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Sample records for factor vii fvii

  1. Pharmacodynamics of recombinant activated factor VII and plasma-derived factor VII in a cohort of severe FVII deficient patients.

    Science.gov (United States)

    van Geffen, Mark; Mathijssen, Natascha C J; Holme, Pål A; Laros-van Gorkom, Britta A P; van Kraaij, Marian G J; Masereeuw, Roselinde; Peyvandi, Flora; van Heerde, Waander L

    2013-07-01

    Recombinant activated factor VII (rFVIIa) and plasma-derived factor VII (pdFVII) are used to prevent bleedings in severe FVII deficient patients, despite their short half-lifes. It is suggested that FVII levels of 15-20 IU/dL are sufficient to maintain hemostasis. We analyzed the pharmacodynamic effects of FVII substitution therapy in the Nijmegen Hemostasis Assay (NHA) that simultaneously measures thrombin and plasmin generation. Ten severe FVII deficient patients were treated with 20 μg/kg rFVIIa or 25 IU/kg pdFVII in a cross-over design. Thrombin generation lag-time (TG-LT) was identified as an effect-response parameter. Pharmacodynamic analysis using a maximum effect model showed 50% reduction of the TG-LT effect at ~2 IU/dL FVII activity for both rFVIIa and pdFVII. The FVII activity to obtain TG-LT comparable to the upper limit of normal range in healthy controls (4 min) was given by the effective concentration (ECnormal), showing sufficient hemostasis at 3-4 IU/dL FVII activity. No association was seen between FVII activity and other thrombin or plasmin generation parameters as measured by NHA. In conclusion, 3-4 IU/dL FVII activity seems sufficient to maintain hemostasis in patients with severe FVII deficiency during prophylaxis. These data may suggest a potential value for measurement of TG-LT in the monitoring of FVII(a) therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Non-fasting factor VII coagulant activity (FVII:C) increased by high-fat diet

    DEFF Research Database (Denmark)

    Bladbjerg, Else-Marie; Marckmann, P; Sandström, B

    1994-01-01

    :Bt/FVII:Am (a measure of FVII activation) increased from fasting levels on both diets, but most markedly on the high-fat diet. In contrast, FVII:Am (a measure of FVII protein) tended to decrease from fasting levels on both diets. FVII:C rose from fasting levels on the high-fat diet, but not on the low-fat diet....... The findings suggest that high-fat diets increase non-fasting FVII:C, and consequently may be associated with increased risk of thrombosis. Udgivelsesdato: 1994-Jun......Preliminary observations have suggested that non-fasting factor VII coagulant activity (FVII:C) may be related to the dietary fat content. To confirm this, we performed a randomised cross-over study. Seventeen young volunteers were served 2 controlled isoenergetic diets differing in fat content (20...

  3. Role of the 2 adenine (g.11293_11294insAA) insertion polymorphism in the 3' untranslated region of the factor VII (FVII) gene: molecular characterization of a patient with severe FVII deficiency.

    Science.gov (United States)

    Peyvandi, F; Garagiola, I; Palla, R; Marziliano, N; Mannucci, P M

    2005-11-01

    Polymorphic variants in the gene encoding factor VII (F7) affect the plasma levels of this coagulation protein and modify the clinical phenotype of FVII deficiency in some patients. In this study we report the in vitro functional analysis of a novel polymorphic variant located in the 3' untranslated region of F7: g.11293_11294insAA. To determine whether this variant regulates FVII expression, we initially compared an expression vector containing FVII cDNA with g.11293_11294insAA with the FVII wild-type (WT) construct. The kinetics of mRNA production showed that the insertion decreases the steady-state FVII mRNA levels. To assess whether the insertion influences the phenotype of FVII-deficient patients, we evaluated its effect on the expression of FVII in a patient with severe FVII deficiency (undetectable FVII activity and antigen) carrying two additional homozygous missense variations (p.Arg277Cys and p.Arg353Gln). The two substitutions alone reduced the expression of FVII activity and antigen in vitro, but with the insertion polymorphism in our expression vector the patient's phenotype of undetectable plasma FVII was recapitulated. The insertion polymorphism in the 3' untranslated region of F7 is another modifier of FVII expression that might explain the poor genotype-phenotype correlation in some FVII-deficient patients. Copyright 2005 Wiley-Liss, Inc.

  4. [Significant decrease in factor VII activity by tissue thromboplastin derived from rabbit brain in a patient with congenital factor VII deficiency (FVII Padua)].

    Science.gov (United States)

    Sekiya, Akiko; Morishita, Eriko; Maruyama, Keiko; Asakura, Hidesaku; Nakao, Shinji; Ohtake, Shigeki

    2012-03-01

    Congenital factor VII (FVII) deficiency is a bleeding disorder that requires optimal hemostatic management for each case due to its wide variety of bleeding symptoms. We experienced a patient with inherited FVII deficiency who demonstrated different FVII activities depending on tissue thromboplastins used for assays. An 82-year-old woman without any episodes of abnormal bleeding was found to have different FVII activities of 1.4% and 32% when assayed using thromboplastins from rabbit brain and human placenta, respectively. DNA sequencing analysis revealed a homozygous missense mutation of G10828A (FVII Padua) that caused an amino acid substitution of Arg304 to Gln (R304Q). Carriers of 304Q alleles are usually clinically asymptomatic and do not require FVII replacement therapies even in cases of homozygotes. In case a prolonged prothrombin time or reduced FVII activity is detected, re-examination using thromboplastins of other sources can be helpful for preliminary diagnosis of R304Q, in order to prevent unnecessary FVII replacement therapies.

  5. Dietary changes in fasting levels of factor VII coagulant activity (FVII:C) are accompanied by changes in factor VII protein and other vitamin K-dependent proteins

    DEFF Research Database (Denmark)

    Bladbjerg, Else-Marie; Tholstrup, T; Marckmann, P

    1995-01-01

    The mechanisms behind dietary effects on fasting coagulant activity of factor VII (FVII:C) are not clarified. In the present study of 15 young volunteers, two experimental diets differing in composition of saturated fatty acids (C18:0 [diet S] or C12:0 + C14:0 [diet ML]) were served for 3 weeks...

  6. Japanese family with congenital factor VII deficiency.

    Science.gov (United States)

    Sakakibara, Kanae; Okayama, Yoshiki; Fukushima, Kenji; Kaji, Shunsaku; Muraoka, Michiko; Arao, Yujiro; Shimada, Akira

    2015-10-01

    Congenital factor VII (FVII) deficiency is a rare bleeding disorder with autosomal recessive inheritance. The present female patient was diagnosed with congenital FVII deficiency because of low hepaplastin test (HPT), although vitamin K was given. Heterozygous p.A191T mutation was detected in the peripheral blood, and the same mutation was also found in the mother and sister. To the best of our knowledge, this is the fourth reported case of p.A191T mutation of FVII in the literature and the first to be reported in Japan. FVII coagulation activity (FVII:C) in asymptomatic heterozygous carriers is mildly reduced. Therefore, some patients may not be accurately diagnosed with congenital FVII deficiency. In infants with low HPT without vitamin K deficiency, congenital FVII deficiency should be considered. © 2015 Japan Pediatric Society.

  7. Plasma concentrations of blood coagulation factor VII measured by immunochemical and amidolytic methods

    DEFF Research Database (Denmark)

    Bladbjerg, E-M; Gram, J; Jespersen, J

    2000-01-01

    Ever since the coagulant activity of blood coagulation factor VII (FVII:C) was identified as a risk indicator of cardiac death, a large number of studies have measured FVII protein concentrations in plasma. FVII protein concentrations are either measured immunologically with an ELISA method (FVII...

  8. Vena porta thrombosis in patient with inherited factor VII deficiency

    DEFF Research Database (Denmark)

    Klovaite, Jolanta; Friis-Hansen, Lennart Jan; Larsen, Fin S

    2010-01-01

    Most clotting factor VII (FVII)-deficient patients suffer from bleeding episodes and occasionally thromboembolic complications after surgical interventions or replacement therapy. However, thromboses without apparent triggering factors may occur as well. We report a case of a pregnant woman...... vein with well expressed portosystemic collaterals, heterozygosity for three common polymorphisms in FVII gene, associated with reduction in plasma FVII levels, and no other factors predisposing to thrombosis....

  9. Mutation in the factor VII hepatocyte nuclear factor 4α-binding site contributes to factor VII deficiency.

    Science.gov (United States)

    Zheng, Xing-Wu; Kudaravalli, Rama; Russell, Theresa T; DiMichele, Donna M; Gibb, Constance; Russell, J Eric; Margaritis, Paris; Pollak, Eleanor S

    2011-10-01

    Severe coagulant factor VII (FVII) deficiency in postpubertal dizygotic twin males results from two point mutations in the FVII gene, a promoter region T→C transition at -60 and a His-to-Arg substitution at amino acid 348; both mutations prevent persistence of plasma functional FVII. This report documents longitudinal laboratory measurements from infancy to adulthood of FVII coagulant activity (FVII:C) in the twin FVII-deficient patients; it also details specific biochemical analyses of the -60 T→C mutation. The results revealed FVII:C levels of less than 1% in infancy that remain severely decreased through puberty and into adulthood. In-vitro analyses utilizing hepatocyte nuclear factor 4α (HNF4α) co-transfection and a chromatin immunoprecipitation assay indicate that the -60 T→C mutation severely diminishes functional interaction between the FVII promoter and transcription factor HNF4α. The importance of interaction between the FVII gene and HNF4α in normal FVII expression provides an in-vivo illustration of the regulated expression of an autosomal gene encoding a coagulation protein. The constancy of FVII:C and peripubertal patient symptomatology reported here illustrates androgen-independent expression in contrast to expression with an analogous mutation in the promoter region of the gene encoding coagulation FIX.

  10. A rare combination: congenital factor VII deficiency with Chiari malformation.

    Science.gov (United States)

    Bay, Ali; Aktekin, Elif; Erkutlu, Ibrahim

    2015-12-01

    Congenital factor (VII) deficiency is a rare bleeding disorder. We present a patient with congenital FVII deficiency and congenital hydrocephalus who underwent a ventriculoperitoneal shunt operation and needed no prophylaxis after the procedure.

  11. In vitro effects of heparin and tissue factor pathway inhibitor on factor VII assays. possible implications for measurements in vivo after heparin therapy

    DEFF Research Database (Denmark)

    Bladbjerg, E-M; Larsen, L F; Ostergaard, P

    2000-01-01

    The coagulant activity of blood coagulation factor VII (FVII:C) can be lowered by changes in lifestyle and by therapeutic intervention, e.g. heparin infusion. The question is, however, whether FVII:C determined ex vivo is a valid measure of the FVII activity in vivo. We measured plasma FVII......:C, activated FVII (FVIIa), FVII protein (FVII:Ag), tissue factor pathway inhibitor (TFPI), triglycerides, and free fatty acids (FFA) before and 15 min after infusion of a bolus of unfractionated heparin (50 IU/kg body weight) in 12 healthy subjects. Additionally, we conducted in vitro experiments...

  12. Continuous infusion of recombinant activated factor VII for bleeding control after lobectomy in a patient with inherited factor VII deficiency.

    Science.gov (United States)

    Miyata, Naoko; Isaka, Mitsuhiro; Kojima, Hideaki; Maniwa, Tomohiro; Takahashi, Shoji; Takamiya, Osamu; Ohde, Yasuhisa

    2016-03-01

    Inherited factor VII (FVII) deficiency is a rare recessive inherited coagulation disorder with limited available information, especially in patients undergoing major thoracic surgery. In addition, an optimal management strategy for the disease has not been defined. We herein report a case involving a 61-year-old man with asymptomatic FVII deficiency who underwent a right middle and lower lobectomy to treat lung cancer. To the best of our knowledge, the present report is the first to describe the use of recombinant activated FVII continuous infusion for bleeding control after a major thoracic surgery in a patient with inherited FVII deficiency.

  13. Inhibitor development after liver transplantation in congenital factor VII deficiency.

    Science.gov (United States)

    See, W-S Q; Chang, K-O; Cheuk, D K-L; Leung, Y-Y R; Chan, G C-F; Chan, S-C; Ha, S-Y

    2016-09-01

    Congenital factor VII (FVII) deficiency is the commonest type of the rare bleeding disorders. Very few cases of congenital FVII deficiency developed inhibitor and liver transplant is considered as definitive treatment. In the literature, twelve patients with congenital FVII deficiency developed inhibitors. Two had spontaneous resolution of inhibitors and one did not respond to high dose recombinant factor VIIa (rFVIIa) and died. Regarding liver transplant in congenital FVII patients, seven patients underwent liver transplant with good prognosis. We report a 5-year-old girl with confirmed severe congenital FVII deficiency since neonatal period. She suffered from recurrent intracranial bleeding despite rFVIIa replacement. After auxiliary liver transplant at the age of 4, she continued to show persistent deranged clotting profile and was found to have inhibitor towards FVII. Interestingly, she was still responsive to rFVIIa replacement. © 2016 John Wiley & Sons Ltd.

  14. A high affinity monoclonal antibody recognizing the light chain of human coagulating factor VII.

    Science.gov (United States)

    Sarial, Sheila; Asadi, Farzad; Jeddi-Tehrani, Mahmood; Hadavi, Reza; Bayat, Ali Ahmad; Mahmoudian, Jafar; Taghizadeh-Jahed, Masoud; Shokri, Fazel; Rabbani, Hodjattallah

    2012-12-01

    Factor VII (FVII) is a serine protease-coagulating element responsible for the initiation of an extrinsic pathway of clot formation. Here we generated and characterized a high affinity monoclonal antibody that specifically recognizes human FVII. Recombinant human FVII (rh-FVII) was used for the production of a monoclonal antibody using BALB/c mice. The specificity of the antibody was determined by Western blot using plasma samples from human, mouse, sheep, goat, bovine, rabbit, and rat. Furthermore, the antibody was used to detect transiently expressed rh-FVII in BHK21 cell line using Western blot and sandwich ELISA. A mouse IgG1 (kappa chain) monoclonal antibody clone 1F1-B11 was produced against rh-FVII. The affinity constant (K(aff)) of the antibody was calculated to be 6.4×10(10) M(-1). The antibody could specifically recognize an epitope on the light chain of hFVII, with no reactivity with factor VII from several other animals. In addition, transiently expressed rh-FVII in BHK21 cells was recognized by 1F1-B11. The high affinity as well as the specificity of 1F1-B11 for hFVII will facilitate the affinity purification of hFVII and also production of FVII deficient plasma and minimizes the risk of bovine FVII contamination when fetal bovine serum-supplemented media are used for production and subsequent purification of rh-FVII.

  15. Self-production of tissue factor-coagulation factor VII complex by ovarian cancer cells

    OpenAIRE

    Yokota, N; Koizume, S; Miyagi, E; Hirahara, F; Nakamura, Y; Kikuchi, K; Ruf, W; Sakuma, Y; Tsuchiya, E; Miyagi, Y

    2009-01-01

    Background: Thromboembolic events are a major complication in ovarian cancer patients. Tissue factor (TF) is frequently overexpressed in ovarian cancer tissue and correlates with intravascular thrombosis. TF binds to coagulation factor VII (fVII), changing it to its active form, fVIIa. This leads to activation of the extrinsic coagulation cascade. fVII is produced by the liver and believed to be supplied from blood plasma at the site of coagulation. However, we recently showed that ovarian ca...

  16. Coagulation factor VII variants resistant to inhibitory antibodies.

    Science.gov (United States)

    Branchini, Alessio; Baroni, Marcello; Pfeiffer, Caroline; Batorova, Angelika; Giansily-Blaizot, Muriel; Schved, Jean F; Mariani, Guglielmo; Bernardi, Francesco; Pinotti, Mirko

    2014-11-01

    Replacement therapy is currently used to prevent and treat bleeding episodes in coagulation factor deficiencies. However, structural differences between the endogenous and therapeutic proteins might increase the risk for immune complications. This study was aimed at identifying factor (F)VII variants resistant to inhibitory antibodies developed after treatment with recombinant activated factor VII (rFVIIa) in a FVII-deficient patient homozygous for the p.A354V-p.P464Hfs mutation, which predicts trace levels of an elongated FVII variant in plasma. We performed fluorescent bead-based binding, ELISA-based competition as well as fluorogenic functional (activated FX and thrombin generation) assays in plasma and with recombinant proteins. We found that antibodies displayed higher affinity for the active than for the zymogen FVII (half-maximal binding at 0.54 ± 0.04 and 0.78 ± 0.07 BU/ml, respectively), and inhibited the coagulation initiation phase with a second-order kinetics. Isotypic analysis showed a polyclonal response with a large predominance of IgG1. We hypothesised that structural differences in the carboxyl-terminus between the inherited FVII and the therapeutic molecules contributed to the immune response. Intriguingly, a naturally-occurring, poorly secreted and 5-residue truncated FVII (FVII-462X) escaped inhibition. Among a series of truncated rFVII molecules, we identified a well-secreted and catalytically competent variant (rFVII-464X) with reduced binding to antibodies (half-maximal binding at 0.198 ± 0.003 BU/ml) as compared to the rFVII-wt (0.032 ± 0.002 BU/ml), which led to a 40-time reduced inhibition in activated FX generation assays. Taken together our results provide a paradigmatic example of mutation-related inhibitory antibodies, strongly support the FVII carboxyl-terminus as their main target and identify inhibitor-resistant FVII variants.

  17. Isotypic analysis of antibodies against activated Factor VII in patients with Factor VII deficiency using the x-MAP technology.

    Science.gov (United States)

    Pfeiffer, Caroline; Mathieu-Dupas, Eve; Logghe, Pauline; Lissalde-Lavigne, Géraldine; Balicchi, Julien; Caliskan, Umran; Valentin, Thomas; Laune, Daniel; Molina, Franck; Schved, Jean François; Giansily-Blaizot, Muriel

    2016-05-01

    While the immune response to hemophilic factors in hemophilia has been widely studied, little is known about the development of anti-Factor VII (FVII) antibodies in FVII deficiency. We developed a robust technique based on the x-MAP technology to detect the presence of antibodies against FVII and characterize their isotype and validated this method using blood samples from 100 patients with FVII deficiency (median FVII clotting activity [FVII:C]: 6%) and 95 healthy controls. Anti-FVII antibodies were detected in patients but also in some controls, although the concentration of total immunoglobulin G (IgGt) and IgG1 and IgG4 subclasses was significantly different between groups. The IgG1 subclass concentrations remained significantly different also when only untreated patients were compared with controls. This difference could partially be related to the F7 genotype, particularly in patients harboring the p.Arg139Gln mutation. This x-MAP-based method might be useful for assessing the immunogenicity of novel FVII compounds and of activated FVII (FVIIa) concentrates. Further prospective studies are needed to better understand the clinical relevance of these antibodies in the management of patients with FVII deficiency. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. The protein concentration of blood coagulation factor VII can be measured equally well in plasma and serum

    DEFF Research Database (Denmark)

    Bladbjerg, E-M; Overgaard, K; Gram, J

    1995-01-01

    In the Northwick Park Heart Study, the coagulant activity of factor VII (FVII:C) has been identified as a risk marker of ischaemic heart disease. In the fasting state, the protein concentration of FVII (FVII:Ag) might be an even better risk marker, because of the low coefficient of variation...

  19. Differences in N-glycosylation of recombinant human coagulation factor VII derived from BHK, CHO, and HEK293 cells.

    Science.gov (United States)

    Böhm, Ernst; Seyfried, Birgit K; Dockal, Michael; Graninger, Michael; Hasslacher, Meinhard; Neurath, Marianne; Konetschny, Christian; Matthiessen, Peter; Mitterer, Artur; Scheiflinger, Friedrich

    2015-09-18

    BACKGROUND & Recombinant factor VII (rFVII), the precursor molecule for recombinant activated FVII (rFVIIa), is, due to its need for complex post translational modifications, produced in mammalian cells. To evaluate the suitability of a human cell line in order to produce rFVII with post-translational modifications as close as possible to pdFVII, we compared the biochemical properties of rFVII synthesized in human embryonic kidney-derived (HEK)293 cells (HEK293rFVII) with those of rFVII expressed in Chinese hamster ovary (CHO, CHOrFVII) and baby hamster kidney (BHK, BHKrFVII) cells, and also with those of plasma derived FVII (pdFVII), using various analytical methods. rFVII was purified from selected production clones derived from BHK, CHO, and HEK293 cells after stable transfection, and rFVII isolates were analyzed for protein activity, impurities and post-translational modifications. RESULTS & The analytical results showed no apparent gross differences between the various FVII proteins, except in their N-linked glycosylation pattern. Most N-glycans found on rFVII produced in HEK293 cells were not detected on rFVII from CHO and BHK cells, or, somewhat unexpectedly, on pdFVII; all other protein features were similar. HEK293rFVII glycans were mainly characterized by a higher structural variety and a lower degree of terminal sialylation, and a high amount of terminal N-acetyl galactosamines (GalNAc). All HEK293rFVII oligosaccharides contained one or more fucoses (Fuc), as well as hybrid and high mannose (Man) structures. From all rFVII isolates investigated, CHOrFVII contained the highest degree of sialylation and no terminal GalNAc, and CHO cells were therefore assumed to be the best option for the production of rFVII.

  20. Sustained correction of FVII deficiency in dogs using AAV-mediated expression of zymogen FVII

    Science.gov (United States)

    Marcos-Contreras, Oscar A.; Smith, Shannon M.; Bellinger, Dwight A.; Raymer, Robin A.; Merricks, Elizabeth; Faella, Armida; Pavani, Giulia; Zhou, Shangzhen; Nichols, Timothy C.; High, Katherine A.

    2016-01-01

    Factor VII (FVII) deficiency is a rare autosomal recessive bleeding disorder treated by infusion of fresh-frozen plasma, plasma-derived FVII concentrates and low-dose recombinant activated FVII. Clinical data suggest that a mild elevation of plasma FVII levels (>10% normal) results in improved hemostasis. Research dogs with a G96E missense FVII mutation (FVII-G96E) have dogs, we determine the feasibility of a gene therapy approach using liver-directed, adeno-associated viral (AAV) serotype 8 vector delivery of a canine FVII (cFVII) zymogen transgene. FVII-G96E dogs received escalating AAV doses (2E11 to 4.95E13 vector genomes [vg] per kg). Clinically therapeutic expression (15% normal) was attained with as low as 6E11 vg/kg of AAV and has been stable for >1 year (ongoing) without antibody formation to the cFVII transgene. Sustained and supraphysiological expression of 770% normal was observed using 4.95E13 vg/kg of AAV (2.6 years, ongoing). No evidence of pathological activation of coagulation or detrimental animal physiology was observed as platelet counts, d-dimer, fibrinogen levels, and serum chemistries remained normal in all dogs (cumulative 6.4 years). We observed a transient and noninhibitory immunoglobulin G class 2 response against cFVII only in the dog receiving the highest AAV dose. In conclusion, in the only large-animal model representing the majority of FVII mutation types, our data are first to demonstrate the feasibility, safety, and long-term duration of AAV-mediated correction of FVII deficiency. PMID:26702064

  1. Isolated acquired factor VII deficiency: review of the literature.

    Science.gov (United States)

    Mulliez, Sylvie M N; Devreese, Katrien M J

    2016-04-01

    Isolated acquired factor VII (FVII) deficiency is a rare haemorrhagic disorder. We report what is currently known about the pathogenesis, clinical features, diagnosis, treatment and prognosis of acquired FVII deficiency. We performed a literature search and included all articles published between 1980 and August 2015. Acquired FVII deficiency has been reported in 42 patients. There are well-established clinical diseases associated with acquired FVII deficiency, most notably infections, malignancy and haematological stem cell transplantation. The exact pathogenesis of the diseases is still unknown, but different pathophysiological hypotheses have been suggested. The clinical manifestation of acquired FVII deficiency varies greatly in severity; asymptomatic course as well as severe life-threatening bleeding diathesis and fatal bleedings have been described.

  2. Coagulation factor VII, serum-triglycerides and the R/Q353 polymorphism: differences between older men and women

    NARCIS (Netherlands)

    Mennen, L. I.; de Maat, M. P.; Schouten, E. G.; Kluft, C.; de Jong, P. T.; Hofman, A.; Grobbee, D. E.

    1997-01-01

    Coagulation factor VII activity (FVII:C) is a risk indicator for cardiovascular disease. It is related to serum-triglycerides and the R/Q353 polymorphism (alleles R and Q) in the gene coding for factor VII is strongly associated with factor VII. The association of serum-triglycerides with factor VII

  3. A ¤high-fat meal does not activate blood coagulation factor vii in minipigs

    DEFF Research Database (Denmark)

    Olsen, A. K.; Larsen, L. F.; Bladbjerg, E.-M.

    2001-01-01

    It is a matter of debate whether postprandial activation of blood coagulation factor VII (FVII) is associated with an increased risk of thrombosis. To clarify this question, an animal model in which consequences of dietary FVII activation can be studied in a more detailed way would be an important...

  4. A new automated method for continuous registration of factor VII activation in vitro. Activation is accelerated by the concentration of factor VII and the activity state of the protein

    DEFF Research Database (Denmark)

    Bladbjerg, Else-Marie; Jespersen, J; Gram, J

    1994-01-01

    When a plasma sample is exposed to tissue factor, single-chain factor VII (FVII) is gradually converted to the active two-chain form (FVIIa). In the present study, we have constructed a measurement system, which allows continuous registration of the activation of FVII to FVIIa in vitro....... In this system, FVII activation follows parabolic kinetic after an initial lag-phase. The slope of the linear phase is a measure of the protein concentration of factor VII (FVIItotal), while the length of the non-linear phase represents the velocity of FVII activation. The time required for complete activation...

  5. Is prophylaxis required for delivery in women with factor VII deficiency?

    Science.gov (United States)

    Baumann Kreuziger, L M; Morton, Colleen T; Reding, Mark T

    2013-11-01

    Factor VII (fVII) deficiency is a rare congenital bleeding disorder in which fVII activity level and bleeding tendency do not completely correlate. Pregnancy and delivery present a significant haemostatic challenge to women with fVII deficiency. Treatment with recombinant factor VIIa (rfVIIa) carries a thrombotic risk and the literature is not clear whether prophylaxis is necessary prior to delivery. The aim of this study was to define management, haemorrhagic and thrombotic complications of pregnant women with fVII deficiency through a systematic review. Medical databases (PubMed, MEDLINE, CINAHL, Academic Search Premier, Cochrane Library, Web of Science and Scopus) were searched using "factor VII deficiency" and "pregnancy" or "surgery." Overall 34 articles, four abstracts, and three institutional cases were reviewed. Literature from 1953 to 2011 reported 94 live births from 62 women with fVII deficiency. The median fVII activity was 5.5%. Haemostatic prophylaxis was used in 32% of deliveries. Without prophylaxis, 40 vaginal deliveries and 16 caesarean sections were completed. The odds of receiving prophylaxis were 2.9 times higher in women undergoing caesarean section compared to vaginal delivery. Post-partum haemorrhage occurred in 10% of deliveries with prophylaxis and 13% of deliveries without prophylaxis. The fVII level did not significantly differ between women who did and did not receive prophylaxis. We present the only systematic review of the management of pregnancy in fVII deficient women. No difference in post-partum haemorrhage was seen in deliveries with and without prophylaxis. Therefore, we recommend that rfVIIa be available in the case of haemorrhage or surgical intervention, but not as mandatory prophylaxis. © 2013 John Wiley & Sons Ltd.

  6. Life-threatening bleeding in a case of autoantibody-induced factor VII deficiency.

    Science.gov (United States)

    Okajima, K; Ishii, M

    1999-02-01

    A male patient presented with life-threatening bleeding induced by autoantibody-induced factor VII (F.VII) deficiency. This patient had macroscopic hematuria, skin ecchymosis, gastrointestinal bleeding, and a neck hematoma that was causing disturbed respiration. He developed acute renal failure and acute hepatic failure, probably due to obstruction of the ureters and the biliary tract, respectively. Although activated partial thromboplastin time was normal, prothrombin time (PT) was remarkably prolonged at 71.8 seconds compared to 14.0 seconds in a normal control. Both the immunoreactive level of F.VII antigen and the F.VII activity of the patient's plasma samples were VII activity. These findings suggested the presence of a plasma inhibitor for F.VII. After administration of large doses of methylprednisolone, PT was gradually shortened and plasma levels of F.VII increased over time. Bleeding, acute renal failure, and acute hepatic failure improved markedly following the steroid treatment. These observations suggest that life-threatening bleeding can be induced by autoantibody-induced F.VII deficiency and that immunosuppressive therapy using large doses of steroid can be successful in inhibiting the production of the autoantibody.

  7. Cerebral Venous Sinus Thrombosis in a Patient with Undiagnosed Factor VII Deficiency.

    Science.gov (United States)

    Qadir, Hira; Rashid, Anila; Adil, Salman Naseem

    2017-09-01

    Factor VII (FVII) deficiency is one of the rare inherited bleeding disorders. Thrombosis has been occasionally described in inherited FVII deficiency. Here, we report a young female with undiagnosed FVII deficiency who presented with cerebral venous sinus thrombosis (CVST). Oral contraceptive pill was found to be prothrombotic risk factor. The CVSToccurred in spite of the congenital FVII deficiency indicating that no definitive antithrombotic protection is assured by this defect. Low molecular weight heparin and anti-Xa assay were found to be safe choice of anticoagulation and monitoring, respectively, in this patient.

  8. Lack of bleeding in patients with severe factor VII deficiency.

    Science.gov (United States)

    Barnett, J Mark; Demel, Kurt C; Mega, Anthony E; Butera, James N; Sweeney, Joseph D

    2005-02-01

    Factor VII deficiency, although rare, is now recognized as the most common autosomal recessive inherited factor deficiency. It is usually considered to be associated with bleeding only in the severely affected subject and heterozygotes (>10%) are not considered at risk. The general recommendation for surgery is to achieve a FVII level in excess of 15% (0.15 1U/mL). We present three cases of severe factor VII deficiency, each of whom appeared hemostatically competent based on clinical history. Subject 1 is a 33 year-old African-American female with a baseline FVII of American female with a factor VII level of 9% who underwent an elective left total hip replacement without any factor replacement and had no excessive bleeding, but who sustained a pulmonary embolism postoperatively. Subject 3 is a 19-year-old African-American male with a baseline FVII of 1% with a history of active participation in football without noticeable injury and who underwent an emergent appendectomy without bleeding. These three cases represent individuals with the severe form of FVII deficiency who did not exhibit excessive bleeding when challenged with surgical procedures. The clinical history would appear the most valuable tool in predicting the likelihood of bleeding in these patients, and we suggest that the presumption that all patients with severe FVII deficiency should receive replacement therapy before surgical procedures may not be valid in all cases. Copyright 2005 Wiley-Liss, Inc.

  9. Factor VII deficiency

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000548.htm Factor VII deficiency To use the sharing features on this page, please enable JavaScript. Factor VII (seven) deficiency is a disorder caused by a ...

  10. Factor VII Tokushima: the first case of factor VII Cys22Gly with the development of myocardial infarction in the proband receiving recombinant factor VIIa replacement therapy.

    Science.gov (United States)

    Shigekiyo, Toshio; Sekimoto, Etsuko; Shibata, Hironobu; Ozaki, Shuji; Okumura, Takanobu; Fujinaga, Hiroyuki; Shibata, Hiroshi; Aihara, Ken-ichi; Akaike, Masashi

    2015-12-01

    An 81-year-old man was referred to our department because of suspected factor VII (FVII) deficiency. His FVII activity was under 1%, whereas the FVII activity levels of his son and granddaughter were 65 and 109%, respectively. The nucleotide at position 3886 of his FVII gene was homozygous for G. A single T to G substitution results in the replacement of wild-type Cys at residue 22 by Gly. His son was heterozygous for G and T at position 3886, whereas his granddaughter was homozygous for wild-type T. These results suggest that he was homozygous for FVII Cys22Gly. He underwent radiofrequency ablation (RFA) for hepatocellular carcinoma, receiving 20 μg/kg of recombinant FVIIa prior to RFA and 10 μg/kg of recombinant FVIIa twice after RFA. He showed no bleeding tendency; however, a myocardial infarction was diagnosed and percutaneous coronary intervention was performed.

  11. Self-production of tissue factor-coagulation factor VII complex by ovarian cancer cells.

    Science.gov (United States)

    Yokota, N; Koizume, S; Miyagi, E; Hirahara, F; Nakamura, Y; Kikuchi, K; Ruf, W; Sakuma, Y; Tsuchiya, E; Miyagi, Y

    2009-12-15

    Thromboembolic events are a major complication in ovarian cancer patients. Tissue factor (TF) is frequently overexpressed in ovarian cancer tissue and correlates with intravascular thrombosis. TF binds to coagulation factor VII (fVII), changing it to its active form, fVIIa. This leads to activation of the extrinsic coagulation cascade. fVII is produced by the liver and believed to be supplied from blood plasma at the site of coagulation. However, we recently showed that ovarian cancer cells express fVII transcripts under normoxia and that this transcription is inducible under hypoxia. These findings led us to hypothesise that ovarian cancer cells are intrinsically associated with TF-fVIIa coagulation activity, which could result in thrombosis. In this study, we examined whether ectopically expressed fVII could cause thrombosis by means of immunohistochemistry, RT-PCR, western blotting and flow cytometry. Ectopic fVII expression occurs frequently in ovarian cancers, particularly in clear cell carcinoma. We further showed that ovarian cancer cells express TF-fVIIa on the cell surface under normoxia and that this procoagulant activity is enhanced by hypoxic stimuli. Moreover, we showed that ovarian cancer cells secrete microparticles (MPs) with TF-fVIIa activity. Production of this procoagulant secretion is enhanced under hypoxia. These results raise the possibility that cancer cell-derived TF-fVIIa could cause thrombotic events in ovarian cancer patients.

  12. [Coagulation factor VII levels in uremic patients and theirs influence factors].

    Science.gov (United States)

    Fang, Jun; Xia, Ling-Hui; Wei, Wen-Ning; Song, Shan-Jun

    2004-12-01

    This study was aimed to investigate coagulation factor VII level in uremic patients with chronic renal failure and to explore theirs influence factors. The plasma levels of coagulation factor VII were detected in 30 uremic patients with chronic renal failure before and after hemodialysis for 1 month, the factor VII activity (FVII:C) was determined by one-stage coagulation method, while activated factor VII (FVIIa) was measured by one-stage coagulation method using recombinant soluble tissue factor, and factor VII antigen was detected by ELISA. The results showed that: (1) The FVIIa, FVII:C and FVIIAg levels in chronic uremic patients before hemodialysis were 4.00 +/- 0.86 microg/L, (148.5 +/- 40.4)% and (99.8 +/- 21.1)% respectively, which were significantly increased, as compared with healthy controls [2.77 +/- 1.02 microg/L, (113.1 +/- 33.0)% and (73.7 +/- 18.3)% respectively, P factor VII was positively correlated with levels of blood uria nitrogen and serum creatinine before hemodialysis but not after hemodialysis. It is concluded that the enhanced levels of coagulation factor VII in chronic uremic patients suggested abnormal activated state, herperactivity and elevated production of factor VII which correlated with renal functional injury. The abnormality of factor VII in uremia may be aggravated by hemodialysis. Coagulation factor (FVII) may be a risk factor for cardiovascular events in uremic patients who especially had been accepted long-term hemodialysis.

  13. Coagulation factor VII, serum-triglycerides and the R/Q353 polymorphism: Differences between older men and women

    NARCIS (Netherlands)

    Mennen, L.I.; Maat, M.P.M. de; Schouten, E.G.; Kluft, C.; Jong, P.T.V.M. de; Hofman, A.; Grobbee, D.E.

    1997-01-01

    Coagulation factor VII activity (FVII:C) is a risk indicator for cardiovascular disease. It is related to serum-triglycerides and the R/Q353 polymorphism (alleles R and Q) in the gene coding for factor VII is strongly associated with factor VU[. The association of serum-triglycerides with factor VII

  14. Expression and fast preparation of biologically active recombinant human coagulation factor VII in CHO-K1 cells.

    Science.gov (United States)

    Xiao, W; Li, C Q; Xiao, X P; Lin, F Z

    2013-12-16

    Human coagulation factor VII (FVII) plays an important role in the blood coagulation process and exists in micro amounts in human plasma; therefore, any attempt at the large-scale production of FVII in significant quantities is challenging. The purpose of this study was to express and obtain biologically active recombinant FVII (rFVII) from Chinese hamster ovary K1 (CHO-K1) cells. The full-length FVII cDNA was isolated from a HepG2 cell line and then subcloned in pcDNA3.1 to construct an expression vector, pcDNA-FVII. CHO-K1 cells were transfected with 1 µg pcDNA-FVII. The cell line that stably expressed secretory FVII was screened using 900 µg/mL G418. The FVII copy number in CHO-K1 cells was detected by quantitative polymerase chain reaction (qPCR). The rFVII was purified in ligand affinity chromatography medium. The purified protein was detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analysis. The biological activity of the purified FVII protein was determined by a prothrombin time assay. Three cell lines that permanently expressed rFVII were screened. The qPCR results demonstrated that each CHO-K1 cell harbored two FVII DNA copies. The SDS-PAGE and Western blot analysis showed that the purified protein was about 50 kDa. The purity of the target protein was 95%. The prothrombin time assay indicated that the FVII-specific activity of rFVII was 2573 ± 75 IU/mg. This method enabled the fast preparation of high-purity rFVII from CHO-K1 cells, and the purified protein had good biological activity.

  15. Effect of individual dietary fatty acids on postprandial activation of blood coagulation factor VII and fibrinolysis in healthy young men

    DEFF Research Database (Denmark)

    Tholstrup, T.; Miller, G.J.; Bysted, Anette

    2003-01-01

    Background: Hypertriglyceridemia may represent a procoagulant state involving disturbances to the hemostatic system. Plasminogen activator inhibitor type 1 (PAI-1) is increased in the presence of hypertriglyceridemia. Free fatty acids (FFAs) in plasma may promote factor VII (FVII) activation...

  16. A comparison between recombinant activated factor VII (Aryoseven) and Novoseven in patients with congenital factor VII deficiency.

    Science.gov (United States)

    Faranoush, M; Abolghasemi, Hassan; Toogeh, Gh; Karimi, M; Eshghi, P; Managhchi, M; Hoorfar, H; Dehdezi, B Keikhaei; Mehrvar, A; Khoeiny, B; Kamyar, K; Heshmat, R; Baghaeipour, M R; Mirbehbahani, N B; Fayazfar, R; Ahmadinejad, M; Naderi, M

    2015-11-01

    In order to establish the efficacy and biosimilar nature of AryoSeven to NovoSeven in the treatment of congenital factor VII (FVII) deficiency, patients received either agent at 30 μg/kg, intravenously per week for 4 weeks, in a randomized fashion. The primary aim was to compare FVII:coagulation activity (FVII:C), 20 minutes after recombinant activated FVII (rFVIIa) injection, in the 2 groups. A secondary measure was self-reported bleeding. The median interquartile baseline range of the plasma level of activated FVII (FVIIa) activity in the 2 groups was 1.6 (1.1-14.0) IU/dL and 5.0 (1.1-25.5) IU/dL. All patients achieved levels of FVIIa (FVII:C) >30 IU/dL, 20 minutes after the injection of rFVIIa. Bleeding was similar between the 2 groups, with a comparable decrease in severity and frequency compared to the last month prior to treatment. AryoSeven is similar to NovoSeven in increasing postinjection FVIIa activity as well as in clinical safety and efficacy. © The Author(s) 2014.

  17. Production of coagulation factor VII in human cell lines Sk-Hep-1 and HKB-11.

    Science.gov (United States)

    Corrêa de Freitas, Marcela Cristina; Bomfim, Aline de Sousa; Mizukami, Amanda; Picanço-Castro, Virgínia; Swiech, Kamilla; Covas, Dimas Tadeu

    2017-09-01

    Recombinant factor VII (rFVII) is the main therapeutic choice for hemophilia patients who have developed inhibitory antibodies against conventional treatments (FVIII and FIX). Because of the post-translational modifications, rFVII needs to be produced in mammalian cell lines. In this study, for the first time, we have shown efficient rFVII production in HepG2, Sk-Hep-1, and HKB-11 cell lines. Experiments in static conditions for a period of 96 h showed that HepG2-FVII produced the highest amounts of rhFVII, with an average of 1843 ng/mL. Sk-hep-1-FVII cells reached a maximum protein production of 1432 ng/mL and HKB-11-FVII cells reached 1468 ng/mL. Sk-Hep-1-rFVII and HKB-11-rFVII were selected for the first step of scale-up. Over 10 days of spinner flask culture, HKB-11 and SK-Hep-1 cells showed a cumulative production of rFVII of 152 μg and 202.6 μg in 50 mL, respectively. Thus, these human cell lines can be used for an efficient production of recombinant FVII. With more investment in basic research, human cell lines can be optimized for the commercial production of different bio therapeutic proteins. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. The molecular basis of low activity levels of coagulation factor VII: a Brazilian cohort.

