.C.

    1982-10-01

    This bibliography contains 812 citations on high-level radioactive wastes included in the Department of Energy's Energy Data Base from January 1981 through July 1982. These citations are to research reports, journal articles, books, patents, theses, and conference papers from worldwide sources. Five indexes are provided: Corporate Author, Personal Author, Subject, Contract Number, and Report Number

  11. Very low level radioactive material

    International Nuclear Information System (INIS)

    Schaller, K.H.; Linsley, G.; Elert, M.

    1993-01-01

    Man's environment contains naturally occurring radionuclides and doses from exposures to these radionuclides mostly cannot be avoided. Consequently, almost everything may be considered as very low level radioactive material. In practical terms, management and the selection of different routes for low level material is confined to material which was subject to industrial processing or which is under a system of radiological control. Natural radionuclides with concentrations reaching reporting or notification levels will be discussed below; nevertheless, the main body of this paper will be devoted to material, mainly of artificial origin, which is in the system involving notification, registration and licensing of practices and sources. It includes material managed in the nuclear sector and sources containing artificially produced radionuclides used in hospitals, and in industry. Radioactive materials emit ionising radiations which are harmful to man and his environment. National and international regulations provide the frame for the system of radiation protection. Nevertheless, concentrations, quantities or types of radionuclide may be such, that the material presents a very low hazard, and may therefore be removed from regulatory control, as it would be a waste of time and effort to continue supervision. These materials are said to be exempted from regulatory control. Material exempted in a particular country is no longer distinguishable from ''ordinary'' material and may be moved from country to country. Unfortunately, criteria for exempting radioactive materials differ strongly between countries and free trade. Therefore there is a necessity for an international approach to be developed for exemption levels

  12. FINANCIAL CRISIS FROM THE MACROECONOMIC LEVEL TO THE MICROECONOMIC LEVEL

    OpenAIRE

    SANDA GHEORGHE GABRIEL; ENEA CONSTANTA

    2014-01-01

    The current economic and financial crisis, beyond the problems it generates both at micro and macro level, should determine an adaptation of the mechanisms, institutions and monetary / financial policies to the real economy we are facing. The issue of financial crises is extremely complex, including a series of quantitative and qualitative factors, financial, economic, social, ethical, technological and human, which can intervene and influence the financial operations in a...

  13. Disposal of high level and intermediate level radioactive wastes

    International Nuclear Information System (INIS)

    Flowers, R.H.

    1991-01-01

    The waste products from the nuclear industry are relatively small in volume. Apart from a few minor gaseous and liquid waste streams, containing readily dispersible elements of low radiotoxicity, all these products are processed into stable solid packages for disposal in underground repositories. Because the volumes are small, and because radioactive wastes are latecomers on the industrial scene, a whole new industry with a world-wide technological infrastructure has grown up alongside the nuclear power industry to carry out the waste processing and disposal to very high standards. Some of the technical approaches used, and the Regulatory controls which have been developed, will undoubtedly find application in the future to the management of non-radioactive toxic wastes. The repository site outlined would contain even high-level radioactive wastes and spent fuels being contained without significant radiation dose rates to the public. Water pathway dose rates are likely to be lowest for vitrified high-level wastes with spent PWR fuel and intermediate level wastes being somewhat higher. (author)

  14. Leptin levels in infertile males

    International Nuclear Information System (INIS)

    Jahan, S.; Bibi, R.; Ahmed, S.

    2011-01-01

    Objective: To determine the leptin levels in the serum of normal, sub fertile and infertile men. Study Design: Analytical study. Place and Duration of Study: Department of Animal Sciences Quaid-e-Azam University, Islamabad, National Institute of Health (NIH), Islamabad and Dr. Salma and Kafeel Medical Centre, Islamabad, from April to December 2009. Methodology: Serum leptin levels hormonal concentrations (LH, FSH and testosterone) were determined by EIA in 154 males including 24 (15.58%) fertile, 19 (12.34%) polyzoospermic (PZs), 26 (16.88%) teratozoospermic (TZs), 27 (17.53%) astheno-teratozoospermic (ATZs), 18 (11.69%) oligozoospermic (OZs), 18 (11.69%) oligo-astheno-teratozoospermic (OATZs), 11 (7.14%) obstructive azoospermic (OBST-AZOOs) and 11 (7.14%) non-obstructive azoospermic (NON-OBST-AZOOs). BMI was also determined, divided into groups of greater than 24. Hormonal concentrations were compared by ANOVA and correlation was performed by using Graph pad prism version 5. Results: Significantly high levels of leptin concentrations were found in fertile (p 24 compared to fertile and infertile male patients with BMI 24. Leptin showed a significant positive correlation with LH (p < 0.01) and FSH (p < 0.002) and a significant negative correlation with testosterone (p < 0.001). Conclusion: Abnormal leptin level was significantly associated with fertility problems in males. Providing a link between leptin and reproduction factors contributing in control of testosterone and gonadotropins secretion in many aspects depending on fertility status in male subjects. BMI appears to have significant association with serum leptin levels. (author)

  15. Level gauge using neutron radiation

    International Nuclear Information System (INIS)

    Mathew, P.J.

    1985-01-01

    Apparatus for determining the level of a solid or liquid material in a container comprises: a vertical guide within or alongside the container; a sensor positioned within the guide; means for moving the sensor along the guide; and means for monitoring the position of the sensor. The sensor comprises a source of fast neutrons, a detector for thermal neutrons, and a body of a neutron moderating material in close proximity to the detector. Thermal neutrons produced by fast neutron irradiation of the solid or liquid material, or thermal neutrons produced by irradiation of the neutron-moderating material by fast or epithermal neutrons reflected by the solid or liquid material, are detected when the sensor is positioned at or below the level of the material in the container

  16. Radon levels in Oslo schools

    International Nuclear Information System (INIS)

    Birovlev, A.

    2004-01-01

    Radon measurements using passive CR-39 detectors have been conducted in all schools in Oslo municipality during winter 2003/2004. Results are presented and discussed in the light of qualitative and quantitative factors, some of which are specific for schools as workplaces. Analysis is conducted with respect to factors relating to building construction type, ventilation principle, age of building, building size etc. The influence of ventilation type on radon levels is studied, and problems of investigations based purely on conventional passive radon detectors are noted. Over-estimation of radon concentration by passive detectors and day-night variations of indoor radon levels in buildings with mechanical ventilation systems are discussed. Several guiding principles for planning similar investigations based on above discussions are outlined. (author)

  17. Technology Performance Level Assessment Methodology.

    Energy Technology Data Exchange (ETDEWEB)

    Roberts, Jesse D.; Bull, Diana L; Malins, Robert Joseph; Costello, Ronan Patrick; Aurelien Babarit; Kim Nielsen; Claudio Bittencourt Ferreira; Ben Kennedy; Kathryn Dykes; Jochem Weber

    2017-04-01

    The technology performance level (TPL) assessments can be applied at all technology development stages and associated technology readiness levels (TRLs). Even, and particularly, at low TRLs the TPL assessment is very effective as it, holistically, considers a wide range of WEC attributes that determine the techno-economic performance potential of the WEC farm when fully developed for commercial operation. The TPL assessment also highlights potential showstoppers at the earliest possible stage of the WEC technology development. Hence, the TPL assessment identifies the technology independent “performance requirements.” In order to achieve a successful solution, the entirety of the performance requirements within the TPL must be considered because, in the end, all the stakeholder needs must be achieved. The basis for performing a TPL assessment comes from the information provided in a dedicated format, the Technical Submission Form (TSF). The TSF requests information from the WEC developer that is required to answer the questions posed in the TPL assessment document.

  18. Mission Level Autonomy for USSV

    Science.gov (United States)

    Huntsberger, Terry; Stirb, Robert C.; Brizzolara, Robert

    2011-01-01

    On-water demonstration of a wide range of mission-proven, advanced technologies at TRL 5+ that provide a total integrated, modular approach to effectively address the majority of the key needs for full mission-level autonomous, cross-platform control of USV s. Wide baseline stereo system mounted on the ONR USSV was shown to be an effective sensing modality for tracking of dynamic contacts as a first step to automated retrieval operations. CASPER onboard planner/replanner successfully demonstrated realtime, on-water resource-based analysis for mission-level goal achievement and on-the-fly opportunistic replanning. Full mixed mode autonomy was demonstrated on-water with a seamless transition between operator over-ride and return to current mission plan. Autonomous cooperative operations for fixed asset protection and High Value Unit escort using 2 USVs (AMN1 & 14m RHIB) were demonstrated during Trident Warrior 2010 in JUN 2010

  19. Students as Math Level Designers

    DEFF Research Database (Denmark)

    Jensen, Erik Ottar; Hanghøj, Thorkild; Schoenau-Fog, Henrik

    The short paper presents preliminary findings from a pilot study on how students become motivated through design of learning games in math. The research is carried out in a Danish public school with two classes of 5th graders (N = 42 students). Over the course of two weeks, the students work...... with a design template for a runner game in the Unity 3D game design engine. The students are introduced to the concept of “flow” (Csikszentmihalyi, 1991) as a game design principle and are asked to design levels for a math runner game, which are both engaging as well as a meaningful way of learning math....... In this way, the students are positioned as “math level designers”, which means that they both have to redesign the difficulty of the runner game as well as the difficulty of the mathematical questions and possible answers....

  20. Feature-level domain adaptation

    DEFF Research Database (Denmark)

    Kouw, Wouter M.; Van Der Maaten, Laurens J P; Krijthe, Jesse H.