    Science.gov (United States)

    Rabelo, F Y; Jardim, L L; Landau, M B; Gadelha, T; Corrêa, M F B; Pereira, I F M; Rezende, S M

    2015-09-01

    Inherited factor VII (FVII) deficiency is the most common among the rare bleeding disorders. It is transmitted as an autosomal recessive inheritance, due to mutations in the FVII gene (F7). Molecular studies of FVII deficiency are rare in non-Caucasian populations. The aim of the study was to evaluate the molecular basis behind low levels of FVII activity (FVII:C) levels in a cohort of Brazilian patients. A total of 34 patients with low FVII levels were clinically evaluated and submitted to laboratory tests, among these, prothrombin time and FVII:C, with different thromboplastins. All exons and intron/exon boundaries of F7 were amplified and sequenced. A total of 14 genetic alterations were identified, of which six were described previously, c.1091G>A, c.1151C>T, c.-323_-313insCCTATATCCT, c.285G>A, c.525C>T, c.1238G>A and eight (54.0%) and eight were new, c.128G>A, c.252C>T, c.348G>A, c.417G>A, c.426G>A, c.745_747delGTG, c.843G>A and c.805+52C>T. In addition to the mutation c.1091G>A, known as FVII Padua, the mutation c.1151C>T also presented discrepant FVII:C levels when tested with human and rabbit brain thromboplastin. There was no association between phenotype and genotype. Most of the identified genetic alterations found were polymorphisms. Low levels of FVII:C in this population were mostly related to polymorphisms in F7 and associated with a mild clinical phenotype. Mutation c.1151C>T was associated with discrepant levels of FVII:C using different thromboplastins, such as reported with FVII Padua. © 2015 John Wiley & Sons Ltd.

  19. Use of global assays to understand clinical phenotype in congenital factor VII deficiency.

    Science.gov (United States)

    Greene, L A; Goldenberg, N A; Simpson, M L; Villalobos-Menuey, E; Bombardier, C; Acharya, S S; Santiago-Borrero, P J; Cambara, A; DiMichele, D M

    2013-09-01

    Congenital factor VII (FVII) deficiency is characterized by genotypic variability and phenotypic heterogeneity. Traditional screening and factor assays are unable to reliably predict clinical bleeding phenotype and guide haemorrhage prevention strategy. Global assays of coagulation and fibrinolysis may better characterize overall haemostatic balance and aid in haemorrhagic risk assessment. We evaluated the ability of novel global assays to better understand clinical bleeding severity in congenital FVII deficiency. Subjects underwent central determination of factor VII activity (FVII:C) as well as clot formation and lysis (CloFAL) and simultaneous thrombin and plasmin generation (STP) global assay analysis. A bleeding score was assigned to each subject through medical chart review. Global assay parameters were analysed with respect to bleeding score and FVII:C. Subgroup analyses were performed on paediatric subjects and subjects with FVII ≥ 1 IU dL(-1). CloFAL fibrinolytic index (FI2 ) inversely correlated with FVII:C while CloFAL maximum amplitude (MA) and STP maximum velocity of thrombin generation (VT max) varied directly with FVII:C. CloFAL FI2 directly correlated with bleeding score among subjects in both the total cohort and paediatric subcohort, but not among subjects with FVII ≥ 1 IU dL(-1) . Among subjects with FVII ≥ 1 IU dL(-1), STP time to maximum velocity of thrombin generation and time to maximum velocity of plasmin generation inversely correlated with bleeding score. These preliminary findings suggest a novel potential link between a hyperfibrinolytic state in bleeding severity and congenital FVII deficiency, an observation that should be further explored. © 2013 John Wiley & Sons Ltd.

  20. Purification and Autoactivation Method for Recombinant Coagulation Factor VII.

    Science.gov (United States)

    Granovski, Vladimir; Freitas, Marcela C C; Abreu-Neto, Mario Soares; Covas, Dimas T

    2018-01-01

    Recombinant coagulation factor VII is a very important and complex protein employed for treatment of hemophiliac patients (hemophilia A/B) who develop inhibitors antibodies to conventional treatments (FVIII and FIX). The rFVII is a glycosylated molecule and circulates in plasma as zymogen of 50 kDa. When activated the molecule is cleaved to 20-30 kDa and has a half-life of about 3 h, needing to be processed fast and efficiently until freeze-drying. Here, we describe a very simple and fast purification sequence for rFVII using affinity FVII Select resin and a dialysis system that can be easily scaled up.

  1. [Haplotype Analysis of Coagulation Factor VII Gene in a Patient with Congenital Coagulation Factor VII Deficiency with Heterozygous p.Arg337Cys Mutation and o.Aro413Gin Polymorphism..

    Science.gov (United States)

    Suzuki, Keijiro; Yoshioka, Tomoko; Obara, Takehiro; Suwabe, Akira

    2016-05-01

    Congenital coagulation factor VII (FVII) deficiency is a rare hemorrhagic disease with an autosomal reces- sive inheritance pattern. We analyzed coagulation factor VII gene (F7) of a patient with FVII deficiency and used expression studies to investigate the effect of a missense mutation on FVII secretion. The proband, a 69-year-old Japanese woman, had a history of postpartum bleeding and excessive bleeding after dental extrac- tion. She was found to have mildly increased PT-INR (1.17) before an ophthalmic operation. FVII activity and antigen were reduced (29.0% and 32.8%). Suspecting that the proband was FVII deficient, we analyzed F7 of the patient. Sequence analysis revealed that the patient was heterozygous for a point mutation (p.Arg337Cys) in the catalytic domain and polymorphisms: the decanucleotide insertion at the promoter re- gion, dimorphism (c.525C >T) in exon 5, and p.Arg413Gln in exon 8. Haplotype analysis clarified that p.Arg337Cys was located on the p.Arg413 allele (Ml allele). The other allele had the p.Arg413Gln polymor- phism(M2 allele) which is known to produce less FVII. Expression studies revealed that p.Arg337Cys causes impairment of FVII secretion. Insufficient secretion of FVII arising from both the p.Arg337Cys/M1 allele and the p.Arg337/M2 allele might lower the FVII level of this patient(<50%). The FVII level in a heterozygous FVII deficient patient might be influenced by F7 polymorphisms on the normal allele. There- fore, genetic analyses are important for the diagnosis of heterozygous FVII deficiency.

  2. Tissue Factor–Factor VII Complex As a Key Regulator of Ovarian Cancer Phenotypes

    OpenAIRE

    Koizume, Shiro; Miyagi, Yohei

    2015-01-01

    Tissue factor (TF) is an integral membrane protein widely expressed in normal human cells. Blood coagulation factor VII (fVII) is a key enzyme in the extrinsic coagulation cascade that is predominantly secreted by hepatocytes and released into the bloodstream. The TF–fVII complex is aberrantly expressed on the surface of cancer cells, including ovarian cancer cells. This procoagulant complex can initiate intracellular signaling mechanisms, resulting in malignant phenotypes. Cancer tissues are...

  3. The effects of three factor VII polymorphisms on factor VII coagulant levels in healthy Singaporean Chinese, Malay and Indian newborns.

    Science.gov (United States)

    Quek, S C; Low, P S; Saha, N; Heng, C K

    2006-11-01

    Factor VII (FVII) is an independent risk factor for coronary artery disease. Three polymorphisms of the factor VII gene (F7) were studied in a group of healthy newborns comprising 561 Chinese, 398 Malays and 226 Asian Indians from Singapore. The allele frequencies of 3 polymorphisms (R353Q, Promoter 0/10bp Del/Ins and Intron 7) in the FVII gene were ascertained through genotyping by polymerase chain reaction and restriction digestion of amplified fragments. In Chinese the minor allele frequencies are Q: 0.04, Ins: 0.03, R7: 0.44; Malays, Q: 0.06, Ins: 0.10, R7: 0.41; and Indians, Q: 0.25, Ins: 0.23, R7: 0.43. Strong linkage disequilibrium (Delta > 0.7) is observed between the 0/10 bp and the R353Q sites in all ethnic groups. We conclude that: (i) the prevalence of the minor Q and Ins alleles of the R353Q and 0/10 bp polymorphisms are significantly higher in the Indian newborns than the Chinese and Malays; (ii) the Q allele is significantly associated (p = 0.01) with a lower plasma FVII coagulant level in the Indian and Malay neonates; and this polymorphism explains up to 3.8% of the variance in FVII coagulant levels; (iii) there is no significant difference in allele frequencies of the three polymorphisms between neonates with and without family histories of CAD.

  4. Factor VII assay

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003676.htm Factor VII assay To use the sharing features on ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  5. Plasma factor VII-activating protease is increased by oral contraceptives and induces factor VII activation in-vivo

    DEFF Research Database (Denmark)

    Sidelmann, Johannes Jakobsen; Skouby, Sven O.; Kluft, Cornelis

    2011-01-01

    progestins. FSAP genotypes, FSAP and factor VII (FVII) plasma measures were assessed at baseline and after 6 cycles of OC. The 1601GA genotype was present in 49 (8.3%) of the women and was associated with significantly reduced levels of FSAP (P≤0.001). OC use increased FSAP antigen by 25% and FSAP activity......Oral contraceptive (OC) use influences the hemostatic system significantly and is a risk factor for development of cardiovascular disease. Factor VII-activating protease (FSAP) has potential effects on hemostasis. The 1601GA genotype of the 1601G/A polymorphism in the FSAP gene expresses a FSAP...... by 59% (P0.05). The relative increase in FSAP activity was significantly higher in women carrying the 1601GG genotype (63%) than in women carrying 1601GA genotype (50%) (P=0.01) and was associated with an increased activation of FVII. In conclusion: OC use increases the plasma measures of FSAP...

  6. Compound heterozygous mutations (p.Leu13Pro and p.Tyr294*) associated with factor VII deficiency cause impaired secretion through ineffective translocation and extensive intracellular degradation of factor VII.

    Science.gov (United States)

    Suzuki, Keijiro; Sugawara, Takeshi; Ishida, Yoji; Suwabe, Akira

    2013-02-01

    Congenital coagulation factor VII (FVII) deficiency is a rare coagulation disease. We investigated the molecular mechanisms of this FVII deficiency in a patient with compound heterozygous mutations. A 22-year-old Japanese female was diagnosed with asymptomatic FVII deficiency. The FVII activity and antigen were greatly reduced (activity, 13.0%; antigen, 10.8%). We analyzed the F7 gene of this patient and characterized mutant FVII proteins using in vitro expression studies. Sequence analysis revealed that the patient was compound heterozygous with a point mutation (p.Leu13Pro) in the central hydrophobic core of the signal peptides and a novel non-sense mutation (p.Tyr294*) in the catalytic domain. Expression studies revealed that mutant FVII with p.Leu13Pro (FVII13P) showed less accumulation in the cells (17.5%) and less secretion into the medium (64.8%) than wild type showed. Truncated FVII resulting from p.Tyr294* (FVII294X) was also decreased in the cells (32.0%), but was not secreted into the medium. Pulse-chase experiments revealed that both mutants were extensively degraded intracellularly compared to wild type. The majority of FVII13P cannot translocate into endoplasmic reticulum (ER). However, a small amount of FVII13P was processed normally with post-translational modifications and was secreted into the medium. The fact that FVII294X was observed only in ER suggests that it is retained in ER. Proteasome apparently plays a central role in these degradations. These findings demonstrate that both mutant FVIIs impaired secretion through ineffective translocation to and retention in ER with extensive intracellular degradation, resulting in an insufficient phenotype. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. A novel missense mutation close to the charge-stabilizing system in a patient with congenital factor VII deficiency.

    Science.gov (United States)

    Jiang, Minghua; Wang, Zhaoyue; Yu, Ziqiang; Bai, Xia; Su, Jian; Cao, Lijuan; Zhang, Wei; Ruan, Changgeng

    2011-06-01

    Congenital factor VII (FVII) deficiency is a rare autosomal recessive bleeding disorder. Its clinical manifestation and mutational spectrum are highly variable. The purpose of this study was to identify and characterize the mutation causing the FVII deficiency in a Chinese patient and his family. The FVII gene was analyzed by genomic DNA sequencing, and the FVII levels in patient's plasma were measured with an enzyme-linked immunoabsorbent assay (ELISA) and one-stage prothrombin time based method. In addition, the FVII-Phe190 mutant identified in the pedigree was expressed in the HEK293 cells, and the subcellular localization experiments in the Chinese hamster ovary (CHO) cells were performed. The patient had a prolonged prothrombin time and low levels of both FVII antigen and activity, and two heterozygous mutations were identified in F7 gene (NG-009262.1): a g.15975 G>A in the splice receptor site of intron 6 and a novel g.16750 C>T in exon 8 resulting in Ser190 to Phe190 replacement. In expression experiments, the reduced antigen and activity levels of FVII-Phe190 in the culture medium were found, whereas an ELISA and Western blotting analysis of FVII revealed that mutant FVII-Phe190 was synthesized in the cells as the wild-type FVII-Ser190. And FVII-Phe190 was found in endoplasmic reticulum and Golgi apparatus. Compound heterozygous mutations in F7 gene should be responsible for the FVII deficiency in this patient. The FVII-Phe190 can normally be synthesized and transported from endoplasmic reticulum to Golgi apparatus, but degraded or inefficiently secreted.

  8. Plasma factor VII-activating protease is increased by oral contraceptives and induces factor VII activation in-vivo

    DEFF Research Database (Denmark)

    Sidelmann, Johannes J; Skouby, Sven O; Kluft, Cornelis

    2011-01-01

    Oral contraceptive (OC) use influences the hemostatic system significantly and is a risk factor for development of cardiovascular disease. Factor VII-activating protease (FSAP) has potential effects on hemostasis. The 1601GA genotype of the 1601G/A polymorphism in the FSAP gene expresses a FSAP...... progestins. FSAP genotypes, FSAP and factor VII (FVII) plasma measures were assessed at baseline and after 6 cycles of OC. The 1601GA genotype was present in 49 (8.3%) of the women and was associated with significantly reduced levels of FSAP (P=0.001). OC use increased FSAP antigen by 25% and FSAP activity...

  9. The link between high-fat meals and postprandial activation of blood coagulation factor VII possibly involves kallikrein

    DEFF Research Database (Denmark)

    Larsen, L F; Marckmann, P; Bladbjerg, Else-Marie

    2000-01-01

    Contrary to low-fat meals, high-fat meals are known to cause postprandial factor VII (FVII) activation, but the mechanism is unknown. To study the postprandial FVII activation in detail, 18 young men consumed in randomized order high-fat or low-fat test meals. Fasting and non-fasting blood samples...... that triglyceride-rich lipoproteins may activate prokallikrein. Neither plasma triglycerides nor kallikrein and activated FVII were statistically associated. This may suggest that additional factors are involved in the postprandial FVII activation. No clear evidence for a role of tissue factor expression...... by monocytes, factor XII or insulin in postprandial FVII activation was observed. Tissue factor pathway inhibitor and prothrombin fragment 1+2, a marker of thrombin generation, were not affected postprandially after either the high-fat or the low-fat meals. Our findings indicate that triglyceride...

  10. The production of coagulation factor VII by adipocytes is enhanced by tumor necrosis factor-α or isoproterenol.

    Science.gov (United States)

    Takahashi, N; Yoshizaki, T; Hiranaka, N; Kumano, O; Suzuki, T; Akanuma, M; Yui, T; Kanazawa, K; Yoshida, M; Naito, S; Fujiya, M; Kohgo, Y; Ieko, M

    2015-05-01

    A relationship has been reported between blood concentrations of coagulation factor VII (FVII) and obesity. In addition to its role in coagulation, FVII has been shown to inhibit insulin signals in adipocytes. However, the production of FVII by adipocytes remains unclear. We herein investigated the production and secretion of FVII by adipocytes, especially in relation to obesity-related conditions including adipose inflammation and sympathetic nerve activation. C57Bl/6J mice were fed a low- or high-fat diet and the expression of FVII messenger RNA (mRNA) was then examined in adipose tissue. 3T3-L1 cells were used as an adipocyte model for in vitro experiments in which these cells were treated with tumor necrosis factor-α (TNF-α) or isoproterenol. The expression and secretion of FVII were assessed by quantitative real-time PCR, Western blotting and enzyme-linked immunosorbent assays. The expression of FVII mRNA in the adipose tissue of mice fed with high-fat diet was significantly higher than that in mice fed with low-fat diet. Expression of the FVII gene and protein was induced during adipogenesis and maintained in mature adipocytes. The expression and secretion of FVII mRNA were increased in the culture medium of 3T3-L1 adipocytes treated with TNF-α, and these effects were blocked when these cells were exposed to inhibitors of mitogen-activated kinases or NF-κB activation. The β-adrenoceptor agonist isoproterenol stimulated the secretion of FVII from mature adipocytes via the cyclic AMP/protein kinase A pathway. Blockade of secreted FVII with the anti-FVII antibody did not affect the phosphorylation of Akt in the isoproterenol-stimulated adipocytes. Obese adipose tissue produced FVII. The production and secretion of FVII by adipocytes was enhanced by TNF-α or isoproterenol via different mechanisms. These results indicate that FVII is an adipokine that plays an important role in the pathogenesis of obesity.

  11. Pathogenetic role of Factor VII deficiency and thrombosis in cross-reactive material positive patients.

    Science.gov (United States)

    Girolami, A; Sambado, L; Bonamigo, E; Ferrari, S; Lombardi, A M

    2013-12-01

    Congenital Factor VII (FVII) deficiency can be divided into two groups: cases of "true" deficiency, or cross-reactive material (CRM) negative and variants that are cross-reactive material positive.The first form is commonly recognized as Type I condition whereas the second one is known as Type II. FVII deficiency has been occasionally associated with thrombotic events, mainly venous. The reasons underlying this peculiar manifestation are unknown even though in the majority of associated patients thrombotic risk factors are present. The purpose of the present study was to investigate if a thrombotic event was more frequent in Type I or in Type II defect.The majority of patients with FVII deficiency and thrombosis belong to Type II defects. In the following paper we discuss the possible role of the dysfunctional FVII cross-reaction material as a contributory cause for the occurrence of thrombosis.

  12. Replacement therapy for bleeding episodes in factor VII deficiency. A prospective evaluation.

    Science.gov (United States)

    Mariani, Guglielmo; Napolitano, Mariasanta; Dolce, Alberto; Pérez Garrido, Rosario; Batorova, Angelika; Karimi, Mehran; Platokouki, Helen; Auerswald, Günter; Bertrand, Anne-Marie; Di Minno, Giovanni; Schved, Jean F; Bjerre, Jens; Ingerslev, Jorgen; Sørensen, Benny; Ruiz-Saez, Arlette

    2013-02-01

    Patients with inherited factor VII (FVII) deficiency display different clinical phenotypes requiring ad hoc management. This study evaluated treatments for spontaneous and traumatic bleeding using data from the Seven Treatment Evaluation Registry (STER). One-hundred one bleeds were analysed in 75 patients (41 females; FVII coagulant activity <1-20%). Bleeds were grouped as haemarthroses (n=30), muscle/subcutaneous haematomas (n=16), epistaxis (n=12), gum bleeding (n=13), menorrhagia (n=16), central nervous system (CNS; n=9), gastrointestinal (GI; n=2) and other (n=3). Of 93 evaluable episodes, 76 were treated with recombinant, activated FVII (rFVIIa), eight with fresh frozen plasma (FFP), seven with plasma-derived FVII (pdFVII) and two with prothrombin-complex concentrates. One-day replacement therapy resulted in very favourable outcomes in haemarthroses, and was successful in muscle/subcutaneous haematomas, epistaxis and gum bleeding. For menorrhagia, single- or multiple-dose schedules led to favourable outcomes. No thrombosis occurred; two inhibitors were detected in two repeatedly treated patients (one post-rFVIIa, one post-pdFVII). In FVII deficiency, most bleeds were successfully treated with single 'intermediate' doses (median 60 µg/kg) of rFVIIa. For the most severe bleeds (CNS, GI) short- or long-term prophylaxis may be optimal.

  13. Monitoring of treatment with vitamin K antagonists: recombinant thromboplastins are more sensitive to factor VII than tissue-extract thromboplastins.

    Science.gov (United States)

    Biedermann, J S; van den Besselaar, A M H P; de Maat, M P M; Leebeek, F W G; Kruip, M J H A

    2017-03-01

    Essentials Differences in sensitivity to factor VII (FVII) have been suggested between thromboplastins. FVII-induced International Normalized Ratio (INR) changes differ between commercial reagents. Recombinant human thromboplastins are more sensitive to FVII than tissue-extract thromboplastins. Thromboplastin choice may affect FVII-mediated INR stability. Background Differences regarding sensitivity to factor VII have been suggested for recombinant human and tissue-extract thromboplastins used for International Normalized Ratio (INR) measurement, but the evidence is scarce. Differences in FVII sensitivity are clinically relevant, as they can affect INR stability during treatment with vitamin K antagonists (VKAs). Objectives To determine whether commercial thromboplastins react differently to changes in FVII. Methods We studied the effect of addition of FVII on the INR in plasma by using three tissue-extract (Neoplastin C1+, Hepato Quick, and Thromborel S) and three recombinant human (Recombiplastin 2G, Innovin, and CoaguChek XS) thromboplastins. Three different concentrations of purified human FVII (0.006, 0.012 and 0.062 μg mL -1 plasma), or buffer, were added to five certified pooled plasmas of patients using VKAs (INR of 1.5-3.5). Changes in FVII activity were measured with two bioassays (Neoplastin and Recombiplastin), and relative INR changes were compared between reagents. Results After addition of 0.062 μg mL -1 FVII, FVII activity in the pooled plasmas increased by approximately 20% (Neoplastin) or 32% (Recombiplastin) relative to the activity in pooled normal plasma. All thromboplastins showed dose-dependent INR decreases. The relative INR change in the pooled plasmas significantly differed between the six thromboplastins. No differences were observed among recombinant or tissue-extract thromboplastins. Pooled results indicated that the FVII-induced INR change was greater for recombinant than for tissue-extract thromboplastins. Conclusions Differences

  14. Two novel cases of cerebral haemorrhages at the neonatal period associated with inherited factor VII deficiency, one of them revealing a new nonsense mutation (Ser52Stop).

    Science.gov (United States)

    Giansily-Blaizot, Muriel; Aguilar-Martinez, Patricia; Briquel, Marie-Elisabeth; d'Oiron, Roseline; De Maistre, Emmanuel; Epelbaum, Serge; Schved, Jean-François

    2003-02-01

    Factor VII (FVII) is a plasma glycoprotein that plays a key role in the initiation of blood coagulation cascade. Inherited FVII deficiency is a rare autosomal recessive disorder with a wide heterogeneous clinical pattern. The severe form may be associated with intracranial haemorrhages occurring closely to birth with a high mortality rate. In the present article, we report two novel cases of neonatal intracerebral bleeding associated with FVII activity levels below 1% of normal. FVII genotyping investigations revealed particular genotypes including the deleterious Cys135Arg mutation and a novel Ser52Stop nonsense mutation at the homozygous state. Both mutations, through different mechanisms, are expected to be inconsistent with the production of functional FVII. These putative mechanisms are discussed through a review of the literature on phenotypic and genotypic characteristics of cerebral haemorrhages in severe inherited FVII deficiency.

  15. Inherited coagulation factor VII and X deficiencies associated with severe bleeding diathesis: Molecular genetics and pathophysiology

    NARCIS (Netherlands)

    Borensztajn, K.; Spek, C. A.

    2005-01-01

    The rare inherited coagulation disorders are a fascinating group of diseases that have provided us with important insights into the structure and functions of their respective deficient proteins. Factor (F)VII deficiency is the commonest of these inherited disorders of coagulation, whereas FX

  16. Serendipitous Discovery of Factor VII Deficiency and the Ensuing Dilemma.

    Science.gov (United States)

    Umakanthan, Jayadev M; Dhakal, Prajwal; Gundabolu, Krishna; Koepsell, Scott A; Baljevic, Muhamed

    2018-03-01

    Congenital factor VII deficiency is a challenging disorder to manage, as it is associated with varied genotypes that do not clinically correlate with a bleeding phenotype. Individuals with severe factor VII deficiency (FVII: c 5%) may experience severe hemorrhages. In modern medicine, due to extensive routine pre-operative laboratory testing, clinically asymptomatic patients without any bleeding history might be incidentally discovered, raising clinical dilemmas. Careful consideration of bleeding versus thrombosis risk has to be made in such cases, especially in the elderly. Clinical history of no prior bleeding complications may be a reassuring factor. Minimal required replacement dosing of recombinant activated factor VII can be given peri-operatively in such situations, with close monitoring.

  17. Tissue factor-dependent vascular endothelial growth factor production by human fibroblasts in response to activated factor VII.

    Science.gov (United States)

    Ollivier, V; Bentolila, S; Chabbat, J; Hakim, J; de Prost, D

    1998-04-15

    The transmembrane protein tissue factor (TF) is the cell surface receptor for coagulation factor VII (FVII) and activated factor VII (FVIIa). Recently, TF has been identified as a regulator of angiogenesis, tumor growth, and metastasis. This study was designed to link the binding of FVII(a) to its receptor, TF, with the subsequent triggering of angiogenesis through vascular endothelial growth factor (VEGF) production by human lung fibroblasts. We report that incubation of fibroblasts, which express constitutive surface TF, with FVII(a) induces VEGF synthesis. FVII(a)-induced VEGF secretion, assessed by a specific enzyme-linked immunosorbent assay, was time- and concentration-dependent. VEGF secretion was maximal after 24 hours of incubation of the cells with 100 nmol/L FVII(a) and represented a threefold induction of the basal VEGF level. Reverse transcriptase-polymerase chain reaction analysis of VEGF detected three mRNA species of 180, 312, and 384 bp corresponding, respectively, to VEGF121, VEGF165, and VEGF189. A 2.5- to 3.5-fold increase was observed for the 180- and 312-bp transcripts at 12 and 24 hours, respectively. FVII(a)-dependent VEGF production was inhibited by a pool of antibodies against TF, pointing to the involvement of this receptor. On specific active-site inhibition with dansyl-glutamyl-glycinyl-arginyl chloromethyl ketone, FVIIa lost 70% of its capacity to elicit VEGF production. Consistent with this, the native form (zymogen) of FVII only had a 1.8-fold stimulating effect. Protein tyrosine kinase and protein kinase C are involved in signal transduction leading to VEGF production, as shown by the inhibitory effects of genistein and GF 109203X. The results of this study indicate that TF is essential for VIIa-induced VEGF production by human fibroblasts and that its role is mainly linked to the proteolytic activity of the TF-VIIa complex.

  18. Heterozygous congenital Factor VII deficiency with the 9729del4 mutation, associated with severe spontaneous intracranial bleeding in an adolescent male.

    Science.gov (United States)

    Cramer, Thomas J; Anderson, Kristin; Navaz, Karanjia; Brown, Justin M; Mosnier, Laurent O; von Drygalski, Annette

    2016-03-01

    In congenital Factor (F) VII deficiency bleeding phenotype and intrinsic FVII activity levels don't always correlate. Patients with FVII activity levels <30% appear to have a higher bleeding propensity, but bleeding can also occur at higher FVII activity levels. Reasons for bleeding at higher FVII activity levels are unknown, and it remains challenging to manage such patients clinically. A 19year old male with spontaneous intracranial hemorrhage and FVII activity levels of 44%, requiring emergent surgical intervention and a strategy for FVII replacement. Genotyping showed the rare heterozygous FVII 9729del4 mutation. Bleed evacuation was complicated by epidural abscess requiring craniectomy, bone graft procedures, and prolonged administration of recombinant human (rh) activated FVII (FVIIa). The patient recovered without neurological deficits, and remains on prophylactic low dose treatment with rhFVIIa in relation to risky athletic activities. For clinicians, it is important to recognize that effects of rhFVIIa within these pathways are independent of its contribution to blood clot formation and cannot be assessed by clotting assays. Reduced FVII levels should therefore not be dismissed, as even a mild reduction may result in spontaneous bleeding. Treatment of mild FVII deficiency requires a careful case-by-case approach, based on the clinical scenario. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Tissue Factor-Factor VII Complex As a Key Regulator of Ovarian Cancer Phenotypes.

    Science.gov (United States)

    Koizume, Shiro; Miyagi, Yohei

    2015-01-01

    Tissue factor (TF) is an integral membrane protein widely expressed in normal human cells. Blood coagulation factor VII (fVII) is a key enzyme in the extrinsic coagulation cascade that is predominantly secreted by hepatocytes and released into the bloodstream. The TF-fVII complex is aberrantly expressed on the surface of cancer cells, including ovarian cancer cells. This procoagulant complex can initiate intracellular signaling mechanisms, resulting in malignant phenotypes. Cancer tissues are chronically exposed to hypoxia. TF and fVII can be induced in response to hypoxia in ovarian cancer cells at the gene expression level, leading to the autonomous production of the TF-fVII complex. Here, we discuss the roles of the TF-fVII complex in the induction of malignant phenotypes in ovarian cancer cells. The hypoxic nature of ovarian cancer tissues and the roles of TF expression in endometriosis are discussed. Arguments will be extended to potential strategies to treat ovarian cancers based on our current knowledge of TF-fVII function.

  20. Increased volume of distribution for recombinant activated factor VII and longer plasma-derived factor VII half-life may explain their long lasting prophylactic effect.

    Science.gov (United States)

    Mathijssen, Natascha C J; Masereeuw, Rosalinde; Holme, Pal Andre; van Kraaij, Marian G J; Laros-van Gorkom, Britta A P; Peyvandi, Flora; van Heerde, Waander L

    2013-08-01

    Prophylaxis with plasma-derived or recombinant activated factor VII is beneficial in severe factor VII deficiency. To understand why prophylactic treatment with both products is efficacious, we conducted a pharmacokinetic study. Ten factor VII deficient patients were treated with either recombinant activated (20 μg/kg) or plasma-derived (25 IU/kg) factor VII in a cross-over design. Pharmacokinetic parameters were analyzed through activated factor VII activity, factor VII clotting activity, and factor VII antigen levels on depicted time points. Factor VII activity half-lifes, determined by non-compartmental and one-compartmental analysis (results in brackets), were shorter for recombinant activated (1.4h; 0.7h) than for plasma-derived factor VII (6.8h; 3.2h); both recombinant activated (5.1h; 2.1h and plasma-derived factor VII (5.8h; 3.2h) resulted in longer half-lives of factor VII antigen. Activated factor VII half-lives (based on activated factor VII activity levels) were significantly higher compared to factor VII clotting activity (1.6h; 0.9h). Volumes of distribution were significantly higher for activated factor VII (236 ml/kg; 175 ml/kg, measured by activated factor VII) as compared to plasma-derived factor VII (206 ml/kg; 64 ml/kg, measured by factor FVII activity), suggesting a plasma- and extracellular fluid distribution for recombinant activated factor VII. Recombinant activated factor VII showed significantly shorter half-lifes than plasma-derived factor VII. Volumes of distribution were significantly higher for treatment with recombinant activated factor VII. The longer half-life for plasma-derived factor VII, compared to recombinant activated factor VII, and the increased volume of distribution for recombinant activated factor VII, compared to plasma-derived factor VII may further elucidate the beneficial effect of prophylactic treatment of both products. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Differential functional readthrough over homozygous nonsense mutations contributes to the bleeding phenotype in coagulation factor VII deficiency.

    Science.gov (United States)

    Branchini, A; Ferrarese, M; Lombardi, S; Mari, R; Bernardi, F; Pinotti, M

    2016-10-01

    Essentials Potentially null homozygous Factor(F)7 nonsense mutations are associated to variable bleeding symptoms. Readthrough of p.Ser112X (life-threatening) and p.Cys132X (moderate) stop codons was investigated. Readthrough-mediated insertion of wild-type or tolerated residues produce functional proteins. Functional readthrough over homozygous F7 nonsense mutations contributes to the bleeding phenotype. Background Whereas the rare homozygous nonsense mutations causing factor (F)VII deficiency may predict null conditions that are almost completely incompatible with life, they are associated with appreciable differences in hemorrhagic symptoms. The misrecognition of premature stop codons (readthrough) may account for variable levels of functional full-length proteins. Objectives To experimentally evaluate the basal and drug-induced levels of FVII resulting from the homozygous p.Cys132X and p.Ser112X nonsense mutations that are associated with moderate (132X) or life-threatening (112X) symptoms, and that are predicted to undergo readthrough with (132X) or without (112X) production of wild-type FVII. Methods We transiently expressed recombinant FVII (rFVII) nonsense and missense variants in human embryonic kidney 293 cells, and evaluated secreted FVII protein and functional levels by ELISA, activated FX generation, and coagulation assays. Results The levels of functional FVII produced by p.Cys132X and p.Ser112X mutants (rFVII-132X, 1.1% ± 0.2% of wild-type rFVII; rFVII-112X, 0.5% ± 0.1% of wild-type rFVII) were compatible with the occurrence of spontaneous readthrough, which was magnified by the addition of G418 - up to 12% of the wild-type value for the rFVII-132X nonsense variant. The predicted missense variants arising from readthrough abolished (rFVII-132Trp/Arg) or reduced (rFVII-112Trp/Cys/Arg, 22-45% of wild-type levels) secretion and function. These data suggest that the appreciable rescue of p.Cys132X function was driven by reinsertion of the wild

  2. [Hereditary heterozygous factor VII deficiency in patients undergoing surgery : Clinical relevance].

    Science.gov (United States)

    Woehrle, D; Martinez, M; Bolliger, D

    2016-10-01

    A hereditary deficiency in coagulation factor VII (FVII) may affect the international normalized ratio (INR) value. However, FVII deficiency is occasionally associated with a tendency to bleed spontaneously. We hypothesized that perioperative substitution with coagulation factor concentrates might not be indicated in most patients. In this retrospective data analysis, we included all patients with hereditary heterozygous FVII deficiency who underwent surgical procedures at the University Hospital Basel between December 2010 and November 2015. In addition, by searching the literature, we identified publications reporting patients with FVII deficiency undergoing surgical procedures without perioperative substitution. We identified 22 patients undergoing 46 surgical procedures, resulting in a prevalence of 1:1500-2000. Coagulation factor concentrates were administered during the perioperative period in 15 procedures (33 %), whereas in the other 31 procedures (66 %), FVII deficiency was not substituted. No postoperative bleeding or thromboembolic events were reported. In addition, we found no differences in pre- and postoperative hemoglobin and coagulation parameters, with the exception of an improved postoperative INR value in the substituted group. In the literature review, we identified five publications, including 125 patients with FVII deficiency, undergoing 213 surgical procedures with no perioperative substitution. Preoperative substitution using coagulation factor concentrates does not seem to be mandatory in patients with an FVII level ≥15 %. For decision-making on preoperative substitution, patient history of an increased tendency to bleed may be more important than the FVII level or increased INR value.

  3. A high fat meal activates blood coagulation factor vii in rats

    DEFF Research Database (Denmark)

    Olsen, A. K.; Bladbjerg, E. M.; Kornerup Hansen, A.

    2002-01-01

    In humans, high fat meals cause postprandial activation of blood coagulation factor VII (FVII), but human studies have not provided definite evidence for a prothrombotic effect of dietary FVII activation. An animal model would be an attractive way to pursue this question and therefore we tested...... the LEW/Mol rat. We gavaged 3 mL of a fat emulsion (n = 42) or 3 mL isotonic glucose (n = 42). Blood was sampled by heart puncture 2, 4 and 6 h (n = 14/group at each time) after the fat/glucose load. Furthermore, blood was sampled from 16 untreated rats to determine the baseline levels. Triglyceride...

  4. Mutagenesis in sequence encoding of human factor VII for gene therapy of hemophilia

    Directory of Open Access Journals (Sweden)

    B Kazemi

    2009-12-01

    Full Text Available "nBackground: Current treatment of hemophilia which is one of the most common bleeding disorders, involves replacement therapy using concentrates of FVIII and FIX .However, these concentrates have been associated with viral infections and thromboembolic complications and development of antibodies. "nThe use of recombinant human factor VII (rhFVII is effective  for the treatment of patients with  hemophilia A or B, who develop antibodies ( referred as inhibitors against  replacement therapy , because it induces coagulation independent of FVIII and FIX. However, its short half-life and high cost have limited its use. One potential solution to this problem may be the use of FVIIa gene transfer, which would attain continuing therapeutic levels of expression from a single injection. The aim of this study was to engineer a novel hFVII (human FVII gene containing a cleavage site for the intracellular protease and furin, by PCR mutagenesis "nMethods: The sequence encoding light and heavy chains of hFVII, were amplified by using hFVII/pTZ57R and specific primers, separately. The PCR products were cloned in pTZ57R vector. "nResults and discussion: Cloning was confirmed by restriction analysis or PCR amplification using specific primers and plasmid universal primers. Mutagenesis of sequence encoding light and heavy chain was confirmed by restriction enzyme. "nConclusion: In the present study, it was provided recombinant plasmids based on mutant form of DNA encoding light and heavy chains.  Joining mutant form of DNA encoding light chain with mutant heavy chain led to a new variant of hFVII. This variant can be activated by furin and an increase in the proportion of activated form of FVII. This mutant form of hFVII may be used for gene therapy of hemophilia.

  5. Ischemic stroke in a patient with moderate to severe inherited factor VII deficiency.

    Science.gov (United States)

    Reddy, Manasa; Tawfik, Bernard; Gavva, Chakri; Yates, Sean; De Simone, Nicole; Hofmann, Sandra L; Rambally, Siayareh; Sarode, Ravi

    2016-12-01

    Thrombosis is known to occur in patients with rare inherited bleeding disorders, usually in the presence of a thrombotic risk factor such as surgery and/or factor replacement therapy, but sometimes spontaneously. We present the case of a 72-year-old African American male diagnosed with congenital factor VII (FVII) deficiency after presenting with ischemic stroke, presumably embolic, in the setting of atherosclerotic carotid artery stenosis. The patient had an international normalized ratio (INR) of 2.0 at presentation, with FVII activity of 6% and normal Extem clotting time in rotational thromboelastometry. He was treated with aspirin (325 mg daily) and clopidogrel (75 mg daily) with no additional bleeding or thrombotic complications throughout his admission. This case provides further evidence that moderate to severe FVII deficiency does not protect against thrombosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Management of Labour and Delivery in a Patient With Acquired Factor VII Deficiency With Inhibitor: A Case Report.

    Science.gov (United States)

    Matei, Anca; Dolan, Sean; Andrews, James; Rivard, Georges-Étienne

    2016-02-01

    Acquired factor VII (FVII) deficiency with inhibitor increases the risk of hemorrhage during pregnancy. However, there are no published reports guiding its management in the peripartum period. A 24-year-old woman with inhibitory antibodies to FVII delivered at 34 weeks of gestation. The patient was administered recombinant factor VIIa (rFVIIa) and tranexamic acid. There were no bleeding-related complications; however, the FVII level was supratherapeutic. The patient returned during a second pregnancy. A reduced dose of rFVIIa was administered. The delivery was complicated by postpartum hemorrhage, which resolved with the addition of uterotonic agents. Recombinant FVIIa and tranexamic acid offer an effective peripartum treatment in women with inhibitory antibody to FVII. Further research should delineate the optimal time of administration. Copyright © 2016 Society of Obstetricians and Gynaecologists of Canada. Published by Elsevier Inc. All rights reserved.

  7. Managing incidentally diagnosed isolated factor VII deficiency perioperatively: a brief expert consensus report.

    Science.gov (United States)

    Sheth, Sujit; Soff, Gerald; Mitchell, Beau; Green, David; Kaicker, Shipra; Fireman, Fernando; Tugal, Oya; Guarini, Ludovico; Giardina, Patricia; Aledort, Louis

    2012-02-01

    While isolated factor VII (FVII) deficiency is being more frequently diagnosed owing to improved preoperative screening procedures, there is no specific guideline for perioperative management of such patients. To complicate the issue, FVII activity levels seem to correlate less well with the risk of hemorrhage than the patient's past and family bleeding history do. We have devised expert consensus recommendations for managing such patients perioperatively, taking into consideration the personal and family bleeding history, the FVII activity level and the inherent bleeding risk of the procedure itself. We hope that clinicians will find this a useful tool in the decision-making process, thereby limiting the use of recombinant factor VIIa to those who need it most, and preventing possible thrombotic complications in those without a strong indication for its use.

  8. Chronic sleep deprivation markedly reduces coagulation factor VII expression

    Science.gov (United States)

    Pinotti, Mirko; Bertolucci, Cristiano; Frigato, Elena; Branchini, Alessio; Cavallari, Nicola; Baba, Kenkichi; Contreras-Alcantara, Susana; Ehlen, J. Christopher; Bernardi, Francesco; Paul, Ketema N.; Tosini, Gianluca

    2010-01-01

    Chronic sleep loss, a common feature of human life in industrialized countries, is associated to cardiovascular disorders. Variations in functional parameters of coagulation might contribute to explain this relationship. By exploiting the mouse model and a specifically designed protocol, we demonstrated that seven days of partial sleep deprivation significantly decreases (−30.5%) the thrombin generation potential in plasma evaluated upon extrinsic (TF/FVIIa pathway) but not intrinsic activation of coagulation. This variation was consistent with a decrease (−49.8%) in the plasma activity levels of factor VII (FVII), the crucial physiologicalal trigger of coagulation, which was even more pronounced at the liver mRNA level (−85.7%). The recovery in normal sleep conditions for three days completely restored thrombin generation and FVII activity in plasma. For the first time, we demonstrate that chronic sleep deprivation on its own reduces, in a reversible manner, the FVII expression levels, thus influencing the TF/FVIIa activation pathway efficiency. PMID:20418241

  9. Severe coagulation factor VII deficiency caused by a novel homozygous mutation (p. Trp284Gly) in loop 140s.

    Science.gov (United States)

    Hao, Xiuping; Cheng, XiaoLi; Ye, Jiajia; Wang, Yingyu; Yang, LiHong; Wang, Mingshan; Jin, Yanhui

    2016-06-01

    Congenital coagulation factor VII (FVII) deficiency is a rare disorder caused by mutation in F7 gene. Herein, we reported a patient who had unexplained hematuria and vertigo with consanguineous parents. He has been diagnosed as having FVII deficiency based on the results of reduced FVII activity (2.0%) and antigen (12.8%). The thrombin generation tests verified that the proband has obstacles in producing thrombin. Direct sequencing analysis revealed a novel homozygous missense mutation p.Trp284Gly. Also noteworthy is the fact that the mutational residue belongs to structurally conserved loop 140s, which majorly undergo rearrangement after FVII activation. Model analysis indicated that the substitution disrupts these native hydrophobic interactions, which are of great importance to the conformation in the activation domain of FVIIa.

  10. Dietary factor VII activation does not increase plasma concentrations of prothrombin fragment 1+2 in patients with stable angina pectoris and coronary atherosclerosis

    DEFF Research Database (Denmark)

    Bladbjerg, E-M; Münster, A M; Marckmann, P

    2000-01-01

    Studies in healthy subjects showed that blood coagulation factor VII (FVII) is activated postprandially after consumption of high-fat meals, but accompanying thrombin formation has not been demonstrated. In patients with coronary atherosclerosis, the arterial intima is supposed to present more...... tissue factor, the cofactor of FVII, to circulating blood; therefore, thrombin formation in response to FVII activation is more likely to occur in such patients. This hypothesis was tested in a randomized crossover study of 30 patients (aged 43 to 70 years) with stable angina pectoris...

  11. Genetics Home Reference: factor VII deficiency

    Science.gov (United States)

    ... Facebook Twitter Home Health Conditions Factor VII deficiency Factor VII deficiency Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Factor VII deficiency is a rare bleeding disorder that varies ...

  12. Management of factor VII-deficient patients undergoing joint surgeries--preliminary results of locally developed treatment regimen.

    Science.gov (United States)

    Windyga, J; Zbikowski, P; Ambroziak, P; Baran, B; Kotela, I; Stefanska-Windyga, E

    2013-01-01

    Inherited factor VII (FVII) deficiency is a rare coagulation disorder with variable haemorrhagic manifestations. In severely affected cases spontaneous haemarthroses leading to advanced arthropathy have been observed. Such cases may require surgery. Therapeutic options for bleeding prevention in FVII deficient patients undergoing surgery comprise various FVII preparations but the use of recombinant activated factor VII (rFVIIa) seems to be the treatment of choice. To present the outcome of orthopaedic surgery under haemostatic coverage of rFVIIa administered according to the locally established treatment regimen in five adult patients with FVII baseline plasma levels below 10 IU dL(-1). Two patients required total hip replacement (THR); three had various arthroscopic procedures. Recombinant activated factor VII was administered every 8 h on day of surgery (D0) followed by every 12-24 h for the subsequent 9-14 days, depending on the type of surgery. Factor VII plasma coagulation activity (FVII:C) was determined daily with no predefined therapeutic target levels. Doses of rFVIIa on D0 ranged from 18 to 37 μg kg(-1) b.w. and on the subsequent days--from 13 to 30 μg kg(-1) b.w. Total rFVIIa dose per procedure ranged from 16 to 37.5 mg, and the total number of doses per procedure was 16-31. None of our patients developed excessive bleeding including those in whom FVII:C trough levels returned nearly to the baseline level on the first post-op day. Preliminary results demonstrate that rFVIIa administered according to our treatment regimen is an effective and safe haemostatic agent for hypoproconvertinaemia patients undergoing orthopaedic surgery. © 2012 Blackwell Publishing Ltd.

  13. Tissue Factor–Factor VII Complex as a Key Regulator of Ovarian Cancer Phenotypes

    Directory of Open Access Journals (Sweden)

    Shiro Koizume

    2015-01-01

    Full Text Available Tissue factor (TF is an integral membrane protein widely expressed in normal human cells. Blood coagulation factor VII (fVII is a key enzyme in the extrinsic coagulation cascade that is predominantly secreted by hepatocytes and released into the bloodstream. The TF–fVII complex is aberrantly expressed on the surface of cancer cells, including ovarian cancer cells. This procoagulant complex can initiate intracellular signaling mechanisms, resulting in malignant phenotypes. Cancer tissues are chronically exposed to hypoxia. TF and fVII can be induced in response to hypoxia in ovarian cancer cells at the gene expression level, leading to the autonomous production of the TF–fVII complex. Here, we discuss the roles of the TF–fVII complex in the induction of malignant phenotypes in ovarian cancer cells. The hypoxic nature of ovarian cancer tissues and the roles of TF expression in endometriosis are discussed. Arguments will be extended to potential strategies to treat ovarian cancers based on our current knowledge of TF–fVII function.

  14. Monoclonal antibodies to human factor VII: a one step immunoradiometric assay for VII:Ag.

    OpenAIRE

    Takase, T; Tuddenham, E G; Chand, S; Goodall, A H

    1988-01-01

    Three mouse monoclonal antibodies (RFF-VII/1, RFF-VII/2, and RFF-VII/3) which bind specifically to different epitopes on human factor VII antigen were raised. Two of the antibodies, RFF-VII/1 and RFF-VII/2, bound strongly to factor VII antigen (VII:Ag), but only RFF-VII/1 and RFF-VII/3 were potent inhibitors of factor VII coagulation activity (VII:C). RFF-VII/1 and RFF-VII/2 were used in a one step, double monoclonal immunoradiometric assay for VII:Ag. This was highly reproducible and detecte...

  15. Primary prophylaxis for children with severe congenital factor VII deficiency - Clinical and laboratory assessment.

    Science.gov (United States)

    Kuperman, A A; Barg, A A; Fruchtman, Y; Shaoul, E; Rosenberg, N; Kenet, G; Livnat, T

    2017-09-01

    Severe congenital factor VII (FVII) deficiency is a rare bleeding disorder. Prophylaxis with replacement therapy has been suggested to patients, yet the most beneficial dosing regimens and therapy intervals are still to be defined. Due to the lack of evidence-based data, we hereby present our experience with long-term administration and monitoring primary prophylaxis in children with severe FVII deficiency and an extremely high bleeding risk. Four children with familial FVII deficiency, treated by prophylactic recombinant activated factor VII (rFVIIa), 15-30μg/kg/dose, given 2-3 times weekly since infancy, are discussed. Clinical follow up and monitoring laboratory assays, including thrombin generation, measured at various time points after prophylactic rFVIIa administration are presented. Among our treated patients neither FVII activity nor thrombin generation parameters (both already declined 24h post rFVIIa administration) were able to predict the impact of prophylaxis, and could not be used as surrogate markers in order to assess the most beneficial treatment frequency. However, the long clinical follow-up and comprehensive laboratory assessment performed, have shown that early primary prophylaxis as administered in our cohort was safe and effective. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Rare coagulation disorders: fibrinogen, factor VII and factor XIII.

    Science.gov (United States)

    de Moerloose, P; Schved, J-F; Nugent, D

    2016-07-01

    Rare coagulation disorders (RCDs) include the inherited deficiencies of fibrinogen, factor (F) II, FV, combined FV and VIII, FVII, FX, combined FVII and X, FXI, FXIII and combined congenital deficiency of vitamin K-dependent factors (VKCFDs). Despite their rarity, a deep comprehension of all these disorders is essential to really understand haemostasis. Indeed, even if they share some common features each RCD has some particularity which makes it unique. In this review, we focus on three disorders: fibrinogen, FVII and FXIII. © 2016 John Wiley & Sons Ltd.

  17. Congenital factor XI and factor VII deficiencies assure an apparent opposite protection against arterial or venous thrombosis: An intriguing observation.

    Science.gov (United States)

    Girolami, A; Peroni, E; Girolami, B; Ferrari, S; Lombardi, A M

    2016-09-01

    To investigate the prevalence and type of thrombotic events reported in patients with congenital factor XI (FXI) or factor VII (FVII) deficiency. Data on all patients with congenital FXI or FVII deficiency and a thrombotic event were gathered by means of a time unlimited PubMed search carried out in June 2014 and in February 2015. Appropriate keywords including the medical subject headings were used in both instances. Side tables were also consulted and cross-checking of the references was carried out to avoid omissions. The thrombosis event had to be proven by objective methods. Forty-three patients with FXI deficiency had arterial thrombosis and only eight had venous thrombosis. On the contrary, only five patients with FVII deficiency had arterial thrombosis whereas 31 patients had venous thrombosis. The arterial/venous ratios were 5.37 and 0.17 for FXI or FVII, respectively. Arterial thrombosis is frequent in FXI deficiency whereas venous thrombosis is rare. The reverse is true for FVII deficiency. The significance of these findings is discussed especially in view of the recent use of synthetic anti-FXI compounds in the prophylaxis of post-orthopedic surgery of venous thrombosis complications.

  18. Canine specific ELISA for coagulation factor VII

    DEFF Research Database (Denmark)

    Knudsen, Tom; Kjelgaard-Hansen, Mads; Tranholm, Mikael

    2011-01-01

    available to date. In this study, a canine specific ELISA for measurement of FVII:Ag in plasma was developed and validated. The FVII:Ag ELISA correctly diagnosed homozygous and heterozygous hereditary FVII deficiency. Together with activity based assays, such as FVII:C, the FVII:Ag ELISA should be valuable...

  19. Factor VII deficiency: Unveiling the cellular and molecular mechanisms underlying three model alterations of the enzyme catalytic domain.

    Science.gov (United States)

    Chollet, Maria Eugenia; Andersen, Elisabeth; Skarpen, Ellen; Myklebust, Christiane F; Koehler, Christian; Morth, Jens Preben; Chuansumrit, Ampaiwan; Pinotti, Mirko; Bernardi, Francesco; Thiede, Bernd; Sandset, Per Morten; Skretting, Grethe

    2018-03-01

    Activated factor (F) VII is a vitamin K-dependent glycoprotein that initiates blood coagulation upon interaction with tissue factor. FVII deficiency is the most common of the rare congenital bleeding disorders. While the mutational pattern has been extensively characterized, the pathogenic molecular mechanisms of mutations, particularly at the intracellular level, have been poorly defined. Here, we aimed at elucidating the mechanisms underlying altered FVII biosynthesis in the presence of three mutation types in the catalytic domain: a missense change, a microdeletion and a frameshift/elongation, associated with severe or moderate to severe phenotypes. Using CHO-K1 cells transiently transfected with expression vectors containing the wild-type FVII cDNA (FVIIwt) or harboring the p.I289del, p.G420V or p.A354V-p.P464Hfs mutations, we found that the secretion of the FVII mutants was severely decreased compared to FVIIwt. The synthesis rate of the mutants was slower than the FVIIwt and delayed, and no degradation of the FVII mutants by proteasomes, lysosomes or cysteine proteases was observed. Confocal immunofluorescence microscopy studies showed that FVII variants were localized into the endoplasmic reticulum (ER) but were not detectable within the Golgi apparatus. These findings suggested that a common pathogenic mechanism, possibly a defective folding of the mutant proteins, was triggered by the FVII mutations. The misfolded state led to impaired trafficking of these proteins causing ER retention, which would explain the low to very low FVII plasma levels observed in patients carrying these mutations. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Enhanced recombinant factor VII expression in Chinese hamster ovary cells by optimizing signal peptides and fed-batch medium.

    Science.gov (United States)

    Peng, Lin; Yu, Xiao; Li, Chengyuan; Cai, Yanfei; Chen, Yun; He, Yang; Yang, Jianfeng; Jin, Jian; Li, Huazhong

    2016-04-01

    Signal peptides play an important role in directing and efficiently transporting secretory proteins to their proper locations in the endoplasmic reticulum of mammalian cells. The aim of this study was to enhance the expression of recombinant coagulation factor VII (rFVII) in CHO cells by optimizing the signal peptides and type of fed-batch culture medium used. Five sub-clones (O2, I3, H3, G2 and M3) with different signal peptide were selected by western blot (WB) analysis and used for suspension culture. We compared rFVII expression levels of 5 sub-clones and found that the highest rFVII expression level was obtained with the IgK signal peptide instead of Ori, the native signal peptide of rFVII. The high protein expression of rFVII with signal peptide IgK was mirrored by a high transcription level during suspension culture. After analyzing culture and feed media, the combination of M4 and F4 media yielded the highest rFVII expression of 20 mg/L during a 10-day suspension culture. After analyzing cell density and cell cycle, CHO cells feeding by F4 had a similar percentage of cells in G0/G1 and a higher cell density compared to F2 and F3. This may be the reason for high rFVII expression in M4+F4. In summary, rFVII expression was successfully enhanced by optimizing the signal peptide and fed-batch medium used in CHO suspension culture. Our data may be used to improve the production of other therapeutic proteins in fed-batch culture.

  1. Recombinant activated factor VII: 30 years of research and innovation.

    Science.gov (United States)

    Hedner, Ulla

    2015-06-01

    Recombinant activated factor VII (rFVIIa) was initially developed to treat bleeding episodes in patients with congenital haemophilia and inhibitors. The story of its development began in the 1970s, when FVIIa was identified as one of the activated coagulation factors that has minimal potential for inducing thromboembolic side-effects. Extensive research over the last 30 years has greatly increased our knowledge of the characteristics of FVII, its activation, and the mechanisms by which rFVIIa restores haemostasis. In haemophilia, the haemostatic effect of rFVIIa is mediated via binding to thrombin-activated platelets at the site of injury, thereby enhancing thrombin generation also in the absence of factor (F) VIII or FIX. The mechanism of action of rFVIIa has also allowed its successful use in other clinical scenarios characterised by impaired thrombin generation, and its licensed uses have now been extended to acquired haemophilia, congenital FVII deficiency and Glanzmann's thrombasthenia. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Factor VII-activating protease

    DEFF Research Database (Denmark)

    Ramanathan, Ramshanker; Gram, Jørgen B; Sand, Niels Peter R

    2017-01-01

    : Factor VII-activating protease (FSAP) may regulate development of cardiovascular disease (CVD). We evaluated sex differences in FSAP measures and examined the association between FSAP and coronary artery calcification (CAC) in a middle-aged population. Participants were randomly selected citizens...

  3. Large-scale production and properties of human plasma-derived activated Factor VII concentrate.

    Science.gov (United States)

    Tomokiyo, K; Yano, H; Imamura, M; Nakano, Y; Nakagaki, T; Ogata, Y; Terano, T; Miyamoto, S; Funatsu, A

    2003-01-01

    An activated Factor VII (FVIIa) concentrate, prepared from human plasma on a large scale, has to date not been available for clinical use for haemophiliacs with antibodies against FVIII and FIX. In the present study, we attempted to establish a large-scale manufacturing process to obtain plasma-derived FVIIa concentrate with high recovery and safety, and to characterize its biochemical and biological properties. FVII was purified from human cryoprecipitate-poor plasma, by a combination of anion exchange and immunoaffinity chromatography, using Ca2+-dependent anti-FVII monoclonal antibody. To activate FVII, a FVII preparation that was nanofiltered using a Bemberg Microporous Membrane-15 nm was partially converted to FVIIa by autoactivation on an anion-exchange resin. The residual FVII in the FVII and FVIIa mixture was completely activated by further incubating the mixture in the presence of Ca2+ for 18 h at 10 degrees C, without any additional activators. For preparation of the FVIIa concentrate, after dialysis of FVIIa against 20 mm citrate, pH 6.9, containing 13 mm glycine and 240 mm NaCl, the FVIIa preparation was supplemented with 2.5% human albumin (which was first pasteurized at 60 degrees C for 10 h) and lyophilized in vials. To inactivate viruses contaminating the FVIIa concentrate, the lyophilized product was further heated at 65 degrees C for 96 h in a water bath. Total recovery of FVII from 15 000 l of plasma was approximately 40%, and the FVII preparation was fully converted to FVIIa with trace amounts of degraded products (FVIIabeta and FVIIagamma). The specific activity of the FVIIa was approximately 40 U/ micro g. Furthermore, virus-spiking tests demonstrated that immunoaffinity chromatography, nanofiltration and dry-heating effectively removed and inactivated the spiked viruses in the FVIIa. These results indicated that the FVIIa concentrate had both high specific activity and safety. We established a large-scale manufacturing process of human plasma

  4. Evaluation of Aryoseven Safety (Recombinant Activated Factor VII) in Patients with Bleeding Disorders (An Observational Post-Marketing Surveillance Study).

    Science.gov (United States)

    Toogeh, Gholamreza; Abolghasemi, Hassan; Eshghi, Peyman; Managhchi, Mohammadreza; Shaverdi-Niasari, Mohammadreza; Karimi, Katayoon; Roostaei, Samin; Emran, Neda; Abdollahi, Alireza

    2016-01-01

    Recombinant activated factor VII induces hemostasis in patients with coagulopathy disorders. AryoSeven™ as a safe Iranian Recombinant activated factor VII has been available on our market. This study was performed to establish the safety of AryoSeven on patients with coagulopathy disorder. This single-center, descriptive, cross sectional study was carried out in Thrombus and Homeostasis Research Center ValiAsr Hospital during 2013-2014. Fifty one patients with bleeding disorders who received at least one dose of Aryoseven were enrolled. Patients' demographic data and adverse effect of drug and reaction related to Aryoseven or previous usage of Recombinant activated FVII were recorded in questionnaires. Finally data were analyzed to compare side effects of Aryoseven and other Recombinant activated FVII brands. Aryoseven was prescribed for 51 Patients. Of all participants with mean age 57.18+21.38 yr, 31 cases were male and 26 subjects had past history of recombinant activated FVII usage. Glanzman was the most frequent disorder followed by congenital FVII deficiency, hemophilia with inhibitors, factor 5 deficiency, acquired hemophilia, hemophilia A with inhibitor, and hemophilia A or B with inhibitor. The majority of bleeding episodes had occurred in joints. Three patients (5.9%) complained about adverse effects of Aryoseven vs. 11.5 % about adverse effects of other brands. However this difference was not significant, statistically. Based on monitor patients closely for any adverse events, we concluded that Aryoseven administration under careful weighing of benefit versus potential harm may comparable with other counterpart drugs.

  5. Congenital Factor VII Deficiency in Children at Tertiary Health Care Facility in Pakistan.

    Science.gov (United States)

    Alam, Muhammad Matloob; Moiz, Bushra; Rehman, Karim Abdur; Jethwani, Priyanka; Fadoo, Zehra

    2015-10-01

    This study presents the demographics, clinical spectrum, and outcome of patients with congenital factor VII (FVII) deficiency at a tertiary care center over a period of 12 years. Of the 49 patients, 27 (55%) patients were males. Consanguinity was found in 92% of the patients. The median age of symptom onset was 2.4 (interquartile range [IQR]: 1.1-6.5) years with a median age of 5.8 (IQR: 3.1-10) years at diagnosis. Life-threatening complications like intracranial bleeding (ICB) and intra-abdominal bleeding (IAB) were observed in 8 (16.4%) patients. We found that 11 (55%) of the 20 patients with FVII coagulant activity (FVIIc) 5% were affected by severe symptoms. Age factor associated with development of life-threatening bleeding episodes (P = .042; odds ratio 6.46). Overall, 4 (8.2%) died as a consequence of ICB (3 patients) and IAB (1 patient). © The Author(s) 2013.

  6. The Story of Serum Prothrombin Conversion Accelerator, Proconvertin, Stable Factor, Cothromboplastin, Prothrombin Accelerator or Autoprothrombin I, and Their Subsequent Merging into Factor VII.

    Science.gov (United States)

    Girolami, Antonio; Cosi, Elisabetta; Santarossa, Claudia; Ferrari, Silvia; Luigia Randi, Maria

    2015-06-01

    Factor VII (FVII) deficiency is one of the two congenital coagulation disorders that was not discovered by the description of a new bleeding patient whose clotting pattern did not fit the blood coagulation knowledge of the time (the other is factor XIII deficiency). The existence of an additional factor capable of accelerating the conversion of prothrombin into thrombin was suspected before 1951, the year in which the first family with FVII deficiency was discovered. As several investigators were involved in the discovery of FVII deficiency from both sides of the Atlantic, several different names were tentatively suggested to define this entity, namely stable factor (in contrast with labile factor or FV), cothromboplastin, proconvertin, serum prothrombin conversion accelerator, prothrombin acceleration, and autoprothrombin I. The last term was proposed by those who denied the existence of this new entity, which was instead considered to be a derivate of prothrombin activation, namely autoprothrombin. The description of several families, from all over the world, of the same defect, however clearly demonstrated the singularity of the condition. Factor VII was then proposed to define this protein. In subsequent years, several variants were described with peculiar reactivity toward tissue thromboplastins of different origin. Molecular biology techniques demonstrated several gene mutations, usually missense mutations, often involving exon 8 of the FVII gene. Later studies dealt with the relation of FVII with tissue factor and activated FVII (FVIIa). The evaluation of circulating FVIIa was made possible by the use of a truncated form of tissue factor, which is only sensitive to FVIIa present in the circulation. The development of FVII concentrates, both plasma derived and recombinant, has facilitated therapeutic management of FVII-deficient patients. The use of FVIIa concentrates was noted to be associated with the occasional occurrence of thrombotic events, mainly

  7. F7 gene variants modulate protein levels in a large cohort of patients with factor VII deficiency. Results from a genotype-phenotype study.

    Science.gov (United States)

    Quintavalle, Gabriele; Riccardi, Federica; Rivolta, Gianna Franca; Martorana, Davide; Di Perna, Caterina; Percesepe, Antonio; Tagliaferri, Annarita

    2017-08-01

    Congenital factor VII (FVII) deficiency is a rare bleeding disorder caused by mutations in F7 gene with autosomal recessive inheritance. A clinical heterogeneity with poor correlation with FVII:C levels has been described. It was the objective of this study to identify genetic defects and to evaluate their relationships with phenotype in a large cohort of patients with FVII:C<50 %. One hundred twenty-three probands were genotyped for F7 mutations and three polymorphic variants and classified according to recently published clinical scores. Forty out of 123 patients (33 %) were symptomatic (43 bleedings). A severe bleeding tendency was observed only in patients with FVII:C<0.10 %. Epistaxis (11 %) and menorrhagia (32 % of females in fertile age) were the most frequent bleedings. Molecular analysis detected 48 mutations, 20 not reported in the F7 international databases. Most mutations (62 %) were missense, large deletions were 6.2 %. Compound heterozygotes/homozygotes for mutations presented lower FVII:C levels compared to the other classes (Chi 2 =43.709, p<0,001). The polymorphisms distribution was significantly different among the three F7 genotypic groups (Chi 2 =72.289, p<0,001). The presence of truncating mutations was associated with lowest FVII:C levels (Chi 2 =21.351, p=0.002). This study confirms the clinical and molecular variability of the disease and the type of symptoms. It shows a good correlation between the type of F7 mutation and/or polymorphisms and FVII:C levels, without a direct link between FVII:C and bleeding tendency. The results suggest that large deletions are underestimated and that they represent a common mechanism of F7 gene inactivation which should always be investigated in the diagnostic testing for FVII deficiency.

  8. Effects of dietary fat quality and quantity on postprandial activation of blood coagulation factor VII

    DEFF Research Database (Denmark)

    Larsen, L. F.; Bladbjerg, E.-M.; Jespersen, J.

    1997-01-01

    , monounsaturated, or polyunsaturated fats differed regarding postprandial activation of FVII. Eighteen healthy young men participated in the study. On 6 separate days each participant consumed two meals (times, 0 and 1 3/4 hours) enriched with 70 g (15 and 55 g) of either rapeseed oil, olive oil, sunflower oil......, palm oil, or butter (42% of energy from fat) or isoenergetic low-fat meals (6% of energy from fat). Fasting and series of nonfasting blood samples (the last at time 8 1/2 hours) were collected. Plasma triglycerides, FVIIc, FVIIa, and free fatty acids were analyzed. There were marked effects of the fat......Acute elevation of the coagulant activity of blood coagulation factor VII (FVIIc) is observed after consumption of high-fat meals. This elevation is caused by an increase in the concentration of activated FVII (FVIIa). In a randomized crossover study, we investigated whether saturated...

  9. Genotype and phenotype relationships in 10 Pakistani unrelated patients with inherited factor VII deficiency.

    Science.gov (United States)

    Borhany, M; Boijout, H; Pellequer, J-L; Shamsi, T; Moulis, G; Aguilar-Martinez, P; Schved, J-F; Giansily-Blaizot, M

    2013-11-01

    Inherited factor VII (FVII) deficiency is one of the commonest rare bleeding disorders. It is characterized by a wide molecular and clinical heterogeneity and an autosomal recessive pattern of inheritance. Factor VII-deficient patients are still scarcely explored in Pakistan although rare bleeding disorders became quite common as a result of traditional consanguineous marriages. The aim of the study was to give a first insight of F7 gene mutations in Pakistani population. Ten unrelated FVII-deficient patients living in Pakistan were investigated (median FVII:C = 2%; range = 2-37%). A clinical questionnaire was filled out for each patient and direct sequencing was performed on the coding regions, intron/exon boundaries and 5' and 3' untranslated regions of the F7 gene. Nine different mutations (eight missense mutations and one located within the F7 promoter) were identified on the F7 gene. Five of them were novel (p.Cys82Tyr, p.Cys322Ser, p.Leu357Phe, p.Thr410Ala, c-57C>T, the last being predicted to alter the binding site of transcription factor HNF-4). Half of the patients had single mutations in Cys residues involved in disulfide bridges. The p.Cys82Arg mutation was the most frequent in our series. Six of seven patients with FVII:C levels below 10% were homozygous in connection with the high percentage of consanguinity in our series. In addition, we graded the 10 patients according to three previously published classifications for rare bleeding disorders. The use of the bleeding score proposed by Tosetto and co-workers in 2006 appears to well qualify the bleeding tendency in our series. © 2013 John Wiley & Sons Ltd.

  10. Quantitative PET Imaging of Tissue Factor Expression Using 18F-labled Active Site Inhibited Factor VII

    DEFF Research Database (Denmark)

    Nielsen, Carsten H; Erlandsson, Maria; Jeppesen, Troels E

    2016-01-01

    Tissue factor (TF) is up regulated in many solid tumors and its expression is linked to tumor angiogenesis, invasion, metastasis and prognosis. A non-invasive assessment of tumor TF expression status is therefore of obvious clinical relevance. Factor VII (FVII) is the natural ligand to TF. Here we...... report the development of a new PET tracer for specific imaging of TF using an (18)F-labeled derivative of FVII. METHODS: Active site inhibited factor VIIa (FVIIai) was obtained by inactivation with phenylalanine-phenylalanine-arginine-chloromethyl ketone. FVIIai was radiolabeled with N-succinimidyl 4......-[(18)F]-fluorobenzoate ([(18)F]SFB) and purified. The corresponding product, [(18)F]FVIIai, was injected into nude mice with subcutaneous human pancreatic xenograft tumors (BxPC-3) and investigated using small animal PET/CT imaging 1, 2 and 4 hours after injection. Ex vivo biodistribution was performed...

  11. Women with congenital factor VII deficiency: clinical phenotype and treatment options from two international studies.

    Science.gov (United States)

    Napolitano, M; Di Minno, M N D; Batorova, A; Dolce, A; Giansily-Blaizot, M; Ingerslev, J; Schved, J-F; Auerswald, G; Kenet, G; Karimi, M; Shamsi, T; Ruiz de Sáez, A; Dolatkhah, R; Chuansumrit, A; Bertrand, M A; Mariani, G

    2016-09-01

    A paucity of data exists on the incidence, diagnosis and treatment of bleeding in women with inherited factor VII (FVII) deficiency. Here we report results of a comprehensive analysis from two international registries of patients with inherited FVII deficiency, depicting the clinical picture of this disorder in women and describing any gender-related differences. A comprehensive analysis of two fully compatible, international registries of patients with inherited FVII deficiency (International Registry of Factor VII deficiency, IRF7; Seven Treatment Evaluation Registry, STER) was performed. In our cohort (N = 449; 215 male, 234 female), the higher prevalence of mucocutaneous bleeds in females strongly predicted ensuing gynaecological bleeding (hazard ratio = 12.8, 95% CI 1.68-97.6, P = 0.014). Menorrhagia was the most prevalent type of bleeding (46.4% of patients), and was the presentation symptom in 12% of cases. Replacement therapies administered were also analysed. For surgical procedures (n = 50), a receiver operator characteristic analysis showed that the minimal first dose of rFVIIa to avoid postsurgical bleeding during the first 24 hours was 22 μg kg(-1) , and no less than two administrations. Prophylaxis was reported in 25 women with excellent or effective outcomes when performed with a total weekly rFVIIa dose of 90 μg kg(-1) (divided as three doses). Women with FVII deficiency have a bleeding disorder mainly characterized by mucocutaneous bleeds, which predicts an increased risk of ensuing gynaecological bleeding. Systematic replacement therapy or long-term prophylaxis with rFVIIa may reduce the impact of menorrhagia on the reproductive system, iron loss and may avoid unnecessary hysterectomies. © 2016 John Wiley & Sons Ltd.

  12. R353Q polymorphism in the factor VII gene and cardiovascular risk in Heterozygous Familial Hypercholesterolemia: a case-control study.

    Science.gov (United States)

    Criado-García, Juan; Fuentes, Francisco; Cruz-Teno, Cristina; García-Rios, Antonio; Jiménez-Morales, Anabel; Delgado-Lista, Javier; Mata, Pedro; Alonso, Rodrigo; López-Miranda, José; Pérez-Jiménez, Francisco

    2011-04-09

    Heterozygous Familial Hypercholesterolemia (FH) is a genetic disorder characterized by a high risk of cardiovascular disease. Certain polymorphisms of the factor VII gene have been associated with the development of coronary artery disease and there is a known association between factor VII levels and polymorphic variants in this gene. To date, no study has evaluated the association between factor VII and coronary artery disease in patients with FH. This case-control study comprised 720 patients (546 with FH and 174 controls). We determined the prevalence and allele frequencies of the R353Q polymorphism of factor VII, the plasma levels of factor VII antigen (FVII Ag) and whether they could be predictive factors for cardiovascular risk. 75% (410) of the patients with FH were RR, 23% (127) RQ and 1.6% (9) QQ; in the control group 75.3% (131) were RR, 21.3% (37) RQ and 3.4% (6) QQ (p = 0.32). No statistically significant associations were observed in the distribution of genotypes and allele frequencies between case (FH) and control groups. Nor did we find differences when we evaluated the relationship between the R353Q polymorphism and cardiovascular risk (including coronary disease, ischemic stroke and peripheral arterial disease), either in the univariate analysis or after adjustment for sex, age, arterial hypertension, body mass index, xanthomas, diabetes, smoking, HDLc and LDLc and lipid-lowering treatment. The FVII Ag concentrations behaved in a similar fashion, with no differences for the interaction between controls and those with FH (RR vs. RQ/QQ; p = 0.96). In the subgroup of patients with FH no association was found among cardiovascular disease, genotype and FVII Ag levels (RR vs. RQ/QQ; p = 0.97). Our study did not find a direct relationship between cardiovascular risk in patients with Heterozygous Familial Hypercholesterolemia, the R353Q polymorphism of factor VII and FVII Ag levels.

  13. R353Q polymorphism in the factor VII gene and cardiovascular risk in Heterozygous Familial Hypercholesterolemia: a case-control study

    Directory of Open Access Journals (Sweden)

    Pérez-Jiménez Francisco

    2011-04-01

    Full Text Available Abstract Background Heterozygous Familial Hypercholesterolemia (FH is a genetic disorder characterized by a high risk of cardiovascular disease. Certain polymorphisms of the factor VII gene have been associated with the development of coronary artery disease and there is a known association between factor VII levels and polymorphic variants in this gene. To date, no study has evaluated the association between factor VII and coronary artery disease in patients with FH. Results This case-control study comprised 720 patients (546 with FH and 174 controls. We determined the prevalence and allele frequencies of the R353Q polymorphism of factor VII, the plasma levels of factor VII antigen (FVII Ag and whether they could be predictive factors for cardiovascular risk. 75% (410 of the patients with FH were RR, 23% (127 RQ and 1.6% (9 QQ; in the control group 75.3% (131 were RR, 21.3% (37 RQ and 3.4% (6 QQ (p = 0.32. No statistically significant associations were observed in the distribution of genotypes and allele frequencies between case (FH and control groups. Nor did we find differences when we evaluated the relationship between the R353Q polymorphism and cardiovascular risk (including coronary disease, ischemic stroke and peripheral arterial disease, either in the univariate analysis or after adjustment for sex, age, arterial hypertension, body mass index, xanthomas, diabetes, smoking, HDLc and LDLc and lipid-lowering treatment. The FVII Ag concentrations behaved in a similar fashion, with no differences for the interaction between controls and those with FH (RR vs. RQ/QQ; p = 0.96. In the subgroup of patients with FH no association was found among cardiovascular disease, genotype and FVII Ag levels (RR vs. RQ/QQ; p = 0.97. Conclusions Our study did not find a direct relationship between cardiovascular risk in patients with Heterozygous Familial Hypercholesterolemia, the R353Q polymorphism of factor VII and FVII Ag levels.

  14. Large deletions play a minor but essential role in congenital coagulation factor VII and X deficiencies.

    Science.gov (United States)

    Rath, M; Najm, J; Sirb, H; Kentouche, K; Dufke, A; Pauli, S; Hackmann, K; Liehr, T; Hübner, C A; Felbor, U

    2015-01-01

    Congenital factor VII (FVII) and factor X (FX) deficiencies belong to the group of rare bleeding disorders which may occur in separate or combined forms since both the F7 and F10 genes are located in close proximity on the distal long arm of chromosome 13 (13q34). We here present data of 192 consecutive index cases with FVII and/or FX deficiency. 10 novel and 53 recurrent sequence alterations were identified in the F7 gene and 5 novel as well as 11 recurrent in the F10 gene including one homozygous 4.35 kb deletion within F7 (c.64+430_131-6delinsTCGTAA) and three large heterozygous deletions involving both the F7 and F10 genes. One of the latter proved to be cytogenetically visible as a chromosome 13q34 deletion and associated with agenesis of the corpus callosum and psychomotor retardation. Large deletions play a minor but essential role in the mutational spectrum of the F7 and F10 genes. Copy number analyses (e. g. MLPA) should be considered if sequencing cannot clarify the underlying reason of an observed coagulopathy. Of note, in cases of combined FVII/FX deficiency, a deletion of the two contiguous genes might be part of a larger chromosomal rearrangement.

  15. PET Imaging of Tissue Factor in Pancreatic Cancer Using 64Cu-Labeled Active Site-Inhibited Factor VII

    DEFF Research Database (Denmark)

    Nielsen, Carsten H; Jeppesen, Troels E; Kristensen, Lotte K

    2016-01-01

    with advanced stage, increased microvessel density, metastasis, and poor overall survival. Imaging of TF expression is of clinical relevance as a prognostic biomarker and as a companion diagnostic for TF-directed therapies currently under clinical development. Factor VII (FVII) is the natural ligand to TF......UNLABELLED: Tissue factor (TF) is the main initiator of the extrinsic coagulation cascade. However, TF also plays an important role in cancer. TF expression has been reported in 53%-89% of all pancreatic adenocarcinomas, and the expression level of TF has in clinical studies correlated...

  16. Factor VII-activating protease in patients with acute deep venous thrombosis

    DEFF Research Database (Denmark)

    Sidelmann, Johannes J; Vitzthum, Frank; Funding, Eva

    2008-01-01

    Factor VII-activating protease (FSAP) is involved in haemostasis and inflammation. FSAP cleaves single chain urokinase-type plasminogen activator (scu-PA). The 1601GA genotype of the 1601G/A polymorphism in the FSAP gene leads to the expression of a FSAP variant with reduced ability to activate scu......-PA, without affecting the ability to activate coagulation Factor VII (FVII). Previous studies have investigated the association of the 1601GA genotype with incidence and progression of carotid stenosis and deep venous thrombosis (DVT). The present study is the first to evaluate the potential association...... between the FSAP phenotype and DVT. We studied the association between the 1601G/A polymorphism, FSAP activity, FSAP antigen, Factor VIIa (FVIIa), prothrombin fragment 1+2 (F1+2), and C-reactive protein (CRP) in plasmas of 170 patients suspected for DVT. FSAP genotypes were equally distributed in patients...

  17. Monoclonal antibodies to human factor VII: production of immunodepleted plasma for VII:C assays.

    OpenAIRE

    Takase, T; Tuddenham, E G; Chand, S; Goodall, A H

    1988-01-01

    A high affinity monoclonal antibody to factor VII (RFF-VII/1), coupled to sepharose, was used to immunodeplete factor VII from normal plasma. The plasma could be used as a substrate in a one stage coagulation assay and performed as well as, or better than, commercially available factor VII deficient plasma or plasma from congenitally deficient factor VII patients. Plasma from normal donors (n = 20), patients with liver disease (n = 20), and patients receiving warfarin (n = 20), or congenitall...

  18. [Molecular genetic analysis for a pedigree with severe hereditary coagulation factor VII deficiency].

    Science.gov (United States)

    Ding, Qiu-lan; Wang, Hong-li; Wang, Xue-feng; Wang, Ming-shan; Fu, Qi-hua; Wu, Wen-man; Hu, Yi-qun; Wang, Zhen-yi

    2003-10-01

    To identify the genetic mutations of a severe inherited coagulation factor VII (FVII) deficiency pedigree. The diagnosis was validated by coagulant and haemostatic parameters. FVII gene mutations were screened in the propositus and his family members by DNA direct sequencing and confirmed by digestions of the restriction enzymes of the PCR production. Two heterozygous missense mutations were found in the propositus of the pedigree: a G to T transversion at position 9482 in exon 6 and a C to T mutation at position 11348 in exon 8 resulting in the amino acid substitution of Arg152 with Leu and Arg304 with Trp, respectively. A heterozygous single nucleotide deletion (C) at position 11487-11489(CCC) within exon 8 was identified, which predicted the frameshift mutation at position His351 followed by the changes of six corresponding amino acids and appearance of a premature protein caused by stop codon. The heterozygous mutations identified in the proband were derived from his father (Arg152 to Leu) and his mother (Arg304 to Trp mutation) and a heterozygous deletion (C) at position 11487-9(CCC). By tracing the other pedigree members, it was found that his grandmother had a heterozygous mutation of Arg304Trp and a heterozygous polymorphism of Arg353Gln and his grandfather had a heterozygous Arg152Leu mutation. Three heterozygous mutations were found in a pedigree with hereditary coagulation factor VII deficiency. Arg152Leu and deletion C at position 11487-9(CCC) were novel mutations.

  19. Targeting tissue factor on tumour cells and angiogenic vascular endothelial cells by factor VII-targeted verteporfin photodynamic therapy for breast cancer in vitro and in vivo in mice

    International Nuclear Information System (INIS)

    Hu, Zhiwei; Rao, Benqiang; Chen, Shimin; Duanmu, Jinzhong

    2010-01-01

    The objective of this study was to develop a ligand-targeted photodynamic therapy (tPDT) by conjugating factor VII (fVII) protein with photosensitiser verteporfin in order to overcome the poor selectivity and enhance the effect of non-targeted PDT (ntPDT) for cancer. fVII is a natural ligand for receptor tissue factor (TF) with high affinity and specificity. The reason for targeting receptor TF for the development of tPDT is that TF is a common but specific target on angiogenic tumour vascular endothelial cells (VEC) and many types of tumour cells, including solid tumours and leukaemia. Murine factor VII protein (mfVII) containing a mutation (Lys341Ala) was covalently conjugated via a cross linker EDC with Veterporfin (VP) that was extracted from liposomal Visudyne, and then free VP was separated by Sephadex G50 spin columns. fVII-tPDT using mfVII-VP conjugate, compared to ntPDT, was tested in vitro for the killing of breast cancer cells and VEGF-stimulated VEC and in vivo for inhibiting the tumour growth of breast tumours in a mouse xenograft model. We showed that: (i) fVII protein could be conjugated with VP without affecting its binding activity; (ii) fVII-tPDT could selectively kill TF-expressing breast cancer cells and VEGF-stimulated angiogenic HUVECs but had no side effects on non-TF expressing unstimulated HUVEC, CHO-K1 and 293 cells; (iii) fVII targeting enhanced the effect of VP PDT by three to four fold; (iii) fVII-tPDT induced significantly stronger levels of apoptosis and necrosis than ntPDT; and (iv) fVII-tPDT had a significantly stronger effect on inhibiting breast tumour growth in mice than ntPDT. We conclude that the fVII-targeted VP PDT that we report here is a novel and effective therapeutic with improved selectivity for the treatment of breast cancer. Since TF is expressed on many types of cancer cells including leukaemic cells and selectively on angiogenic tumour VECs, fVII-tPDT could have broad therapeutic applications for other solid cancers

  20. Correlation between Packed Cell Volume and ‎Concentration of Clotting Factors FI, FVII, and ‎FVIII in Smokers Polycythemic males in Babylon ‎Province

    Directory of Open Access Journals (Sweden)

    Dakhel Ghani Omran

    2017-11-01

    Full Text Available Smoking represents a worldwide problem and affects various body functions. The present study was conducted to evaluate the available concentration of some clotting factors in smokers polycythemic male patients. A total number of subjects was 120, 80 smokers males were affected with polycythemia and the remainders 40 males were healthy and served as a control group. The polycythemic patients were subdivided into two groups according to their ages (first group ranged between 30-40 years old and the second group ranged between 41-50 years old. PCV, clotting factor (FI, FVII and FVIII were detected. The results of present study indicated that the levels of prothrombin time (PT and activated partial thromboplastine time (APTT were significantly increased (p˂ 0.05 in both groups of polycythemia in comparison with control group. Regarding concentration of fibrinogen factor (FI and serum prothrombin conversion accelerator factor (FVII were elevated (P˂ 0.05 in both groups and pointed  out a positive correlation (r = 0.437, r = 0.378, respectively with packed cell volume (PCV when compared with those of control group. On the other hand, concentration of antihemophilic factor (FVIII recorded a significant fall (p˂ 0.05 in both tested groups and indicated a low correlation (r = 0.292. The possible explanation to the changes mentioned above is based on the fact that confirm smoking is a dangerous material containing different toxic substances that affect the vital organs of the body and induce abnormalities of hemostatic mechanism

  1. 11p15 duplication and 13q34 deletion with Beckwith-Wiedemann syndrome and factor VII deficiency.