    2016-01-01

    -level domain adaptation (flda), that models the dependence between the two domains by means of a feature-level transfer model that is trained to describe the transfer from source to target domain. Subsequently, we train a domain-adapted classifier by minimizing the expected loss under the resulting transfer...... modeled via a dropout distribution, which allows the classiffier to adapt to differences in the marginal probability of features in the source and the target domain. Our experiments on several real-world problems show that flda performs on par with state-of-the-art domainadaptation techniques.......Domain adaptation is the supervised learning setting in which the training and test data are sampled from different distributions: training data is sampled from a source domain, whilst test data is sampled from a target domain. This paper proposes and studies an approach, called feature...

  1. Low-level radioactive waste

    International Nuclear Information System (INIS)

    McLaren, L.H.

    1983-03-01

    This bibliography contains information on low-level radioactive waste included in the Department of Energy's Energy Data Base for January through December 1982. The abstracts are grouped by subject category as shown in the table of contents. Entries in the subject index also facilitate access by subject, e.g., Low-Level Radioactive Wastes/Transport. Within each category the arrangement is by report number for reports, followed by nonreports in reverse chronological order. These citations are to research reports, journal articles, books, patents, theses, and conference papers from worldwide sources. Five indexes, each proceded by a brief description, are provided: Corporate Author, Personal Author, Subject, Contract Number, and Report Number. 492 references

  2. Multiple Level Crowding: Crowding at the Object Parts Level and at the Object Configural level.

    Science.gov (United States)

    Kimchi, Ruth; Pirkner, Yossef

    2015-01-01

    In crowding, identification of a peripheral target in the presence of nearby flankers is worse than when the target appears alone. Prevailing theories hold that crowding occurs because of integration or "pooling" of low-level features at a single, relatively early stage of visual processing. Recent studies suggest that crowding can occur also between high-level object representations. The most relevant findings come from studies with faces and may be specific to faces. We examined whether crowding can occur at the object configural level in addition to part-level crowding, using nonface objects. Target (a disconnected square or diamond made of four elements) identification was measured at varying eccentricities. The flankers were similar either to the target parts or to the target configuration. The results showed crowding in both cases: Flankers interfered with target identification such that identification accuracy decreased with an increase in eccentricity, and no interference was observed at the fovea. Crowding by object parts, however, was weaker and had smaller spatial extent than crowding by object configurations; we related this finding to the relationship between crowding and perceptual organization. These results provide strong evidence that crowding occurs not only between object parts but also between configural representations of objects. © The Author(s) 2015.

  3. Level-3 Calorimetric Resolution available for the Level-1 and Level-2 CDF Triggers

    CERN Document Server

    Canepa, A.; Liu, T.; Cortiana, G.; Flanagan, G.; Frisch, H.; Krop, D.; Pilcher, C.; Rusu, V.; Cavaliere, V.; Greco, V.; Giannetti, P.; Piendibene, M.; Sartori, L.; Vidal, Miguel

    2008-01-01

    As the Tevatron luminosity increases sophisticated selections are required to be efficient in selecting rare events among a very huge background. To cope with this problem, CDF has pushed the offline calorimeter algorithm reconstruction resolution up to Level 2 and, when possible, even up to Level 1, increasing efficiency and, at the same time, keeping under control the rates. The CDF Run II Level 2 calorimeter trigger is implemented in hardware and is based on a simple algorithm that was used in Run I. This system has worked well for Run II at low luminosity. As the Tevatron instantaneous luminosity increases, the limitation due to this simple algorithm starts to become clear: some of the most important jet and MET (Missing ET) related triggers have large growth terms in cross section at higher luminosity. In this paper, we present an upgrade of the Level 2 Calorimeter system which makes the calorimeter trigger tower information available directly to a CPU allowing more sophisticated algorithms to be impleme...

  4. System-level musings about system-level science (Invited)

    Science.gov (United States)

    Liu, W.

    2009-12-01

    In teleology, a system has a purpose. In physics, a system has a tendency. For example, a mechanical system has a tendency to lower its potential energy. A thermodynamic system has a tendency to increase its entropy. Therefore, if geospace is seen as a system, what is its tendency? Surprisingly or not, there is no simple answer to this question. Or, to flip the statement, the answer is complex, or complexity. We can understand generally why complexity arises, as the geospace boundary is open to influences from the solar wind and Earth’s atmosphere and components of the system couple to each other in a myriad of ways to make the systemic behavior highly nonlinear. But this still begs the question: What is the system-level approach to geospace science? A reductionist view might assert that as our understanding of a component or subsystem progresses to a certain point, we can couple some together to understand the system on a higher level. However, in practice, a subsystem can almost never been observed in isolation with others. Even if such is possible, there is no guarantee that the subsystem behavior will not change when coupled to others. Hence, there is no guarantee that a subsystem, such as the ring current, has an innate and intrinsic behavior like a hydrogen atom. An absolutist conclusion from this logic can be sobering, as one would have to trace a flash of aurora to the nucleosynthesis in the solar core. The practical answer, however, is more promising; it is a mix of the common sense we call reductionism and awareness that, especially when strongly coupled, subsystems can experience behavioral changes, breakdowns, and catastrophes. If the stock answer to the systemic tendency of geospace is complexity, the objective of the system-level approach to geospace science is to define, measure, and understand this complexity. I will use the example of magnetotail dynamics to illuminate some key points in this talk.

  5. Biosafety Level 3 Recon Training

    Energy Technology Data Exchange (ETDEWEB)

    Dickens, Brian Scott [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Chavez, Melanie Ann [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Heimer, Donovan J. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Knudsen, Ryan [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Velasquez, Celina Carmelita [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-04-12

    The Biosafety Level 3 Recon training is a 3D virtual tool developed for the Counter WMD Analysis Cell (CWAC) and the Asymmetric Warfare Group (AWG) by the Application Modeling and Development Team within the NEN-3 International Threat Reduction Group. The training simulates a situation where friendly forces have secured from hostile forces a suspected bioweapons development laboratory. The trainee is a squad member tasked to investigate the facility, locate laboratories within the facility, and identify hazards to entrants and the surrounding area. Before beginning the 3D simulation, the trainee must select the appropriate MOPP level for entering the facility. The items in the simulation, including inside and outside the bioweapon facility, are items that are commonly used by scientists in Biosafety Level (BSL) laboratories. Each item has clickable red tags that, when activated, give the trainee a brief description of the item and a controllable turn-around view. The descriptions also contain information about potential hazards the item can present. Trainees must find all tagged items in order to complete the simulation, but can also reference descriptions and turn-around view of the items in a glossary menu. Training is intended to familiarize individuals whom have little or no biology or chemistry background with technical equipment used in BSL laboratories. The revised edition of this simulation (Biosafety Level 3 Virtual Lab) changes the trainee into a investigator instead of a military combatant. Many doors now require a virtual badge swipe to open. Airlock doors may come in sets such that the open door must be closed before the next door in the set can be opened. A user interface was added so that the instructor can edit the information about the items (the brief descriptions mentioned above) using the simulation software instead of the previous method of manually entering the material in xml settings files. Facility labels, such as "No Parking" and "Men

  6. Low level photoneutron detection equipment

    International Nuclear Information System (INIS)

    Ji Changsong; Zhang Yuqin; Li Yuansui

    1991-01-01

    A low level photoneutron detection equipment has been developed. The photoneutrons produced by interaction of 226 Ra gamma quanta and deutron (D) target are detected with n-n discrimination detector made up of 3 He proportional counter array. The D-content information in the target can be obtained from the measured photoneutron counts. The equipment developed is mainly used for nondestructive D-content measurement of D-devices

  7. Level structure of 154Ho

    Science.gov (United States)

    Moon, Chang-Bum; Komatsubara, Tetsuro; Furuno, Kohei

    2013-10-01

    The excited states of the odd-odd 154Ho nucleus have been studied by using in-beam γ-ray spectroscopy with the 141Pr (16O, 3n) 154Ho reaction at Elab=75 MeV. The beam was provided by the 12UD Pelletron accelerator at the University of Tsukuba. In this work, the complicated decay pattern of low energy transitions just above the T1/2=3.10 min isomer have been established. In addition, a number of new states and γ-ray transitions, especially those associated with energetically favored band termination, have been observed for the first time in 154Ho. A negative collective band and its signature partner built on the 11- level are interpreted as being based on the πh11/2⊗νi13/2 configuration. A positive band built on the 10+ level is based on the πh11/2⊗νh9/2 configuration while another positive band built on the 9+ level is being associated with the πh11/2⊗νf7/2 configuration. An energetically favored level Jπ=19- can be interpreted as being attributed to the πh11/2⊗νi13/2 configuration coupled to the 8+ state in neighboring core 152Dy, namely, a four-quasiparticle alignment based on the [πh11/2νi13/2]11-⊗[ν(h9/2f7/2)]8- configuration. Another energetically favored state at Jπ=27- is assigned the six-quasiparticle [π(h11/2)3]27/2-⊗[ν(f7/2h9/2i13/2)]27/2- configuration.

  8. Parathyroid Hormone Levels and Cognition

    Science.gov (United States)

    Burnett, J.; Smith, S.M.; Aung, K.; Dyer, C.

    2009-01-01

    Hyperparathyroidism is a well-recognized cause of impaired cognition due to hypercalcemia. However, recent studies have suggested that perhaps parathyroid hormone itself plays a role in cognition, especially executive dysfunction. The purpose of this study was to explore the relationship of parathyroid hormone levels in a study cohort of elders with impaied cognition. Methods: Sixty community-living adults, 65 years of age and older, reported to Adult Protective Services for self-neglect and 55 controls matched (on age, ethnicity, gender and socio-economic status) consented and participated in this study. The research team conducted in-home comprehensive geriatric assessments which included the Mini-mental state exam (MMSE), the 15-item geriatric depression scale (GDS) , the Wolf-Klein clock test and a comprehensive nutritional panel, which included parathyroid hormone and ionized calcium. Students t tests and linear regression analyses were performed to assess for bivariate associations. Results: Self-neglecters (M = 73.73, sd=48.4) had significantly higher PTH levels compared to controls (M =47.59, sd=28.7; t=3.59, df=98.94, p<.01). There was no significant group difference in ionized calcium levels. Overall, PTH was correlated with the MMSE (r=-.323, p=.001). Individual regression analyses revealed a statistically significant correlation between PTH and MMSE in the self-neglect group (r=-.298, p=.024) and this remained significant after controlling for ionized calcium levels in the regression. No significant associations were revealed in the control group or among any of the other cognitive measures. Conclusion: Parathyroid hormone may be associated with cognitive performance.

  9. Landau levels on a torus

    OpenAIRE

    Enrico OnofriDipartimento di Fisica, Universita` di Parma, and INFN, Gruppo Collegato di Parma, Parma, Italy

    2015-01-01

    Landau levels have represented a very rich field of research, which has gained widespread attention after their application to quantum Hall effect. In a particular gauge, the holomorphic gauge, they give a physical implementation of Bargmann's Hilbert space of entire functions. They have also been recognized as a natural bridge between Feynman's path integral and Geometric Quantization. We discuss here some mathematical subtleties involved in the formulation of the problem when one tries to s...

  10. System level modeling and component level control of fuel cells

    Science.gov (United States)

    Xue, Xingjian

    This dissertation investigates the fuel cell systems and the related technologies in three aspects: (1) system-level dynamic modeling of both PEM fuel cell (PEMFC) and solid oxide fuel cell (SOFC); (2) condition monitoring scheme development of PEM fuel cell system using model-based statistical method; and (3) strategy and algorithm development of precision control with potential application in energy systems. The dissertation first presents a system level dynamic modeling strategy for PEM fuel cells. It is well known that water plays a critical role in PEM fuel cell operations. It makes the membrane function appropriately and improves the durability. The low temperature operating conditions, however, impose modeling difficulties in characterizing the liquid-vapor two phase change phenomenon, which becomes even more complex under dynamic operating conditions. This dissertation proposes an innovative method to characterize this phenomenon, and builds a comprehensive model for PEM fuel cell at the system level. The model features the complete characterization of multi-physics dynamic coupling effects with the inclusion of dynamic phase change. The model is validated using Ballard stack experimental result from open literature. The system behavior and the internal coupling effects are also investigated using this model under various operating conditions. Anode-supported tubular SOFC is also investigated in the dissertation. While the Nernst potential plays a central role in characterizing the electrochemical performance, the traditional Nernst equation may lead to incorrect analysis results under dynamic operating conditions due to the current reverse flow phenomenon. This dissertation presents a systematic study in this regard to incorporate a modified Nernst potential expression and the heat/mass transfer into the analysis. The model is used to investigate the limitations and optimal results of various operating conditions; it can also be utilized to perform the

  11. Serum zinc level in thalassemia

    International Nuclear Information System (INIS)

    Keikhaei, B.; Badavi, M.; Pedram, M.; Zandian, K.

    2010-01-01

    To compare serum zinc level between Thalassemia Major (TM) patients and normal population at Shafa Hospital in South West of Iran. A total of 25 male and 36 female of TM patients were enrolled in this study. Out of 61 patients thirty were treated by deferroxamine (DFO) and 31 were on the combination of DFO and deferiprone (DEF) protocol therapy. Sixty normal subjects of the matching age and gender were recruited as controls. From each patient and control group 2 ml of blood was taken in fasting condition. Cell blood count and serum zinc were carried out for both thalassemia patients and normal subjects. The mean age of patients and control group was 15+- 5 years. Mean serum zinc level was 68.97+- 21.12 mu g/dl, 78.10-28.50 mu g/dl, and 80.16+- 26.54 mu g/dl in the TM with DFO, TM with DFO + DEF combination protocol and control group respectively. There was no significant correlation between patients and control group. However 50 percent of TM with DFO, 38.7 percent of TM with DFO + DEF and 32.8 percent of control group had hypozincemia. Nearly 40 to 50 percent of TM patients and one third of normal subjects are suffering from hypozincemia. This study shows that low level of serum zinc is a health problem in both thalassemia patients and normal population in South West of Iran. (author)

  12. [Alternative nutrition and glutathione levels].

    Science.gov (United States)

    Krajcovicová-Kudlácková, M; Simoncic, R; Béderová, A; Brtková, A; Magálová, T; Barteková, S

    1999-08-30

    Low protein quality and quantity is reported to be a possible risk of alternative nutrition. Pulses contain 18-41% of methionine in relation to reference protein, moreover, its content in cereals is by one half lower. Therefore vegetarians and vegans may have an insufficient intake of sulphur-containing amino acids that may subsequently affect glutathione values (precursors of its synthesis). In groups of adults on an alternative diet--lactoovovegetarians (n = 47) and vegans (n = 44) aged 19-62 years with average duration on a vegetarian or vegan diet of 7.6 and 4.9 years, respectively, glutathione levels (GSH) were measured in erythrocytes (spectrophotometrically), as well as the activity of GSH-dependent enzymes. As nutritional control (n = 42) served an average sample of omnivores selected from a group of 489 examined, apparently healthy subjects of the same age range living in the same region. One to low protein intake (56% of RDA) exclusively of plant origin significantly lower levels of total proteins were observed in vegans with a 16% frequency of hypoproteinaemia (vs 0% in omnivores). In comparison to omnivores a significantly lower glutathione level was found (4.28 +/- 0.12 vs 4.84 +/- 0.14 mumol/g Hb, P vegan diet also in adult age.

  13. Level of Sexual Myths Level in Premature Ejaculation Cases

    Directory of Open Access Journals (Sweden)

    Mehmet Gunes

    2016-06-01

    Full Text Available Objective: The aim of this study is to determine level of belief in sexual myths in the cases of premature ejacula­tion (PE which is the most common sexual dysfunction in men. Methods: This study included 100 cases who applied Di­cle University Faculty of Medicine hospitals meet prema­ture ejaculation criteria of DSM-5 and 70 healthy controls. Sociodemographic data form, Hamilton Depression Rat­ing Scale (HDS, Hamilton Anxiety Rating Scale (HAS, Arizona Sexual Experience Scale (ASES-Men form and Sexual Myths Evaluation Form were applied to partici­pants. Results: In the study, rate of belief in sexual myths in PE cases was found significantly higher than healthy controls. In the PE cases, education time less than 10 years, the presence of comorbid sexual dysfunction were found to be statistically significant factors that increase the level of belief in sexual myths in the PE cases, HDS (p=0.0002, HAS (p=0.0001, ASES (p=0.0004 scores were statisti­cally significantly higher than the control group. In the loss of sexual desire in men with comorbid ASES (p=0.0001, with ED, ASES (p=0.001 and HDS (p=0.040 scores were found statistically significantly higher. Conclusions: Sexual information should be given in the appropriate age by educated person in educational insti­tutions.

  14. Parathyroid Hormone Levels and Cognition

    Science.gov (United States)

    Burnett, J.; Smith, S.M.; Aung, K.; Dyer, C.

    2009-01-01

    Hyperparathyroidism is a well-recognized cause of impaired cognition due to hypercalcemia. However, recent studies have suggested that perhaps parathyroid hormone itself plays a role in cognition, especially executive dysfunction. The purpose of this study was to explore the relationship of parathyroid hormone levels in a study cohort of elders with impaied cognition. Methods: Sixty community-living adults, 65 years of age and older, reported to Adult Protective Services for self-neglect and 55 controls matched (on age, ethnicity, gender and socio-economic status) consented and participated in this study. The research team conducted in-home comprehensive geriatric assessments which included the Mini-mental state exam (MMSE), the 15-item geriatric depression scale (GDS) , the Wolf-Klein clock test and a comprehensive nutritional panel, which included parathyroid hormone and ionized calcium. Students t tests and linear regression analyses were performed to assess for bivariate associations. Results: Self-neglecters (M = 73.73, sd=48.4) had significantly higher PTH levels compared to controls (M =47.59, sd=28.7; t=3.59, df=98.94, plevels. Overall, PTH was correlated with the MMSE (r=-.323, p=.001). Individual regression analyses revealed a statistically significant correlation between PTH and MMSE in the self-neglect group (r=-.298, p=.024) and this remained significant after controlling for ionized calcium levels in the regression. No significant associations were revealed in the control group or among any of the other cognitive measures. Conclusion: Parathyroid hormone may be associated with cognitive performance.

  15. Uridine adenosine tetraphosphate (Up4A) is a strong inductor of smooth muscle cell migration via activation of the P2Y2 receptor and cross-communication to the PDGF receptor

    International Nuclear Information System (INIS)

    Wiedon, Annette; Tölle, Markus; Bastine, Joschika; Schuchardt, Mirjam; Huang, Tao; Jankowski, Vera; Jankowski, Joachim; Zidek, Walter; Giet, Markus van der

    2012-01-01

    Highlights: ► Up 4 A induces VSMC migration. ► VSMC migration towards Up 4 A involves P2Y 2 activation. ► Up 4 A-induced VSMC migration is OPN-dependent. ► Activation of ERK1/2 pathway is necessary for VSMC migration towards Up 4 A. ► Up 4 A-directed VSMC migration cross-communicates with the PDGFR. -- Abstract: The recently discovered dinucleotide uridine adenosine tetraphosphate (Up 4 A) was found in human plasma and characterized as endothelium-derived vasoconstrictive factor (EDCF). A further study revealed a positive correlation between Up 4 A and vascular smooth muscle cell (VSMC) proliferation. Due to the dominant role of migration in the formation of atherosclerotic lesions our aim was to investigate the migration stimulating potential of Up 4 A. Indeed, we found a strong chemoattractant effect of Up 4 A on VSMC by using a modified Boyden chamber. This migration dramatically depends on osteopontin secretion (OPN) revealed by the reduction of the migration signal down to 23% during simultaneous incubation with an OPN-blocking antibody. Due to inhibitory patterns using specific and unspecific purinoreceptor inhibitors, Up 4 A mediates it’s migratory signal mainly via the P2Y 2 . The signaling behind the receptor was investigated with luminex technique and revealed an activation of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) pathway. By use of the specific PDGF receptor (PDGFR) inhibitor AG1296 and siRNA technique against PDGFR-β we found a strongly reduced migration signal after Up 4 A stimulation in the PDGFR-β knockdown cells compared to control cells. In this study, we present substantiate data that Up 4 A exhibits migration stimulating potential probably involving the signaling cascade of MEK1 and ERK1/2 as well as the matrix protein OPN. We further suggest that the initiation of the migration process occurs predominant through direct activation of the P2Y 2 by Up 4 A and via transactivation of the PDGFR.