    Science.gov (United States)

    Jurkiewicz, Dorota; Kugaudo, Monika; Tańska, Anna; Wawrzkiewicz-Witkowska, Angelika; Tomaszewska, Agnieszka; Kucharczyk, Marzena; Cieślikowska, Agata; Ciara, Elżbieta; Krajewska-Walasek, Małgorzata

    2015-06-01

    Here we report a patient with 11p15.4p15.5 duplication and 13q34 deletion presenting with Beckwith-Wiedemann syndrome (BWS) and moderate deficiency of factor VII (FVII). The duplication was initially diagnosed on methylation-sensitive multiplex ligation-dependent probe amplification. Array comparative genome hybridization confirmed its presence and indicated a 13q34 distal deletion. The patient's clinical symptoms, including developmental delay and facial dysmorphism, were typical of BWS with paternal 11p15 trisomy. Partial 13q monosomy in this patient is associated with moderate deficiency of FVII and may also overlap with a few symptoms of paternal 11p15 trisomy such as developmental delay and some facial features. To our knowledge this is the first report of 11p15.4p15.5 duplication associated with deletion of 13q34 and FVII deficiency. Moreover, this report emphasizes the importance of detailed clinical as well as molecular examinations in patients with BWS features and developmental delay. © 2015 Japan Pediatric Society.

  2. Factors Influencing Title VII Bilingual Program Institutionalization.

    Science.gov (United States)

    Lewis, Gerald R.; And Others

    1985-01-01

    This study of the primary restraining and driving forces that influence Title VII bilingual education programs found the external environment, the local community, to be the main factor influencing institutionalization and self-renewal. The internal environment--the local school, and the local school's organization or central office, school board,…

  3. Factor VII and incidence of myocardial infarction in a Japanese population: The Jichi Medical School Cohort Study.

    Science.gov (United States)

    Shiraishi, Takuya; Ishikawa, Shizukiyo; Kario, Kazuomi; Kayaba, Kazunori; Kajii, Eiji

    2017-11-01

    The role of factor VII (FVII) as a risk factor in myocardial infarction (MI) has been the subject of numerous studies. However, it remains uncertain whether the FVII levels are associated with development of MI. The subjects were 4142 men and women whose activated FVII (FVIIa) and FVII coagulant (FVIIc) levels were measured in the Jichi Medical School Cohort Study. Subjects were divided into tertiles by FVIIa and FVIIc levels, and Cox's proportional hazard model was used to calculate hazard ratios (HRs) for MI. The multivariate-adjusted HRs (95% confidential interval [CI]) for FVIIa in men were 0.67 (0.67-1.78) in tertile 2 (T2), and 0.52 (0.17-1.60) in T3. In women, the multivariate-adjusted HRs (95% CI) were 0.18 (0.02-1.60) in T2, and 0.39 (0.07-2.20) in T3. The multivariate-adjusted HRs (95% CI) for FVIIc in men were 0.54 (0.21-1.36) in T2, and 0.20 (0.04-0.91) in T3. In women, the multivariate-adjusted HRs (95% CI) were 0.44 (0.07-2.85) in T2, and 0.35 (0.06-2.22) in T3. We used T1 as a reference for all measures. Our findings revealed a significant association between low FVIIc level and incidence of MI in men. The FVIIa and FVIIc levels were inversely related to increased MI risk, but did not reach statistical significance. Future studies are needed to confirm this association. © 2017 Wiley Periodicals, Inc.

  4. Defective thrombus formation in mice lacking endogenous factor VII activating protease (FSAP).

    Science.gov (United States)

    Subramaniam, Saravanan; Thielmann, Ina; Morowski, Martina; Pragst, Ingo; Sandset, Per Morten; Nieswandt, Bernhard; Etscheid, Michael; Kanse, Sandip M

    2015-04-01

    Factor VII (FVII) activating protease (FSAP) is a circulating protease with a putative function in blood coagulation and fibrinolysis. Genetic epidemiological studies have implied a role for FSAP in carotid stenosis, stroke and thrombosis. To date, no in vivo evidence is available to support these claims. We have, for the first time, used FSAP-/- mice to define its role in thrombosis and haemostasis in vivo and to characterise the molecular mechanisms involved. FeCl3-induced arterial thrombosis in carotid and mesenteric artery revealed that the occlusion time was significantly increased in FSAP-/- mice (pendogenous FSAP impaired the formation of stable, occlusive thrombi in mice. The underlying in vivo effect of FSAP is more likely to be related to the modulation of TFPI rather than FVIIa.

  5. Safety update on the use of recombinant activated factor VII in approved indications.

    Science.gov (United States)

    Neufeld, Ellis J; Négrier, Claude; Arkhammar, Per; Benchikh el Fegoun, Soraya; Simonsen, Mette Duelund; Rosholm, Anders; Seremetis, Stephanie

    2015-06-01

    This updated safety review summarises the large body of safety data available on the use of recombinant activated factor VII (rFVIIa) in approved indications: haemophilia with inhibitors, congenital factor VII (FVII) deficiency, acquired haemophilia and Glanzmann's thrombasthenia. Accumulated data up to 31 December 2013 from clinical trials as well as post-marketing data (registries, literature reports and spontaneous reports) were included. Overall, rFVIIa has shown a consistently favourable safety profile, with no unexpected safety concerns, in all approved indications. No confirmed cases of neutralising antibodies against rFVIIa have been reported in patients with congenital haemophilia, acquired haemophilia or Glanzmann's thrombasthenia. The favourable safety profile of rFVIIa can be attributed to the recombinant nature of rFVIIa and its localised mechanism of action at the site of vascular injury. Recombinant FVIIa activates factor X directly on the surface of activated platelets, which are present only at the site of injury, meaning that systemic activation of coagulation is avoided and the risk of thrombotic events (TEs) thus reduced. Nonetheless, close monitoring for signs and symptoms of TE is warranted in all patients treated with any pro-haemostatic agent, including rFVIIa, especially the elderly and any other patients with concomitant conditions and/or predisposing risk factors to thrombosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Synergistic effect of factor VII gene polymorphisms causing mild factor VII deficiency in a case of severe factor X deficiency.

    Science.gov (United States)

    Deshpande, Rutuja; Ghosh, Kanjaksha; Shetty, Shrimati

    2017-01-01

    Congenital combined deficiency of coagulation factors VII and X are mainly attributed to large deletions involving both the genes in chromosome 13 or occasionally due to the coincidental occurrence of independently occurring mutations. We report the molecular basis of congenital combined deficiency of factors VII and X in a 6-year-old female child. Direct DNA sequencing of both factor VII (F7) and factor X (F10) genes showed a novel homozygous missense mutation p.Cys90Tyr (c.307G>A) in exon 4 of F10. No mutations were detected in F7; however, the patient was homozygous for three polymorphic alleles known to be associated with reduced factor VII levels. The present case illustrates the synergistic effect of multiple polymorphisms resulting in phenotypic factor VII deficiency in the absence of a pathogenic mutation.

  7. Role of hepsin in factor VII activation in zebrafish.

    Science.gov (United States)

    Khandekar, Gauri; Jagadeeswaran, Pudur

    2014-01-01

    Factor VII, the initiator of the extrinsic coagulation cascade, circulates in human plasma mainly in its zymogen form, factor VII and in small amounts in its activated form, factor VIIa. However, the mechanism of initial generation of factor VIIa is not known despite intensive research using currently available model systems. Earlier findings suggested serine proteases factor VII activating protease and hepsin play a role in activating factor VII, however, it has remained controversial. In this paper we estimated the levels of factor VIIa and factor VII for the first time in zebrafish adult population and also reevaluated the role of the above two serine proteases in activating factor VII in vivo using zebrafish as a model system. Knockdown of factor VII activating protease and hepsin was performed followed by assaying for their effect on factor VIIa concentration and extrinsic coagulation as measured by the kinetic prothrombin time. Factor VII activating protease knockdown showed no change in kinetic prothrombin time and no effect on factor VIIa levels while hepsin knockdown increased the kinetic prothrombin time and significantly reduced the factor VIIa plasma levels. Our results thus indicate that hepsin plays a physiologically important role in factor VII activation and hemostasis in zebrafish. © 2013.

  8. Uso de fator VII recombinante ativado para tratamento e profilaxia de grandes sangramentos Use of recombinant activated factor VII for treatment and prophylaxis of major bleeding

    Directory of Open Access Journals (Sweden)

    Flávio Augusto Henriques Vince

    2009-09-01

    pacientes. Dessa forma, o recente aumento do uso de rFVIIa em situações ainda não aprovadas levou ao crescente questionamento sobre eficácia e segurança desta específica medicação em tais situações.INTRODUCTION: Recombinant activated factor VII (rFVIIa is a protein produced by genetic engineering, the structure is very similar to the structure of intrinsic activated factor VII (FVII. Its action is based on knowledge of the coagulation mechanism in vivo by acting in direct activation of factor X independent resulting in formation of thrombin at the injury site and thereby contributing to the formation of stable fibrin clots without the action of factor VIII and factor IX. METHODS: Was conducted extensive review of the literature in order to determine the new findings related to the use of recombinant activated factor VII in patients with severe bleeding. RESULTS: It was found that the use of rFVIIa started in the 80's for prophylaxis and treatment of bleeding in patients with a history of hemophilia A or B with inhibitors to factor VIII and IX, factor VII deficiency and Glanzmann's thrombasthenia refractory to replacement platelet. In 1999 its use was expanded to other clinical situations and thus began to be published several studies showing the efficacy of rFVIIa as a pro-hemostatic agent in patients with bleeding disorders or other previously healthy patients with a history of acute bleeding of major consequence. Trauma is the leading cause of mortality worldwide and uncontrolled bleeding the main challenge in caring for these patients. It is common for the association of trauma with coagulopathy, requiring in some cases specific therapy to treat it. At this point in adjuvant therapy with rFVIIa should be considered. Other common causes of bleeding are the heart, gynecologic/obstetric surgeries and diseases involving the liver. The coagulopathy in these cases is deficiency of factors dependent on vitamin K, and the FVII factor with smaller half life. CONCLUSION

  9. Association of factor VII protein concentration with lifestyle factors

    DEFF Research Database (Denmark)

    Bladbjerg, E-M; Møller, L; Jespersen, J

    1998-01-01

    -sectional study examined the association between several behavioural variables (body mass index, physical activity, tobacco or alcohol consumption) or physiological variables (total cholesterol, HDL-cholesterol, triglycerides, glucose, insulin, fibrinogen, resting pulse, systolic blood pressure, bleeding time......) and FVII:Ag in 439 51-y-old Danish men. In the multivariate analyses, body mass index (BMI), low physical activity, total cholesterol, short bleeding time, and insulin showed an independent positive association with FVII:Ag. The strongest independent association with FVII:Ag was found for total cholesterol...

  10. Similarities and discrepancies in homozygous factor VII defects due to mutations in the region of residues Met298 to Cys310 (exon 8) in the catalytic domain of factor VII.

    Science.gov (United States)

    Girolami, A; Berti de Marinis, G; Bonamigo, E; Vettore, S

    2011-06-01

    Patients with the Arg304Gln mutation in factor VII Padua (FVII Padua) show discrepant activity levels that depend on the thromboplastin used in the assay system. This report investigates the possibility that residues close to Arg304 (exon 8) show the same discrepant behavior. All available homozygous patients with a mutation in a 13-residue region (preceding and following Arg304) have been evaluated. Only the Arg304Trp mutation showed a discrepancy similar to that shown by the Arg304Gln mutation. Other homozygotes failed to show differences, despite their all being positive for cross-reacting material. Another FVII amino acid residue involved in tissue factor binding and activation is Arg79 (exon 4). No comparison could be carried out because no homozygotes for deficiency in this region have ever been described. The relationship between these 2 residues involved in tissue factor binding and activation has not yet been completely clarified; however, Arg residues 79 and 304 are the only 2 residues definitely shown thus far to be involved in this important function.

  11. Recombinant Activated Factor VII (Eptacog Alfa Activated, NovoSeven®) in Patients with Rare Congenital Bleeding Disorders. A Systematic Review on its Use in Surgical Procedures.

    Science.gov (United States)

    Di Minno, Matteo Nicola Dario; Ambrosino, Pasquale; Myasoedova, Veronika; Amato, Manuela; Ventre, Itala; Tremoli, Elena; Minno, Alessandro Di

    2017-01-01

    In the absence of definite guidelines in the area, we have carried a systemic review to provide a thorough overview concerning the efficacy and safety of recombinant activated factor VII (rFVIIa, NovoSeven®, Novo Nordisk A/S, Bagsværd, Denmark) in patients with Glanzmann's thrombasthenia (GT) and FVII deficiency, undergoing surgical procedures. PubMed, Web of Science, Scopus and EMBASE databases was employed for the search. Three multicenter registries were identified: the Glanzmann's Thrombasthenia Registry (GTR), the Seven Treatment Evaluation Registry (STER), and a German post-marketing surveillance registry (the WIRK study). In addition, data from 10 case-series and/or single-center experiences have been summarized. We have found that the following; perioperatively, the hemostatic effectiveness of rFVIIa was high in GT patients and in those with FVII deficiency undergoing both minor and major surgical procedures. Moreover, in all studies, rFVIIa was well tolerated. Thus, the current evidence shows an optimal perioperative safety/efficacy profile of rFVIIa in the setting of these rare bleeding disorders, and provides the rationale for further studies aimed at evaluating the optimal perioperative anti-hemorrhagic prophylaxis with rFVIIa in GT and in FVII deficient patients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Factor VII assay performance: an analysis of the North American Specialized Coagulation Laboratory Association proficiency testing results.

    Science.gov (United States)

    Zantek, N D; Hsu, P; Refaai, M A; Ledford-Kraemer, M; Meijer, P; Van Cott, E M

    2013-06-01

    The performance of factor VII (FVII) assays currently used by clinical laboratories was examined in North American Specialized Coagulation Laboratory Association (NASCOLA) proficiency tests. Data from 12 surveys conducted between 2008 and 2010, involving 20 unique specimens plus four repeat-tested specimens, were analyzed. The number of laboratories per survey was 49-54 with a total of 1224 responses. Numerous reagent/instrument combinations were used. For FVII > 80 or 50 U/dL, among commonly used methods, one thromboplastin and one calibrator produced results 5-6 U/dL higher and another thromboplastin and calibrator produced results 5-6 U/dL lower than all other methods, and human thromboplastin differed from rabbit by +7.6 U/dL. Preliminary evidence suggests these differences could be due to the calibrator. For FVII <50 U/dL, differences among the commonly used reagents and calibrators were generally not significant. © 2013 Blackwell Publishing Ltd.

  13. Use of recombinant factor VII for tooth extractions in a patient with severe congenital factor VII deficiency: a case report.

    Science.gov (United States)

    Weinstock, Robert J; Onyejiuwa, Andrew; Shnayder, Garry; Clarkson, Earl I

    2015-04-01

    Patients with factor VII deficiency have an increased risk of prolonged perioperative hemorrhage. In this article, the authors present a case of severe factor VII deficiency in a patient who required tooth extraction. A 44-year-old woman with severe congenital factor VII deficiency sought care for a symptomatic, carious, and nonrestorable maxillary right second molar that required extraction. The authors obtained hematologic consultation, and the patient underwent the extraction under general anesthesia in the inpatient setting. Perioperative management included performing relevant laboratory studies, preoperative recombinant factor VII infusion, and postoperative intravenous aminocaproic acid administration. No hemorrhagic complications occurred throughout the perioperative course. The degree of factor VII deficiency correlates poorly with bleeding risk. Perioperative management is variable, requiring preoperative consultation with a hematologist. Copyright © 2015 American Dental Association. Published by Elsevier Inc. All rights reserved.

  14. Monoclonal anti-human factor VII antibodies. Detection in plasma of a second protein antigenically and genetically related to factor VII.

    OpenAIRE

    Broze, G J; Hickman, S; Miletich, J P

    1985-01-01

    Several murine monoclonal anti-human Factor VII antibodies were produced using hybridoma technology. Two noncompetitive monoclonal antibodies were used to examine by Western blotting the Factor VII cross-reactive material (CRM) in normal human plasma and three commercially available congenitally Factor VII-deficient plasmas, and to construct a facile "sandwich" immunoassay for plasma Factor VII. A second, previously undescribed, form of Factor VII CRM was detected in human plasma, which on We...

  15. Recombinant factor VIIa treatment for asymptomatic factor VII deficient patients going through major surgery.

    Science.gov (United States)

    Livnat, Tami; Shenkman, Boris; Spectre, Galia; Tamarin, Ilia; Dardik, Rima; Israeli, Amnon; Rivkind, Avraham; Shabtai, Moshe; Marinowitz, Uri; Salomon, Ophira

    2012-07-01

    Factor VII deficiency is the most common among the rare autosomal recessive coagulation disorders worldwide. In factor VII deficient patients, the severity and clinical manifestations cannot be reliably determined by factor VII levels. Severe bleeding tends to occur in individuals with factor VII activity levels of 2% or less of normal. Patients with 2-10% factor VII vary between asymptomatic to severe life threatening haemorrhages behaviour. Recombinant factor VIIa (rFVIIa) is the most common replacement therapy for congenital factor VII deficiency. However, unlike haemophilia patients for whom treatment protocols are straight forward, in asymptomatic factor VII deficiency patients it is still debatable. In this study, we demonstrate that a single and very low dose of recombinant factor VIIa enabled asymptomatic patients with factor VII deficiency to go through major surgery safely. This suggestion was also supported by thrombin generation, as well as by thromboelastometry.

  16. Using a minigene approach to characterize a novel splice site mutation in human F7 gene causing inherited factor VII deficiency in a Chinese pedigree.

    Science.gov (United States)

    Yu, T; Wang, X; Ding, Q; Fu, Q; Dai, J; Lu, Y; Xi, X; Wang, H

    2009-11-01

    Factor VII deficiency which transmitted as an autosomal recessive disorder is a rare haemorrhagic condition. The aim of this study was to identify the molecular genetic defect and determine its functional consequences in a Chinese pedigree with FVII deficiency. The proband was diagnosed as inherited coagulation FVII deficiency by reduced plasma levels of FVII activity (4.4%) and antigen (38.5%). All nine exons and their flanking sequence of F7 gene were amplified by polymerase chain reaction (PCR) for the proband and the PCR products were directly sequenced. The compound heterozygous mutations of F7 (NM_000131.3) c.572-1G>A and F7 (NM_000131.3) c.1165T>G; p.Cys389Gly were identified in the proband's F7 gene. To investigate the splicing patterns associated with F7 c.572-1G>A, ectopic transcripts in leucocytes of the proband were analyzed. F7 minigenes, spanning from intron 4 to intron 7 and carrying either an A or a G at position -1 of intron 5, were constructed and transiently transfected into human embryonic kidney (HEK) 293T cells, followed by RT-PCR analysis. The aberrant transcripts from the F7 c.572-1G>A mutant allele were not detected by ectopic transcription study. Sequencing of the RT-PCR products from the mutant transfectant demonstrated the production of an erroneously spliced mRNA with exon 6 skipping, whereas a normal splicing occurred in the wide type transfectant. The aberrant mRNA produced from the F7 c.572-1G>A mutant allele is responsible for the factor VII deficiency in this pedigree.

  17. Acquired factor VII deficiency associated with acute myeloid leukemia.

    Science.gov (United States)

    Anoun, Soumaya; Lamchahab, Mouna; Oukkache, Bouchra; Qachouh, Maryam; Benchekroun, Said; Quessar, Asmaa

    2015-04-01

    Isolated acquired factor VII deficiency is a rare coagulopathy. It has been reported in 31 patients with malignancy, sepsis, postoperatively, aplastic anemia, and during bone marrow transplantation. We discuss, through a new case of acquired factor VII deficiency, the characteristics of this disease when it is associated with acute myeloid leukemia. Acquired factor VII deficiency in hematological diseases can be caused by intensive chemotherapy, infections, or hepatic dysfunction. The best treatment in developing countries remains corticosteroids associated with plasma exchange, frozen plasma, and antibiotics.

  18. An engineered tale-transcription factor rescues transcription of factor VII impaired by promoter mutations and enhances its endogenous expression in hepatocytes.

    Science.gov (United States)

    Barbon, Elena; Pignani, Silvia; Branchini, Alessio; Bernardi, Francesco; Pinotti, Mirko; Bovolenta, Matteo

    2016-06-24

    Tailored approaches to restore defective transcription responsible for severe diseases have been poorly explored. We tested transcription activator-like effectors fused to an activation domain (TALE-TFs) in a coagulation factor VII (FVII) deficiency model. In this model, the deficiency is caused by the -94C > G or -61T > G mutation, which abrogate the binding of Sp1 or HNF-4 transcription factors. Reporter assays in hepatoma HepG2 cells naturally expressing FVII identified a single TALE-TF (TF4) that, by targeting the region between mutations, specifically trans-activated both the variant (>100-fold) and wild-type (20-40-fold) F7 promoters. Importantly, in the genomic context of transfected HepG2 and transduced primary hepatocytes, TF4 increased F7 mRNA and protein levels (2- to 3-fold) without detectable off-target effects, even for the homologous F10 gene. The ectopic F7 expression in renal HEK293 cells was modestly affected by TF4 or by TALE-TF combinations. These results provide experimental evidence for TALE-TFs as gene-specific tools useful to counteract disease-causing promoter mutations.

  19. Phenotypic and genotypic characterization of four factor VII deficiency patients from central China.

    Science.gov (United States)

    Liu, Hui; Wang, Hua-Fang; Cheng, Zhi-peng; Wang, Qing-yun; Hu, Bei; Zeng, Wei; Wu, Ying-ying; Guo, Tao; Tang, Liang; Hu, Yu

    2015-06-01

    Hereditary coagulation factor VII deficiency (FVIID) is a rare autosomal, recessive inherited hemorrhagic disorder related to a variety of mutations or polymorphisms throughout the factor VII (FVII) gene (F7). The aims of this study were to characterize the molecular defect of the F7 gene in four unrelated patients with FVIID and to find the genotype-phenotype correlation. All nine exons, exon-intron boundaries, and 5' and 3'-untranslated regions of the F7 gene were amplified by PCR and the purified PCR products were sequenced directly. Suspected mutations were confirmed by another PCR and sequencing of the opposite strand. Family studies were also performed. A total of five unique lesions were identified, including three missense mutations (c.384A>G, c.839A>C, c.1163T>G, predicting p.Tyr128Cys, p.Glu280Ala and p.Phe388Cys substitution, respectively) and two splice junction mutations (c.572-1G>A, c.681+1G>T), among which two (p.Glu280Ala, p.Phe388Cys) were novel. A previously reported mutation p.Tyr128Cys was seen in the homozygous state in two unrelated patients. The other two cases were both compound heterozygotes of a missense mutation and a splicing site mutation. Multiple sequence alignment using DNAMAN analysis showed that all the missense mutations were found in residues that highly conserved across species and vitamin K-dependent serine proteases. Online software Polyphen and SIFT were used to confirm the pathogenic of the missense mutation. p.Tyr128Cys seems to be a hotspot of the F7 gene in ethnic Han Chinese population.

  20. The importance of residues 195-206 of human blood clotting factor VII in the interaction of factor VII with tissue factor

    International Nuclear Information System (INIS)

    Wildgoose, P.; Kisiel, W.; Kazim, A.L.

    1990-01-01

    Previous studies indicated that human and bovine factor VII exhibit 71% amino acid sequence identity. In the present study, competition binding experiments revealed that the interaction of human factor VII with cell-surface human tissue factor was not inhibited by 100-fold molar excess of bovine factor VII. This finding indicated that bovine and human factor VII are not structurally homologous in the region(s) where human factor VII interacts with human tissue factor. On this premise, the authors synthesized three peptides corresponding to regions of human factor VII that exhibited marked structural dissimilarity to bovine factor VII; these regions of dissimilarity included residues 195-206, 263-274, and 314-326. Peptide 195-206 inhibited the interaction of factor VII with cell-surface tissue factor and the activation of factor X by a complex of factor VIIa and tissue factor half-maximally at concentrations of 1-2 mM. A structurally rearranged form of peptide 195-206 containing an aspartimide residue inhibited these reactions half-maximally at concentrations of 250-300 μM. In contrast, neither peptide 263-274 nor peptide 314-326, at 2 mM concentration, significantly affected either factor VIIa interaction with tissue factor or factor VIIa-mediated activation of factor X. The data provide presumptive evidence that residues 195-206 of human factor VII are involved in the interaction of human factor VII with the extracellular domain of human tissue factor apoprotein

  1. Age-related changes in factor VII proteolysis in vivo.

    Science.gov (United States)

    Ofosu, F A; Craven, S; Dewar, L; Anvari, N; Andrew, M; Blajchman, M A

    1996-08-01

    Previous studies have reported that pre-operative plasmas of patients over the age of 40 years who developed post-operative deep vein thrombosis (DVT) had approximately twice the amount of proteolysed factor VII found in plasmas of patients in whom prophylaxis with heparin or low M(r) heparin was successful. These and other studies also reported higher concentrations of thrombin-antithrombin III in pre- and post-operative plasmas of patients who developed post-operative thrombosis than in plasmas of patients in whom prophylaxis was successful. Whether the extent of factor VII proteolysis seen in the patients who developed post-operative DVT is related to the severity of their disease or age is not known. This report investigated age-related changes in the concentrations of total factor VII protein, factor VII zymogen, factor VIIa, tissue factor pathway inhibitor, thrombin-antithrombin III, and prothrombin fragment 1 + 2 in normal plasmas and the relationships between these parameters. With the exception of thrombin-antithrombin III, statistically significant increases in the concentrations of these parameters with age were found. Additionally, the differences between the concentrations of total factor VII protein and factor VII zymogen, an index factor VII proteolysis in vivo, were statistically significant only for individuals over age 40. Using linear regression analysis, a significant correlation was found to exist between the concentrations of plasma factor VIIa and prothrombin fragment 1 + 2. Since factor VIIa-tissue factor probably initiates coagulation in vivo, we hypothesize that the elevated plasma factor VIIa (reflecting a less tightly regulated tissue factor activity and therefore increased thrombin production in vivo) accounts for the high risk for post-operative thrombosis seen in individuals over the age of 40.

  2. Long-term prophylaxis in severe factor VII deficiency.

    Science.gov (United States)

    Siboni, S M; Biguzzi, E; Mistretta, C; Garagiola, I; Peyvandi, F

    2015-11-01

    The spectrum of bleeding problems in FVII deficiency is highly variable and FVII levels and causative genetic mutations correlate poorly with the bleeding risk. Long-term prophylaxis is generally initiated in order to prevent subsequent CNS bleeding after a first event or in patients with other major/ life threatening/ frequent bleeding symptoms as gastrointestinal bleeding or hemarthrosis. However few data are available in the literature regarding FVII prophylaxis and clinical decisions cannot be based on evidence. We report the data available in the literature on FVII prophylaxis and our personal experience regarding three patients affected by severe FVII deficiency. Specific papers on long-term prophylaxis in severe FVII deficiency were identified using the database, PUBMED. The most frequent indications for long-term prophylaxis were CNS bleeding (58%), hemartrosis (15%) and GI bleeding (9%). Patients were treated with various dosages and frequency. Prophylactic treatment with 10-30U/kg (pdFVII) or 20-30mcg/kg (rFVIIa) twice or three times/weeks was described to be effective. In the literature and in our experience, prophylaxis can be considered in patients with severe FVII deficiency and severe bleeding phenotype. A dose of 10-30U/kg (pdFVII) or 20-30 microg/kg (rFVIIa) twice or three times/week is usually administrated, but dose and frequency can be tailored based on the clinical follow-up of the patients. Since hemarthrosis is a frequent manifestation, a suggestion to improve the outcomes of patients with severe FVII deficiency is to monitor joint condition in order to identify early arthropathy that could be another indication to start secondary prophylaxis. © 2015 John Wiley & Sons Ltd.

  3. Preparation of factor VII concentrate using CNBr-activated Sepharose 4B immunoaffinity chromatography

    OpenAIRE

    Mousavi Hosseini, Kamran; Nasiri, Saleh

    2015-01-01

    Background: Factor VII concentrates are used in patients with congenital or acquired factor VII deficiency or treatment of hemophilia patients with inhibitors. In this research, immunoaffinity chromatography was used to purify factor VII from prothrombin complex (Prothrombin- Proconvertin-Stuart Factor-Antihemophilic Factor B or PPSB) which contains coagulation factors II, VII, IX and X. The aim of this study was to improve purity, safety and tolerability as a highly purified factor VII conce...

  4. Increased volume of distribution for recombinant activated factor VII and longer plasma-derived factor VII half-life may explain their long lasting prophylactic effect

    NARCIS (Netherlands)

    Mathijssen, N.C.J.; Masereeuw, R.; Holme, P.A.; Kraaij, M.G.J. van; Laros, B.A.P.; Peyvandi, F.; Heerde, W.L. van

    2013-01-01

    INTRODUCTION: Prophylaxis with plasma-derived or recombinant activated factor VII is beneficial in severe factor VII deficiency. To understand why prophylactic treatment with both products is efficacious, we conducted a pharmacokinetic study. MATERIALS AND METHODS: Ten factor VII deficient patients

  5. Newly diagnosed congenital factor VII deficiency and utilization of recombinant activated factor VII (NovoSeven(®)).

    Science.gov (United States)

    Bartosh, Nicole S; Tomlin, Tara; Cable, Christian; Halka, Kathleen

    2013-01-01

    This case report presents a newly diagnosed congenital factor VII deficiency treated with recombinant activated factor VII (rFVIIa). Congenital factor VII deficiency is a rare autosomal-recessive bleeding disorder that occurs in fewer than 1/500,000 persons. Its presentation can vary from epistaxis to hemarthroses and severe central nervous system bleeding, and correlates poorly with factor VII levels. Our patient had not had a significant hemostatic challenge prior to his presentation and therefore never had any symptomatology suggestive of this disease. He was treated with rFVIIa, and was able to undergo repair of his fractures without bleeding. A 19-year-old African-American male presented to the emergency room after an altercation that resulted in significant trauma. He sustained bilateral mandibular angle fractures and orbital floor fractures, requiring urgent surgical correction. On initial evaluation, he was noted to have a prolonged prothrombin time of 40.1 seconds, with an International Normalized Ratio of 4.0, a normal activated partial thromboplastin time of 29.9 seconds, and a platelet count of 241. After receiving vitamin K and fresh frozen plasma, he was taken to the operating room for a temporary rigid maxillomandibular fixation. A 1:1 mixing study with normal plasma corrected the prothrombin time (decreasing from 40.7 to 14.7 seconds) and a factor VII assay revealed 5% of the normal factor VII level. The patient was diagnosed with congenital factor VII deficiency. Due to his coagulopathy and the extensive surgical correction needed, rFVIIa was administered and surgery was accomplished without hemorrhagic sequelae. This case report and review describes a rare congenital disease, the history of rFVIIa use, and its mechanism. rFVIIA use in our patient provided a treatment option that allowed the necessary surgical correction, but further prospective studies on dose optimization would ensure adequate dosing with minimal risk of severe side effects.

  6. Newly diagnosed congenital factor VII deficiency and utilization of recombinant activated factor VII (NovoSeven®)

    Science.gov (United States)

    Bartosh, Nicole S; Tomlin, Tara; Cable, Christian; Halka, Kathleen

    2013-01-01

    This case report presents a newly diagnosed congenital factor VII deficiency treated with recombinant activated factor VII (rFVIIa). Congenital factor VII deficiency is a rare autosomal-recessive bleeding disorder that occurs in fewer than 1/500,000 persons. Its presentation can vary from epistaxis to hemarthroses and severe central nervous system bleeding, and correlates poorly with factor VII levels. Our patient had not had a significant hemostatic challenge prior to his presentation and therefore never had any symptomatology suggestive of this disease. He was treated with rFVIIa, and was able to undergo repair of his fractures without bleeding. Case report A 19-year-old African-American male presented to the emergency room after an altercation that resulted in significant trauma. He sustained bilateral mandibular angle fractures and orbital floor fractures, requiring urgent surgical correction. On initial evaluation, he was noted to have a prolonged prothrombin time of 40.1 seconds, with an International Normalized Ratio of 4.0, a normal activated partial thromboplastin time of 29.9 seconds, and a platelet count of 241. After receiving vitamin K and fresh frozen plasma, he was taken to the operating room for a temporary rigid maxillomandibular fixation. A 1:1 mixing study with normal plasma corrected the prothrombin time (decreasing from 40.7 to 14.7 seconds) and a factor VII assay revealed 5% of the normal factor VII level. The patient was diagnosed with congenital factor VII deficiency. Due to his coagulopathy and the extensive surgical correction needed, rFVIIa was administered and surgery was accomplished without hemorrhagic sequelae. Conclusion This case report and review describes a rare congenital disease, the history of rFVIIa use, and its mechanism. rFVIIA use in our patient provided a treatment option that allowed the necessary surgical correction, but further prospective studies on dose optimization would ensure adequate dosing with minimal risk of

  7. Factor VII deficiency: a single-center experience.

    Science.gov (United States)

    Salcioglu, Zafer; Akcay, Arzu; Sen, Hulya Sayilan; Aydogan, Gonul; Akici, Ferhan; Tugcu, Deniz; Ayaz, Nuray Aktay; Baslar, Zafer

    2012-11-01

    Congenital factor VII deficiency is the most common form of rare coagulation factor deficiencies. This article presents a retrospective evaluation of 73 factor VII deficiency cases that had been followed at our center. The study consisted of 48 males and 25 females (2 months-19 years). Thirty-one (42.5%) of them were asymptomatic. Out of symptomatic patients, 17 had severe clinical symptoms, whereas 8 presented with moderate and 17 with mild symptoms. The symptoms listed in order of frequency were as follows: epistaxis, petechia or ecchymose, easy bruising, and oral cavity bleeding. The genotype was determined in 8 patients. Recombinant activated factor VII (rFVIIa) was used to treat 49 bleeding episodes in 8 patients after 2002. In 2 patients with repeated central nervous system bleeding prophylaxis with rFVIIa was administered. No allergic and thrombotic events were observed during both treatment and prophylaxis courses. Antibody occurrence was not detected in the patients during treatment.

  8. Factor VII Deficiency: Clinical Phenotype, Genotype and Therapy.

    Science.gov (United States)

    Napolitano, Mariasanta; Siragusa, Sergio; Mariani, Guglielmo

    2017-03-28

    Factor VII deficiency is the most common among rare inherited autosomal recessive bleeding disorders, and is a chameleon disease due to the lack of a direct correlation between plasma levels of coagulation Factor VII and bleeding manifestations. Clinical phenotypes range from asymptomatic condition-even in homozygous subjects-to severe life-threatening bleedings (central nervous system, gastrointestinal bleeding). Prediction of bleeding risk is thus based on multiple parameters that challenge disease management. Spontaneous or surgical bleedings require accurate treatment schedules, and patients at high risk of severe hemorrhages may need prophylaxis from childhood onwards. The aim of the current review is to depict an updated summary of clinical phenotype, laboratory diagnosis, and treatment of inherited Factor VII deficiency.

  9. Activation of factor VII bound to tissue factor: A key early step in the tissue factor pathway of blood coagulation

    International Nuclear Information System (INIS)

    Rao, L.V.M.; Rapaport, S.I.

    1988-01-01

    Whether the factor VII/tissue factor complex that forms in tissue factor-dependent blood coagulation must be activated to factor VIIa/tissue factor before it can activate its substrates, factor X and IX, has been a difficult question to answer because the substrates, once activated, back-activate factor VII. The earlier studies suggested that human factor VII/tissue factor cannot activate factor IX. Studies have now been extended to the activation of factor X. Reaction mixtures were made with purified factor VII, X, and tissue factor; in some experiments antithrombin III and heparin were added to prevent back-activation of factor VII. Factor X was activated at similar rates in reaction mixtures containing either VII or factor VIIa after an initial 30-sec lag with factor VII. In reaction mixtures with factor VII a linear activation of factor X was established several minutes before cleavage of 125 I-labeled factor VII to the two-chain activated molecule was demonstrable on gel profiles. These data suggest that factor VII/tissue factor cannot activate measurable amounts of factor X over several minutes. Overall, the results support the hypothesis that a rapid preferential activation of factor VII bound to tissue factor by trace amounts of factor Xa is a key early step in tissue factor-dependent blood coagulation

  10. PET Imaging of Tissue Factor in Pancreatic Cancer Using 64Cu-Labeled Active Site-Inhibited Factor VII.

    Science.gov (United States)

    Nielsen, Carsten H; Jeppesen, Troels E; Kristensen, Lotte K; Jensen, Mette M; El Ali, Henrik H; Madsen, Jacob; Wiinberg, Bo; Petersen, Lars C; Kjaer, Andreas

    2016-07-01

    Tissue factor (TF) is the main initiator of the extrinsic coagulation cascade. However, TF also plays an important role in cancer. TF expression has been reported in 53%-89% of all pancreatic adenocarcinomas, and the expression level of TF has in clinical studies correlated with advanced stage, increased microvessel density, metastasis, and poor overall survival. Imaging of TF expression is of clinical relevance as a prognostic biomarker and as a companion diagnostic for TF-directed therapies currently under clinical development. Factor VII (FVII) is the natural ligand to TF. The purpose of this study was to investigate the possibility of using active site-inhibited FVII (FVIIai) labeled with (64)Cu for PET imaging of TF expression. FVIIai was conjugated to 2-S-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA) and labeled with (64)Cu ((64)Cu-NOTA-FVIIai). Longitudinal in vivo PET imaging was performed at 1, 4, 15, and 36 h after injection of (64)Cu-NOTA-FVIIai in mice with pancreatic adenocarcinomas (BxPC-3). The specificity of TF imaging with (64)Cu-NOTA-FVIIai was investigated in subcutaneous pancreatic tumor models with different levels of TF expression and in a competition experiment. In addition, imaging of orthotopic pancreatic tumors was performed using (64)Cu-NOTA-FVIIai and PET/MRI. In vivo imaging data were supported by ex vivo biodistribution, flow cytometry, and immunohistochemistry. Longitudinal PET imaging with (64)Cu-NOTA-FVIIai showed a tumor uptake of 2.3 ± 0.2, 3.7 ± 0.3, 3.4 ± 0.3, and 2.4 ± 0.3 percentage injected dose per gram at 1, 4, 15, and 36 h after injection, respectively. An increase in tumor-to-normal-tissue contrast was observed over the imaging time course. Competition with unlabeled FVIIai significantly (P < 0.001) reduced the tumor uptake. The tumor uptake observed in models with different TF expression levels was significantly different from each other (P < 0.001) and was in agreement with

  11. Prophylactic treatment of hereditary severe factor VII deficiency in pregnancy.

    Science.gov (United States)

    Pfrepper, Christian; Siegemund, Annelie; Hildebrandt, Sven; Kronberg, Juliane; Scholz, Ute; Niederwieser, Dietger

    2017-09-01

    : Severe hereditary factor VII deficiency is a rare bleeding disorder and may be associated with a severe bleeding phenotype. We describe a pregnancy in a 33-year-old woman with compound heterozygous factor VII deficiency and a history of severe menorrhagia and mucocutaneous bleedings. After discontinuation of contraceptives, menstruation was covered with recombinant activated factor VII (rFVIIa), and during pregnancy, rFVIIa had to be administered in first trimester in doses ranging from 15 to 90 μg/kg per day because of recurrent retroplacental hematomas and vaginal bleedings. Thrombin generation was measured in first trimester at different doses of rFVIIa and showed an increase in lag time when doses of less than 30 μg/kg/day were administered, whereas time to thrombin peak and peak thrombin were not influenced. A low-dose rFVIIa prophylactic treatment of 15 μg/kg every other day in the late second and in the third trimester was sufficient to allow a successful childbirth in this patient with severe factor VII deficiency.