  16. Ground level cosmic ray observations

    Energy Technology Data Exchange (ETDEWEB)

    Stephens, S.A. [Tata Institute of Fundamental Research, Bombay (International Commission on Radiation Units and Measurements); Grimani, C.; Brunetti, M.T.; Codino, A. [Perugia Univ. (Italy)]|[INFN, Perugia (Italy); Papini, P.; Massimo Brancaccio, F.; Piccardi, S. [Florence Univ. (Italy)]|[INFN, Florence (Italy); Basini, G.; Bongiorno, F. [INFN, Laboratori Nazionali di Frascati, Rome (Italy); Golden, R.L. [New Mexico State Univ., Las Cruces, NM (United States). Particle Astrophysics Lab.; Hof, M. [Siegen Univ. (Germany). Fachbereich Physik

    1995-09-01

    Cosmic rays at ground level have been collected using the NMSU/Wizard - MASS2 instrument. The 17-hr observation run was made on September 9. 1991 in Fort Sumner, New Mexico, Usa. Fort Sumner is located at 1270 meters a.s.l., corresponding to an atmospheric depth of about 887 g/cm{sup 2}. The geomagnetic cutoff is 4.5 GV/c. The charge ratio of positive and negative muons and the proton to muon ratio have been determined. These observations will also be compared with data collected at a higher latitude using the same basic apparatus.

  17. Low level radioactive waste disposal

    International Nuclear Information System (INIS)

    Balaz, J.; Chren, O.

    2015-01-01

    The Mochovce National Radwaste Repository is a near surface multi-barrier disposal facility for disposal of processed low and very low level radioactive wastes (radwastes) resulting from the operation and decommissioning of nuclear facilities situated in the territory of the Slovak Republic and from research institutes, laboratories, hospitals and other institutions (institutional RAW) which are in compliance with the acceptance criteria. The basic safety requirement of the Repository is to avoid a radioactive release to the environment during its operation and institutional inspection. This commitment is covered by the protection barrier system. The method of solution designed and implemented at the Repository construction complies with the latest knowledge and practice of the repository developments all over the world and meets requirements for the safe radwaste disposal with minimum environmental consequences. All wastes are solidified and have to meet the acceptance criteria before disposal into the Repository. They are processed and treated at the Bohunice RAW Treatment Centre and Liquid RAW Final Treatment Facility at Mochovce. The disposal facility for low level radwastes consists of two double-rows of reinforced concrete vaults with total capacity 7 200 fibre reinforced concrete containers (FCCs) with RAW. One double-row contains 40 The operation of the Repository was started in year 2001 and after ten years, in 2011 was conducted the periodic assessment of nuclear safety with positive results. Till the end of year 2014 was disposed to the Repository 11 514 m 3 RAW. The analysis of total RAW production from operation and decommissioning of all nuclear installation in SR, which has been carried out in frame of the BIDSF project C9.1, has showed that the total volume estimation of conditioned waste is 108 thousand m 3 of which 45.5 % are low level waste (LLW) and 54,5 % very low level waste (VLLW). On the base of this fact there is the need to build 7

  18. NASA Technology Readiness Level Definitions

    Science.gov (United States)

    Mcnamara, Karen M.

    2012-01-01

    This presentation will cover the basic Technology Readiness Level (TRL) definitions used by the National Aeronautics and Space Administration (NASA) and their specific wording. We will discuss how they are used in the NASA Project Life Cycle and their effectiveness in practice. We'll also discuss the recent efforts by the International Standards Organization (ISO) to develop a broadly acceptable set of TRL definitions for the international space community and some of the issues brought to light. This information will provide input for further discussion of the use of the TRL scale in manufacturing.

  19. Biopower at the molar level

    DEFF Research Database (Denmark)

    Frandsen, Martin; Triantafillou, Peter

    2011-01-01

    Over the last decade or so much social science research on the developments in the life sciences and biomedicine seems to be focusing too narrowly on individualization or, more recently, on geneticization, that is, the ‘molecular’ level. This article argues that current public health policies......, the society and ‘its’ population today serves as a benchmark for a wide array public interventions seeking to make individuals and groups live a life that is longer and of a better quality. This new strategy, which goes well beyond reducing mortality and sickness, seems in principle to be without political...

  20. Radiation Levels around the LHC

    CERN Document Server

    Mala, P; Calviani, M; Nordt, A

    2013-01-01

    This work discuss on the radiation levels measured around the LHC machine during the 2012 operational year. The doses and particle fluences are measured primarily by RadMon detectors – about 300 RadMons are installed around the accelerator – and by thermoluminescent detectors. In addition, BLMs, IG5/PMI ionisation chambers as well as FGCs can be used for corresponding cumulated dose evaluations. The probability of SEE depends directly on the high-energy hadron (HEH) fluence, so this is the main parameter that is calculated based on RadMons counts.

  1. Macroeconomic level of technology transfer

    Directory of Open Access Journals (Sweden)

    Smirnova Nadezhda

    2016-04-01

    Full Text Available World practice of economic management has proved that the best indicator of competitiveness is achieved by that economic system, the economic units of which timely and adequately update the resource and technical base, thus achieving higher financial and economic indicators. Ensuring that sustainable development becomes possible due to the transfer of technological innovations, namely the diffusion from the developer to the customer on both commercial and free of charge basis. The article focuses on functioning of technology transfer at the macro level, namely the creation of its domestic models.

  2. Business plan: LevelUp

    OpenAIRE

    Zhak, Viktor; Sokolov, Ilya

    2013-01-01

    The following thesis was created to enable the writers to produce a business plan for LevelUp Company, gaming café that is going to operate in the center of Helsinki and provide customers playing hours on PC, PS4 and X-box One. The entire business plan describes all aspects concerning marketing analysis, financial data and basic information on the gaming café as location, number of staff, prices open hours etc. The theoretical framework was based on the most reliable marketing and finance...

  3. Level Scheme of 223Fr

    International Nuclear Information System (INIS)

    Gaeta, R.; Gonzalez, J.A.; Gonzalez, L.; Roldan, C.

    1972-01-01

    A study has been made of the decay of 2 27 Ac at levels of 223 F r, means of alpha Spectrometers of Si barrier detector and gamma Spectrometers of Ge(Li). The rotational bands 1/2-(541 ↓ ] , 1/2-(530 ↑ ) and 3/2-(532 ↓ ) have been identified, as well as two octupolar bands associated with the fundamental one. The results obtained indicate that the unified model is applicable in this intermediate zone of the nuclide chart. (Author) 150 refs

  4. Developing State Level Approaches under the State Level Concept

    International Nuclear Information System (INIS)

    Budlong Sylvester, K.; Murphy, C.L.; Boyer, B.; Pilat, J.F.

    2015-01-01

    With the pursuit of the State-Level Concept (SLC), the IAEA has sought to further evolve the international safeguards system in a manner which maintains (or improves) the effectiveness of the system in an environment of expanding demands and limited resources. The IAEA must not remain static and should continuously examine its practices to ensure it can capture opportunities for cost reductions while adapting to, and staying ahead of, emerging proliferation challenges. Contemporary safeguards have been focused on assessing the nuclear programme of the State as a whole, rather than on the basis of individual facilities. Since the IAEA's integrated safeguards program, State-level Approaches (SLAs) have been developed that seek to optimally combine the measures provided for by the Additional Protocol with those of traditional safeguards. This process resulted in facility specific approaches that, while making use of a State's broader conclusion, were nonetheless prescriptive. Designing SLAs on a State-by-State basis would avoid the shortcomings of a one-size-fits-all system. It would also enable the effective use of the Agency's information analysis and State evaluation efforts by linking this analysis to safeguards planning efforts. Acquisition Path Analysis (APA), along with the State Evaluation process, can be used to prioritize paths in a State in terms of their attractiveness for proliferation. While taking advantage of all safeguards relevant information, and tailoring safeguards to individual characteristics of the State, paths of the highest priority in all States will necessarily meet the same standard of coverage. Similarly, lower priority paths will have lower performance targets, thereby promoting nondiscrimination. Such an approach would improve understanding of safeguards implementation under the SLC and the rational for safeguards resource allocation. The potential roles for APA and performance targets in SLA development will be reviewed

  5. Why control blood glucose levels?

    Science.gov (United States)

    Rossini, A A

    1976-03-01

    The controversy as to the relationship between the degree of control of diabetes and the progression of the complications of the disease has not been solved. However, in this review, various studies suggesting a relationship between the metabolic abnormality and the diabetic complications are examined. The disadvantages of the uncontrolled diabetes mellitus can be divided into two major categories-short-term and long-term. The short-term disadvantages of controlled diabetes mellitus include the following: (1) ketoacidosis and hyperosmolar coma; (2) intracellular dehydration; (3) electrolyte imbalance; (4) decreased phagocytosis; (5) immunologic and lymphocyte activity; (6) impairment of wound healing; and (7) abnormality of lipids. The long-term disadvantages of uncontrolled diabetes melitus include the following: (1) nephropathy; (2) neuropathy; (3) retinopathy; (4) cataract formation; (5) effect on perinatal mortality; (6) complications of vascular disease; and (7) the evaluation of various clinical studies suggesting the relationship of elevated blood glucose levels and complications of diabetes mellitus. It is suggested that until the question of control can absolutely be resolved, the recommendation is that the blood glucose levels should be controlled as close to the normal as possible.

  6. Parathyroid Hormone Levels and Cognition

    Science.gov (United States)

    Burnett, J.; Smith, S.M.; Aung, K.; Dyer, C.

    2009-01-01

    Hyperparathyroidism is a well-recognized cause of impaired cognition due to hypercalcemia. However, recent studies have suggested that perhaps parathyroid hormone itself plays a role in cognition, especially executive dysfunction. The purpose of this study was to explore the relationship of parathyroid hormone levels in a study cohort of elders with impaied cognition. Methods: Sixty community-living adults, 65 years of age and older, reported to Adult Protective Services for self-neglect and 55 controls matched (on age, ethnicity, gender and socio-economic status) consented and participated in this study. The research team conducted in-home comprehensive geriatric assessments which included the Mini-mental state exam (MMSE), the 15-item geriatric depression scale (GDS) , the Wolf-Klein clock test and a comprehensive nutritional panel, which included parathyroid hormone and ionized calcium. Students t tests and linear regression analyses were performed to assess for bivariate associations. Results: Self-neglecters (M = 73.73, sd=48.4) had significantly higher PTH levels compared to controls (M =47.59, sd=28.7; t=3.59, df=98.94, pcognitive measures. Conclusion: Parathyroid hormone may be associated with cognitive performance.

  7. Low level radiation: biological effects

    International Nuclear Information System (INIS)

    Loken, M.K.

    1983-01-01

    It is imperative that physicians and scientists using radiations in health care delivery continue to assess the benefits derived, vs. potential risk, to patients and radiation workers being exposed to radiation in its various forms as part of our health delivery system. Insofar as possible we should assure our patients and ourselves that the benefits outweigh the potential hazards involved. Inferences as to the possible biological effects of low level radiation are generally based on extrapolations from those effects observed and measured following acute exposures to considerably higher doses of radiation. Thus, in order to shed light on the question of the possible biological effects of low level radiation, a wide variety of studies have been carried out using cells in culture and various species of plant and animal life. This manuscript makes reference to some of those studies with indications as to how and why the studies were done and the conclusions that might be drawn there from. In addition reference is made to the handling of this information by scientists, by environmentalists, and by the news media. Unfortunately, in many instances the public has been misled by what has been said and/or written. It is hoped that this presentation will provide an understandable and reasonable perspective on the various appropriate uses of radiation in our lives and how such uses do provide significant improvement in our health and in our quality of life

  8. Humidity level In psychrometric processes

    International Nuclear Information System (INIS)

    Mojsovski, Filip

    2008-01-01

    When a thermal engineer needs to control, rather than merely moderate humidity, he must focus on the moisture level as a separate variable - not simply an addition of temperature control. Controlling humidity generally demands a correct psychrometric approach dedicated to that purpose [1].Analysis of the humidity level in psychrometric thermal processes leads to relevant data for theory and practice [2]. This paper presents: (1) the summer climatic curve for the Skopje region, (2) selected results of investigation on farm dryers made outside laboratories. The first purpose of such activity was to examine relations between weather conditions and drying conditions. The estimation of weather condition for the warmest season of the year was realized by a summer climatic curve. In the science of drying, basic drying conditions are temperature, relative humidity and velocity of air, thickness of dried product and dryer construction. The second purpose was to realize correct prediction of drying rates for various psychrometrics drying processes and local products. Test runs with the dryer were carried out over a period of 24 h, using fruits and vegetables as experimental material. Air flow rate through the dryer of 150 m3/h, overall drying rate of 0.04 kg/h and air temperature of 65 oC were reached. Three types of solar dryers, were exploited in the research.

  9. International harmonization of intervention levels

    International Nuclear Information System (INIS)

    Jensen, P.H.

    1994-05-01

    A summary is given on international guidance on intervention levels in circumstances in which remedial actions might be considered in nuclear accident situations. The nature and limitations of international work and their effect on the resulting guidance are discussed. The basic international principles recommended can be expressed in the following compressed form: (1) serious deterministic effects should be avoided by intervention, (2) each protective measure should be justified, i.e. do more good than harm, (3) the level at which the protective measures are to be introduced should be optimized, i.e. do most good, and (4) each protective measure should be optimized separately and independent of all other countermeasures. It is of great importance that decision makers inform the public of all aspects of their decisions in order to make the decisions transparent, especially when the interventions chosen are mainly for political or social reason rather than health protection grounds. Otherwise the public may be misled and the radiological protection community will be mistrusted. 17 refs., 6 tabs

  10. The JET level-1 software

    International Nuclear Information System (INIS)

    McCullen, P.A.; Farthing, J.W.

    1998-01-01

    The complex nature of the JET machine requires a large amount of control parameter preparation, selection and validation before a pulse may be started. Level-1 is defined as the centralized, cross-subsystem control of JET. Before it was introduced over 10 years ago, the Session Leader (SL) who is responsible for specifying the parameter settings for a JET pulse, had virtually no software available to help him except for a simple editor used for the creation of control waveforms. Most of the required parameter settings were calculated by hand and then passed on either verbally or via hand-written forms. These parameters were then set by a large number of people - Local Unit Responsible Officers (LUROs) and CODAS Duty Officers (CDOs) using a wide selection of dedicated software. At this time the Engineer in Charge (EiC) would largely depend on the LUROs to inform him that conditions were ready. He never set control parameters personally and had little or no software available to him to see what many of the settings were. The first implementation of Level-1 software went some way towards improving the task of pulse schedule preparation in that the SL could specify his requirements via a computer interface and store them in a database for later use. At that time the maximum number of parameters that could be handled was 500. (author)

  11. MIPAS level 2 operational analysis

    Directory of Open Access Journals (Sweden)

    P. Raspollini

    2006-01-01

    Full Text Available The MIPAS (Michelson Interferometer for Passive Atmospheric Sounding instrument has been operating on-board the ENVISAT satellite since March 2002. In the first two years, it acquired in a nearly continuous manner high resolution (0.025 cm−1 unapodized emission spectra of the Earth's atmosphere at limb in the middle infrared region. This paper describes the level 2 near real-time (NRT and off-line (OL ESA processors that have been used to derive level 2 geophysical products from the calibrated and geolocated level 1b spectra. The design of the code and the analysis methodology have been driven by the requirements for NRT processing. This paper reviews the performance of the optimized retrieval strategy that has been implemented to achieve these requirements and provides estimated error budgets for the target products: pressure, temperature, O3, H2O, CH4, HNO3, N2O and NO2, in the altitude measurement range from 6 to 68 km. From application to real MIPAS data, it was found that no change was needed in the developed code although an external algorithm was introduced to identify clouds with high opacity and to exclude affected spectra from the analysis. In addition, a number of updates were made to the set-up parameters and to auxiliary data. In particular, a new version of the MIPAS dedicated spectroscopic database was used and, in the OL analysis, the retrieval range was extended to reduce errors due to uncertainties in extrapolation of the profile outside the retrieval range and more stringent convergence criteria were implemented. A statistical analysis on the χ2 values obtained in one year of measurements shows good agreement with the a priori estimate of the forward model errors. On the basis of the first two years of MIPAS measurements the estimates of the forward model and instrument errors are in general found to be conservative with excellent performance demonstrated for frequency calibration. It is noted that the total retrieval

  12. Low-level radwaste solidification

    International Nuclear Information System (INIS)

    Naughton, M.D.; Miller, C.C.; Nelson, R.A.; Tucker, R.F.

    1983-01-01

    This paper reports on a study of ''Advanced Low-Level Radioactive Waste Treatment Systems'' conducted under an EPRI contract. The object of the study is to identify advanced lowlevel radwaste treatment systems that are commercially available or are expected to be in the near future. The current state-ofthe-art in radwaste solidification technology is presented. Related processing technologies, such as the compaction of dry active waste (DAW), containers available for radwaste disposal, and the regulatory aspects of radwaste transportation and solidification, are described. The chemical and physical properties of the currently acceptable solidification agents, as identified in the Barnwell radwaste burial site license, are examined. The solidification agents investigated are hydraulic cements, thermoplastic polymers, and thermosetting polymers. It is concluded that solidification processes are complex and depend not only on the chemical and physical properties of the binder material and the waste, but also on how these materials are mixed

  13. Symmetry and Asymmetry Level Measures

    Directory of Open Access Journals (Sweden)

    Angel Garrido

    2010-04-01

    Full Text Available Usually, Symmetry and Asymmetry are considered as two opposite sides of a coin: an object is either totally symmetric, or totally asymmetric, relative to pattern objects. Intermediate situations of partial symmetry or partial asymmetry are not considered. But this dichotomy on the classification lacks of a necessary and realistic gradation. For this reason, it is convenient to introduce "shade regions", modulating the degree of Symmetry (a fuzzy concept. Here, we will analyze the Asymmetry problem by successive attempts of description and by the introduction of the Asymmetry Level Function, as a new Normal Fuzzy Measure. Our results (both Theorems and Corollaries suppose to be some new and original contributions to such very active and interesting field of research. Previously, we proceed to the analysis of the state of art.

  14. Reactor Emergency Action Level Monitor

    International Nuclear Information System (INIS)

    Touchton, R.A.