  12. Production and properties of monoclonal antibodies to human blood coagulation factor VII and factor VIIa

    International Nuclear Information System (INIS)

    Mann, P.; Nesbitt, J.A.; Ge, M.; Kisiel, W.

    1986-01-01

    Human factor VII is a trace vitamin K-dependent protein that circulates in blood as a single-chain precursor to a serine protease. Upon activation, two-chain factor VIIa activates factor x in the presence of tissue factor and calcium. Purified preparations of single-chain (SC) human factor VII and two-chain (TC) factor VIIa were utilized to immunize Balb/c mice. Spleen cells from these immunized mice were fused to a non-secreting NS-1 derivative of X63-Ag8 myeloma cells and grown in selective medium. Analysis of culture supernatants by EIA revealed several hybridomas that were secreting IgG specific for Sc-factor VII and TC-factor VIIa. In addition, several hybridomas secreted IgG that reacted equally well with factor VII and factor VIIa. One of the latter McAb (A-29) reacted with the heavy chain of factor VIIa and the intact factor VII molecule equally as judged by Western blotting. A-29 was produced in ascites fluid, purified and coupled to activated CH-Sepharose. Application of one liter of normal human plasma to 10 ml of this immunoadsorbent column, elution of factor VII and subsequent Western blot using 125 I-rabbit anti-human factor VII indicated a single species of factor VII(M/sub r/ = 50 KDa) in normal plasma. These specific factor VII/VIIa McAbs may prove useful in the analysis of these factors, and in the separation of SC-factor VII from TC-factor VIIa

  13. Thrombin generation by activated factor VII on platelet activated by different agonists. Extending the cell-based model of hemostasis

    Directory of Open Access Journals (Sweden)

    Herrera Maria

    2006-04-01

    Full Text Available Abstract Background Platelet activation is crucial in normal hemostasis. Using a clotting system free of external tissue factor, we investigated whether activated Factor VII in combination with platelet agonists increased thrombin generation (TG in vitro. Methods and results TG was quantified by time parameters: lag time (LT and time to peak (TTP, and by amount of TG: peak of TG (PTG and area under thrombin formation curve after 35 minutes (AUC→35min in plasma from 29 healthy volunteers using the calibrated automated thrombography (CAT technique. TG parameters were measured at basal conditions and after platelet stimulation by sodium arachidonate (AA, ADP, and collagen (Col. In addition, the effects of recombinant activated FVII (rFVIIa alone or combined with the other platelet agonists on TG parameters were investigated. We found that LT and TTP were significantly decreased (p 35min were significantly increased (p 35min (but not PTG when compared to platelet rich plasma activated with agonists in the absence of rFVIIa. Conclusion Platelets activated by AA, ADP, Col or rFVIIa triggered TG. This effect was increased by combining rFVIIa with other agonists. Our intrinsic coagulation system produced a burst in TG independent of external tissue factor activity an apparent hemostatic effect with little thrombotic capacity. Thus we suggest a modification in the cell-based model of hemostasis.

  14. Preparation of factor VII concentrate using CNBr-activated Sepharose 4B immunoaffinity chromatography.

    Science.gov (United States)

    Mousavi Hosseini, Kamran; Nasiri, Saleh

    2015-01-01

    Factor VII concentrates are used in patients with congenital or acquired factor VII deficiency or treatment of hemophilia patients with inhibitors. In this research, immunoaffinity chromatography was used to purify factor VII from prothrombin complex (Prothrombin- Proconvertin-Stuart Factor-Antihemophilic Factor B or PPSB) which contains coagulation factors II, VII, IX and X. The aim of this study was to improve purity, safety and tolerability as a highly purified factor VII concentrate. PPSB was prepared using DEAE-Sephadex and was used as the starting material for purification of coagulation factor VII. Prothrombin complex was treated by solvent/detergent at 24°C for 6 h with constant stirring. The mixture of PPSB in the PBS buffer was filtered and then chromatographed using CNBr-activated Sepharose 4B coupled with specific antibody. Factors II, IX, VII, X and VIIa were assayed on the fractions. Fractions of 48-50 were pooled and lyophilized as a factor VII concentrate. Agarose gel electrophoresis was performed and Tween 80 was measured in the factor VII concentrate. Specific activity of factor VII concentrate increased from 0.16 to 55.6 with a purificationfold of 347.5 and the amount of activated factor VII (FVIIa) was found higher than PPSB (4.4-fold). RESULTS of electrophoresis on agarose gel indicated higher purity of Factor VII compared to PPSB; these finding revealed that factor VII migrated as alpha-2 proteins. In order to improve viral safety, solvent-detergent treatment was applied prior to further purification and nearly complete elimination of tween 80 (2 μg/ml). It was concluded that immuonoaffinity chromatography using CNBr-activated Sepharose 4B can be a suitable choice for large-scale production of factor VII concentrate with higher purity, safety and activated factor VII.

  15. Vena porta thrombosis in patient with inherited factor VII deficiency

    DEFF Research Database (Denmark)

    Klovaite, Jolanta; Friis-Hansen, Lennart Jan; Larsen, Fin S

    2010-01-01

    with inherited FVII deficiency and chronic vena porta thrombosis. She presented at 32 weeks of gestation with spontaneously increased international normalized ratio, severe thrombocytopenia and very few unspecific symptoms. The extensive examination of the patient revealed cavernous transformation of the portal...

  16. First living-related liver transplant to cure factor VII deficiency.

    Science.gov (United States)

    Mohan, Neelam; Karkra, Sakshi; Jolly, Anu S; Vohra, Vijay; Mohanka, Ravi; Rastogi, Amit; Soin, A S

    2015-09-01

    Congenital factor VII deficiency is an autosomal recessive serious disorder of blood coagulation with wide genotypic and phenotypic variations. The clinical presentation can vary from asymptomatic patients to patients with major bleedings in severe deficiency (factor VII factor VII. Treatment modalities include FFP and repeated recombinant factor VII infusions. We hereby report the first successful LRLT for factor VII deficiency in an infant, the first-ever youngest baby reported worldwide. A six-month-old male child presented with easy bruisability, ecchymotic patches, hematuria, and convulsions. CT of the head showed subdural hemorrhage, which was treated conservatively. He had markedly increased PT (120 s) with normal platelets, and aPTT with factor VII level factor VII level was 57%. A factor VII infusion plan for pre-, intra- and postoperative periods was formulated and TEG followed. Postoperatively, his factor VII started increasing from third day and was 38% on 24th day with PT factor VII deficiency. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Activation of factor VII bound to tissue factor: a key early step in the tissue factor pathway of blood coagulation.

    OpenAIRE

    Rao, L V; Rapaport, S I

    1988-01-01

    Whether the factor VII/tissue factor complex that forms in tissue factor-dependent blood coagulation must be activated to factor VIIa/tissue factor before it can activate its substrates, factor X and factor IX, has been a difficult question to answer because the substrates, once activated, back-activate factor VII. Our earlier studies suggested that human factor VII/tissue factor cannot activate factor IX. Studies have now been extended to the activation of factor X. Reaction mixtures were ma...

  18. Manipulation of the membrane binding site of vitamin K-dependent proteins: Enhanced biological function of human factor VII

    OpenAIRE

    Shah, Amit M.; Kisiel, Walter; Foster, Donald C.; Nelsestuen, Gary L.

    1998-01-01

    Recent studies suggested that modification of the membrane contact site of vitamin K-dependent proteins may enhance the membrane affinity and function of members of this protein family. The properties of a factor VII mutant, factor VII-Q10E32, relative to wild-type factor VII (VII, containing P10K32), have been compared. Membrane affinity of VII-Q10E32 was about 20-fold higher than that of wild-type factor VII. The rate of autoactivation VII-Q10E32 with soluble tissue factor was 100-fold fast...

  19. Evidence supporting the use of recombinant activated factor VII in congenital bleeding disorders

    DEFF Research Database (Denmark)

    Johansson, Pär I; Ostrowski, Sisse R

    2010-01-01

    Recombinant activated factor VII (rFVIIa, NovoSeven) was introduced in 1996 for the treatment of hemophilic patients with antibodies against coagulation factor VIII or IX.......Recombinant activated factor VII (rFVIIa, NovoSeven) was introduced in 1996 for the treatment of hemophilic patients with antibodies against coagulation factor VIII or IX....

  20. Mechanism of action of recombinant activated factor VII: an update.

    Science.gov (United States)

    Hedner, Ulla

    2006-01-01

    Bleeding episodes in patients with hemophilia and inhibitors must be managed using agents that are hemostatically active in the absence of factor VIII or IX. Activated prothrombin complex concentrates have long been used in this context. However, the search for safer and more effective agents has led to the development of recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark). This paper presents an update on the mechanism of action of rFVIIa, and describes how pharmacologic doses of this agent enhance thrombin production and thus contribute to the development of a stable, lysis-resistant fibrin plug at the site of vessel damage. This mechanism explains the reported efficacy of rFVIIa in a range of clinical situations characterized by impaired thrombin generation.

  1. Effects of different progestin regimens in hormone replacement therapy on blood coagulation factor VII and tissue factor pathway inhibitor

    DEFF Research Database (Denmark)

    Bladbjerg, E-M; Skouby, S O.; Andersen, L F

    2002-01-01

    BACKGROUND: Long-term hormone replacement therapy (HRT) reduces cardiovascular risk, but an early increased risk was reported in women with coronary heart disease. In such women the arterial intima can express tissue factor, and changes in coagulation factor VII (factor VII) and tissue factor...... pathway inhibitor (TFPI) may be deleterious. METHODS: We measured factor VII clotting activity, activated factor VII, and concentrations of factor VII and TFPI during 12 months in healthy post-menopausal women randomized to: (i). cyclic oral estrogen/progestin (n = 25); (ii). long-cycle oral estrogen......: No variations were observed in the reference group. There was a substantial decrease in TFPI concentrations in the HRT groups irrespective of the type of progestin. In women receiving long-cycle treatment, all factor VII measures increased during the unopposed estrogen periods, and the increase was reversed...

  2. Recombinant activated factor VII in cardiac surgery: single-center experience.

    Science.gov (United States)

    Singh, Sarvesh Pal; Chauhan, Sandeep; Choudhury, Minati; Malik, Vishwas; Choudhary, Shiv Kumar

    2014-02-01

    The widespread off-label use of recombinant activated factor VII for the control of refractory postoperative hemorrhage continues despite a warning from the Food and Drug Administration. Although effective in reducing the need for transfusion of blood and blood products, safety concerns still prevail. To compare the dosing and efficacy of recombinant activated factor VII between pediatric and adult patients, and in the operating room and intensive care unit. The records of 69 patients (33 children and 36 adults) who underwent cardiovascular surgery and received recombinant activated factor VII were reviewed retrospectively. The dose of recombinant activated factor VII, mediastinal drainage, use of blood and blood products, incidence of thrombosis, and 28-day mortality were studied. the efficacy of recombinant activated factor VII was comparable in adults and children, despite the lower dose in adults. Prophylactic use of recombinant activated factor VII decreased the incidence of mediastinal exploration and the duration of intensive care unit stay. A 4.3% incidence of thrombotic complications was observed in this study. The efficacious dose of recombinant activated factor VII is much less in adults compared to children. Prophylactic use of recombinant activated factor VII decreases the dose required, the incidence of mediastinal exploration, and intensive care unit stay, with no survival benefit.

  3. Inhibition of thrombin generation by the zymogen factor VII: implications for the treatment of hemophilia A by factor VIIa

    NARCIS (Netherlands)

    van 't Veer, C.; Golden, N. J.; Mann, K. G.

    2000-01-01

    Factor VII circulates as a single chain inactive zymogen (10 nmol/L) and a trace ( approximately 10-100 pmol/L) circulates as the 2-chain form, factor VIIa. Factor VII and factor VIIa were studied in a coagulation model using plasma concentrations of purified coagulation factors with reactions

  4. In vitro evidence of a tissue factor-independent mode of action of recombinant factor VIIa in hemophilia.

    Science.gov (United States)

    Augustsson, Cecilia; Persson, Egon

    2014-11-13

    Successful competition of activated factor VII (FVIIa) with zymogen factor VII (FVII) for tissue factor (TF) and loading of the platelet surface with FVIIa are plausible driving forces behind the pharmacological effect of recombinant FVIIa (rFVIIa) in hemophilia patients. Thrombin generation measurements in platelet-rich hemophilia A plasma revealed competition for TF, which potentially could reduce the effective (r)FVIIa:TF complex concentration and thereby attenuate factor Xa production. However, (auto)activation of FVII apparently counteracted the negative effect of zymogen binding; a small impact was observed at endogenous concentrations of FVII and FVIIa but was virtually absent at pharmacological amounts of rFVIIa. Moreover, corrections of the propagation phase in hemophilia A required rFVIIa concentrations above the range where a physiological level of FVII was capable to downregulate thrombin generation. These data strongly suggest that rFVIIa acts independently of TF in hemophilia therapy and that FVII displacement by rFVIIa is a negligible mechanistic component. © 2014 by The American Society of Hematology.

  5. Associations of activated coagulation factor VII and factor VIIa-antithrombin levels with genome-wide polymorphisms and cardiovascular disease risk.

    Science.gov (United States)

    Olson, N C; Raffield, L M; Lange, L A; Lange, E M; Longstreth, W T; Chauhan, G; Debette, S; Seshadri, S; Reiner, A P; Tracy, R P

    2018-01-01

    Essentials A fraction of coagulation factor VII circulates in blood as an activated protease (FVIIa). We evaluated FVIIa and FVIIa-antithrombin (FVIIa-AT) levels in the Cardiovascular Health Study. Polymorphisms in the F7 and PROCR loci were associated with FVIIa and FVIIa-AT levels. FVIIa may be an ischemic stroke risk factor in older adults and FVIIa-AT may assess mortality risk. Background A fraction of coagulation factor (F) VII circulates as an active protease (FVIIa). FVIIa also circulates as an inactivated complex with antithrombin (FVIIa-AT). Objective Evaluate associations of FVIIa and FVIIa-AT with genome-wide single nucleotide polymorphisms (SNPs) and incident coronary heart disease, ischemic stroke and mortality. Patients/Methods We measured FVIIa and FVIIa-AT in 3486 Cardiovascular Health Study (CHS) participants. We performed a genome-wide association scan for FVIIa and FVIIa-AT in European-Americans (n = 2410) and examined associations of FVII phenotypes with incident cardiovascular disease. Results In European-Americans, the most significant SNP for FVIIa and FVIIa-AT was rs1755685 in the F7 promoter region on chromosome 13 (FVIIa, β = -25.9 mU mL -1 per minor allele; FVIIa-AT, β = -26.6 pm per minor allele). Phenotypes were also associated with rs867186 located in PROCR on chromosome 20 (FVIIa, β = 7.8 mU mL -1 per minor allele; FVIIa-AT, β = 9.9 per minor allele). Adjusted for risk factors, a one standard deviation higher FVIIa was associated with increased risk of ischemic stroke (hazard ratio [HR], 1.12; 95% confidence interval [CI], 1.01, 1.23). Higher FVIIa-AT was associated with mortality from all causes (HR, 1.08; 95% CI, 1.03, 1.12). Among European-American CHS participants the rs1755685 minor allele was associated with lower ischemic stroke (HR, 0.69; 95% CI, 0.54, 0.88), but this association was not replicated in a larger multi-cohort analysis. Conclusions The results support the importance of the F7 and PROCR loci in

  6. Diagnostic Error of a Patient with Combined Inherited Factor VII and Factor X Deficiency due to Accidental Ingestion of a Diphacinone Rodenticide.

    Science.gov (United States)

    Li, Min; Jin, Yanhui; Wang, Mingshan; Xie, Yaosheng; Ding, Hongxiang

    2016-11-01

    To explore the characteristics of laboratory examination and confirm the diagnosis of a patient with combined inherited FVII and FX deficiency after he ingested diphacinone rodenticide accidentally. The coagulant parameter screening tests and coagulation factor activities were tested many times in the patient due to accidental ingestion of a diphacinone rodenticide. After the patient was treated for more than one year, gene analysis of correlated coagulation factors was analyzed in the patient and other family members by DNA direct sequencing. 106 persons were selected as controls from routine health examinations. After the patient was admitted to hospital, routine coagulation screening tests revealed the prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT) and low levels of vitamin K-dependent coagulation factors (FII, FVII, FIX, FX) activity, which was 102.4 seconds, 88.5 seconds, 7%, 3%, 8%, and 2%, respectively. During more than one year of treatment, the value of PT and APTT still showed significantly prolonged activity and FVII and FX activity levels were about 5%. While FII and FIX activity levels were in the normal range after 12 weeks of treatment. Two homozygous mutations, g.11267C>T of F7 gene resulting in the substitution Arg277Cys and g.28139G>T of F10 gene leading to the substitution Val384Phe, were identified in the patient. The patient's parents and sister was heterozygous for Arg277Cys and Val384Phe mutations. FVII and FX antigen levels in the patient were 7% and 30%, respectively. There were many similarities in the characteristics of laboratory examination between combined inherited FVII and FX deficiency and acquired vitamin K deficiency. The best way to identify them was gene analysis.

  7. Expression of Recombinant Human Coagulation Factor VII by the Lizard Leishmania Expression System

    Directory of Open Access Journals (Sweden)

    Sina Mirzaahmadi

    2011-01-01

    Full Text Available The variety of recombinant protein expression systems have been developed as a resource of FVII gene expression. In the current study, the authors used a novel protein expression system based on the Iranian Lizard Leishmania, a trypanosomatid protozoan as a host for expression of FVII. Plasmid containing cDNA encoding full-length human FVII was introduced into Lizard Leishmania and positive transfectants were analyzed by SDS-PAGE and Western blot analysis. Furthermore, biological activity of purified protein was detected by PT assay. The recombinant strain harboring a construct was analyzed for expression of FVII at the mRNA and protein level. Purified rFVII was obtained and in order to confirm the purified compound was in fact rFVII. Western blot analysis was carried out. Clotting time in PT assay was reduced about 30 seconds with the purified rFVII. In Conclusion, this study has demonstrated, for the first time, that Leishmania cells can be used as an expression system for producing recombinant FVII.

  8. Age-dependent regulation of ERF-VII transcription factor activity in Arabidopsis thaliana.

    Science.gov (United States)

    Giuntoli, Beatrice; Shukla, Vinay; Maggiorelli, Federica; Giorgi, Federico M; Lombardi, Lara; Perata, Pierdomenico; Licausi, Francesco

    2017-10-01

    The Group VII Ethylene Responsive Factors (ERFs-VII) RAP2.2 and RAP2.12 have been mainly characterized with regard to their contribution as activators of fermentation in plants. However, transcriptional changes measured in conditions that stabilize these transcription factors exceed the mere activation of this biochemical pathway, implying additional roles performed by the ERF-VIIs in other processes. We evaluated gene expression in transgenic Arabidopsis lines expressing a stabilized form of RAP2.12, or hampered in ERF-VII activity, and identified genes affected by this transcriptional regulator and its homologs, including some involved in oxidative stress response, which are not universally induced under anaerobic conditions. The contribution of the ERF-VIIs in regulating this set of genes in response to chemically induced or submergence-stimulated mitochondria malfunctioning was found to depend on the plant developmental stage. A similar age-dependent mechanism also restrained ERF-VII activity upon the core-hypoxic genes, independently of the N-end rule pathway, which is accounted for the control of the anaerobic response. To conclude, this study shed new light on a dual role of ERF-VII proteins under submergence: as positive regulators of the hypoxic response and as repressors of oxidative-stress related genes, depending on the developmental stage at which plants are challenged by stress conditions. © 2017 John Wiley & Sons Ltd.

  9. Topical application of recombinant activated factor VII during cesarean delivery for placenta previa.

    Science.gov (United States)

    Schjoldager, Birgit T B G; Mikkelsen, Emmeli; Lykke, Malene R; Præst, Jørgen; Hvas, Anne-Mette; Heslet, Lars; Secher, Niels J; Salvig, Jannie D; Uldbjerg, Niels

    2017-06-01

    During cesarean delivery in patients with placenta previa, hemorrhaging after removal of the placenta is often challenging. In this condition, the extraordinarily high concentration of tissue factor at the placenta site may constitute a principle of treatment as it activates coagulation very effectively. The presumption, however, is that tissue factor is bound to activated factor VII. We hypothesized that topical application of recombinant activated factor VII at the placenta site reduces bleeding without affecting intravascular coagulation. We included 5 cases with planned cesarean delivery for placenta previa. After removal of the placenta, the surgeon applied a swab soaked in recombinant activated factor VII containing saline (1 mg in 246 mL) to the placenta site for 2 minutes; this treatment was repeated once if the bleeding did not decrease sufficiently. We documented the treatment on video recordings and measured blood loss. Furthermore, we determined hemoglobin concentration, platelet count, international normalized ratio, activated partial thrombin time, fibrinogen (functional), factor VII:clot, and thrombin generation in peripheral blood prior to and 15 minutes after removal of the placenta. We also tested these blood coagulation variables in 5 women with cesarean delivery planned for other reasons. Mann-Whitney test was used for unpaired data. In all 5 cases, the uterotomy was closed under practically dry conditions and the median blood loss was 490 (range 300-800) mL. There were no adverse effects of recombinant activated factor VII and we did not measure factor VII to enter the circulation. Neither did we observe changes in thrombin generation, fibrinogen, activated partial thrombin time, international normalized ratio, and platelet count in the peripheral circulation (all P values >.20). This study indicates that in patients with placenta previa, topical recombinant activated factor VII may diminish bleeding from the placenta site without initiation

  10. Factor VII deficiency: a novel missense variant and genotype-phenotype correlation in patients from Southern Italy.

    Science.gov (United States)

    Tiscia, Giovanni; Favuzzi, Giovanni; Chinni, Elena; Colaizzo, Donatella; Fischetti, Lucia; Intrieri, Mariano; Margaglione, Maurizio; Grandone, Elvira

    2017-01-01

    This study aimed at attempting to correlate genotype and phenotype in factor VII deficiency. Here, we present molecular and clinical findings of 10 patients with factor VII deficiency. From 2013 to 2016, 10 subjects were referred to our center because of a prolonged prothrombin time identified during routine or presurgery examinations or after a laboratory assessment of a bleeding episode. Mutation characterization was performed using the bioinformatics applications PROMO, SIFT, and Polyphen-2. Structural changes in the factor VII protein were analyzed using the SPDB viewer tool. Of the 10 variants we identified, 1 was responsible for a novel missense change (c.1199G>C, p.Cys400Ser); in 2 cases we identified the c.-54G>A and c.509G>A (p.Arg170His) polymorphic variants in the 5'-upstream region of the factor VII gene and exon 6, respectively. To our knowledge, neither of these polymorphic variants has been described previously in factor VII-deficient patients. In silico predictions showed differences in binding sites for transcription factors caused by the c.-54G>A variant and a probable damaging effect of the p.Cys400Ser missense change on factor VII active conformation, leading to breaking of the Cys400-Cys428 disulfide bridge. Our findings further suggest that, independently of factor VII levels and of variants potentially affecting factor VII levels, environmental factors, e.g., trauma, could heavily influence the clinical phenotype of factor VII-deficient patients.

  11. Coagulation factor VII is regulated by androgen receptor in breast cancer.

    Science.gov (United States)

    Naderi, Ali

    2015-02-01

    Androgen receptor (AR) is widely expressed in breast cancer; however, there is limited information on the key molecular functions and gene targets of AR in this disease. In this study, gene expression data from a cohort of 52 breast cancer cell lines was analyzed to identify a network of AR co-expressed genes. A total of 300 genes, which were significantly enriched for cell cycle and metabolic functions, showed absolute correlation coefficients (|CC|) of more than 0.5 with AR expression across the dataset. In this network, a subset of 35 "AR-signature" genes were highly co-expressed with AR (|CC|>0.6) that included transcriptional regulators PATZ1, NFATC4, and SPDEF. Furthermore, gene encoding coagulation factor VII (F7) demonstrated the closest expression pattern with AR (CC=0.716) in the dataset and factor VII protein expression was significantly associated to that of AR in a cohort of 209 breast tumors. Moreover, functional studies demonstrated that AR activation results in the induction of factor VII expression at both transcript and protein levels and AR directly binds to a proximal region of F7 promoter in breast cancer cells. Importantly, AR activation in breast cancer cells induced endogenous factor VII activity to convert factor X to Xa in conjunction with tissue factor. In summary, F7 is a novel AR target gene and AR activation regulates the ectopic expression and activity of factor VII in breast cancer cells. These findings have functional implications in the pathobiology of thromboembolic events and regulation of factor VII/tissue factor signaling in breast cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Prophylaxis in congenital factor VII deficiency: indications, efficacy and safety. Results from the Seven Treatment Evaluation Registry (STER).

    Science.gov (United States)

    Napolitano, Mariasanta; Giansily-Blaizot, Muriel; Dolce, Alberto; Schved, Jean F; Auerswald, Guenter; Ingerslev, Jørgen; Bjerre, Jens; Altisent, Carmen; Charoenkwan, Pimlak; Michaels, Lisa; Chuansumrit, Ampaiwan; Di Minno, Giovanni; Caliskan, Umran; Mariani, Guglielmo

    2013-04-01

    Because of the very short half-life of factor VII, prophylaxis in factor VII deficiency is considered a difficult endeavor. The clinical efficacy and safety of prophylactic regimens, and indications for their use, were evaluated in factor VII-deficient patients in the Seven Treatment Evaluation Registry. Prophylaxis data (38 courses) were analyzed from 34 patients with severe factor VII deficiency (factor VII (24 courses), four received plasma-derived factor VII, and ten received fresh frozen plasma. Prophylactic schedules clustered into "frequent" courses (three times weekly, n=23) and "infrequent" courses (≤ 2 times weekly, n=15). Excluding courses for menorrhagia, "frequent" and "infrequent" courses produced 18/23 (78%) and 5/12 (41%) "excellent" outcomes, respectively; relative risk, 1.88; 95% confidence interval, 0.93-3.79; P=0.079. Long term prophylaxis lasted from 1 to >10 years. No thrombosis or new inhibitors occurred. In conclusion, a subset of patients with factor VII deficiency needed prophylaxis because of severe bleeding. Recombinant activated factor VII schedules based on "frequent" administrations (three times weekly) and a 90 μg/kg total weekly dose were effective. These data provide a rationale for long-term, safe prophylaxis in factor VII deficiency.

  13. Contribution of coagulation factor VII R353Q polymorphism to the ...

    African Journals Online (AJOL)

    Hanan Azzam

    2016-12-05

    Dec 5, 2016 ... Conclusion: FVII R353Q polymorphism did not contribute to an increased risk of thrombosis (arterial and venous); also .... smoking and obesity were assessed in the AMI and DVT groups as well as the control ..... perspectives.

  14. Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects.

    Science.gov (United States)

    Hsia, Chien-Hsun; Shen, Ming-Ching; Lin, Jen-Shiou; Wen, Yao-Ke; Hwang, Kai-Lin; Cham, Thau-Ming; Yang, Nae-Cherng

    2009-03-01

    Nattokinase, a serine proteinase from Bacillus subtilis, is considered to be one of the most active functional ingredients found in natto. In this study, we hypothesized that nattokinase could reduce certain factors of blood clotting and lipids that are associated with an increase risk for cardiovascular disease (CVD). Thus, an open-label, self-controlled clinical trial was conducted on subjects of the following groups: healthy volunteers (Healthy Group), patients with cardiovascular risk factors (Cardiovascular Group), and patients undergoing dialysis (Dialysis Group). All subjects ingested 2 capsules of nattokinase (2000 fibrinolysis units per capsule) daily orally for 2 months. The laboratory measurements were performed on the screening visit and, subsequently, regularly after the initiation of the study. The intent-to-treat analysis was performed on all 45 enrolled subjects. By use of mixed model analysis, a significant time effect, but not group effect, was observed in the change from baseline of fibrinogen (P = .003), factor VII (P nattokinase. No significant changes of uric acid or notable adverse events were observed in any of the subjects. In summary, this study showed that oral administration of nattokinase could be considered as a CVD nutraceutical by decreasing plasma levels of fibrinogen, factor VII, and factor VIII.

  15. Association of protein Z and factor VII gene polymorphisms with risk ...

    Indian Academy of Sciences (India)

    Protein Z (PZ) and factor (F) VII are two important factors in the clotting pathway ..... found in NCBI (http://www.ncbi.nlm.nih.gov/projects/SNP), chosen from the largest population .... power of this population-based case–control study was lim-.

  16. Synthesis and characterization of 18F-labeled active site inhibited factor VII (ASIS)

    DEFF Research Database (Denmark)

    Erlandsson, Maria; Nielsen, Carsten Haagen; Jeppesen, Troels Elmer

    2015-01-01

    Activated factor VII blocked in the active site with Phe-Phe-Arg-chloromethyl ketone (active site inhibited factor VII (ASIS)) is a 50-kDa protein that binds with high affinity to its receptor, tissue factor (TF). TF is a transmembrane glycoprotein that plays an important role in, for example......, thrombosis, metastasis, tumor growth, and tumor angiogenesis. The aim of this study was to develop an 18F-labeled ASIS derivative to assess TF expression in tumors. Active site inhibited factor VII was labeled using N-succinimidyl-4-[18F]fluorobenzoate, and the [18F]ASIS was purified on a PD-10 desalting...... column. The radiochemical yield was 25 ± 6%, the radiochemical purity was >97%, and the pseudospecific radioactivity was 35 ± 9 GBq/µmol. The binding efficacy was evaluated in pull-down experiments, which monitored the binding of unlabeled ASIS and [18F]ASIS to TF and to a specific anti-factor VII...

  17. Case report: a 70-year-old man with undiagnosed factor VII deficiency presented with acute ischemic stroke.

    Science.gov (United States)

    Ip, Hing-Lung; Chan, Anne Yin-Yan; Ng, Kit-Chung; Soo, Yannie Oi-Yan; Wong, Lawrence Ka-Sing

    2013-11-01

    Factor VII deficiency is an uncommon coagulation disorder that patient usually presents with bleeding diathesis, but thrombotic event has been reported. We report a case of unusual clinical presentation in a patient with undiagnosed factor VII deficiency who presented with acute ischemic stroke. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  18. Hormone therapy affects plasma measures of factor VII-activating protease in younger postmenopausal women

    DEFF Research Database (Denmark)

    Mathiasen, Jørn Sidelmann; Skouby, S.O.; Vitzthum, F.

    2010-01-01

    Objectives Current reviews indicate that hormone therapy (HT) has a protective role in coronary heart disease (CHD) in younger postmenopausal women, whereas HT contributes to CHD in older women Factor VII-activating protease (FSAP) is a serine protease that accumulates in unstable atherosclerotic...

  19. Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage

    DEFF Research Database (Denmark)

    Mayer, Stephan A; Brun, Nikolai C; Begtrup, Kamilla

    2008-01-01

    BACKGROUND: Intracerebral hemorrhage is the least treatable form of stroke. We performed this phase 3 trial to confirm a previous study in which recombinant activated factor VII (rFVIIa) reduced growth of the hematoma and improved survival and functional outcomes. METHODS: We randomly assigned 841...

  20. Plasma fibrinogen and factor VII concentrations in adults after prenatal exposure to famine

    NARCIS (Netherlands)

    Roseboom, T. J.; van der Meulen, J. H.; Ravelli, A. C.; Osmond, C.; Barker, D. J.; Bleker, O. P.

    2000-01-01

    To assess the effect of maternal malnutrition during different stages of gestation on plasma concentrations of fibrinogen and factor VII, we investigated 725 people, aged 50 years, born around the time of the Dutch famine 1944-5. After adjustment for sex, plasma fibrinogen concentrations differed by

  1. Factor VII-activating protease : Unraveling the release and regulation of dead cell nuclear damps

    NARCIS (Netherlands)

    Marsman, G.

    2017-01-01

    Upon inflammation, uncleared dying cells are an important source of pro-inflammatory damage-associated molecular patterns (DAMPs). Major DAMPs are histones and double-stranded DNA, which together form chromatin. Factor VII-activating protease (FSAP) is activated upon contact with dead cells, and its

  2. Recombinant coagulation factor VIIa labelled with the fac-99 mTc(CO)3-core: synthesis and in vitro evaluation of a putative new radiopharmaceutical for imaging in acute bleeding lesion

    DEFF Research Database (Denmark)

    Madsen, Jacob; Christensen, Jesper B.; Olsen, Ole H.

    2011-01-01

    Coagulation in blood is initiated when coagulation factor VII (FVII) binds to exposed TF and is activated to FVIIa, and the TF/ FVIIa complex may therefore provide a marker of vascular injury potentially applicable in diagnostic imaging of acute gastrointestinal (GI) bleeding. Methods: Recombinant...... yield and in 495% radiochemical purity. Pull down experiments showed that the biological activity (binding to tissue factor and to anti-FVII antibody) of the radiolabelled product remained intact in the formulation mixture as well as in human serum. By computer modeling analysis, two candidate sites...

  3. Tissue factor is an angiogenic-specific receptor for factor VII-targeted immunotherapy and photodynamic therapy.

    Science.gov (United States)

    Hu, Zhiwei; Cheng, Jijun; Xu, Jie; Ruf, Wolfram; Lockwood, Charles J

    2017-02-01

    Identification of target molecules specific for angiogenic vascular endothelial cells (VEC), the inner layer of pathological neovasculature, is critical for discovery and development of neovascular-targeting therapy for angiogenesis-dependent human diseases, notably cancer, macular degeneration and endometriosis, in which vascular endothelial growth factor (VEGF) plays a central pathophysiological role. Using VEGF-stimulated vascular endothelial cells (VECs) isolated from microvessels, venous and arterial blood vessels as in vitro angiogenic models and unstimulated VECs as a quiescent VEC model, we examined the expression of tissue factor (TF), a membrane-bound receptor on the angiogenic VEC models compared with quiescent VEC controls. We found that TF is specifically expressed on angiogenic VECs in a time-dependent manner in microvessels, venous and arterial vessels. TF-targeted therapeutic agents, including factor VII (fVII)-IgG1 Fc and fVII-conjugated photosensitizer, can selectively bind angiogenic VECs, but not the quiescent VECs. Moreover, fVII-targeted photodynamic therapy can selectively and completely eradicate angiogenic VECs. We conclude that TF is an angiogenic-specific receptor and the target molecule for fVII-targeted therapeutics. This study supports clinical trials of TF-targeted therapeutics for the treatment of angiogenesis-dependent diseases such as cancer, macular degeneration and endometriosis.

  4. Expression of Tissue factor in Adenocarcinoma and Squamous Cell Carcinoma of the Uterine Cervix: Implications for immunotherapy with hI-con1, a factor VII-IgGFc chimeric protein targeting tissue factor

    International Nuclear Information System (INIS)

    Cocco, Emiliano; Azodi, Masoud; Schwartz, Peter E; Rutherford, Thomas J; Pecorelli, Sergio; Lockwood, Charles J; Santin, Alessandro D; Varughese, Joyce; Buza, Natalia; Bellone, Stefania; Glasgow, Michelle; Bellone, Marta; Todeschini, Paola; Carrara, Luisa; Silasi, Dan-Arin

    2011-01-01

    Cervical cancer continues to be an important worldwide health problem for women. Up to 35% of patients who are diagnosed with and appropriately treated for cervical cancer will recur and treatment results are poor for recurrent disease. Given these sobering statistics, development of novel therapies for cervical cancer remains a high priority. We evaluated the expression of Tissue Factor (TF) in cervical cancer and the potential of hI-con1, an antibody-like-molecule targeted against TF, as a novel form of immunotherapy against multiple primary cervical carcinoma cell lines with squamous- and adenocarcinoma histology. Because TF is a transmembrane receptor for coagulation factor VII/VIIa (fVII), in this study we evaluated the in vitro expression of TF in cervical carcinoma cell lines by immunohistochemistry (IHC), real time-PCR (qRT-PCR) and flow cytometry. Sensitivity to hI-con1-dependent cell-mediated-cytotoxicity (IDCC) was evaluated in 5-hrs- 51 chromium-release-assays against cervical cancer cell lines in vitro. Cytoplasmic and/or membrane TF expression was observed in 8 out of 8 (100%) of the tumor tissues tested by IHC and in 100% (11 out of 11) of the cervical carcinoma cell lines tested by real-time-PCR and flow cytometry but not in normal cervical keratinocytes (p = 0.0023 qRT-PCR; p = 0.0042 flow cytometry). All primary cervical cancer cell lines tested overexpressing TF, regardless of their histology, were highly sensitive to IDCC (mean killing ± SD, 56.2% ± 15.9%, range, 32.4%-76.9%, p < 0.001), while negligible cytotoxicity was seen in the absence of hI-con1 or in the presence of rituximab-control-antibody. Low doses of interleukin-2 further increased the cytotoxic effect induced by hI-con1 (p = 0.025) while human serum did not significantly decrease IDCC against cervical cancer cell lines (p = 0.597). TF is highly expressed in squamous and adenocarcinoma of the uterine cervix. hI-con1 induces strong cytotoxicity against primary cervical cancer cell

  5. Prophylactic Level VII Nodal Dissection as a Prognostic Factor in Papillary Thyroid Carcinoma: a Pilot Study of 27 Patients.

    Science.gov (United States)

    Fayek, Ihab Samy

    2015-01-01

    Prognostic value of prophylactic level VII nodal dissection in papillary thyroid carcinoma has been highlighted. A total of 27 patients with papillary thyroid carcinoma with N0 neck underwent total thyroidectomy with level VI and VII nodal dissection through same collar neck incision. Multicentricity, bilaterality, extrathyroidal extension, level VI and VII lymph nodes were studied as separate and independent prognostic factors for DFS at 24 months. 21 females and 6 males with a mean age of 34.6 years old, tumor size was 5-24 mm. (mean 12.4 mm.), multicentricity in 11 patients 2-4 foci (mean 2.7), bilaterality in 8 patients and extrathyroidal extension in 8 patients. Dissected level VI LNs 2-8 (mean 5 LNs) and level VII LNs 1-4 (mean 1.9). Metastatic level VI LNs 0-3 (mean 1) and level VII LNs 0-2 (mean 0.5). Follow-up from 6-51 months (mean 25.6) with 7 patients showed recurrence (3 local and 4 distant). Cumulative DFS at 24 months was 87.8% and was significantly affected in relation to bilaterality (p-valueVII positive ((p-valueVII nodal involvement. Level VII prophylactic nodal dissection is an important and integral prognostic factor in papillary thyroid carcinoma. A larger multicenter study is crucial to reach a satisfactory conclusion about the necessity and safety of this approach.

  6. Synthesis and characterization of (18)F-labeled active site inhibited factor VII (ASIS).

    Science.gov (United States)

    Erlandsson, Maria; Nielsen, Carsten H; Jeppesen, Troels E; Kristensen, Jesper B; Petersen, Lars C; Madsen, Jacob; Kjaer, Andreas

    2015-05-15

    Activated factor VII blocked in the active site with Phe-Phe-Arg-chloromethyl ketone (active site inhibited factor VII (ASIS)) is a 50-kDa protein that binds with high affinity to its receptor, tissue factor (TF). TF is a transmembrane glycoprotein that plays an important role in, for example, thrombosis, metastasis, tumor growth, and tumor angiogenesis. The aim of this study was to develop an (18)F-labeled ASIS derivative to assess TF expression in tumors. Active site inhibited factor VII was labeled using N-succinimidyl-4-[(18)F]fluorobenzoate, and the [(18)F]ASIS was purified on a PD-10 desalting column. The radiochemical yield was 25 ± 6%, the radiochemical purity was >97%, and the pseudospecific radioactivity was 35 ± 9 GBq/µmol. The binding efficacy was evaluated in pull-down experiments, which monitored the binding of unlabeled ASIS and [(18)F]ASIS to TF and to a specific anti-factor VII antibody (F1A2-mAb). No significant difference in binding efficacy between [(18)F]ASIS and ASIS could be detected. Furthermore, [(18)F]ASIS was relatively stable in vitro and in vivo in mice. In conclusion, [(18)F]ASIS has for the first time been successfully synthesized as a possible positron emission tomography tracer to image TF expression levels. In vivo positron emission tomography studies to evaluate the full potential of [(18)F]ASIS are in progress. Copyright © 2015 John Wiley & Sons, Ltd.