    1987-01-01

    The Reactor Emergency Action Level Monitor (REALM) Expert System is designed to provide assistance in the identification of a nuclear power plant emergency situation and the determination of its severity. REALM has been developed to operate in a real-time processing environment. REALM embodies a hybrid architecture utilizing both rule-based reasoning and object-oriented programming techniques borrowed from the Artificial Intelligence discipline of Computer Sciences. The rulebase consists of event-based rules and symptom-based rules. The symptom-based rules go beyond the current EAL structure to address the more problematic scenarios and entail a more symbolic representation of the plant information. The results to date have been encouraging that expert system technology can provide improved emergency decision-making capability in nuclear power plants

  15. Excited levels of Pa-233

    International Nuclear Information System (INIS)

    Vara Cuadrado, J. M.

    1969-01-01

    A study of Pa-233 excited levels from the alpha decay of Np-237 and from beta decay of Th-233 has been performed. The alpha decay spectrum was measured with a semiconductor spectrometer of 18 keV effective resolution (FWHM). Over 13 new lines were identified. The gamma ray spectra of Np-237 and Th-233 were obtained with a Ge-Li detector low and medium range energy lines, and with Si-Li detector for the low energy region. A continuous purification method of Np-237 from its comparatively short-lived daughter Pa-233 was applied. A high number of new lines were identified in both spectra. The gamma-gamma coincidence spectra were obtained with INa(T 1 ) detectors. (Author) 54 refs

  16. Sentence-Level Attachment Prediction

    Science.gov (United States)

    Albakour, M.-Dyaa; Kruschwitz, Udo; Lucas, Simon

    Attachment prediction is the task of automatically identifying email messages that should contain an attachment. This can be useful to tackle the problem of sending out emails but forgetting to include the relevant attachment (something that happens all too often). A common Information Retrieval (IR) approach in analyzing documents such as emails is to treat the entire document as a bag of words. Here we propose a finer-grained analysis to address the problem. We aim at identifying individual sentences within an email that refer to an attachment. If we detect any such sentence, we predict that the email should have an attachment. Using part of the Enron corpus for evaluation we find that our finer-grained approach outperforms previously reported document-level attachment prediction in similar evaluation settings.

  17. Wafer level packaging of MEMS

    International Nuclear Information System (INIS)

    Esashi, Masayoshi

    2008-01-01

    Wafer level packaging plays many important roles for MEMS (micro electro mechanical systems), including cost, yield and reliability. MEMS structures on silicon chips are encapsulated between bonded wafers or by surface micromachining, and electrical interconnections are made from the cavity. Bonding at the interface, such as glass–Si anodic bonding and metal-to-metal bonding, requires electrical interconnection through the lid vias in many cases. On the other hand, lateral electrical interconnections on the surface of the chip are used for bonding with intermediate melting materials, such as low melting point glass and solder. The cavity formed by surface micromachining is made using sacrificial etching, and the openings needed for the sacrificial etching are plugged using deposition sealing methods. Vacuum packaging methods and the structures for electrical feedthrough for the interconnection are discussed in this review. (topical review)

  18. Principles for system level electrochemistry

    Science.gov (United States)

    Thaller, L. H.

    1986-01-01

    The higher power and higher voltage levels anticipated for future space missions have required a careful review of the techniques currently in use to preclude battery problems that are related to the dispersion characteristics of the individual cells. Not only are the out-of-balance problems accentuated in these larger systems, but the thermal management considerations also require a greater degree of accurate design. Newer concepts which employ active cooling techniques are being developed which permit higher rates of discharge and tighter packing densities for the electrochemical components. This paper will put forward six semi-independent principles relating to battery systems. These principles will progressively address cell, battery and finally system related aspects of large electrochemical storage systems.

  19. Ionizing radiation: levels and effects. Volume I. Levels

    International Nuclear Information System (INIS)

    1972-01-01

    This is the sixth substantive report of the United Nations Scientific Committee on the Effects of Atomic Radiation to the General Assembly. It reviews the levels of radiation received from all sources to which man is exposed and, among the effects of ionizing radiation, it considers the genetic effects, the effects on the immune response and the induction of malignancies in animals and man. These are not the only effects of ionizing radiation. The acute consequences of massive amounts of radiation that may be received accidentally or during nuclear warfare are not reviewed here (the short discussion of this subject in the 1962 report is still largely valid, at least as an introduction), nor are the effects on the nervous system and the induction of chromosome anomalies in somatic cells, which were both considered by the Committee in its 1969 report. Unlike previous reports of the Committee, the present report is submitted to the General Assembly without the technical annexes in which the evidence considered by the Committee is discussed in detail and in which the bases for the Committee's conclusions, which are stated in the report, are fully documented. However, the annexes are being made available at the same time as the report in a separate publication, issued in two volumes and the Committee wishes to draw the attention of the General Assembly to the fact that the separation of the report from the annexes is for convenience only and that major importance attaches to the scientific evidence given in the annexes.

  20. Colloids related to low level and intermediate level waste

    International Nuclear Information System (INIS)

    Ramsay, J.D.F.; Russell, P.J.; Avery, R.G.

    1991-03-01

    A comprehensive investigation has been undertaken to improve the understanding of the potential role of colloids in the context of disposal and storage of low and intermediate level waste immobilised in cement. Several topics have been investigated using a wide range of advanced physico-chemical and analytical techniques. These include: (a) the study of formation and characteristics of colloids in cement leachates, (b) the effects of the near-field aqueous chemistry on the characteristics of colloids in repository environments, (c) colloid sorption behaviour, (d) interactions of near-field materials with leachates, and (e) preliminary assessment of colloid migration behaviour. It has been shown that the generation of colloids in cement leachates can arise from a process of nucleation and growth leading to an amorphous phase which is predominantly calcium silicate hydrate. Such colloidal material has a capacity for association with polyvalent rare earths and actinides and these may be significant in the source term and processes involving radionuclide retention in the near field. It has also been shown that the near-field aqueous chemistry (pH, Ca 2+ concentration) has a marked effect on colloid behaviour (deposition and stability). A mechanistic approach to predict colloid sorption affinity has been developed which highlights the importance of colloid characteristics and the nature of the ionic species. (author)

  1. Nuclear power: levels of safety

    International Nuclear Information System (INIS)

    Lidsky, L.M.

    1988-01-01

    The rise and fall of the nuclear power industry in the United States is a well-documented story with enough socio-technological conflict to fill dozens of scholarly, and not so scholarly, books. Whatever the reasons for the situation we are now in, and no matter how we apportion the blame, the ultimate choice of whether to use nuclear power in this country is made by the utilities and by the public. Their choices are, finally, based on some form of risk-benefit analysis. Such analysis is done in well-documented and apparently logical form by the utilities and in a rather more inchoate but not necessarily less accurate form by the public. Nuclear power has failed in the United States because both the real and perceived risks outweigh the potential benefits. The national decision not to rely upon nuclear power in its present form is not an irrational one. A wide ranging public balancing of risk and benefit requires a classification of risk which is clear and believable for the public to be able to assess the risks associated with given technological structures. The qualitative four-level safety ladder provides such a framework. Nuclear reactors have been designed which fit clearly and demonstrably into each of the possible qualitative safety levels. Surprisingly, it appears that safer may also mean cheaper. The intellectual and technical prerequisites are in hand for an important national decision. Deployment of a qualitatively different second generation of nuclear reactors can have important benefits for the United States. Surprisingly, it may well be the nuclear establishment itself, with enormous investments of money and pride in the existing nuclear systems, that rejects second generation reactors. It may be that we will not have a second generation of reactors until the first generation of nuclear engineers and nuclear power advocates has retired

  2. Involve women at many levels.

    Science.gov (United States)

    Huq, N

    1995-03-01

    The organizers of the 1994 International Conference on Population and Development (ICPD) realize that slowing the rate of population growth requires the involvement of women at many levels. The planning processes in countries leading up to the ICPD were required to include women, and funds became available for women to attend regional and international preparatory meetings. National delegations at the ICPD also included many more women than the previous two world population conferences in 1974 and 1984. Space was also provided at the ICPD for the involvement of nongovernmental organizations. Naripokkho, a women's advocacy organization in Bangladesh, was therefore able to communicate its message at the conference. In preparation, the organization held consultations and workshops with grassroots women in thirteen regions of Bangladesh. Approximately one third of the women in the workshops had more children than they desired, many felt that they had to have at least two sons, poor services led women to discontinue contraceptive use, and very few women reported that a lack of access to contraception or method failure was responsible for their large families. It was also determined during the preparatory phase that environmental damage cannot be linked to population in a simplistic manner, history, politics, geography, business, and economics play important roles. Once at the ICPD, Naripokkho they negotiated and lobbied the governments to influence the ICPD program of action. Gains for women were made in both language and substance. Indeed, the program of action is the most progressive population document ever issued by a mainstream institution, gives women's goals new legitimacy, and is a powerful tool for groups working at the grassroots level. Governments must now be held to their commitments made in the program.

  3. Low-level Radioactive waste Management

    International Nuclear Information System (INIS)

    1991-01-01

    This meeting describes low-level radioactive waste management problems and contains 8 papers: 1 Low-level radioactive waste management: exemption concept and criteria used by international organizations. 2 Low-level radioactive waste management: french and foreign regulations 3 Low-level radioactive waste management in EDF nuclear power plants (FRANCE) 4 Low-level radioactive waste management in COGEMA (FRANCE) 5 Importance of low-level radioactive wastes in dismantling strategy in CEA (FRANCE) 6 Low-level radioactive waste management in hospitals 7 Low-level radioactive waste disposal: radiation protection laws 8 Methods of low-level radioactive materials measurements during reactor dismantling or nuclear facilities demolition (FRANCE)

  4. Removing high-level contaminants

    International Nuclear Information System (INIS)

    Wallace, Paula

    2013-01-01

    Full text: Using biomimicry, an Australian cleantech innovation making inroads intoChinas's industrial sector offers multiple benefits to miners and processors in Australia. Stephen Shelley, the executive chairman of Creative Water Technology (CWT), was on hand at a recent trade show to explain how his Melbourne company has developed world-class techniques in zero liquid discharge and fractional crystallization of minerals to apply to a wide range of water treatment and recycling applications. “Most existing technologies operate with high energy distillation, filters or biological processing. CWT's appliance uses a low temperature, thermal distillation process known as adiabatic recovery to desalinate, dewater and/or recycle highly saline and highly contaminated waste water,” said Shelley. The technology has been specifically designed to handle the high levels of contaminant that alternative technologies struggle to process, with proven water quality results for feed water samples with TDS levels over 300,000ppm converted to clean water with less than 20ppm. Comparatively, reverse osmosis struggles to process contaminant levels over 70,000ppm effectively. “CWT is able to reclaim up to 97% clean usable water and up to 100% of the contaminants contained in the feed water,” said Shelley, adding that soluble and insoluble contaminants are separately extracted and dried for sale or re-use. In industrial applications CWT has successfully processed feed water with contaminant levels over 650,000 mg/1- without the use of chemicals. “The technology would be suitable for companies in oil exploration and production, mining, smelting, biofuels, textiles and the agricultural and food production sectors,” said Shelley. When compared to a conventional desalination plant, the CWT system is able to capture the value in the brine that most plants discard, not only from the salt but the additional water it contains. “If you recover those two commodities... then you

  5. FINANCIAL CRISIS FROM THE MACROECONOMIC LEVEL TO THE MICROECONOMIC LEVEL

    Directory of Open Access Journals (Sweden)

    SANDA GHEORGHE GABRIEL

    2014-08-01

    Full Text Available The current economic and financial crisis, beyond the problems it generates both at micro and macro level, should determine an adaptation of the mechanisms, institutions and monetary / financial policies to the real economy we are facing. The issue of financial crises is extremely complex, including a series of quantitative and qualitative factors, financial, economic, social, ethical, technological and human, which can intervene and influence the financial operations in a country or several countries simultaneously. We believe that it is difficult to appreciate that a traditional model might explain a financial crisis, given that every context of occurrence, conditions of development and crisis settlement programs are unique and unrepeatable. Every crisis has in its structure certain issues that may be capitalized and can lead to success. Perhaps more obvious are the ways that can lead to total failure of the organization. Finding and capitalizing the potential success is the essence of the crisis management. The essence of the mismanagement of the crisis is to worse situation. The successful management of a crisis involves admitting that you are facing a crisis, taking reasonable measures to remedy the situation, to be seen taking them and heard saying the right words. The issue at this stage of crisis management is that perception becomes true reality. Crisis management is a set of factors designed to combat the crisis and reduce the damage caused by the crisis. In other words, crisis management attempts to prevent or reduce the negative effects of the crisis and protect the organization, the public involved and the specific field by the possible damages. The effective management of the crisis includes crisis communication. This is an essential component through which the organization faced with the difficult situation can rehabilitate it’s publicly image or even to improve it. The crisis communication occurs between the organization and

  6. The Aquarius Level 2 Algorithm

    Science.gov (United States)

    Meissner, T.; Wentz, F. J.; Hilburn, K. A.; Lagerloef, G. S.; Le Vine, D. M.

    2012-12-01

    The Aquarius L-band radiometer/scatterometer system is designed to provide monthly salinity maps at 150 km spatial scale to an accuracy of 0.2 psu. The sensor was launched on June 10, 2011, aboard the Argentine CONAE SAC-D spacecraft. The L-band radiometers and the scatterometer have been taking science data observations since August 25, 2011. This presentation discusses the current state of the Aquarius Level processing algorithm, which transforms radiometer counts ultimately into sea surface salinity (SSS). We focus on several topics that we have investigated since launch: 1. Updated Pointing A detailed check of the Aquarius pointing angles was performed, which consists in making adjustments of the two pointing angles, azimuth angle and off-nadir angle, for each horn. It has been found that the necessary adjustments for all 3 horns can be explained by a single offset for the antenna pointing if we introduce a constant offset in the roll angle by - 0.51 deg and the pitch angle by + 0.16 deg. 2. Antenna Patterns and Instrument Calibration In March 2012 JPL has produced a set of new antenna patterns using the GRASP software. Compared with the various pre-launch patterns those new patterns lead to an increase in the spillover coefficient by about 1%. We discuss its impact on several components of the Level 2 processing: the antenna pattern correction (APC), the correction for intrusion of galactic and solar radiation that is reflected from the ocean surface into the Aquarius field of view, and the correction of contamination from land surface radiation entering into the sidelobes. We show that the new antenna patterns result in a consistent calibration of all 3 Stokes parameters, which can be best demonstrated during spacecraft pitch maneuvers. 3. Cross Polarization Couplings of the 3rd Stokes Parameter Using the APC values for the cross polarization coupling of the 3rd Stokes parameter into the 1st and 2nd Stokes parameter lead to a spurious image of the 3rd Stokes

  7. Jupiter's Multi-level Clouds

    Science.gov (United States)

    1997-01-01

    Clouds and hazes at various altitudes within the dynamic Jovian atmosphere are revealed by multi-color imaging taken by the Near-Infrared Mapping Spectrometer (NIMS) onboard the Galileo spacecraft. These images were taken during the second orbit (G2) on September 5, 1996 from an early-morning vantage point 2.1 million kilometers (1.3 million miles) above Jupiter. They show the planet's appearance as viewed at various near-infrared wavelengths, with distinct differences due primarily to variations in the altitudes and opacities of the cloud systems. The top left and right images, taken at 1.61 microns and 2.73 microns respectively, show relatively clear views of the deep atmosphere, with clouds down to a level about three times the atmospheric pressure at the Earth's surface.By contrast, the middle image in top row, taken at 2.17 microns, shows only the highest altitude clouds and hazes. This wavelength is severely affected by the absorption of light by hydrogen gas, the main constituent of Jupiter's atmosphere. Therefore, only the Great Red Spot, the highest equatorial clouds, a small feature at mid-northern latitudes, and thin, high photochemical polar hazes can be seen. In the lower left image, at 3.01 microns, deeper clouds can be seen dimly against gaseous ammonia and methane absorption. In the lower middle image, at 4.99 microns, the light observed is the planet's own indigenous heat from the deep, warm atmosphere.The false color image (lower right) succinctly shows various cloud and haze levels seen in the Jovian atmosphere. This image indicates the temperature and altitude at which the light being observed is produced. Thermally-rich red areas denote high temperatures from photons in the deep atmosphere leaking through minimal cloud cover; green denotes cool temperatures of the tropospheric clouds; blue denotes cold of the upper troposphere and lower stratosphere. The polar regions appear purplish, because small-particle hazes allow leakage and reflectivity

  8. Forbedret SCM gennem koordineret lagerstyring

    DEFF Research Database (Denmark)

    Larsen, Christian; Thorstenson, Anders

    2009-01-01

    Effektiv lagerstyring er en vigtig del af god supply chain management (SCM). At opnå en sådan lagerstyring er imidlertid ikke en triviel opgave. Det kræver indsigt i virkemåden af flertrins (engelsk: multi-echelon, multi-level eller multi-stage) lagersystemer med usikker fremtidig efterspørgsel...

  9. High level white noise generator

    International Nuclear Information System (INIS)

    Borkowski, C.J.; Blalock, T.V.

    1979-01-01

    A wide band, stable, random noise source with a high and well-defined output power spectral density is provided which may be used for accurate calibration of Johnson Noise Power Thermometers (JNPT) and other applications requiring a stable, wide band, well-defined noise power spectral density. The noise source is based on the fact that the open-circuit thermal noise voltage of a feedback resistor, connecting the output to the input of a special inverting amplifier, is available at the amplifier output from an equivalent low output impedance caused by the feedback mechanism. The noise power spectral density level at the noise source output is equivalent to the density of the open-circuit thermal noise or a 100 ohm resistor at a temperature of approximately 64,000 Kelvins. The noise source has an output power spectral density that is flat to within 0.1% (0.0043 db) in the frequency range of from 1 KHz to 100 KHz which brackets typical passbands of the signal-processing channels of JNPT's. Two embodiments, one of higher accuracy that is suitable for use as a standards instrument and another that is particularly adapted for ambient temperature operation, are illustrated in this application

  10. Tritium Level in Romanian Precipitation

    Energy Technology Data Exchange (ETDEWEB)

    Varlam, C.; Stefanescu, I.; Faurescu, I.; Bogdan, D.; Soare, A. [Institute for Cryogenic and Isotope Technologies, Rm. Valcea (Romania); Duliu, O. G. [Faculty of Physics, University of Bucharest, Magurele (Romania)

    2013-07-15

    Romania is one of the countries that has no station included in GNIP (Global Network of Isotopes in Precipitation) on its territory. This paper presents results regarding the tritium concentration in precipitation for the period 1999-2009. The precipitation fell at the Institute for cryogenic and Isotope technologies (geographical coordinates: altitude 237 m, latitude 45{sup o}02'07' N, longitude 24{sup o}17'03' E) an was collected both individually and as a composite average of each month. It was individually measured and the average was calculated and compared with the tritium concentration measured in the composite sample. tritium concentration levels ranged from 9.9 {+-} 2.1 TU for 2004 and 13.7 {+-} 2.2 TU for 2009. Comparing the arithmetic mean values with the weighted mean for the period of observation, it was noticed that the higher absolute values of the weighted means were constant. It was found that for the calculated monthly average for the period of observation (1999-2009), the months with the maximum tritium concentration are the same as the months with the maximum amount of precipitation. This behaviour is typical for the monitored location. (author)

  11. On reinitializing level set functions

    Science.gov (United States)

    Min, Chohong

    2010-04-01

    In this paper, we consider reinitializing level functions through equation ϕt+sgn(ϕ0)(‖∇ϕ‖-1)=0[16]. The method of Russo and Smereka [11] is taken in the spatial discretization of the equation. The spatial discretization is, simply speaking, the second order ENO finite difference with subcell resolution near the interface. Our main interest is on the temporal discretization of the equation. We compare the three temporal discretizations: the second order Runge-Kutta method, the forward Euler method, and a Gauss-Seidel iteration of the forward Euler method. The fact that the time in the equation is fictitious makes a hypothesis that all the temporal discretizations result in the same result in their stationary states. The fact that the absolute stability region of the forward Euler method is not wide enough to include all the eigenvalues of the linearized semi-discrete system of the second order ENO spatial discretization makes another hypothesis that the forward Euler temporal discretization should invoke numerical instability. Our results in this paper contradict both the hypotheses. The Runge-Kutta and Gauss-Seidel methods obtain the second order accuracy, and the forward Euler method converges with order between one and two. Examining all their properties, we conclude that the Gauss-Seidel method is the best among the three. Compared to the Runge-Kutta, it is twice faster and requires memory two times less with the same accuracy.