  7. Heparanase enhances the generation of activated factor X in the presence of tissue factor and activated factor VII.

    Science.gov (United States)

    Nadir, Yona; Brenner, Benjamin; Fux, Liat; Shafat, Itay; Attias, Judith; Vlodavsky, Israel

    2010-11-01

    Heparanase is an endo-β-D-glucuronidase dominantly involved in tumor metastasis and angiogenesis. Recently, we demonstrated that heparanase is involved in the regulation of the hemostatic system. Our hypothesis was that heparanase is directly involved in activation of the coagulation cascade. Activated factor X and thrombin were studied using chromogenic assays, immunoblotting and thromboelastography. Heparanase levels were measured by enzyme-linked immunosorbent assay. A potential direct interaction between tissue factor and heparanase was studied by co-immunoprecipitation and far-western assays. Interestingly, addition of heparanase to tissue factor and activated factor VII resulted in a 3- to 4-fold increase in activation of the coagulation cascade as shown by increased activated factor X and thrombin production. Culture medium of human embryonic kidney 293 cells over-expressing heparanase and its derivatives increased activated factor X levels in a non-enzymatic manner. When heparanase was added to pooled normal plasma, a 7- to 8-fold increase in activated factor X level was observed. Subsequently, we searched for clinical data supporting this newly identified role of heparanase. Plasma samples from 35 patients with acute leukemia at presentation and 20 healthy donors were studied for heparanase and activated factor X levels. A strong positive correlation was found between plasma heparanase and activated factor X levels (r=0.735, P=0.001). Unfractionated heparin and an inhibitor of activated factor X abolished the effect of heparanase, while tissue factor pathway inhibitor and tissue factor pathway inhibitor-2 only attenuated the procoagulant effect. Using co-immunoprecipitation and far-western analyses it was shown that heparanase interacts directly with tissue factor. Overall, our results support the notion that heparanase is a potential modulator of blood hemostasis, and suggest a novel mechanism by which heparanase increases the generation of activated

  8. Engineering the substrate and inhibitor specificities of human coagulation Factor VIIa

    DEFF Research Database (Denmark)

    Larsen, Katrine S; Østergaard, Henrik; Bjelke, Jais R

    2007-01-01

    The remarkably high specificity of the coagulation proteases towards macromolecular substrates is provided by numerous interactions involving the catalytic groove and remote exosites. For FVIIa [activated FVII (Factor VII)], the principal initiator of coagulation via the extrinsic pathway, several...... for FVIIa by marked changes in primary substrate specificity and decreased rates of antithrombin III inhibition. Interestingly, these changes do not necessarily coincide with an altered ability to activate Factor X, demonstrating that inhibitor and macromolecular substrate selectivity may be engineered...

  9. Activation of 125I-Factor IX and 125I-Factor X: Effect of tissue factor and Factor VII, Factor Xsub(a) and thrombin

    International Nuclear Information System (INIS)

    Oesterud, B.; Rapaport, S.I.

    Activation of Factor IX and Factor X was studied by adding 125 I-Factor IX or 125 I-Factor X to reaction mixtures and quantitating cleavage products by reduced sodium dodecylsulfate gel electrophoresis. Thrombin failed to activate Factors IX or X; Factor Xsub(a) produced insignificant amounts of cleavage products of both factors. In contrast, the reaction product of tissue factor and Factor VII cleaved large amounts of both Factor IX and Factor X in purified systems and in plasma. In incubation mixtures of plasma containing added 125 I-Factor IX or 125 I-Factor X, tissue factor and Ca 2+ ions, the percentage of total radioactivity in the heavy chain peak of 125 I-IXsub(a) and the heavy chain of 125 I-Xsub(a) increased at a similar rate. When the tissue factor was diluted, similar curves were obtained for percent cleavage of 125 I-Factor IX and percent cleavage of 125 I-Factor X plotted against tissue factor concentration. These findings support the hypothesis that activation of Factor IX by the tissue factor-Factor VII reaction product represents a physiologically significant step in normal haemostasis. (author)

  10. Monocytes can be induced by lipopolysaccharide-triggered T lymphocytes to express functional factor VII/VIIa protease activity

    OpenAIRE

    1984-01-01

    In the present study we demonstrate that human monocytes can be induced by the model stimulus, lipopolysaccharide (LPS), to produce and assemble on their surface functional Factor VII/VIIa. This protease was not induced in relatively purified monocytes alone following exposure to LPS; but was induced in the presence of Leu-3a positive helper/inducer T cells. The Factor VII/VIIa protease activity represented 35-40% of the potential initiating activity for the extrinsic coagulation pathway and ...

  11. Factor VII and protein C are phosphatidic acid-binding proteins.

    Science.gov (United States)

    Tavoosi, Narjes; Smith, Stephanie A; Davis-Harrison, Rebecca L; Morrissey, James H

    2013-08-20

    Seven proteins in the human blood clotting cascade bind, via their GLA (γ-carboxyglutamate-rich) domains, to membranes containing exposed phosphatidylserine (PS), although with membrane binding affinities that vary by 3 orders of magnitude. Here we employed nanodiscs of defined phospholipid composition to quantify the phospholipid binding specificities of these seven clotting proteins. All bound preferentially to nanobilayers in which PS headgroups contained l-serine versus d-serine. Surprisingly, however, nanobilayers containing phosphatidic acid (PA) bound substantially more of two of these proteins, factor VIIa and activated protein C, than did equivalent bilayers containing PS. Consistent with this finding, liposomes containing PA supported higher proteolytic activity by factor VIIa and activated protein C toward their natural substrates (factors X and Va, respectively) than did PS-containing liposomes. Moreover, treating activated human platelets with phospholipase D enhanced the rates of factor X activation by factor VIIa in the presence of soluble tissue factor. We hypothesize that factor VII and protein C bind preferentially to the monoester phosphate of PA because of its accessibility and higher negative charge compared with the diester phosphates of most other phospholipids. We further found that phosphatidylinositol 4-phosphate, which contains a monoester phosphate attached to its myo-inositol headgroup, also supported enhanced enzymatic activity of factor VIIa and activated protein C. We conclude that factor VII and protein C bind preferentially to monoester phosphates, which may have implications for the function of these proteases in vivo.

  12. Synthesis, purification, and characterization of an Arg152 → Glu site-directed mutant of recombinant human blood clotting factor VII

    International Nuclear Information System (INIS)

    Wildgoose, P.; Kisiel, W.; Berkner, K.L.

    1990-01-01

    Coagulation factor VII circulates in blood as a single-chain zymogen of a serine protease and is converted to its activated two-chain form, factor VIIa, by cleavage of an internal peptide bond located at Arg 152 -Ile 153 . Previous studies using serine protease active-site inhibitors suggest that zymogen factor VII may possess sufficient proteolytic activity to initiate the extrinsic pathway of blood coagulation. In order to assess the putative intrinsic proteolytic activity of single-chain factor VII, the authors have constructed a site-specific mutant of recombinant human factor VII in which arginine-152 has been replaced with a glutamic acid residue. Mutant factor VII was purified in a single step from culture supernatants of baby hamster kidney cells transfected with a plasmid containing the sequence for Arg 152 → Glu factor VII using a calcium-dependent, murine anti-factor VII monoclonal antibody column. The clotting activity of mutant factor VII was completely inhibited following incubation with dansyl-Glu-Gly-Arg chloromethyl ketone, suggesting that the apparent clotting activity of mutant factor VII was due to a contaminating serine protease. Immunoblots of mutant factor VII with human factor IXa revealed no cleavage, whereas incubation of mutant factor VII with human factor Xa resulted in cleavage of mutant factor VII and the formation of a lower molecular weight degradation product migrating at M r ∼40 000. The results are consistent with the proposal that zymogen factor VII possesses no intrinsic proteolytic activity toward factor X or factor IX

  13. Synthesis, purification, and characterization of an Arg sub 152 yields Glu site-directed mutant of recombinant human blood clotting factor VII

    Energy Technology Data Exchange (ETDEWEB)

    Wildgoose, P.; Kisiel, W. (Univ. of New Mexico, Albuquerque (USA)); Berkner, K.L. (ZymoGenetics, Inc., Seattle, WA (USA))

    1990-04-03

    Coagulation factor VII circulates in blood as a single-chain zymogen of a serine protease and is converted to its activated two-chain form, factor VIIa, by cleavage of an internal peptide bond located at Arg{sub 152}-Ile{sub 153}. Previous studies using serine protease active-site inhibitors suggest that zymogen factor VII may possess sufficient proteolytic activity to initiate the extrinsic pathway of blood coagulation. In order to assess the putative intrinsic proteolytic activity of single-chain factor VII, the authors have constructed a site-specific mutant of recombinant human factor VII in which arginine-152 has been replaced with a glutamic acid residue. Mutant factor VII was purified in a single step from culture supernatants of baby hamster kidney cells transfected with a plasmid containing the sequence for Arg{sub 152} {yields} Glu factor VII using a calcium-dependent, murine anti-factor VII monoclonal antibody column. The clotting activity of mutant factor VII was completely inhibited following incubation with dansyl-Glu-Gly-Arg chloromethyl ketone, suggesting that the apparent clotting activity of mutant factor VII was due to a contaminating serine protease. Immunoblots of mutant factor VII with human factor IXa revealed no cleavage, whereas incubation of mutant factor VII with human factor Xa resulted in cleavage of mutant factor VII and the formation of a lower molecular weight degradation product migrating at M{sup r}{approx}40 000. The results are consistent with the proposal that zymogen factor VII possesses no intrinsic proteolytic activity toward factor X or factor IX.

  14. A hypothesis: factor VII governs clot formation, tissue repair and apoptosis.

    Science.gov (United States)

    Coleman, Lewis S

    2007-01-01

    A hypothesis: thrombin is a "Universal Enzyme of Energy Transduction" that employs ATP energy in flowing blood to activate biochemical reactions and cell effects in both hemostasis and tissue repair. All cells possess PAR-1 (thrombin) receptors and are affected by thrombin elevations, and thrombin effects on individual cell types are determined by their unique complement of PAR-1 receptors. Disruption of the vascular endothelium (VE) activates a tissue repair mechanism (TRM) consisting of the VE, tissue factor (TF), and circulating Factors VII, IX and X that governs localized thrombin elevations to activate clot formation and cellular effects that repair tissue damage. The culmination of the repair process occurs with the restoration of the VE followed by declines in thrombin production that causes Apoptosis ("programmed cell death") in wound-healing fibroblasts, which functions as a mechanism to draw wound edges together. The location and magnitude of TRM activity governs the location and magnitude of Factor VIII activity and clot formation, but the large size of Factor VIII prevents it from penetrating the clot formed by its activity, so that its effects are self-limiting. Factors VII, IX and X function primarily as tissue repair enzymes, while Factor VIII and Factor XIII are the only serine protease enzymes in the "Coagulation Cascade" that are exclusively associated with hemostasis.

  15. One amino acid in mouse activated factor VII defines its endothelial protein C receptor (EPCR) binding and modulates its EPCR-dependent hemostatic activity in vivo.

    Science.gov (United States)

    Pavani, G; Zintner, S M; Ivanciu, L; Small, J C; Stafford, K A; Szeto, J H; Margaritis, P

    2017-03-01

    Essentials The lack of factor (F) VIIa-endothelial protein C receptor (EPCR) binding in mice is unresolved. A single substitution of Leu4 to Phe in mouse FVIIa (mFVIIa) enables its interaction with EPCR. mFVIIa with a Phe4 shows EPCR binding-dependent enhanced hemostatic function in vivo vs. mFVIIa. Defining the FVIIa-EPCR interaction in mice allows for further investigating its biology in vivo. Background Human activated factor VII (hFVIIa), which is used in hemophilia treatment, binds to the endothelial protein C (PC) receptor (EPCR) with unclear hemostatic consequences. Interestingly, mice lack the activated FVII (FVIIa)-EPCR interaction. Therefore, to investigate the hemostatic consequences of this interaction in hemophilia, we previously engineered a mouse FVIIa (mFVIIa) molecule that bound mouse EPCR (mEPCR) by using three substitutions from mouse PC (mPC), i.e. Leu4→Phe, Leu8→Met, and Trp9→Arg. The resulting molecule, mFVIIa-FMR, modeled the EPCR-binding properties of hFVIIa and showed enhanced hemostatic capacity in hemophilic mice versus mFVIIa. These data implied a role of EPCR in the action of hFVIIa in hemophilia treatment. However, the substitutions in mFVIIa-FMR only broadly defined the sequence determinants for its mEPCR interaction and enhanced function in vivo. Objectives To determine the individual contributions of mPC Phe4, Met8 and Arg9 to the in vitro/in vivo properties of mFVIIa-FMR. Methods The mEPCR-binding properties of single amino acid variants of mFVIIa or mPC at position 4, 8 or 9 were investigated. Results and conclusions Phe4 in mFVIIa or mPC was solely critical for interaction with mEPCR. In hemophilic mice, administration of mFVIIa harboring a Phe4 resulted in a 1.9-2.5-fold increased hemostatic capacity versus mFVIIa that was EPCR binding-dependent. This recapitulated previous observations made with triple-mutant mFVIIa-FMR. As Leu8 is crucial for hFVIIa-EPCR binding, we describe the sequence divergence of this interaction in

  16. Association of ACE and FACTOR VII gene variability with the risk of coronary heart disease in north Indian population.

    Science.gov (United States)

    Sobti, R C; Maithil, Nishi; Thakur, Hitender; Sharma, Yashpaul; Talwar, K K

    2010-08-01

    The angiotensin converting enzyme (ACE) is a key factor in the production of angiotensin II and in the degradation of bradykinin. Chronic exposure to high levels of circulating and tissue ACE predispose to vascular wall thickening and atherosclerosis. Factor VII (FACTOR VII) is the first enzyme in the extrinsic pathway of the blood coagulation system and plays a key role in hemostasis; it also contributes to the occurrence of thrombotic events. In this study, we have examined the association of ACE and FACTOR VII gene in coronary heart disease patients (n = 300) and their age-matched controls (n = 300). Genotyping was done by PCR-RFLP method. No significant difference was observed in the distribution of I/D genotypes of ACE between cases and controls. In case of FACTOR VII R353Q polymorphism, there was not much difference in the distribution of alleles. AA genotype had protective effect for CHD (OR 0.56, 95% CI 0.37-0.83, P = 0.001). In case of FACTOR VII VNTR, there was difference in the distribution of alleles, H6 (73.5) and H7 (25.5) in cases, and H6 (70.5) and H7 (30.5) in controls. H6H7 and H7H7 genotypes had a protective effect for CHD with OR 0.27, 95% CI 0.18-0.41, P FACTOR VII R353Q and H6H7 and H7H7 genotypes of FACTOR VII VNTR showed protective effect for CHD.

  17. Common polymorphisms and cardiovascular factors in patients with myocardial infarction of Costa Rica

    Directory of Open Access Journals (Sweden)

    Lizbeth Salazar-Sánchez

    2006-03-01

    Full Text Available Eight common polymorphisms of known myocardial infarction (MIrisk factors (factor V Leiden (FVL, factor V HR2 (FVHR2,factor II 20210G>A (FII,factor VII IVS7 (FVII IVS7,factor VII Arg353Gln (FVII, factor XIII Val34Leu (FXIII,Methylenetetrahydrofolate reductase C677T (MTHFR, Angiotensin Converting Enzyme (ACEand environmental risk factors were analyzed in a MI patients of Costa Rica.This case-control study included 186 MI subjects,95 of them Se estudiaron ocho polimorfismos comunes asociados como factores de riesgo para el infarto al miocardio (IM:factor V Leiden (FVL,factor VHR2 (FVHR2, factor II 20210G>A (FII,factor VII IVS7 (FVII IVS7, factor VIIArg353Gln (FVII,factor XIIIVal34Leu (FXIII, metilentetrahidrofolato reductase C677T (MTHFR, enzima convertidora de la angiotensina (ACE y factores ambientales de riesgo,en pacientes costarricenses.Este es un estudio de casos y controles,donde participan 186 pacientes,95 de ellos con edades <45 años y 201 sujetos controles.Se utilizó la técnica de reacción en cadena de la polimerasa (PCRy por medio de entrevistas personales se recolectó información epidemiológica adicional.Se encontró que la hipercolesterolemia y el fumado estan asociados como factores de riesgo en los pacientes jóvenes.Niveles elevados del fibrinógeno fueron detectados como un factor de riesgo importante y se observo interacción entre fumado y estos valores aumentados de fibrinógeno. El genotipo 34LeuLeu del FXIII presentó un efecto protector significante mientras que los otros polimorfimos estudiados no mostraron diferencia estadísticamente significativa entre los casos y controles. Los polimorfismos del FVII y FXIII demostraron interación con el fibrinógeno,según el análisis estadístico aplicado. Se evidencia, la interación entre factores de riesgo común y ciertos polimorfismos (FVII;FXIIIen la patogénesis del IM.Este es uno de los primeros informes sobre estos marcadores moleculares y su asociación con IM en

  18. Administration of recombinant activated factor VII in the intensive care unit after complex cardiovascular surgery: clinical and economic outcomes.

    Science.gov (United States)

    Uber, Walter E; Toole, John M; Stroud, Martha R; Haney, Jason S; Lazarchick, John; Crawford, Fred A; Ikonomidis, John S

    2011-06-01

    Refractory bleeding after complex cardiovascular surgery often leads to increased length of stay, cost, morbidity, and mortality. Recombinant activated factor VII administered in the intensive care unit can reduce bleeding, transfusion, and surgical re-exploration. We retrospectively compared factor VII administration in the intensive care unit with reoperation for refractory bleeding after complex cardiovascular surgery. From 1501 patients who underwent cardiovascular procedures between December 2003 and September 2007, 415 high-risk patients were identified. From this cohort, 24 patients were divided into 2 groups based on whether they either received factor VII in the intensive care unit (n = 12) or underwent reoperation (n = 12) for refractory bleeding. Preoperative and postoperative data were collected to compare efficacy, safety, and economic outcomes. In-hospital survival for both groups was 100%. Factor VII was comparable with reoperation in achieving hemostasis, with both groups demonstrating decreases in chest tube output and need for blood products. Freedom from reoperation was achieved in 75% of patients receiving factor VII, whereas reoperation was effective in achieving hemostasis alone in 83.3% of patients. Prothrombin time, international normalized ratio, and median operating room time were significantly less (P factor VII. Both groups had no statistically significant differences in other efficacy, safety, or economic outcomes. Factor VII administration in the intensive care unit appears comparable with reoperation for refractory bleeding after complex cardiovascular surgical procedures and might represent an alternative to reoperation in selected patients. Future prospective, randomized controlled trials might further define its role. Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  19. Effective treatment of chemoresistant breast cancer in vitro and in vivo by a factor VII-targeted photodynamic therapy.

    Science.gov (United States)

    Duanmu, J; Cheng, J; Xu, J; Booth, C J; Hu, Z

    2011-04-26

    The purpose of this study was to test a novel, dual tumour vascular endothelial cell (VEC)- and tumour cell-targeting factor VII-targeted Sn(IV) chlorin e6 photodynamic therapy (fVII-tPDT) by targeting a receptor tissue factor (TF) as an alternative treatment for chemoresistant breast cancer using a multidrug resistant (MDR) breast cancer line MCF-7/MDR. The TF expression by the MCF-7/MDR breast cancer cells and tumour VECs in MCF-7/MDR tumours from mice was determined separately by flow cytometry and immunohistochemistry using anti-human or anti-murine TF antibodies. The efficacy of fVII-tPDT was tested in vitro and in vivo and was compared with non-targeted PDT for treatment of chemoresistant breast cancer. The in vitro efficacy was determined by a non-clonogenic assay using crystal violet staining for monolayers, and apoptosis and necrosis were assayed to elucidate the underlying mechanisms. The in vivo efficacy of fVII-tPDT was determined in a nude mouse model of subcutaneous MCF-7/MDR tumour xenograft by measuring tumour volume. To our knowledge, this is the first presentation showing that TF was expressed on tumour VECs in chemoresistant breast tumours from mice. The in vitro efficacy of fVII-tPDT was 12-fold stronger than that of ntPDT for MCF-7/MDR cancer cells, and the mechanism of action involved induction of apoptosis and necrosis. Moreover, fVII-tPDT was effective and safe for the treatment of chemoresistant breast tumours in the nude mouse model. We conclude that fVII-tPDT is effective and safe for the treatment of chemoresistant breast cancer, presumably by simultaneously targeting both the tumour neovasculature and chemoresistant cancer cells. Thus, this dual-targeting fVII-tPDT could also have therapeutic potential for the treatment of other chemoresistant cancers.

  20. Molecular cloning, characterization and expression analysis of coagulation factor VII gene in grass carp (Ctenopharyngodon idella).

    Science.gov (United States)

    Liu, Qiaolin; Xu, Baohong; Xiao, Tiaoyi; Su, Jianming; Zhong, Lei

    2013-08-01

    Coagulation factor VII has been studied in several species but, to date, not in grass carp (Ctenopharyngodon idella), a commercially important freshwater fish found in China. In this study, the full-length cDNA of grass carp coagulation factor VII (GcCFVII) was cloned using a RACE-Ready cDNA Kit, grass carp were challenged with a hemorrhagic virus, and temporal expression profiles of GcCFVII in the thymus, gills, liver, spleen, and head kidney were examined at 0 h, 24 h, 48 h, 72 h, 96 h, and 138 h using fluorescence quantitative PCR. The results showed the 1480 bp GcCFVII to contain three conservative motifs: Gla, EGF-CA, and Tryp-SPc, similar to other species. Phylogenetic analysis showed the evolution of GcCFVII gene to be consistent with the evolution of the species. After viral challenge, GcCFVII expression in five tissues of grass carp showed different patterns of fluctuation. These results provide a solid basis for further investigation of GcCFVII and its relationship with grass carp hemorrhage. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Beneficial nutritional properties of olive oil: implications for postprandial lipoproteins and factor VII.

    Science.gov (United States)

    Williams, C M

    2001-08-01

    Previous research concerning protective cardiovascular properties of olive oil has focussed on the beneficial consequences on blood cholesterol levels of substituting dietary saturated fatty acids with oleic acid. Despite evidence implicating raised circulating triglycerides in the postprandial state in the pathogenesis of atherosclerosis and thrombosis, little research had been conducted to investigate effects of monounsaturated fatty acids on postprandial events. In a case control study of southern (n = 30) versus northern European (n = 30) men, significant differences in postprandial triglyceride and apolipoprotein (apo) B-48 response were observed, with evidence of attenuated and potentially beneficial responses in the Southern Europeans. In a randomised controlled study manufactured foods typical of the Northern European food culture, were used to deliver diets rich in either saturated or monounsaturated fatty acids (from olive oil). During the period of the olive oil enriched diet, LDL-cholesterol levels were 15% lower (p factor VII, as well as the production of factor VII antigen, was reduced on the olive oil diet. The study demonstrated significant improvements in biomarkers for cardiovascular disease in subjects osed to high olive oil diets (Southern Europeans) or transferred to such diets in the short term (Northern European volunteers). The study produced novel findings with respect to potential mechanisms by which diets high in monounsaturated fatty acids (MUFA) can reduce population risk of cardiovascular disease.

  2. Nucleotide sequence of the gene coding for human factor VII, a vitamin K-dependent protein participating in blood coagulation

    International Nuclear Information System (INIS)

    O'Hara, P.J.; Grant, F.J.; Haldeman, B.A.; Gray, C.L.; Insley, M.Y.; Hagen, F.S.; Murray, M.J.

    1987-01-01

    Activated factor VII (factor VIIa) is a vitamin K-dependent plasma serine protease that participates in a cascade of reactions leading to the coagulation of blood. Two overlapping genomic clones containing sequences encoding human factor VII were isolated and characterized. The complete sequence of the gene was determined and found to span about 12.8 kilobases. The mRNA for factor VII as demonstrated by cDNA cloning is polyadenylylated at multiple sites but contains only one AAUAAA poly(A) signal sequence. The mRNA can undergo alternative splicing, forming one transcript containing eight segments as exons and another with an additional exon that encodes a larger prepro leader sequence. The latter transcript has no known counterpart in the other vitamin K-dependent proteins. The positions of the introns with respect to the amino acid sequence encoded by the eight essential exons of factor VII are the same as those present in factor IX, factor X, protein C, and the first three exons of prothrombin. These exons code for domains generally conserved among members of this gene family. The comparable introns in these genes, however, are dissimilar with respect to size and sequence, with the exception of intron C in factor VII and protein C. The gene for factor VII also contains five regions made up of tandem repeats of oligonucleotide monomer elements. More than a quarter of the intron sequences and more than a third of the 3' untranslated portion of the mRNA transcript consist of these minisatellite tandem repeats

  3. Model of a ternary complex between activated factor VII, tissue factor and factor IX.

    Science.gov (United States)

    Chen, Shu-wen W; Pellequer, Jean-Luc; Schved, Jean-François; Giansily-Blaizot, Muriel

    2002-07-01

    Upon binding to tissue factor, FVIIa triggers coagulation by activating vitamin K-dependent zymogens, factor IX (FIX) and factor X (FX). To understand recognition mechanisms in the initiation step of the coagulation cascade, we present a three-dimensional model of the ternary complex between FVIIa:TF:FIX. This model was built using a full-space search algorithm in combination with computational graphics. With the known crystallographic complex FVIIa:TF kept fixed, the FIX docking was performed first with FIX Gla-EGF1 domains, followed by the FIX protease/EGF2 domains. Because the FIXa crystal structure lacks electron density for the Gla domain, we constructed a chimeric FIX molecule that contains the Gla-EGF1 domains of FVIIa and the EGF2-protease domains of FIXa. The FVIIa:TF:FIX complex has been extensively challenged against experimental data including site-directed mutagenesis, inhibitory peptide data, haemophilia B database mutations, inhibitor antibodies and a novel exosite binding inhibitor peptide. This FVIIa:TF:FIX complex provides a powerful tool to study the regulation of FVIIa production and presents new avenues for developing therapeutic inhibitory compounds of FVIIa:TF:substrate complex.

  4. Treatment of massive gastrointestinal bleeding occurred during autologous stem cell transplantation with recombinant activated factor VII and octreotide

    Directory of Open Access Journals (Sweden)

    Erman Atas

    2015-01-01

    Full Text Available After hematopoietic stem cell transplantation (HSCT, patients may suffer from bleeding. One of the bleeding type is gastrointestinal (GI which has serious morbidity and mortality in children with limited treatment options. Herein, we presented a child with upper GI bleeding post autologous HSCT controlled successfully by using recombinant activated factor VII (rFVIIa and octreotide infusion.

  5. A case presenting concurrence of Marfan syndrome, Basedow's disease and Arg353Gln polymorphism-related factor VII deficiency.

    Science.gov (United States)

    Tanaka, Kotoko; Seino, Yoshihiko; Inokuchi, Koiti; Ohmura, Kazuko; Kobayashi, Yoshinori; Takano, Teruo

    2005-02-15

    We report the case of a 48-year-old Japanese man who suffered from Marfan syndrome with severe aortic regurgitation, mitral regurgitation and rapid atrial fibrillation, which were aggravated by hyperdynamic circulatory conditions associated with coexistent Basedow's disease. Furthermore, concurrence of Arg353Gln polymorphism-related factor VII deficiency was discovered at the preoperative assessments. Both of his two brothers suffered from Marfan syndrome; however they had no findings of Arg353Glu polymorphism-related factor VII deficiency or Basedow's disease. After normalization of thyroid function, he had successfully the operations of Bentall procedure: a composite prosthetic graft: replacement of both the ascending aorta and aortic valve, and mitral valve annuloplasty. No specific therapy such as fresh frozen plasma or factor VII replacement therapy was required. He completely returned to his business work 6 weeks after the operation. Concurrence of Marfan syndrome and factor VII deficiency induced by two-hit genomic abnormalities and furthermore Basedow's disease, which significantly compromised the pathophysiological condition of Marfan syndrome, is extremely rare.

  6. Evidence supporting the use of recombinant activated factor VII in congenital bleeding disorders

    Directory of Open Access Journals (Sweden)

    Pär I Johansson

    2010-06-01

    Full Text Available Pär I Johansson, Sisse R OstrowskiCapital Region Blood Bank, Section for Transfusion Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, DenmarkBackground: Recombinant activated factor VII (rFVIIa, NovoSeven® was introduced in 1996 for the treatment of hemophilic patients with antibodies against coagulation factor VIII or IX.Objective: To review the evidence supporting the use of rFVIIa for the treatment of patients with congenital bleeding disorders.Patients and methods: English-language databases were searched in September 2009 for reports of randomized controlled trials (RCTs evaluating the ability of rFVIIa to restore hemostasis in patients with congenital bleeding disorders.Results: Eight RCTs involving 256 hemophilic patients with antibodies against coagulation factors, also known as inhibitors, were identified. The evidence supporting the use of rFVIIa in these patients was weak with regard to dose, clinical setting, mode of administration, efficacy, and adverse events, given the limited sample size of each RCT and the heterogeneity of the studies.Conclusion: The authors suggest that rFVIIa therapy in hemophilic patients with inhibitors should be based on the individual’s ability to generate thrombin and form a clot, and not on the patient’s weight alone. Therefore, assays for thrombin generation, such as whole-blood thromboelastography, have the potential to significantly improve the treatment of these patients.Keywords: hemophilia, inhibitors, coagulation factor VIII, coagulation factor IX, rFVIIa, NovoSeven, FEIBA, hemostasis, RCT

  7. Upregulation of the coagulation factor VII gene during glucose deprivation is mediated by activating transcription factor 4.

    Science.gov (United States)

    Cronin, Katherine R; Mangan, Thomas P; Carew, Josephine A

    2012-01-01

    Constitutive production of blood coagulation proteins by hepatocytes is necessary for hemostasis. Stressful conditions trigger adaptive cellular responses and delay processing of most proteins, potentially affecting plasma levels of proteins secreted exclusively by hepatocytes. We examined the effect of glucose deprivation on expression of coagulation proteins by the human hepatoma cell line, HepG2. Expression of coagulation factor VII, which is required for initiation of blood coagulation, was elevated by glucose deprivation, while expression of other coagulation proteins decreased. Realtime PCR and ELISA demonstrated that the relative percentage expression +/- SD of steady-state F7 mRNA and secreted factor VII antigen were significantly increased (from 100+/-15% to 188+/-27% and 100+/-8.8% to 176.3+/-17.3% respectively, pfactor ATF4 and of additional stress-responsive genes. Small interfering RNAs directed against ATF4 potently reduced basal F7 expression, and prevented F7 upregulation by glucose deprivation. The response of the endogenous F7 gene was replicated in reporter gene assays, which further indicated that ATF4 effects were mediated via interaction with an amino acid response element in the F7 promoter. Our data indicated that glucose deprivation enhanced F7 expression in a mechanism reliant on prior ATF4 upregulation primarily due to increased transcription from the ATF4 gene. Of five coagulation protein genes examined, only F7 was upregulated, suggesting that its functions may be important in a systemic response to glucose deprivation stress.

  8. Recombinant activated factor VII: its mechanism of action and role in the control of hemorrhage.

    Science.gov (United States)

    Allen, Geoffrey A; Hoffman, Maureane; Roberts, Harold R; Monroe, Dougald M

    2002-12-01

    Recombinant activated factor VII (rFVIIa) has proven both safe and efficacious in the treatment of bleeding episodes in patients with hemophilia A or B who have developed inhibitors. More recently, a growing number of reports suggests that rFVIIa may also have indications for the treatment of bleeding in patients with other hemostatic disorders, including qualitative and quantitative platelet defects, factor deficiencies other than hemophilia, and in otherwise healthy patients with uncontrollable hemorrhage following surgery or trauma. We have attempted to reconcile the various proposed mechanisms of action of rFVIIa with its apparent efficacy in such diverse clinical settings. A review of the literature was performed to determine those clinical scenarios in which rFVIIa appears to have been effective in controlling associated hemorrhage. Findings from our group and others have demonstrated that rFVIIa is able to directly activate factor X and increase thrombin production on the surface of activated platelets in the absence of factor VIII or IX, as well as to improve thrombin generation in thrombocytopenia, and to yield a fibrin dot more resistant to fibrinolysis in vitro. Through these primary mechanisms, we believe that rFVIIa may be able to compensate for a variety of defects in hemostasis and merits further investigation as a general therapeutic for uncontrollable hemorrhage.

  9. Evidence for an Overlapping Role of CLOCK and NPAS2 Transcription Factors in Liver Circadian Oscillators▿

    Science.gov (United States)

    Bertolucci, Cristiano; Cavallari, Nicola; Colognesi, Ilaria; Aguzzi, Jacopo; Chen, Zheng; Caruso, Pierpaolo; Foá, Augusto; Tosini, Gianluca; Bernardi, Francesco; Pinotti, Mirko

    2008-01-01

    The mechanisms underlying the circadian control of gene expression in peripheral tissues and influencing many biological pathways are poorly defined. Factor VII (FVII), the protease triggering blood coagulation, represents a valuable model to address this issue in liver since its plasma levels oscillate in a circadian manner and its promoter contains E-boxes, which are putative DNA-binding sites for CLOCK-BMAL1 and NPAS2-BMAL1 heterodimers and hallmarks of circadian regulation. The peaks of FVII mRNA levels in livers of wild-type mice preceded those in plasma, indicating a transcriptional regulation, and were abolished in Clock−/−; Npas2−/− mice, thus demonstrating a role for CLOCK and NPAS2 circadian transcription factors. The investigation of Npas2−/− and ClockΔ19/Δ19 mice, which express functionally defective heterodimers, revealed robust rhythms of FVII expression in both animal models, suggesting a redundant role for NPAS2 and CLOCK. The molecular bases of these observations were established through reporter gene assays. FVII transactivation activities of the NPAS2-BMAL1 and CLOCK-BMAL1 heterodimers were (i) comparable (a fourfold increase), (ii) dampened by the negative circadian regulators PER2 and CRY1, and (iii) abolished upon E-box mutagenesis. Our data provide the first evidence in peripheral oscillators for an overlapping role of CLOCK and NPAS2 in the regulation of circadianly controlled genes. PMID:18316400

  10. Human extrahepatic portal vein obstruction correlates with decreased factor VII and protein C transcription but increased hepatocyte proliferation.

    Science.gov (United States)

    Chiu, Bill; Melin-Aldana, Hector; Superina, Riccardo A

    2007-10-01

    A 3-year-old girl developed extrahepatic portal vein obstruction (EHPVO) after a liver transplant. She had sequelae of portal hypertension that required another transplantation. The circumstances allowed for comparison of liver-dependent coagulation factor production between the second donor liver and the explanted liver with EHPVO. Liver samples from the explanted first graft and the second transplant were obtained. Fresh tissue was used to perform reverse transcription-polymerase chain reaction with primers against factors V, VII, as well as VIII, protein C, and paraffin-embedded sections for hepatocyte proliferation using Ki-67 antibody as well as for apoptosis using TUNEL assay. The transcription of factor VII and that of protein C were decreased in the explant as compared with the newly transplanted liver (factor VII, 77% of the donor; protein C, 88% of the donor). The transcription of factor V and that of factor VIII were unchanged. The explant had a greater percentage of proliferating hepatocytes than the new organ (0.85% +/- 0.75% vs 0.11% +/- 0.21%). The percentage of apoptotic cells was similar between the 2 livers (0.09% +/- 0.13% vs 0.09% +/- 0.13%). Idiopathic EHPVO is associated with a reduction in liver-dependent coagulation factor transcription and an increase in hepatocyte proliferation. Portal blood flow deprivation alters hepatic homeostasis and initiates mechanisms that attempt to restore liver-dependent coagulation factors.

  11. Upregulation of the coagulation factor VII gene during glucose deprivation is mediated by activating transcription factor 4.

    Directory of Open Access Journals (Sweden)

    Katherine R Cronin

    Full Text Available BACKGROUND: Constitutive production of blood coagulation proteins by hepatocytes is necessary for hemostasis. Stressful conditions trigger adaptive cellular responses and delay processing of most proteins, potentially affecting plasma levels of proteins secreted exclusively by hepatocytes. We examined the effect of glucose deprivation on expression of coagulation proteins by the human hepatoma cell line, HepG2. METHODOLOGY/PRINCIPAL FINDINGS: Expression of coagulation factor VII, which is required for initiation of blood coagulation, was elevated by glucose deprivation, while expression of other coagulation proteins decreased. Realtime PCR and ELISA demonstrated that the relative percentage expression +/- SD of steady-state F7 mRNA and secreted factor VII antigen were significantly increased (from 100+/-15% to 188+/-27% and 100+/-8.8% to 176.3+/-17.3% respectively, p<0.001 at 24 hr of treatment. The integrated stress response was induced, as indicated by upregulation of transcription factor ATF4 and of additional stress-responsive genes. Small interfering RNAs directed against ATF4 potently reduced basal F7 expression, and prevented F7 upregulation by glucose deprivation. The response of the endogenous F7 gene was replicated in reporter gene assays, which further indicated that ATF4 effects were mediated via interaction with an amino acid response element in the F7 promoter. CONCLUSIONS/SIGNIFICANCE: Our data indicated that glucose deprivation enhanced F7 expression in a mechanism reliant on prior ATF4 upregulation primarily due to increased transcription from the ATF4 gene. Of five coagulation protein genes examined, only F7 was upregulated, suggesting that its functions may be important in a systemic response to glucose deprivation stress.

  12. Prediction of human pharmacokinetics of activated recombinant factor VII and B-domain truncated factor VIII from animal population pharmacokinetic models of haemophilia

    DEFF Research Database (Denmark)

    Larsen, Malte Selch; Juul, Rasmus Vestergaard; Groth, Andreas Velsing

    2018-01-01

    activated factor VII (rFVIIa) and recombinant factor VIII (rFVIII) in several experimental animal models using population PK modelling, and apply a simulation-based approach to evaluate how well the developed animal population PK models predict human PK. PK models were developed for rFVIIa and r...

  13. Recombinant-activated factor VII in patients with uncontrolled bleeding: A retrospective observational analysis

    Directory of Open Access Journals (Sweden)

    Said D Abuhasna

    2012-01-01

    Full Text Available Background: Factor VIIa (recombinant has an off-label use to control life-threatening bleeding that is refractory to other measures and was shown to decrease transfusion requirements. Objective: The primary objective of this study was to assess the safety and effectiveness of factor VIIa (recombinant on blood transfusion requirements and coagulation parameters when used in patients whose bleeding was uncorrected by other means. The pharmacoeconomic impact for any discrepancy from our protocol was evaluated. Secondary outcomes included 4-hour and 28-day mortality, as well as safety of this agent in terms of thromboembolic complications. Materials and Methods: We retrospectively evaluated patients who received recombinant-activated factor VII (rFVIIa for uncontrolled bleeding from June 2008 to April 2011. The medical records of 33 patients were evaluated. Coagulation parameters and blood products were determined 24 hours before and 24 hours after administration of rFVIIa, and the results compared. Patients were also screened for any thromboembolic complications. Results: Administration of rFVIIa reduced blood transfusion requirements and improved coagulation parameters significantly (P<0.05. No thromboembolic complications were reported. Most of the dosing was consistent with those recommended in our institutional protocol, with discrepancies resulting in an average cost of $56 058. Moreover, pH was reported in only 67% of patients. All patients treated with rFVIIa survived up to 4 hours after receiving this agent, while the 28-day mortality was 24% (8/33. Conclusion: The use of rFVIIa appears to be safe and effective in promoting hemostasis, as evident from reducing transfusion requirements and improving the coagulation variables.

  14. The Effect of Recombinant Activated Factor VII on Mortality in Combat-Related Casualties With Severe Trauma and Massive Transfusion

    Science.gov (United States)

    2008-02-01

    acidosis and hypocalcemia are corrected. In addition, these guidelines recommend rFVIIa for patients with adequate concentrations of platelets, fibrinogen...1.00 Data on physiologic cause of death available for 51 of 53 deaths recorded. rFVIIa, recombinant activated factor VII; CNS, central nervous ... system ; MOF, multi-organ failure. Table 10 Comparison of Adverse Events Between Study Groups Variable rFVIIa N 75 rFVIIa N 49 p Value Bacteremia 12

  15. Critical appraisal of the role of recombinant activated factor VII in the treatment of hemophilia patients with inhibitors

    Directory of Open Access Journals (Sweden)

    Ampaiwan Chuansumrit

    2010-03-01

    Full Text Available Ampaiwan Chuansumrit1, Pantep Angchaisuksiri2, Nongnuch Sirachainan11Departments of Pediatrics and 2Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University,  Bangkok, ThailandAbstract: Hemophilia patients with inhibitors faced the constraint of inadequate treatment for several years before the era of recombinant factor VIIa (rFVII. Initially, rFVIIa was used in the compassionate-use programs. After a worldwide license was issued, more than 1.5 million doses were administered. Bleeding of joints and muscles was controlled effectively by means of an early home treatment program, with either a standard dose of 90 μg/kg every 2 to 3 hours for a few doses or a single dose of 270 μg/kg. For more serious bleeding episodes or minor surgery, an initial dose of 90 μg/kg was given every 2 hours for 24 to 48 hours followed by increased intervals of 3 to 6 hours according to the severity of bleeding and efficacy of bleeding control. In cases of major surgery such as orthopedic procedures, the same regimen can be applied except for a higher initial dose of 120 to 180 μg/kg. However, increasing the dose should be considered if there are unexpected bleeding complications since the half-life and clearance of rFVIIa differ between individuals. In addition, prophylaxis is administered to a small number of patients. Finally, the reported thromboembolic events found in hemophilia patients with inhibitors receiving rFVIIa are extremely low, much less than 1%.Keywords: bleeding disorder, hemophilia, inhibitor, NovoSeven, recombinant factor VIIa

  16. Management of Surgical Third Lower Molar Extraction and Postoperative Progress in Patients With Factor VII Deficiency: A Clinical Protocol and Focus on This Rare Pathologic Entity.

    Science.gov (United States)

    Passarelli, Pier Carmine; Pasquantonio, Guido; D'Addona, Antonio

    2017-10-01

    The purpose of the present study was to analyze the management of surgical third molar extraction and postoperative progress in patients with a diagnosis of factor VII deficiency. Close collaboration between the oral-maxillofacial surgeon and hematologist will allow the team to categorize the risk and operate safely, thereby minimizing the incidence and severity of intraoperative and postoperative complications. The present retrospective study included 7 patients with factor VII deficiency who had undergone third lower molar surgery. Their factor VII deficiency ranged from 10.5 to 21.0%. Recombinant activated factor VII (rFVIIa) (coagulation factor VIIa [recombinant]; NovoSeven RT; Novo Nordisk, Bagsvaerd, Denmark) was transfused intravenously in a single dose of 25 μg/kg body weight, 30 minutes before surgical extractions. After the surgery, betamethasone, an analgesic, and an ice pack were administered. Pretreatment with recombinant activated factor VII resulted in excellent hemostasis. No hemorrhagic complications and no postoperative major bleeding were observed. The extraction of the third lower molar appears to be a safe procedure for patients with factor VII deficiency when appropriate prophylaxis with rFVIIa is used. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  17. Quantitative PET Imaging of Tissue Factor Expression Using 18F-Labeled Active Site-Inhibited Factor VII.

    Science.gov (United States)

    Nielsen, Carsten H; Erlandsson, Maria; Jeppesen, Troels E; Jensen, Mette M; Kristensen, Lotte K; Madsen, Jacob; Petersen, Lars C; Kjaer, Andreas

    2016-01-01

    Tissue factor (TF) is upregulated in many solid tumors, and its expression is linked to tumor angiogenesis, invasion, metastasis, and prognosis. A noninvasive assessment of tumor TF expression status is therefore of obvious clinical relevance. Factor VII is the natural ligand to TF. Here we report the development of a new PET tracer for specific imaging of TF using an (18)F-labeled derivative of factor VII. Active site-inhibited factor VIIa (FVIIai) was obtained by inactivation with phenylalanine-phenylalanine-arginine-chloromethyl ketone. FVIIai was radiolabeled with N-succinimidyl 4-(18)F-fluorobenzoate and purified. The corresponding product, (18)F-FVIIai, was injected into nude mice with subcutaneous human pancreatic xenograft tumors (BxPC-3) and investigated using small-animal PET/CT imaging 1, 2, and 4 h after injection. Ex vivo biodistribution was performed after the last imaging session, and tumor tissue was preserved for molecular analysis. A blocking experiment was performed in a second set of mice. The expression pattern of TF in the tumors was visualized by immunohistochemistry and the amount of TF in tumor homogenates was measured by enzyme-linked immunosorbent assay and correlated with the uptake of (18)F-FVIIai in the tumors measured in vivo by PET imaging. The PET images showed high uptake of (18)F-FVIIai in the tumor regions, with a mean uptake of 2.5 ± 0.3 percentage injected dose per gram (%ID/g) (mean ± SEM) 4 h after injection of 7.3-9.3 MBq of (18)F-FVIIai and with an average maximum uptake in the tumors of 7.1 ± 0.7 %ID/g at 4 h. In comparison, the muscle uptake was 0.2 ± 0.01 %ID/g at 4 h. At 4 h, the tumors had the highest uptake of any organ. Blocking with FVIIai significantly reduced the uptake of (18)F-FVIIai from 2.9 ± 0.1 to 1.4 ± 0.1 %ID/g (P < 0.001). The uptake of (18)F-FVIIai measured in vivo by PET imaging correlated (r = 0.72, P < 0.02) with TF protein level measured ex vivo. (18)F-FVIIai is a promising PET tracer for

  18. Outcomes Following Three-Factor Inactive Prothrombin Complex Concentrate Versus Recombinant Activated Factor VII Administration During Cardiac Surgery.

    Science.gov (United States)

    Harper, Patrick C; Smith, Mark M; Brinkman, Nathan J; Passe, Melissa A; Schroeder, Darrell R; Said, Sameh M; Nuttall, Gregory A; Oliver, William C; Barbara, David W

    2018-02-01

    To compare outcomes following inactive prothrombin complex concentrate (PCC) or recombinant activated factor VII (rFVIIa) administration during cardiac surgery. Retrospective propensity-matched analysis. Academic tertiary-care center. Patients undergoing cardiac surgery requiring cardiopulmonary bypass who received either rFVIIa or the inactive 3-factor PCC. Outcomes following intraoperative administration of rFVIIa (263) or factor IX complex (72) as rescue therapy to treat bleeding. In the 24 hours after surgery, propensity-matched patients receiving PCC versus rFVIIa had significantly less chest tube outputs (median difference -464 mL, 95% confidence interval [CI] -819 mL to -110 mL), fresh frozen plasma transfusion rates (17% v 38%, p = 0.028), and platelet transfusion rates (26% v 49%, p = 0.027). There were no significant differences between propensity-matched groups in postoperative stroke, deep venous thrombosis, pulmonary embolism, myocardial infarction, or intracardiac thrombus. Postoperative dialysis was significantly less likely in patients administered PCC versus rFVIIa following propensity matching (odds ratio = 0.3, 95% CI 0.1-0.7). No significant difference in 30-day mortality in patients receiving PCC versus rFVIIa was present following propensity matching. Use of rFVIIa versus inactive PCCs was significantly associated with renal failure requiring dialysis and increased postoperative bleeding and transfusions. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Federal Programs Supporting Educational Change, Vol. VII: Factors Affecting Implementation and Continuation.

    Science.gov (United States)

    Berman, Paul; And Others

    This report is one of three volumes that describe the second phase of a study that examined the implementation of four federal change agent programs related to education. Phase 2 of the study focused on what happens to local projects in the two largest change agent programs--ESEA Title III and ESEA Title VII--when federal funding stops. This…

  20. DNA-polymorphisms and plasma levels of vascular disease risk factors in Greenland Inuit--is there a relation with the low risk of cardiovascular disease in the Inuit?

    DEFF Research Database (Denmark)

    Maat, M de; Bladbjerg, E-M; Johansen, L G

    1999-01-01

    Greenland Inuit are a population with a low risk of cardiovascular disease. Recently, we stated that frequencies of potentially high risk alleles of the apolipoproteins, fibrinogen, factor V, glycoprotein IIIa and factor VII (FVII) genes have different allele frequencies in the Inuit when compared...... and CVD risk in Caucasian populations, but for other measures this was not the case (allele frequencies of the PAI-1 polymorphism, and plasma levels of fibrinogen, FVII and t-PA). In conclusion there are clear differences in genetic background and plasma levels of risk factors in Greenland Inuit compared......, aged 30-34 gamma. In addition, we compared the plasma levels of these factors and those of C-reactive protein (CRP) and D-Dimer in Inuit and in Danes, comparable for age and gender. Frequencies (f) were assessed of the alleles that are known as the potential high risk alleles in Caucasians...

  1. Intraoperative use of low-dose recombinant activated factor VII during thoracic aortic operations.

    Science.gov (United States)

    Andersen, Nicholas D; Bhattacharya, Syamal D; Williams, Judson B; Fosbol, Emil L; Lockhart, Evelyn L; Patel, Mayur B; Gaca, Jeffrey G; Welsby, Ian J; Hughes, G Chad

    2012-06-01

    Numerous studies have supported the effectiveness of recombinant activated factor VII (rFVIIa) for the control of bleeding after cardiac procedures; however safety concerns persist. Here we report the novel use of intraoperative low-dose rFVIIa in thoracic aortic operations, a strategy intended to improve safety by minimizing rFVIIa exposure. Between July 2005 and December 2010, 425 consecutive patients at a single referral center underwent thoracic aortic operations with cardiopulmonary bypass (CPB); 77 of these patients received intraoperative low-dose rFVIIa (≤60 μg/kg) for severe coagulopathy after CPB. Propensity matching produced a cohort of 88 patients (44 received intraoperative low-dose rFVIIa and 44 controls) for comparison. Matched patients receiving intraoperative low-dose rFVIIa got an initial median dose of 32 μg/kg (interquartile range [IQR], 16-43 μg/kg) rFVIIa given 51 minutes (42-67 minutes) after separation from CPB. Patients receiving intraoperative low-dose rFVIIa demonstrated improved postoperative coagulation measurements (partial thromboplastin time 28.6 versus 31.5 seconds; p=0.05; international normalized ratio, 0.8 versus 1.2; pproduct transfusions (2.5 versus 5.0 units; p=0.05) compared with control patients. No patient receiving intraoperative low-dose rFVIIa required postoperative rFVIIa administration or reexploration for bleeding. Rates of stroke, thromboembolism, myocardial infarction, and other adverse events were equivalent between groups. Intraoperative low-dose rFVIIa led to improved postoperative hemostasis with no apparent increase in adverse events. Intraoperative rFVIIa administration in appropriately selected patients may correct coagulopathy early in the course of refractory blood loss and lead to improved safety through the use of smaller rFVIIa doses. Appropriately powered randomized studies are necessary to confirm the safety and efficacy of this approach. Copyright © 2012 The Society of Thoracic Surgeons

  2. Prophylactic administration of recombinant activated factor VII in coronary revascularization surgery

    Directory of Open Access Journals (Sweden)

    Mohamed Essam Abdel-Meguid

    2013-01-01

    Full Text Available Objective: The objective of this clinical trial is to study the effectiveness of administering recombinant activated factor VII (rFVIIa in reducing the amount of bleeding and the need for homologous blood and products transfusion in cardiac surgical coronary revascularization procedures done under cardiopulmonary bypass (CPB. Methods: In a randomized controlled prospective observational study, 30 patients were scheduled for elective cardiac revascularization under CPB. Patients were randomly allocated into two groups. In Group I (Control group, no rFVIIa was administered following CPB. In Group II (Study group, a dose of 90 ug/Kg of rFVIIa was administered following weaning off CPB. The total amount of chest tube drain during the 1 st 24 h following surgery was recorded as well as the qualitative and quantitative assessments of homologous blood and products transfusion. Serial analysis of hematological parameters including hemoglobin level and coagulation test in a definite data points was done. T0=baseline readings prior to CPB, T1=off CPB after protamine administration and before administration of the study drug, T2=on Cardiac Intensive Care Unit (CICU admission, T3=12 h post-CICU admission, and T4=24 h post-CICU admission. Results: Considering the total chest tube drainage, mean values showed statistically significant results with a P value of 0.001. Homologous blood and products transfusion were statistically lower in the study group. Regarding the mean values for hematological assessment, results showed statistically lower International Normalized Ratio values at CICU admission and 12 h post-CICU admission with a P value of 0.018 and 0.004, respectively. Also, the Partial Thromboplastin Time mean values were statistically lower at same timings with estimated P values of 0.04 and 0.001, respectively. Conclusion: It is concluded that the prophylactic use of rFVIIa in patients undergoing coronary revascularization surgery under the management

  3. Decreased plasma levels of factor II + VII + X correlate with increased levels of soluble cytokine receptors in patients with malaria and meningococcal infections

    DEFF Research Database (Denmark)

    Bygbjerg, I C; Hansen, M B; Rønn, A M

    1997-01-01

    The levels of coagulation factors II + VII + X and of blood platelets (thrombocytes) as well as of cytokines and soluble cytokine receptors were studied in the patients with malaria or meningococcal infections. The coagulation factors were decreased particularly in the meningococcal patients, while...... thrombocytes were lowest in the Plasmodium falciparum malaria patients. There was no correlation between factors II + VII + X and thrombocytes, but plasma levels of coagulation factors II + VII + X were found to correlate inversely with levels of soluble interleukin-2 receptor (sIL-2R) and soluble tumour...... necrosis factor-I (sTNF-RI) in patients with malaria and meningococcal infections. Elevated sIL-2R and sTNF-RI levels and decreased coagulation factors reverted to normal within 3-5 days after initiation of therapy in P. falciparum patients followed consecutively. Estimation of coagulation factors may...

  4. A new manufacturing process to remove thrombogenic factors (II, VII, IX, X, and XI) from intravenous immunoglobulin gamma preparations.

    Science.gov (United States)

    Park, Dong Hwarn; Kang, Gil Bu; Kang, Dae Eun; Hong, Jeung Woon; Lee, Min Gyu; Kim, Ki Yong; Han, Jeung Whan

    2017-01-01

    Coagulation factors (II, VII, IX, X, and particularly XIa) remaining in high concentrations in intravenous immunoglobulin (IVIG) preparations can form thrombi, causing thromboembolic events, and in serious cases, result in death. Therefore, manufacturers of biological products must investigate the ability of their production processes to remove procoagulant activities. Previously, we were able to remove coagulation factors II, VII, IX, and X from our IVIG preparation through ethanol precipitation, but factor XIa, which plays an important role in thrombosis, remained in the intermediate products. Here, we used a chromatographic process using a new resin that binds with high capacity to IgG and removes procoagulant activities. The procoagulant activities were reduced to low levels as determined by the thrombin generation assay: 250 s, FXI/FXIa ELISA: <0.31 ng/mL. Even after spiking with FXIa at a concentration 32.5 times higher than the concentration in normal specimens, the procoagulant activities were below the detection limit (<0.31 ng/mL). These results demonstrate the ability of our manufacturing process to remove procoagulant activities to below the detection limit (except by NaPTT), suggesting a reduced risk of thromboembolic events that maybe potentially caused by our IVIG preparation. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  5. Double heterozygous mutations Gln100Leu and His348Gln of the F7 gene in a patient with factor VII deficiency.

    Science.gov (United States)

    Li, Min; Zheng, Fangxiu; Jin, Yanhui; Wang, Mingshan; Zhu, Liqing; Yang, Lihong

    2013-03-01

    A 25-year-old Chinese woman who had a history of easy bruising was admitted to hospital due to uncontrolled epistaxis. She showed factor VII activity level of 2% and factor VII antigen level of 4% of the normal value. We detected a novel missense mutation g.8355 A>T (p.Gln100Leu) in the second epidermal growth factor-like (EGF) domain and a g.11482 T>G (p.His348Gln) in the catalytic domain. Although the Gln100 residue is close to the junction of EGF-2 domain with the serine protease domain, we infer that the substitution of polar negatively charged Gln residue at the position 100 with introduction of nonpolar Leu residue may be likely to perturb proper folding, resulting in decreasing factor VII activity.

  6. Contribution of coagulation factor VII R353Q polymorphism to the risk of thrombotic disorders development (venous and arterial: A case-control study

    Directory of Open Access Journals (Sweden)

    Hanan Azzam

    2017-07-01

    Conclusion: FVII R353Q polymorphism did not contribute to an increased risk of thrombosis (arterial and venous; also carrying the Q allele (of R353Q did not confer protection against acute thrombotic events.

  7. In vitro effects of recombinant activated factor VII on thrombin generation and coagulation following inhibition of platelet procoagulant activity by prasugrel.

    Science.gov (United States)

    Mazzeffi, Michael; Szlam, Fania; Jakubowski, Joseph A; Tanaka, Kenichi A; Sugidachi, Atsuhiro; Levy, Jerrold H

    2013-07-01

    Prasugrel is a thienopyridyl P2Y12 antagonist with potent antiplatelet effects. At present, little is known about its effects on thrombin generation or what strategies may emergently reverse its anticoagulant effects. In the current study we evaluated whether recombinant activated factor VII may reverse prasugrel induced effects and increase thrombin generation in an in vitro model. The effect of prasugrel active metabolite, PAM (R-138727), was evaluated on platelet aggregation, thrombin generation, and rotational thromboelastometry parameters using blood from 20 healthy volunteers. Additionally, we evaluated the effects of adenosine diphosphate (ADP) and recombinant activated factor VII on restoring these parameters towards baseline values. PAM reduced maximum platelet aggregation and led to platelet disaggregation. It also decreased peak thrombin, increased lag time, and increased time to peak thrombin. Treatment with recombinant activated factor VII restored all three parameters of thrombin generation towards baseline. ADP decreased lag time and time to peak thrombin, but had no effect on peak thrombin. When recombinant activated factor VII and ADP were combined they had a greater effect on thrombin parameters than either drug alone. PAM also increased thromboelastometric clotting time and clot formation time, but had no effect on maximum clot firmness. Treatment with either recombinant activated factor VII or ADP restored these values towards baseline. Recombinant activated factor VII restores thrombin generation in the presence of PAM. In patients taking prasugrel with life-threatening refractory bleeding it has the potential to be a useful therapeutic approach. Additional clinical studies are needed to validate our findings. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. A role for very low-dose recombinant activated factor VII in refractory bleeding after cardiac surgery: Lessons from an observational study.

    Science.gov (United States)

    Hoffmann, Till; Assmann, Alexander; Dierksen, Angelika; Roussel, Elisabeth; Ullrich, Sebastian; Lichtenberg, Artur; Albert, Alexander; Sixt, Stephan

    2018-04-18

    Although off-label use of recombinant activated factor VII against refractory bleeding is incorporated in current guideline recommendations, safety concerns persist predominantly with respect to thromboembolic complications. We analyzed the safety and efficacy of recombinant activated factor VII at a very low dose in cardiosurgical patients with refractory bleeding. This prospective study includes 1180 cardiosurgical patients at risk of bleeding. Goal-directed substitution was based on real-time laboratory testing and clinical scoring of the bleeding intensity. All patients who fulfilled the criteria for enhanced risk of bleeding (n = 281) were consequently included in the present analysis. Patients in whom refractory bleeding developed despite substitution with specific hemostatic compounds (n = 167) received a single shot of very low-dose recombinant activated factor VII (≤20 μg/kg). Mortality and risk of thromboembolic complications, and freedom from stroke and acute myocardial infarction in particular, were analyzed (vs patients without recombinant activated factor VII) by multivariable logistic and Cox regression analyses, as well as Kaplan-Meier estimates. There was no increase in rates of mortality (30-day mortality 4.2% vs 7.0% with P = .418; follow-up survival 85.6% at 13.0 [interquartile range, 8.4-15.7] months vs 80.7% at 10.2 [interquartile range, 7.2-16.1] months with P = .151), thromboembolic complications (6.6% vs 9.6% with P = .637), renal insufficiency, need for percutaneous coronary intervention, duration of ventilation, duration of hospital stay, or rehospitalization in patients receiving very low-dose recombinant activated factor VII compared with patients not receiving recombinant activated factor VII. Complete hemostasis without any need for further hemostatic treatment was achieved after very low-dose recombinant activated factor VII administration in the majority of patients (up to 88.6% vs 0% with P factor VII treatment of

  9. Increasing plasma fibrinogen, but unchanged levels of intraplatelet cyclic nucleotides, plasma endothelin-1, factor VII, and neopterin during cholesterol lowering with fluvastatin.

    Science.gov (United States)

    Gottsäter, A; Anwaar, I; Lind, P; Mattiasson, I; Lindgärde, F

    1999-04-01

    Lipid-lowering statin treatment reduces cardiovascular morbidity and mortality and improves endothelial function in patients with hypercholesterolemia. The aim of the present study was to evaluate plasma levels of fibrinogen, factor VII, and the macrophage-derived inflammatory mediator neopterin during lipid lowering. In addition, the endothelial production of platelet antiaggregatory and vasodilatory factors such as nitric oxide and prostacyclin, and vasoconstrictive factors such as endothelin-1, was assessed. Plasma fibrinogen, factor VII, endothelin-1, and the neopterin and intraplatelet nitric oxide and prostacyclin mediators cyclic 3'-5'guanosine monophosphate (cGMP) and cyclic 3'-5'adenosine monophosphate (cAMP) were measured before and 6 months after the institution of treatment with fluvastatin in 17 patients (eight men and nine women, median age 60 years) with vascular disease and previously untreated hypercholesterolemia. After 6 months, a decrease of 1.62 mmol/l [1.26-2.18 (19%); P factor VII [from 1.14 IE/ml (0.58-1.38) to 1.22 IE/ml (0.96-1.46); NS], or plasma neopterin [from 8.6 nmol/l (7.1-11.5) to 8.7 nmol/l (7.9-11.3); NS]. In conclusion, during cholesterol-lowering treatment with fluvastatin, plasma levels of fibrinogen increased whereas intraplatelet cyclic nucleotide levels and plasma endothelin-1, factor VII and neopterin levels were unchanged.

  10. Factor VII-Induced MicroRNA-135a Inhibits Autophagy and Is Associated with Poor Prognosis in Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Kuang-Tzu Huang

    2017-12-01

    Here, we identified miR-135a as a highly upregulated miRNA in HCC in response to TF/FVII/PAR2 activation. Analyzing 103 HCC patient specimens, we confirmed that miR-135a was frequently elevated in HCC tissues with higher FVII expression compared to adjacent non-cancerous counterparts. Increased miR-135a levels in HCC were also associated with tumor staging, recurrence, microvascular invasion, and decreased disease-free survival. We subsequently identified Atg14, a key component that regulates the formation of autophagosome as a direct target of miR-135a. Ectopic expression of miR-135a suppressed Atg14 levels and inhibited the autophagic processes. Our results indicate strong positive correlations between miR-135a levels and malignant behaviors in HCC patients and also suggest novel functions of miR-135a in regulation of autophagy, which could be useful as a potential target for prognostic and therapeutic uses.

  11. Safety and efficacy of recombinant activated factor VII: a randomized placebo-controlled trial in the setting of bleeding after cardiac surgery

    DEFF Research Database (Denmark)

    Gill, Ravi; Herbertson, Mike; Vuylsteke, Alain

    2009-01-01

    BACKGROUND: Blood loss is a common complication of cardiac surgery. Evidence suggests that recombinant activated factor VII (rFVIIa) can decrease intractable bleeding in patients after cardiac surgery. Our objective was to investigate the safety and possible benefits of rFVIIa in patients who bleed...

  12. Elevated prothrombin time on routine preoperative laboratory results in a healthy infant undergoing craniosynostosis repair: Diagnosis and perioperative management of congenital factor VII deficiency.

    Science.gov (United States)

    Jones, Kareen L; Greenberg, Robert S; Ahn, Edward S; Kudchadkar, Sapna R

    2016-01-01

    Congenital factor VII deficiency is a rare bleeding disorder with high phenotypic variability. It is critical that children with congenital Factor VII deficiency be identified early when high-risk surgery is planned. Cranial vault surgery is common for children with craniosynostosis, and these surgeries are associated with significant morbidity mostly secondary to the risk of massive blood loss. A two-month old infant who presented for elective craniosynostosis repair was noted to have an elevated prothrombin time (PT) with a normal activated partial thromboplastin time (aPTT) on preoperative labs. The infant had no clinical history or reported family history of bleeding disorders, therefore a multidisciplinary decision was made to repeat the labs under general anesthesia and await the results prior to incision. The results confirmed the abnormal PT and the case was canceled. Hematologic workup during admission revealed factor VII deficiency. The patient underwent an uneventful endoscopic strip craniectomy with perioperative administration of recombinant Factor VIIa. Important considerations for perioperative laboratory evaluation and management in children with factor VII deficiency are discussed. Anesthetic and surgical management of the child with factor VII deficiency necessitates meticulous planning to prevent life threatening bleeding during the perioperative period. A thorough history and physical examination with a high clinical suspicion are vital in preventing hemorrhage during surgeries in children with coagulopathies. Abnormal preoperative lab values should always be confirmed and addressed before proceeding with high-risk surgery. A multidisciplinary discussion is essential to optimize the risk-benefit ratio during the perioperative period. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. High-level secretion of tissue factor-rich extracellular vesicles from ovarian cancer cells mediated by filamin-A and protease-activated receptors.

    Science.gov (United States)

    Koizume, Shiro; Ito, Shin; Yoshioka, Yusuke; Kanayama, Tomohiko; Nakamura, Yoshiyasu; Yoshihara, Mitsuyo; Yamada, Roppei; Ochiya, Takahiro; Ruf, Wolfram; Miyagi, Etsuko; Hirahara, Fumiki; Miyagi, Yohei

    2016-01-01

    Thromboembolic events occur frequently in ovarian cancer patients. Tissue factor (TF) is often overexpressed in tumours, including ovarian clear-cell carcinoma (CCC), a subtype with a generally poor prognosis. TF-coagulation factor VII (fVII) complexes on the cell surface activate downstream coagulation mechanisms. Moreover, cancer cells secrete extracellular vesicles (EVs), which act as vehicles for TF. We therefore examined the characteristics of EVs produced by ovarian cancer cells of various histological subtypes. CCC cells secreted high levels of TF within EVs, while the high-TF expressing breast cancer cell line MDA-MB-231 shed fewer TF-positive EVs. We also found that CCC tumours with hypoxic tissue areas synthesised TF and fVII in vivo, rendering the blood of xenograft mice bearing these tumours hypercoagulable compared with mice bearing MDA-MB-231 tumours. Incorporation of TF into EVs and secretion of EVs from CCC cells exposed to hypoxia were both dependent on the actin-binding protein, filamin-A (filA). Furthermore, production of these EVs was dependent on different protease-activated receptors (PARs) on the cell surface. These results show that CCC cells could produce large numbers of TF-positive EVs dependent upon filA and PARs. This phenomenon may be the mechanism underlying the increased incidence of venous thromboembolism in ovarian cancer patients.

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

    Science.gov (United States)

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

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

  15. Enhanced functional recombinant factor VII production by HEK 293 cells stably transfected with VKORC1 where the gamma-carboxylase inhibitor calumenin is stably suppressed by shRNA transfection.

    Science.gov (United States)

    Wajih, Nadeem; Owen, John; Wallin, Reidar

    2008-01-01

    Recombinant members of the vitamin K-dependent protein family (factors IX and VII and protein C) have become important pharmaceuticals in treatment of bleeding disorders and sepsis. However, because the in vivo gamma-carboxylation system in stable cell lines used for transfection has a limited capacity of post translational gamma-carboxylation, the recovery of fully gamma-carboxylated and functional proteins is low. In this work we have engineered recombinant factor VII producing HEK 293 cells to stably overexpress VKORC1, the reduced vitamin K gamma-carboxylase cofactor and in addition stably silenced the gamma-carboxylase inhibitory protein calumenin. Stable cell lines transfected with only a factor VII cDNA had a 9% production of functional recombinant factor VII. On the other hand, these recombinant factor VII producing cells when engineered to overexpress VKORC1 and having calumenin stably suppressed more than 80% by shRNA expression, produced 68% functional factor VII. The technology presented should be applicable to all vertebrae members of the vitamin K-dependent protein family and should lower the production cost of the clinically used factors VII, IX and protein C.

  16. Syndromes, Disorders and Maternal Risk Factors Associated With Neural Tube Defects (VII

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2008-09-01

    Full Text Available Neural tube defects (NTDs may be associated with syndromes, disorders and maternal risk factors. This article provides a comprehensive review of the syndromes, disorders and maternal risk factors associated with NTDs, including DK phocomelia syndrome (von Voss-Cherstvoy syndrome, Siegel-Bartlet syndrome, fetal warfarin syndrome, craniotelencephalic dysplasia, Czeizel-Losonci syndrome, maternal cocaine abuse, Weissenbacher-Zweymüller syndrome, parietal foramina (cranium bifidum, Apert syndrome, craniomicromelic syndrome, XX-agonadism with multiple dysraphic lesions including omphalocele and NTDs, Fryns microphthalmia syndrome, Gershoni-Baruch syndrome, PHAVER syndrome, periconceptional vitamin B6 deficiency, and autosomal dominant Dandy-Walker malformation with occipital cephalocele. NTDs associated with these syndromes, disorders and maternal risk factors are a rare but important cause of NTDs. The recurrence risk and the preventive effect of maternal folic acid intake in NTDs associated with syndromes, disorders and maternal risk factors may be different from those of nonsyndromic multifactorial NTDs. Perinatal diagnosis of NTDs should alert doctors to the syndromes, disorders and maternal risk factors associated with NTDs, and prompt thorough etiologic investigation and genetic counseling.

  17. Decreased plasma levels of activated factor VII in patients with deep vein thrombosis

    NARCIS (Netherlands)

    Schut, A. M.; Meijers, J. C. M.; Lisman-van Leeuwen, Y.; van Montfoort, M. L.; Roest, M.; de Groot, P. G.; Urbanus, R. T.; Coppens, M.; Lisman, T.

    BackgroundThe initiating trigger in the development of deep vein thrombosis (DVT) remains unidentified. It has been suggested that tissue factor (TF)-bearing microparticles play a key role, which indicates a role for the TF pathway in the initiation of DVT. ObjectiveTo assess the role of the TF

  18. Decreased plasma levels of activated factor VII in patients with deep vein thrombosis

    NARCIS (Netherlands)

    Schut, A. M.; Meijers, J. C M; Lisman- van Leeuwen, Y.; van Montfoort, M. L.; Roest, M.; de Groot, P. G.; Urbanus, R. T.; Coppens, M.; Lisman, T.

    2015-01-01

    Background: The initiating trigger in the development of deep vein thrombosis (DVT) remains unidentified. It has been suggested that tissue factor (TF)-bearing microparticles play a key role, which indicates a role for the TF pathway in the initiation of DVT. Objective: To assess the role of the TF

  19. Decreased plasma levels of activated factor VII in patients with deep vein thrombosis

    NARCIS (Netherlands)

    Schut, A. M.; Meijers, J. C. M.; Lisman-van Leeuwen, Y.; van Montfoort, M. L.; Roest, M.; de Groot, P. G.; Urbanus, R. T.; Coppens, M.; Lisman, T.

    2015-01-01

    The initiating trigger in the development of deep vein thrombosis (DVT) remains unidentified. It has been suggested that tissue factor (TF)-bearing microparticles play a key role, which indicates a role for the TF pathway in the initiation of DVT. To assess the role of the TF pathway in the

  20. Warfarin dose requirement in Turkish patients: the influences of patient characteristics and polymorphisms in CYP2C9, VKORC1 and factor VII.

    Science.gov (United States)

    Yildirim, E; Erol, K; Birdane, A

    2014-01-01

    To determine the contribution of cytochrome P4502C9 (CYP2C9), vitamin K epoxide reductase (VKORC1) and factor VII genotypes, age, body mass index (BMI), international normalized ratio (INR) and other individual patient characteristics on warfarin dose requirements in an adult Turkish population. Blood samples were collected from 101 Turkish patients. Genetic analyses for CYP2C9*2 and *3, VKORC1 -1639 G>A and factor VII -401 G>T polymorphisms were performed. Age, INR, BMI values and other individual patient characteristics were also recorded. The mean daily warfarin dosage was significantly higher in patients with the CYP2C9*1/*1 genotype than in the CYP2C9*2/*2 and CYP2C9*1/*3 groups (p ≤ 0.05). With respect to the VKORC1 -1639 G>A polymorphism, the mean warfarin daily dose requirement was higher in the wild type group compared to the heterozygous group (p≤0.001). The mean daily dose requirement for patients with the GG form of factor VII was significantly higher than that of patients with the TT genotype (p ≤ 0.05). Age, gender, BMI, INR had no statistically significant correlation with warfarin dose (p ≥ 0.05). Polymorphisms in CYP2C9, VKORC1 and factor VII did partially affect daily warfarin dose requirements, while age, gender, BMI and INR do not. However, further case-control studies with a larger study size and different genetic loci are needed to confirm our study.

  1. Concentration factors of uranium mineralization in VII depositional cycle of Shuixigou group, lower-middle Jurassic at Wukurqi uranium deposit, Yili basin

    International Nuclear Information System (INIS)

    Liu Taoyong

    2004-01-01

    Starting with the analysis on uranium mineralization, this paper emphatically discusses factors related to uranium concentration in VII depositional cycle, such as the structure, the paleoclimate, the lithofacies-paleogeography, the lithology, the hydrogeology, the geochemistry, and the content of effective reductant. The author suggests that key factors of uranium migration and concentration at Wukurqi uranium deposit are the existence of ore-hosting formation (sand body), the long-term recharge of oxygen and uranium-bearing groundwater, the existence of effective reductant in ore-hosting formation

  2. Factor VII R353Q genetic polymorphism is associated with altered warfarin sensitivity among CYP2C9 *1/*1 carriers.

    Science.gov (United States)

    Mlynarsky, Liat; Bejarano-Achache, Idit; Muszkat, Mordechai; Caraco, Yoseph

    2012-05-01

    Warfarin responsiveness is characterized by marked interindividual variability. A major portion of this variability is attributed to CYP2C9 and VKORC1 polymorphisms, but almost 50% is still unaccounted for. This paper reports the first prospective study on the association between factor VII R353Q polymorphism and warfarin responsiveness during induction. Genotyping for factor VII R353Q and 323D/I polymorphisms was performed in a cohort consisting of 374 patients (198 CYP2C9*1/*1) treated with warfarin who were prospectively followed from warfarin initiation. Compared with *1/*1-R/R and *1/*1-R/Q genotype carriers, *1/*1-Q/Q homozygotes achieved higher International Normalized Ratio (INR) values while consuming lower warfarin doses. The greater sensitivity was illustrated by 82.1% higher Warfarin Sensitivity Index During Induction (WSIDI) (0.14 ± 0.11 vs. 0.08 ± 0.50 mg⁻¹ Mann-Whitney, P = 0.043). Multiple regression analysis consisting of both genetic and nongenetic factors explained 26% of WSIDI variability, with R353Q genetic polymorphism having a modest yet significant effect and accounting for 1.7% of the overall variability. Moreover, the incidence of overanticoagulation (i.e., INR > 4) was 6.94-fold higher among *1/*1-Q/Q vs. *1/*1-R/R&R/Q carriers during warfarin induction (Pearson chi-square, P = 0.005). These findings were not accounted for by a chance difference in the distribution of VKORC1 genotypes. Analysis of these parameters among the entire cohort, including CYP2C9*2 and CYP2C9*3 variant allele carriers, did not reach statistical significance. Warfarin responsiveness during induction was unrelated to factor VII 323D/I genetic polymorphism. The response to warfarin during induction is influenced by factor VII R353Q polymorphism. The prospective use of this polymorphism, along with CYP2C9 and VKORC1, may enhance the accuracy of warfarin loading. However, the impact of R353Q polymorphism on overall warfarin response is subtle, and it is therefore

  3. Opposite Smad and chicken ovalbumin upstream promoter transcription factor inputs in the regulation of the collagen VII gene promoter by transforming growth factor-beta.

    Science.gov (United States)

    Calonge, María Julia; Seoane, Joan; Massagué, Joan

    2004-05-28

    A critical component of the epidermal basement membrane, collagen type VII, is produced by keratinocytes and fibroblasts, and its production is stimulated by the cytokine transforming growth factor-beta (TGF-beta). The gene, COL7A1, is activated by TGF-beta via Smad transcription factors in cooperation with AP1. Here we report a previously unsuspected level of complexity in this regulatory process. We provide evidence that TGF-beta may activate the COL7A1 promoter by two distinct inputs operating through a common region of the promoter. One input is provided by TGF-beta-induced Smad complexes via two Smad binding elements that function redundantly depending on the cell type. The second input is provided by relieving the COL7A1 promoter from chicken ovalbumin upstream promoter transcription factor (COUP-TF)-mediated transcriptional repression. We identified COUP-TFI and -TFII as factors that bind to the TGF-beta-responsive region of the COL7A1 promoter in an expression library screening. COUP-TFs bind to a site between the two Smad binding elements independently of Smad or AP1 and repress the basal and TGF-beta-stimulated activities of this promoter. We provide evidence that endogenous COUP-TF activity represses the COL7A1 promoter. Furthermore, we show that TGF-beta addition causes a rapid and profound down-regulation of COUP-TF expression in keratinocytes and fibroblasts. The results suggest that TGF-beta signaling may exert tight control over COL7A1 by offsetting the balance between opposing Smad and COUP-TFs.

  4. Comparison of three-factor and four-factor prothrombin complex concentrates regarding reversal of the anticoagulant effects of rivaroxaban in healthy volunteers

    NARCIS (Netherlands)

    Levi, M. [=Marcel M.; Moore, K. T.; Castillejos, C. F.; Kubitza, D.; Berkowitz, S. D.; Goldhaber, S. Z.; Raghoebar, M.; Patel, M. R.; Weitz, J. I.; Levy, J. H.

    2014-01-01

    Four-factor prothrombin complex concentrates (PCCs), which contain factor II, FVII, FIX, and FX, have shown the potential to reverse the anticoagulant effect of rivaroxaban in healthy volunteers. The purpose of this study was to determine whether a three-factor PCC, which contains little FVII, has a

  5. Factor VII deficiency and developmental abnormalities in a patient with partial monosomy of 13q and trisomy of 16p: case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Meck Jeanne M

    2006-01-01

    Full Text Available Abstract Background Unbalanced chromosomal translocations may present with a variety of clinical and laboratory findings and provide insight into the functions of genes on the involved chromosomal segments. Case Presentation A 9 year-old boy presented to our clinic with Factor VII deficiency, microcephaly, a seizure disorder, multiple midline abnormalities (agenesis of the corpus callosum, imperforate anus, bilateral optic nerve hypoplasia, developmental delay, hypopigmented macules, short 5th fingers, and sleep apnea due to enlarged tonsils. Cytogenetic and fluorescence in situ hybridization analyses revealed an unbalanced translocation involving the segment distal to 16p13 replacing the segment distal to 13q33 [46, XY, der(13t(13;16(q33;p13.3]. Specific BAC-probes were used to confirm the extent of the 13q deletion. Conclusion This unique unbalanced chromosomal translocation may provide insights into genes important in midline development and underscores the previously-reported phenotype of Factor VII deficiency in 13q deletions.

  6. Effect of N-acetylcysteine on the accuracy of the prothrombin time assay of plasma coagulation factor II+VII+X activity in subjects infused with the drug. Influence of time and temperature

    DEFF Research Database (Denmark)

    Thorsen, Sixtus; Teisner, Ane; Jensen, Søren Astrup

    2009-01-01

    OBJECTIVES: The prothrombin time (PT) assay of factor II+VII+X activity is an important predictor of liver damage in paracetamol poisoned patients. It complicates interpretation of results that the antidote, acetylcysteine (NAC) depresses this activity. The aim was to investigate if NAC influences...... to plasma in vitro decreased factor II+VII+X activity at 37 degrees C in a time-dependent manner. This effect was quenched at temperatures ... to a significant additional depression of factor II+VII+X activity in plasma from subjects infused with NAC during the first 3h of infusion indicating that it contained reactive NAC. The risk that this NAC interfered with the accuracy of the PT assay was considered minimal with samples stored below 24 degrees C...

  7. Effect of N-acetylcysteine on the accuracy of the prothrombin time assay of plasma coagulation factor II plus VII plus X activity in subjects infused with the drug. Influence of time and temperature

    DEFF Research Database (Denmark)

    Thorsen, S.; Teisner, A.; Jensen, S.A.

    2009-01-01

    Objectives: The prothrombin time (PT) assay of factor II+VII+X activity is an important predictor of liver damage in paracetamol poisoned patients. It complicates interpretation of results that the antidote, acetylcysteine (NAC) depresses this activity. The aim was to investigate if NAC influences...... added to plasma in vitro decreased factor II+VII+X activity at 37 degrees C in a time-dependent manner. This effect was quenched at temperatures 24 degrees C. Activity lost at 37 degrees C could partly be recovered by subsequent incubation at 5 or 20 degrees C. Incubation at 37 degrees C prior to assay...... led to a significant additional depression of factor II+VII+X activity in plasma from subjects infused with NAC during the first 3h of infusion indicating that it contained reactive NAC. The risk that this NAC interfered with the accuracy of the PT assay was considered minimal with samples stored...

  8. Two-incision laparoscopic appendectomy for a severe hemophilia A child patient with coagulation factor VII deficiency: Case report and review of literature.

    Science.gov (United States)

    He, Jin Peng; Feng, Jie Xiong

    2017-10-01

    The main complication of patients with severe hemophilia is recurrent bleeding events that usually affected musculoskeletal contractures. And replacement therapy methods were continuously improved to minimize adverse impacts brought by those complications. However, only several cases reported about the appendectomy for hemophilia A. We report a case of acute appendicitis treated by two-incision laparoscopy in a boy with hemophilia A and coagulation factor VII deficiency for the first time. An 8y7m-old Chinese boy presented with half a day of right sided abdominal pain, fever, nausea, and vomiting. He received a computed tomography (CT) scan which revealed an enlarged appendix, thickened wall and appendiceal fecalith, and had received a conservative anti-bacterial treatment for his acute appendicitis but failed. He was diagnosed with hemophilia A and coagulation factor VII deficiency. Two-incision laparoscopic appendectomy was made in success with a careful management of perioperative period. We monitored the clotting factor FVIII level and gave him a replacement therapy. The patient had an uneventful recovery. It is important to exclude intraabdominal or retroperitoneal hemorrhage in patients suffering from hemophilia and acute abdominal pain. Pre-operative evaluation of validity of the FVIII replacement therapy is another effective strategy to assess the safety and feasibility of applying an operation procedure. The two-incision laparoscopic appendectomy is an effective treatment for this kind of patients for its minimal trauma and fast recovery characteristics. Our report shows that laparoscopic appendectomy is feasible in a child suffering from hemophilia after adequate blood clotting factor replacement treatment.