  12. The LHC at level best

    CERN Multimedia

    Katarina Anthony

    2013-01-01

    On 10 March, a team of CERN surveyors descended into the LHC tunnel. Their aim: to take measurements of the height of the LHC magnets to see how geological shifts might be affecting the machine and to take reference positions of the machine before the interconnects are opened.    CERN surveyors take levelling measurements of the LHC magnets during LS1. The LHC tunnel is renowned for its geological stability: set between layers of sandstone and molasse, it has allowed the alignment of the world’s largest accelerators to be within sub-millimetre precision. But even the most stable of tunnels can be affected by geological events. To ensure the precise alignment of the LHC, the CERN survey team performs regular measurements of the vertical position of the magnets (a process known as “levelling”). Over the past month, the team has been taking measurements of the LHC before the temperature of the magnets reaches 100 K, beyond which there may be some mechanic...

  13. Radiation levels in eastern Europe

    International Nuclear Information System (INIS)

    Webb, G.A.M.; Simmonds, J.R.; Wilkins, B.T.

    1986-01-01

    Immediately after news of the accident at Chernobyl became available on 28 April, the National Radiological Protection Board (NRPB) was asked by the UK Foreign and Commonwealth Office (FCO) for an appraisal of the radiation situation on the basis of which advice would be given to embassy staff, residents in affected countries and prospective travellers. The first Swedish measurements, external gamma dose rates and, later, concentrations of atmospheric and ground radioactivity, were used to estimate the quantity of radioactivity released by means of NRPB's accident consequence code (1), MARC. Our first predictions of 29 April indicated a substantial release of the order of 10 17 - 10 18 Bq, which was expected to lead to tens of early radiation-induced deaths in the area around the site. On the basis of NRPB's recommended Emergency Reference Levels (ERL's), it was thought that there would be a need for evacuation out to 20 to 30 km and for temporary food restrictions out to a few hundred kilometres from the site. FCO accordingly decided to evacuate students from Kiev and Minsk and to advise people not to travel to the western Soviet Union or to north-east Poland unless absolutely necessary

  14. ATLAS Level-1 Topological Trigger

    CERN Document Server

    Zheng, Daniel; The ATLAS collaboration

    2018-01-01

    The ATLAS experiment has introduced and recently commissioned a completely new hardware sub-system of its first-level trigger: the topological processor (L1Topo). L1Topo consist of two AdvancedTCA blades mounting state-of-the-art FPGA processors, providing high input bandwidth (up to 4 Gb/s) and low latency data processing (200 ns). L1Topo is able to select collision events by applying kinematic and topological requirements on candidate objects (energy clusters, jets, and muons) measured by calorimeters and muon sub-detectors. Results from data recorded using the L1Topo trigger will be presented. These results demonstrate a significantly improved background event rejection, thus allowing for a rate reduction without efficiency loss. This improvement has been shown for several physics processes leading to low-pT leptons, including H->tau tau and J/Psi->mu mu. In addition to describing the L1Topo trigger system, we will discuss the use of an accurate L1Topo simulation as a powerful tool to validate and optimize...

  15. The LHC Low Level RF

    CERN Document Server

    Baudrenghien, Philippe; Molendijk, John Cornelis; Olsen, Ragnar; Rohlev, Anton; Rossi, Vittorio; Stellfeld, Donat; Valuch, Daniel; Wehrle, Urs

    2006-01-01

    The LHC RF consists of eight 400 MHz superconducting cavities per ring, with each cavity independently powered by a 300 kW klystron, via a circulator. The challenge for the Low Level is to cope with very high beam current (more than 1 A RF component) and achieve excellent beam lifetime (emittance growth time in excess of 25 hours). Each cavity has an associated Cavity Controller rack consisting of two VME crates which implement high gain RF Feedback, a Tuner Loop with a new algorithm, a Klystron Ripple Loop and a Conditioning system. In addition each ring has a Beam Control system (four VME crates) which includes a Frequency Program, Phase Loop, Radial Loop and Synchronization Loop. A Longitudinal Damper (dipole and quadrupole mode) acting via the 400 MHz cavities is included to reduce emittance blow-up due to filamentation from phase and energy errors at injection. Finally an RF Synchronization system implements the bunch into bucket transfer from the SPS into each LHC ring. When fully installed in 2007, the...

  16. Reactor water level measuring device

    International Nuclear Information System (INIS)

    Kuroki, Reiji; Asano, Tamotsu.

    1996-01-01

    A condensation vessel is connected to the upper portion of a reactor pressure vessel by way of a pipeline. The lower portion of the condensation vessel is connected to a low pressure side of a differential pressure transmission device by way of a reference leg pipeline. The high pressure side of the differential pressure transmission device is connected to the lower portion of the pressure vessel by way of a pipeline. The condensation vessel is equipped with a temperature sensor. When a temperature of a gas phase portion in the condensation vessel is lowered below a predetermined level, and incondensible gases in the condensation vessel starts to be dissolved in water, signals are sent from the temperature sensor to a control device and a control valve is opened. With such a constitution, CRD driving water flows into the condensation vessel, and water in which gases at the upper portion of the condensation vessel is dissolved flows into the pressure vessel by way of a pipeline. Then, gases dissolved in a reference water column in the reference leg pipeline are eliminated and the value of a reference water pressure does not change even upon abrupt lowering of pressure. (I.N.)

  17. High level white noise generator

    Science.gov (United States)

    Borkowski, Casimer J.; Blalock, Theron V.

    1979-01-01

    A wide band, stable, random noise source with a high and well-defined output power spectral density is provided which may be used for accurate calibration of Johnson Noise Power Thermometers (JNPT) and other applications requiring a stable, wide band, well-defined noise power spectral density. The noise source is based on the fact that the open-circuit thermal noise voltage of a feedback resistor, connecting the output to the input of a special inverting amplifier, is available at the amplifier output from an equivalent low output impedance caused by the feedback mechanism. The noise power spectral density level at the noise source output is equivalent to the density of the open-circuit thermal noise or a 100 ohm resistor at a temperature of approximately 64,000 Kelvins. The noise source has an output power spectral density that is flat to within 0.1% (0.0043 db) in the frequency range of from 1 KHz to 100 KHz which brackets typical passbands of the signal-processing channels of JNPT's. Two embodiments, one of higher accuracy that is suitable for use as a standards instrument and another that is particularly adapted for ambient temperature operation, are illustrated in this application.

  18. Controlling low-level radioactive waste

    International Nuclear Information System (INIS)

    1990-01-01

    This series of information sheets describes at a popular level the sources of low-level radioactive wastes, their associated hazards, methods of storage, transportation and disposal, and the Canadian regulations that cover low-level wastes

  19. Optimizing High Level Waste Disposal

    International Nuclear Information System (INIS)

    Dirk Gombert

    2005-01-01

    If society is ever to reap the potential benefits of nuclear energy, technologists must close the fuel-cycle completely. A closed cycle equates to a continued supply of fuel and safe reactors, but also reliable and comprehensive closure of waste issues. High level waste (HLW) disposal in borosilicate glass (BSG) is based on 1970s era evaluations. This host matrix is very adaptable to sequestering a wide variety of radionuclides found in raffinates from spent fuel reprocessing. However, it is now known that the current system is far from optimal for disposal of the diverse HLW streams, and proven alternatives are available to reduce costs by billions of dollars. The basis for HLW disposal should be reassessed to consider extensive waste form and process technology research and development efforts, which have been conducted by the United States Department of Energy (USDOE), international agencies and the private sector. Matching the waste form to the waste chemistry and using currently available technology could increase the waste content in waste forms to 50% or more and double processing rates. Optimization of the HLW disposal system would accelerate HLW disposition and increase repository capacity. This does not necessarily require developing new waste forms, the emphasis should be on qualifying existing matrices to demonstrate protection equal to or better than the baseline glass performance. Also, this proposed effort does not necessarily require developing new technology concepts. The emphasis is on demonstrating existing technology that is clearly better (reliability, productivity, cost) than current technology, and justifying its use in future facilities or retrofitted facilities. Higher waste processing and disposal efficiency can be realized by performing the engineering analyses and trade-studies necessary to select the most efficient methods for processing the full spectrum of wastes across the nuclear complex. This paper will describe technologies being

  20. Average County-Level IQ Predicts County-Level Disadvantage and Several County-Level Mortality Risk Rates

    Science.gov (United States)

    Barnes, J. C.; Beaver, Kevin M.; Boutwell, Brian B.

    2013-01-01

    Research utilizing individual-level data has reported a link between intelligence (IQ) scores and health problems, including early mortality risk. A growing body of evidence has found similar associations at higher levels of aggregation such as the state- and national-level. At the same time, individual-level research has suggested the…