  9. Association between polymorphisms in the coagulation factor VII gene and coronary heart disease risk in different ethnicities: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Mo Xingbo

    2011-08-01

    Full Text Available Abstract Background Previous studies have examined the association between polymorphisms in the coagulation factor VII gene and the risk of coronary heart disease (CHD, but those studies have been inconclusive. This study was conducted to assess the associations between these polymorphisms and CHD and evaluated the associations in different ethnicities. Methods Literature-based searching was conducted to collect data and two methods, namely fixed-effects and random-effects, were performed to pool the odds ratio (OR, together with the 95% confidence interval (CI. Publication bias and between-study heterogeneity were also examined. Results Thirty-nine case-control studies of the three polymorphisms, R353Q (rs6046, HVR4 and -323Ins10 (rs36208070 in factor VII gene and CHD were enrolled in this meta-analysis, including 9,151 cases of CHD and 14,099 controls for R353Q, 2,863 cases and 2,727 controls for HVR4, and 2,862 cases and 4,240 controls for -323Ins10. Significant association was only found in Asian population for R353Q (Q vs R, with pooled OR of 0.70(95%CI: 0.55, 0.90. For the -323Ins10 polymorphism (10 vs 0, we found significant associations in both Asian and European populations, with pooled ORs of 0.74(95%CI: 0.61, 0.88 and 0.63(95%CI: 0.53, 0.74, respectively. Marginal significant association was found between HVR4 (H7 vs H5+H6 and CHD (OR = 0.88, 95% CI: 0.78, 1.00. There was no evidence of publication bias, but between-study heterogeneity was found in the analyses. Conclusions The -323Ins10 polymorphism in factor VII gene is significantly associated with CHD in both Asian and European populations, while R353Q polymorphism showed trend for association with CHD in Asians. Lack of association was found for HVR4 polymorphism. Further studies are needed to confirm the association, especially for -323Ins10 polymorphism.

  10. The role of recombinant activated factor VII in the haematological management of elective orthopaedic surgery in haemophilia A patients with inhibitors

    Science.gov (United States)

    Castaman, Giancarlo

    2017-01-01

    The clinical profile and expectations of haemophilic patients with inhibitors have changed over the last three decades, mainly because of the prolongation of life-expectancy, often resulting in an increase of the orthopaedic burden. Recombinant activated factor VII (rFVIIa) is the most frequently used bypassing agent in haemophilia patients with inhibitors during elective orthopaedic surgery. For nearly 30 years, rFVIIa has been successfully used to control haemostasis in several major and minor surgical procedures. Clinical trials, case series, reports and surveys were progressively aimed at optimising rFVIIa usage in very demanding conditions managed in highly specialised centres. Recommendations from consensus opinions and guidelines have been provided on the basis of this clinical experience. PMID:28686157

  11. [Correlation between polymorphisms in the coagulation factor VII gene hypervariable region 4 site and the risk of coronary heart disease in population with different ethnic backgrounds: a Meta-analysis].

    Science.gov (United States)

    Wang, Li-li; Ma, Bin; Qian, Dun; Pang, Jun; Yao, Ya-li

    2013-12-01

    To assess the correlation between polymorphisms in the coagulation factor VII (F VII)gene hypervariable region 4 (HVR4)site and risk related to coronary heart disease (CHD)in different ethnic populations, especially the Asian populations. Publications up to April 2013, from CBM, CNKI, Wanfang Database,VIP, PubMed, Cochrane Library and Embase were searched to collect data from case-control studies related to F VII gene HVR4 site and CHD in populations from different ethnicities. Quality of studies was evaluated, available data extracted and both RevMan 5.1 and Stata 11.0 softwares were used for Meta-analysis. Fifteen case-control studies were included, involving 3167 cases with CHD group and 3168 cases in the control group. on this Meta-analysis showed that:a)polymorphism of the F VII gene HVR4 site H7/H6+H5 and CHD, b)H7H7/H6H6 + H7H6 and CHD were both slightly correlated between people with different ethnic backgrounds. However, the H6 allele versus H7+H5 allele and CHD showed different results-a high correlation seen in different ethnic groups. H5 allele versus H6+H7 allele and CHD did not appear significant difference(OR = 1.20, 95%CI:0.76-1.90, P = 0.43). Both F VII gene HVR4 polymorphisms H7 allele and the H7H7 genotype might have served as protective factors for CHD in different ethnic groups, H6 allele might serve as a risk factor for CHD, but H5 allele was likely not to be associated with CHD in different ethnic groups.

  12. Gene Delivery of Activated Factor VII Using Alternative Adeno-Associated Virus Serotype Improves Hemostasis in Hemophiliac Mice with FVIII Inhibitors and Adeno-Associated Virus Neutralizing Antibodies.

    Science.gov (United States)

    Sun, Junjiang; Hua, Baolai; Chen, Xiaojing; Samulski, Richard J; Li, Chengwen

    2017-08-01

    While therapeutic expression of coagulation factors from adeno-associated virus (AAV) vectors has been successfully achieved in patients with hemophilia, neutralizing antibodies to the vector and inhibitory antibodies to the transgene severely limit efficacy. Indeed, approximately 40% of mice transduced with human factor VIII using the AAV8 serotype developed inhibitory antibodies to factor VIII (FVIII inhibitor), as well as extremely high titers (≥1:500) of neutralizing antibodies to AAV8. To correct hemophilia in these mice, AAV9, a serotype with low in vitro cross-reactivity (≤1:5) to anti-AAV8, was used to deliver mouse-activated factor VII (mFVIIa). It was found that within 6 weeks of systemic administration of 2 × 10 13 particles/kg of AAV9/mFVIIa, hemophiliac mice with FVIII inhibitors and neutralizing antibodies (NAb) to AAV8 achieved hemostasis comparable to that in wild-type mice, as measured by rotational thromboelastometry. A level of 737 ng/mL mFVIIa was achieved after AAV9/mFVIIa adminstration compared to around 150 ng/mL without vector treatment, and concomitantly prothrombin time was shortened. Tissues collected after intra-articular hemorrhage from FVIII-deficient mice and mice with FVIII inhibitors were scored 4.7 and 5.5, respectively, on a scale of 0-10, indicating significant pathological damage. However, transduction with AAV9/mFVIIa decreased pathology scores to 3.6 and eliminated hemosiderin iron deposition in the synovium in most mice. Collectively, these results suggest that application of alternative serotypes of AAV vector to deliver bypassing reagents has the potential to correct hemophilia and prevent hemoarthrosis, even in the presence of FVIII inhibitor and neutralizing antibodies to AAV.

  13. Genetic polymorphisms of hemostatic factors and thrombotic risk in non BCR-ABL myeloproliferative neoplasms: A pilot study

    Directory of Open Access Journals (Sweden)

    Dambrauskienė R

    2017-06-01

    Full Text Available The most important complications of Philadelphianegagive (non BCR-ABL myeloproliferative neoplasms (MPNs are vascular events. Our aim was to evaluate the effects of single nucleotide polymorphisms (SNPs, platelet glycoproteins (GPs (Ia/IIa, Ibα, IIb/IIIa and VI, von Willebrand factor (vWF, coagulation factor VII (FVII, β-fibrinogen, and the risk of thrombosis in patients with non BCR-ABL MPNs at the Lithuanian University of Health Sciences. Kaunas, Lithuania. Genotyping was done for 108 patients. The TT genotype of the GP Ia/IIa c.807C>T polymorphism was more frequently found in the group of MPN patients with arterial thrombosis compared to MPN patients who were thrombosis-free [26.5 vs. 11.5%, p = 0.049; odds ratio (OR 2.68; 95% confidence interval (95% CI 1.01-7.38]. The CT genotype of the β-fibrinogen c.-148C>T polymorphism occurred more frequently in MPN patients with arterial, and total thrombosis compared to the wild or homozygous genotype (57.7 vs. 40.0 vs. 12.5%; p = 0.027, (64.7 vs. 44.4 vs. 25%; p = 0.032, respectively. The carrier state for the c.-323P10 variant of FVII SNP (summation of P10/10 and P0/10 was more frequent in MPN patients with thrombosis compared to the wild-type genotype carriers (71.4 vs. 43.4%; p = 0.049; OR 3.26; 95% CI 1.01-11.31. The coexistence of heterozygous β-fibrinogen c.-148C>T and FVII c.-323P0/10 SNP, increased the risk of arterial thrombosis (21.1 vs. 3.7%, p = 0.008; OR 6.93; 95% CI 1.38-34.80. The TT genotype of GP Ia/IIa c.807C>T, the CT genotype of β-fibrinogen c.-148C>T and FVII c.-323P0/10 SNP could be associated with risk of thrombosis in MPN patients.

  14. Recombinant activated factor VII in the treatment of bleeds and for the prevention of surgery-related bleeding in congenital haemophilia with inhibitors.

    Science.gov (United States)

    Santagostino, Elena; Escobar, Miguel; Ozelo, Margareth; Solimeno, Luigi; Arkhammar, Per; Lee, Hye Youn; Rosu, Gabriela; Giangrande, Paul

    2015-06-01

    The availability of recombinant activated factor VII (rFVIIa, eptacog alfa activated) has greatly advanced the care of patients with haemophilia A or B who have developed inhibitors against the infused replacement factor. Recombinant FVIIa is licensed for the on-demand treatment of bleeding episodes and the prevention of bleeding in surgery or invasive procedures in patients with congenital haemophilia with inhibitors. This article attempts to review in detail the extensive evidence of rFVIIa in congenital haemophilia patients with inhibitors. Patients with acute bleeding episodes are best treated on demand at home, to achieve the short- and long-term benefits of rapid bleed control. Key prospective studies have shown that rFVIIa achieves consistently high efficacy rates in the management of acute (including joint) bleeds in inhibitor patients in the home treatment setting. Substantial post-approval data from key registries also support the on-demand efficacy profile of rFVIIa established by the prospective clinical trials. The availability of rFVIIa has allowed major surgery to become a reality for inhibitor patients. Studies in key surgery, including orthopaedic procedures, have found that rFVIIa provides consistently high efficacy rates. Importantly, the wealth of data does not raise any unexpected safety concerns surrounding rFVIIa use; this is likely because rFVIIa is a recombinant product with a localised mechanism of action at the site of vascular injury. In summary, rFVIIa is established as an effective and well-tolerated first-line treatment for on-demand bleeding control and bleed prevention during minor and major (including elective orthopaedic) surgery in inhibitor patients. Use of rFVIIa has been a major step towards narrowing the gap in outcomes between inhibitor patients and non-inhibitor patients. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Important comments on KERMA factors and DPA cross-section data in ACE files of JENDL-4.0, JEFF-3.2 and ENDF/B-VII.1

    Science.gov (United States)

    Konno, Chikara; Tada, Kenichi; Kwon, Saerom; Ohta, Masayuki; Sato, Satoshi

    2017-09-01

    We have studied reasons of differences of KERMA factors and DPA cross-section data among nuclear data libraries. Here the KERMA factors and DPA cross-section data included in the official ACE files of JENDL-4.0, ENDF/B-VII.1 and JEFF-3.2 are examined in more detail. As a result, it is newly found out that the KERMA factors and DPA cross-section data of a lot of nuclei are different among JENDL-4.0, ENDF/B-VII.1 and JEFF-3.2 and reasons of the differences are the followings: 1) large secondary particle production yield, 2) no secondary gamma data, 3) secondary gamma data in files12-15 mt = 3, 4) mt = 103-107 data without mt = 600 s-800 s data in file6. The issue 1) is considered to be due to nuclear data, while the issues 2)-4) seem to be due to NJOY. The ACE files of JENDL-4.0, ENDF/B-VII.1 and JEFF-3.2 with these problems should be revised after correcting wrong nuclear data and NJOY problems.

  16. Effect of N-acetylcysteine on the accuracy of the prothrombin time assay of plasma coagulation factor II+VII+X activity in subjects infused with the drug. Influence of time and temperature.

    Science.gov (United States)

    Thorsen, Sixtus; Teisner, Ane; Jensen, Søren Astrup; Philips, Malou; Dalhoff, Kim; Bendtsen, Flemming

    2009-01-01

    The prothrombin time (PT) assay of factor II+VII+X activity is an important predictor of liver damage in paracetamol poisoned patients. It complicates interpretation of results that the antidote, acetylcysteine (NAC) depresses this activity. The aim was to investigate if NAC influences the accuracy of the plasma PT assay. The accuracy of Nycotest PT was studied using plasma added NAC in vitro and plasma from subjects infused with NAC. The latter results were compared with those obtained by analysis of PT by CoaguChek S. Therapeutic NAC concentrations added to plasma in vitro decreased factor II+VII+X activity at 37 degrees C in a time-dependent manner. This effect was quenched at temperatures depression of factor II+VII+X activity in plasma from subjects infused with NAC during the first 3h of infusion indicating that it contained reactive NAC. The risk that this NAC interfered with the accuracy of the PT assay was considered minimal with samples stored below 24 degrees C. This was supported by similarity of results obtained by analysis of appropriately stored plasma and simultaneously drawn blood by CoaguChek S. Residual reactive NAC does not interfere with the accuracy of the PT assay of plasma stored below 24 degrees C, but NAC-induced loss in activity at 37 degrees C may be partly recovered during subsequent storage below 24 degrees C.

  17. Clinical use of recombinant human activated factor VII (rFVIIa in the prevention and treatment of bleeding episodes in patients with Glanzmann’s thrombasthenia

    Directory of Open Access Journals (Sweden)

    Man-Chiu Poon

    2007-11-01

    Full Text Available Man-Chiu PoonDepartments of Medicine, Pediatrics and Oncology and Southern Alberta Bleeding Disorders Clinic, University of Calgary and Calgary Health Region, Calgary, Alberta, CanadaAbstract: Glanzmann’s thrombasthenia (GT is a congenital qualitative platelet disorders due to the deficiency or defect of platelet membrane GPIIb/IIIa (integrin αIIbβ3. The standard treatment for bleeding is platelet transfusion but repeated transfusion may result in the development of anti-platelet antibodies (to HLA and/or GPIIbIIIa rendering future platelet transfusion ineffective. Alternative effective agent(s are needed. There are increasing reports documenting efficacy of high dose rFVIIa in GT patients with adverse events uncommon. The efficacy is supported by evidence that high concentration FVIIa binds to activated platelet surface and improves thrombin generation to enhance deposition (adhesion and aggregation of platelets lacking GPIIb/IIIa. While there are increasing clinical experiences, evidence-based clinical data are not available. There is a need for more clinical studies, particularly clinical trials, to further assess the efficacy, safety (particularly thrombotic events and optimal regimen of rFVIIa in GT patients, either singly or in combination with other hemostatic agents such as platelet transfusion. In the absence of this data, for treatment of severe bleeding in GT patients with platelet antibodies and platelet refractoriness, rFVIIa at dose 90 μg/kg every 2 h for 3 or more doses could be considered. This more “optimal regimen” derived from a recent International Survey needs confirmation with larger studies. What the optimal regimen for surgical coverage is remains unresolved.Keywords: Glanzmann’s thrombasthenia, recombinant human activated factor VII (rFVIIa, bleeding, surgery, platelet transfusion, GPIIb/IIIa

  18. Elevated expression of type VII collagen in the skin of patients with systemic sclerosis. Regulation by transforming growth factor-beta.

    OpenAIRE

    Rudnicka, L; Varga, J; Christiano, A M; Iozzo, R V; Jimenez, S A; Uitto, J

    1994-01-01

    A hallmark of systemic sclerosis (SSc) is the development of tissue fibrosis. Excessive production of several connective tissue components normally present in the dermis, including type I, III, V, and VI collagens as well as fibronectin and proteoglycans, is a consistent finding in the skin of SSc patients. Type VII collagen is a major constituent of anchoring fibrils, present in the skin at the dermal-epidermal basement membrane zone. TGF-beta has been shown to upregulate the expression of t...

  19. The regulation of the factor VII-dependent coagulation pathway: rationale for the effectiveness of recombinant factor VIIa in refractory bleeding disorders

    NARCIS (Netherlands)

    van't Veer, C.; Mann, K. G.

    2000-01-01

    We have explored the molecular basis of the clinical therapeutic effect of factor VIIa in hemophilia A using empirical reconstituted in vitro thrombin generation models. Tissue factor acts as a receptor and activator of preexistent but virtually inactive two-chain plasma factor VIIa. However, most

  20. [Genetic control of the sensitivity of Aspergillus nidulans to mutagenic factors. VII. Inheritance of cross-sensitivity to different mutagenic factors by uvs-mutants].

    Science.gov (United States)

    Evseeva, G V; Kameneva, S V

    1977-01-01

    To study the inheritance of the sensitivity to UV, X-rays, methylmethanesulphonate (MMS), nitrosoguanidine (NG) and nitrous acid (NA) in five uvs mutants of Aspergillus nidulans, having multiple sensitivity to these factors, the sensitivity of recombinants obtained from crossing uvs mutants with uvs+ strain, resistant to all the factors analysed, and uvs leads to uvs+ revertants is investigated. Four uvs mutants (15, 17, 19 and 26) are found to have a nomogenic control of sensitivity to different mutagens. In one mutant (uvs11) the sensitivity to five factors is controlled by two non-linked mutations, one of them determining the sensitivity to UV, NG, NA, and the other--to X-rays and MMC. Phenotypic manifestations of uvs mutations is modified by cell genotype, both chromosomal and cytoplasmic factors being responsible for the modification. Phenotypic modification of uvs mutation results in the change to some (but not to all) mutagenic factors. It suggests, that not the product of uvs gene, but some other components of the reparation complex are modified. Otherwise, reparation of different DNA damages can be carried out by a single enzyme acting in different reparation complexes.

  1. EKÜL VII Foorum = VII Forum SKTE / Sven Lillepalu

    Index Scriptorium Estoniae

    Lillepalu, Sven

    2004-01-01

    7. oktoobril toimus hotell Olümpia Alfa saalis EKÜL VII foorum. Ettekanded puudutasid järgmisi teemasid: korteriühistu remondi planeerimine, finantseerimine, nõuanded korteriühistuid puudutava seadusandluse kohta. Vt. samas: Eesti Korteriühistute VII Foorumi avalik pöördumine Eesti Vabariigi Valitsuse, Eesti Vabariigi Riigikogu, Eesti Vabariigi Presidendi poole lk. 9, 39

  2. What Are Rare Clotting Factor Deficiencies?

    Science.gov (United States)

    ... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ...

  3. In silico dissection of Type VII Secretion System components across ...

    Indian Academy of Sciences (India)

    2016-02-12

    Feb 12, 2016 ... Bio-Sciences R&D Division, TCS Innovation Labs, Tata Research Development & Design Centre, ... Type VII Secretion System (T7SS) is one of the factors involved in virulence of ... Such wide distribution of T7SS and.

  4. In silico dissection of Type VII Secretion System components across

    Indian Academy of Sciences (India)

    Type VII Secretion System (T7SS) is one of the factors involved in virulence of Mycobacteriun tuberculosis H37Rv. Numerous research efforts have been made in the last decade towards characterizing the components of this secretion system. An extensive genome-wide analysis through compilation of isolated information ...

  5. Are olive oil diets antithrombotic?

    DEFF Research Database (Denmark)

    Larsen, L. F.; Jespersen, J.; Marckmann, Peter

    1999-01-01

    compared the effects of virgin olive oil with those of rapeseed and sunflower oils on blood coagulation factor VII (FVII), a key factor in thrombogenesis. DESIGN: In a randomized and strictly controlled crossover study, 18 healthy young men consumed diets enriched with 5 g/MJ (19% of total energy) olive...... FVII (FVIIa) were 11.3 +/- 5.1 U/L lower after olive oil than after sunflower oil, an 18% reduction (P diets...... with respect to nonfasting factor VII coagulant activity (FVII:c), prothrombin fragment 1+2 (F1+2), and tissue factor pathway inhibitor (TFPI) concentrations, or with respect to fasting plasma values of FVII protein, FVII:c, FVIIa, F1+2, or TFPI. CONCLUSION: A background diet rich in olive oil may attenuate...

  6. Positivity VII (Zaanen Centennial Conference)

    CERN Document Server

    Pagter, Ben; Gaans, Onno; Veraar, Mark

    2016-01-01

    This book presents the proceedings of Positivity VII, held from 22-26 July 2013, in Leiden, the Netherlands. Positivity is the mathematical field concerned with ordered structures and their applications in the broadest sense of the word. A biyearly series of conferences is devoted to presenting the latest developments in this lively and growing discipline. The lectures at the conference covered a broad spectrum of topics, ranging from order-theoretic approaches to stochastic processes, positive solutions of evolution equations and positive operators on vector lattices, to order structures in the context of algebras of operators on Hilbert spaces. The contributions in the book reflect this variety and appeal to university researchers in functional analysis, operator theory, measure and integration theory and operator algebras. Positivity VII was also the Zaanen Centennial Conference to mark the 100th birth year of Adriaan Cornelis Zaanen, who held the chair of Analysis in Leiden for more than 25 years and was ...

  7. Large enhancement of functional activity of active site-inhibited factor VIIa due to protein dimerization: insights into mechanism of assembly/disassembly from tissue factor.

    Science.gov (United States)

    Stone, Matthew D; Harvey, Stephen B; Martinez, Michael B; Bach, Ronald R; Nelsestuen, Gary L

    2005-04-26

    Active site-inhibited blood clotting factor VIIa (fVIIai) binds to tissue factor (TF), a cell surface receptor that is exposed upon injury and initiates the blood clotting cascade. FVIIai blocks binding of the corresponding enzyme (fVIIa) or zymogen (fVII) forms of factor VII and inhibits coagulation. Although several studies have suggested that fVIIai may have superior anticoagulation effects in vivo, a challenge for use of fVIIai is cost of production. This study reports the properties of dimeric forms of fVIIai that are cross-linked through their active sites. Dimeric wild-type fVIIai was at least 75-fold more effective than monomeric fVIIai in blocking fVIIa association with TF. The dimer of a mutant fVIIai with higher membrane affinity was 1600-fold more effective. Anticoagulation by any form of fVIIai differed substantially from agents such as heparin and showed a delayed mode of action. Coagulation proceeded normally for the first minutes, and inhibition increased as equilibrium binding was established. It is suggested that association of fVIIa(i) with TF in a collision-dependent reaction gives equal access of inhibitor and enzyme to TF. Assembly was not influenced by the higher affinity and slower dissociation of the dimer. As a result, anticoagulation was delayed until the reaction reached equilibrium. Properties of different dissociation experiments suggested that dissociation of fVIIai from TF occurred by a two-step mechanism. The first step was separation of TF-fVIIa(i) while both proteins remained bound to the membrane, and the second step was dissociation of the fVIIa(i) from the membrane. These results suggest novel actions of fVIIai that distinguish it from most of the anticoagulants that block later steps of the coagulation cascade.

  8. FAKTOR-FAKTOR YANG MEMENGARUHI PRODUKSI GULA PTPN VII (PERSERO

    Directory of Open Access Journals (Sweden)

    Rizky Savitri

    2014-09-01

    Full Text Available ABSTRACTThis study aimed to analyze the influence of the level of sugar cane yield, labor, production process period, and supporting materials on the production of PTPN VII (Persero PG. Cinta Manis, as well as analyzing the elasticity of production and business scale  of PTPN VII (Persero PG. Cinta Manis. The method used to analyze the data were quantitative analysis of Cobb Douglas production function with ordinary least square method to observe variable influences of PG. Cinta Manis sugar production. Cobb Douglas estimation results indicate that the level of sugar cane yield, labor, production process period, and supporting materials affect sugar production in PTPN VII (Persero PG. Cinta Manis. Production elasticity of each production factor shows that the use of production factors is not yet optimal, while the production scale of the company is Increasing Return to Scale (IRTS in which the proportion of additional input will produce output with the larger proportion. Accordingly, company should utilize the factors of production optimally, improve the quality of human resources with various activities to improve skills, increase the productivity of land by having land intensification, and optimize milling period by improving the quality of machine.Keywords: PG. Cinta Manis, increasing return to scale, Cobb Douglas function, PTPN VIIABSTRAKPenelitian ini bertujuan menganalisis pengaruh tingkat rendemen, tenaga kerja, bahan pembantu dan lama lama giling terhadap produksi gula PTPN VII (Persero PG. Cinta Manis, sekaligus menganalisis elastisitas produksi dan skala usaha PTPN VII (Persero PG. Cinta Manis. Metode analisis data yang digunakan adalah  analisis kuantitatif. Analisis kuantitatif pada penelitian ini menggunakan fungsi produksi cobb douglas dengan metode ordinary least square untuk melihat pengaruh variabel-variabel yang telah ditentukan terhadap produksi gula PG. Cinta Manis. Hasil estimasi cobb douglas menunjukkan  bahwa tingkat

  9. Overview on W VII-X

    International Nuclear Information System (INIS)

    Wobig, H.

    1988-01-01

    Configurations for the W VII-X stellarator are reviewed. The MHD analysis of the Helias configuration with four field periods previously considered shows that the ballooning mode limit of the maximum plasma pressure increases with increasing number of field periods. Interest is focused on five-period Helias configurations with ballooning mode limits around a Beta factor of 5 %. Four configurations are discussed: HS4-12, an improved version of HS4-8; HS5-6, based on a quasi-helical equilibrium; plus two slightly different configurations designated as HS5-7 and HS5-8. It is proposed to increase the dimensions of the whole experiment to R=6.5m and to reduce the magnetic field to B=3T on the axis

  10. What Is Combined Deficiency of Vitamin K-Dependent Clotting Factors?

    Science.gov (United States)

    ... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ...

  11. Genetics Home Reference: glycogen storage disease type VII

    Science.gov (United States)

    ... Home Health Conditions Glycogen storage disease type VII Glycogen storage disease type VII Printable PDF Open All ... Javascript to view the expand/collapse boxes. Description Glycogen storage disease type VII (GSDVII) is an inherited ...

  12. Cost-utility analysis of immune tolerance induction therapy versus on-demand treatment with recombinant factor VII for hemophilia A with high titer inhibitors in Iran

    Directory of Open Access Journals (Sweden)

    Rasekh HR

    2011-11-01

    Full Text Available Hamid Reza Rasekh1, Ali Imani1, Mehran Karimi2, Mina Golestani11Shahid Beheshti University of Medical Sciences, Department of Pharmaceutical Management and Pharmacoeconomics, School of Pharmacy, Tehran, 2University of Shiraz Medical Sciences, Hematology Research Center, Shiraz, IranBackground: In developing countries, the treatment of hemophilia patients with inhibitors is presently the most challenging and serious issue in hemophilia management, direct costs of clotting factor concentrates accounting for >98% of the highest economic burden absorbed for the health care of patients in this setting. In the setting of chronic diseases, cost-utility analysis, which takes into account the beneficial effects of a given treatment/health care intervention in terms of health-related quality of life, is likely to be the most appropriate approach.Objective: The aim of this study was to assess the incremental cost-effectiveness ratios of immune tolerance induction (ITI therapy with plasma-derived factor VIII concentrates versus on-demand treatment with recombinant-activated FVIIa (rFVIIa in hemophilia A with high titer inhibitors from an Iranian Ministry of Health perspective.Methods: This study was based on the study of Knight et al, which evaluated the cost-effectiveness ratios of different treatments for hemophilia A with high-responding inhibitors. To adapt Knight et al's results to the Iranian context, a few clinical parameters were varied, and cost data were replaced with the corresponding Iranian estimates of resource use. The time horizon of the analysis was 10 years. One-way sensitivity analyses were performed, varying the cost of the clotting factor, the drug dose, and the administration frequency, to test the robustness of the analysis.Results: Comparison of the incremental cost-effectiveness ratios between the three ITI protocols and the on-demand regimen with rFVIIa shows that all three ITI protocols dominate the on-demand regimen with r

  13. Assessment of individual dose utilization vs. physician prescribing recommendations for recombinant activated factor VII (rFVIIa) in paediatric and adult patients with congenital haemophilia and alloantibody inhibitors (CHwI): the Dosing Observational Study in Hemophilia (DOSE).

    Science.gov (United States)

    Gruppo, R A; Kessler, C M; Neufeld, E J; Cooper, D L

    2013-07-01

    Recent data from the Dosing Observational Study in Hemophilia diary study has described home treatment with recombinant activated factor VII (rFVIIa) in congenital haemophilia with inhibitors (CHwI). The current analysis compares prescribed and patient/caregiver-reported rFVIIa administration in paediatric and adult CHwI patients in this study. Patients with ≥ 4 bleeding episodes within a 3-month period prescribed rFVIIa as first-line therapy for bleeding episodes were eligible. Patients/caregivers completed a diary for ≥ 90 days or until the patient experienced four bleeds. Initial, total and mean rFVIIa doses reported for each bleeding episode were calculated and compared with the physician-prescribed doses. Of 52 enrolled patients (25 children; 27 adults), 39 (75%) completed the study. Children and adults had similar mean durations of bleeding episodes. Both patient groups were administered higher initial rFVIIa doses for joint bleeds than prescribed: median (range) 215.2 (74.1-400.0) mcg kg(-1) vs. 200.0 (61.0-270.0) mcg kg(-1) for children, and 231.3 (59.3-379.7) mcg kg(-1) vs. 123.0 (81.0-289.0) mcg kg(-1) for adults. The median infused dose for joint bleeds was higher in adults than children (175.2 vs. 148.0 mcg kg(-1) ), but children received significantly more doses per joint bleed than adults (median 6.5 vs. 3.0). The median total dose per joint bleed was higher in children than adults (1248.7 vs. 441.6). For children and adults, both initial and additional doses administered for bleeds were higher than prescribed. Children received higher total doses per bleed due to an increased number of infusions per bleed. © 2013 John Wiley & Sons Ltd.

  14. Creactive protein and interleukin-6 as markers of systemic inflammatory response and as prognostic factors for metastatic colorectal cancer. Data from the randomized phase III NORDIC-VII study

    DEFF Research Database (Denmark)

    Thomsen, M.; Kersten, C.; Sorbye, H.

    2015-01-01

    -6 (IL-6). Methods: The study was based on data from the randomized phase III NORDIC-VII study (Nordic FLOX +/cetuximab as first line treatment of mCRC). The effect of different markers of SIR, including modified Glasgow Prognostic Score (mGPS), derived Neutrophil Lymphocyte Ratio (dNLR), levels...

  15. Neutral transport calculations for W VII-X. First applications to W VII-X

    International Nuclear Information System (INIS)

    Sardei, F.

    1988-01-01

    Results of neutral gas transport calculations obtained with the DEGAS code are presented for a W VII-AS model plasma and a source of neutrals due to limiter recycling. For typical profiles of the plasma parameters as predicted for an ECRH discharge, the simulation yields a radial drop of the average neutral population by a factor of 30. The neutrals are strongly localized near the limiter and have a poloidal minimum at its opposite side. For a W VII-X configuration (HS4-12), a neutral source given by a high recycling ion flux equally distributed over the wall is considered. For an ion density of 5 x 10 1 3 /cc and 30 eV edge temperature, the neutrals originating from the wall completely ionize within the ergodic region. The corresponding average energy of cx neutrals hitting the wall is less than 30 eV. Neutral penetration into the plasma locally depends on the distance between wall and separatrix

  16. Reaction of Pu(VII) with certain aliphatic alcohols in basic media

    International Nuclear Information System (INIS)

    Tananaev, I.G.

    1992-01-01

    The kinetics of Pu(VII) reduction by methanol and ethanol in 0.5-5.0 M NaOH are studied by spectrophotometry. The rate constants of the studied reactions are calculated. The rate constants increase in concert with the reductant concentration but sharply decrease with increasing base concentration in the reaction medium. The principal factor affecting the rate of Pu(VII) reduction by alcohols is probably steric in nature. Secondary alcohols are more active in basic medium. The resulting experimental data also confirm the very strong oxidizing capability of Pu(VII), the rate of reduction of which by CH 3 OH or C 2 H 5 OH compared with Np(VII) under similar conditions is 20-50 times faster

  17. Wendelstein VII-A in torsatron mode

    International Nuclear Information System (INIS)

    Harmeyer, E.; Kisslinger, J.; Rau, F.; Wobig, H.

    1985-03-01

    Variable shear - positive or negative, up to about 20 percent - can be introduced into the Wendelstein VII-A Stellarator vacuum field configuration by different currents in the two helix systems, and balancing the resulting vertical field. (orig.)

  18. Extraction of Tc(VII) and Re(VII) on TRU resin

    Energy Technology Data Exchange (ETDEWEB)

    Guerin, Nicolas; Riopel, Remi; Kramer-Tremblay, Sheila [Canadian Nuclear Laboratories (CNL), Chalk River, ON (Canada). Radiobiology and Health Branch; De Silva, Nimal; Cornett, Jack [Ottawa Univ., ON (Canada). Dept. of Earth and Environmental Sciences; Dai, Xiongxin [China Institute for Radiation Protection, Beijing (China)

    2017-06-01

    TRU resin can be used to rapidly and selectively extract Tc(VII) and Re(VII). The retention capacity curves of Tc(VII) and Re(VII) for HNO{sub 3}, HCl, H{sub 2}SO{sub 4} and H{sub 3}PO{sub 4} solutions were studied and prepared. Tc(VII) and Re(VII) were simultaneously extracted in 2 M H{sub 2}SO{sub 4} and 1.5 M H{sub 3}PO{sub 4} and were effectively separated from Mo(VI) and Ru(III). Tc(VII) and Re(VII) remained strongly bonded to the resin even after washing using a large volume of 2 M H{sub 2}SO{sub 4} at a relatively high flow rate. Also, they were both completely eluted from the resin using 15 mL of near boiling water, an eluent directly compatible for ICP-MS instrument measurements.

  19. Inflammation, thrombosis, and atherosclerosis

    DEFF Research Database (Denmark)

    de Maat, M.P.M.; Bladbjerg, E.M.; Drivsholm, T.

    2003-01-01

    artery and the assessment of plaque occurrence. Plasma samples were analyzed for the concentration of C-reactive protein (CRP), fibrinogen, d-dimer, plasminogen activator inhibitor type-1 (PAI-1) antigen and activity, tissue-type plasminogen activator (t-PA) antigen and activity, factor VII (FVII......) antigen, FVII coagulant activity (FVII:C) and activated FVII (FVIIa). DNA variations were determined for fibrinogen, PAI-1, t-PA, FVII, factor XIII and methylene tetrahydrofolate reductase (MTHFR). Subjects with high IMT (upper 10% of distribution, n = 63) had higher CRP levels [2.2 mg L-1 (SE 0.3)] than...... subjects with IMT in the lowest tertile (n = 217) [1.7 mg L-1 (SE 0.1), P = 0.04], whereas there was no association between the hemostatic variables and IMT. There was an association between fibrinogen and d-dimer concentrations and number of plaques (P

  20. European Energy Law. Report VII

    Energy Technology Data Exchange (ETDEWEB)

    Hammer, U.; Roggenkamp, M.M. (eds.)

    2010-04-15

    The European Energy Law Report VII presents in four parts an overview of the most important legal developments in the field of EU and national energy and climate change law as discussed at the 2009 European Energy Law Seminar. The first part examines recent developments in EU climate change regulation. It includes an overview of the revision of the EU Directive governing CO2 emissions trading and a more detailed analysis of the new allocation regime, including the auctioning of emission rights. This is followed by an analysis of the competitiveness of the new EU emissions trading Directive and recent developments in the US regarding emissions trading. The second part focuses on the energy liberalisation process and the Third Energy Package. Following an overview of recent developments in EU competition law and the impact of the Sector Inquiry on the energy sector, this part concentrates particularly on the new Internal Energy Market Directives and most particularly on the legality of the unbundling provisions. Subsequently, the focus is on the role of the TSOs. After an analysis of the need for an increased cooperation of the German TSOs, another chapter discusses the need for more consolidation in the European gas transmission market and the role of regulation therein. Is there a new role for nuclear energy? In order to secure long term energy supply, the focus turns again to nuclear energy. The third part of this report discusses two elements of nuclear liability. First, it analyses the issue of the possible privatisation of the nuclear sector and its impact on long term liability. Although the focus is on the UK nuclear sector, a comparison is made with some other regulatory regimes. Next, the role of nuclear energy is discussed as an instrument to reduce CO2 emissions and, more particularly as a means to reach the 20-20-20 targets. The question is raised whether the international rules on civil liability provide sufficient protection to victims of nuclear

  1. Quantitative analysis of the synthesis and secretion of type VII collagen in cultured human dermal fibroblasts with a sensitive sandwich enzyme-linked immunoassay.

    Science.gov (United States)

    Amano, Satoshi; Ogura, Yuki; Akutsu, Nobuko; Nishiyama, Toshio

    2007-02-01

    Type VII collagen is the major component of anchoring fibrils in the epidermal basement membrane. Its expression has been analyzed by immunostaining or Northern blotting, but rarely at the protein level. In this study, we have quantitatively examined the effects of ascorbic acid and various cytokines/growth factors on the protein synthesis and secretion of type VII collagen by human dermal fibroblasts in culture, using a developed, highly sensitive sandwich enzyme-linked immunoassay with two kinds of specific monoclonal antibodies against the non-collagenous domain-1. Ascorbic acid and its derivative induced a twofold increase in type VII collagen synthesis, and markedly increased the secretion of type VII collagen into the medium when compared with the control culture. This effect was not influenced by the presence of transforming growth factor-beta1 (TGF-beta1). The synthesis of type VII collagen was elevated by TGF-beta1, platelet-derived growth factor, tumor necrosis factor-alpha, and interleukin-1beta, but not by TGF-alpha. Thus, our data indicate that the synthesis and secretion of type VII collagen in human dermal fibroblasts are regulated by ascorbate and the enhancement of type VII collagen gene expression by cytokines/growth factors is accompanied with elevated production of type VII collagen at the protein level.

  2. 77 FR 64400 - Order of Succession for HUD Region VII

    Science.gov (United States)

    2012-10-19

    ... DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT [FR-5550-D-10] Order of Succession for HUD Region VII... Offices (Region VII). This Order of Succession supersedes all previous Orders of Succession for HUD Region...). This publication supersedes all previous Orders of Succession for Region VII. Accordingly, the...

  3. Pseudane-VII Isolated from Pseudoalteromonas sp. M2 Ameliorates LPS-Induced Inflammatory Response In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Mi Eun Kim

    2017-11-01

    Full Text Available The ocean is a rich resource of flora, fauna, food, and biological products. We found a wild-type bacterial strain, Pseudoalteromonas sp. M2, from marine water and isolated various secondary metabolites. Pseudane-VII is a compound isolated from the Pseudoalteromonas sp. M2 metabolite that possesses anti-melanogenic activity. Inflammation is a response of the innate immune system to microbial infections. Macrophages have a critical role in fighting microbial infections and inflammation. Recent studies reported that various compounds derived from natural products can regulate immune responses including inflammation. However, the anti-inflammatory effects and mechanism of pseudane-VII in macrophages are still unknown. In this study, we investigated the anti-inflammatory effects of pseudane-VII. In present study, lipopolysaccharide (LPS-induced nitric oxide (NO production was significantly decreased by pseudane-VII treatment at 6 μM. Moreover, pseudane-VII treatment dose-dependently reduced mRNA levels of pro-inflammatory cytokines including inos, cox-2, il-1β, tnf-α, and il-6 in LPS-stimulated macrophages. Pseudane-VII also diminished iNOS protein levels and IL-1β secretion. In addition, Pseudane-VII elicited anti-inflammatory effects by inhibiting ERK, JNK, p38, and nuclear factor (NF-κB-p65 phosphorylation. Consistently, pseudane-VII was also shown to inhibit the LPS-stimulated release of IL-1β and expression of iNOS in mice. These results suggest that pseudane-VII exerted anti-inflammatory effects on LPS-stimulated macrophage activation via inhibition of ERK, JNK, p38 MAPK phosphorylation, and pro-inflammatory gene expression. These findings may provide new approaches in the effort to develop anti-inflammatory therapeutics.

  4. Pseudane-VII Isolated from Pseudoalteromonas sp. M2 Ameliorates LPS-Induced Inflammatory Response In Vitro and In Vivo.

    Science.gov (United States)

    Kim, Mi Eun; Jung, Inae; Lee, Jong Suk; Na, Ju Yong; Kim, Woo Jung; Kim, Young-Ok; Park, Yong-Duk; Lee, Jun Sik

    2017-11-01

    The ocean is a rich resource of flora, fauna, food, and biological products. We found a wild-type bacterial strain, Pseudoalteromonas sp. M2, from marine water and isolated various secondary metabolites. Pseudane-VII is a compound isolated from the Pseudoalteromonas sp. M2 metabolite that possesses anti-melanogenic activity. Inflammation is a response of the innate immune system to microbial infections. Macrophages have a critical role in fighting microbial infections and inflammation. Recent studies reported that various compounds derived from natural products can regulate immune responses including inflammation. However, the anti-inflammatory effects and mechanism of pseudane-VII in macrophages are still unknown. In this study, we investigated the anti-inflammatory effects of pseudane-VII. In present study, lipopolysaccharide (LPS)-induced nitric oxide (NO) production was significantly decreased by pseudane-VII treatment at 6 μM. Moreover, pseudane-VII treatment dose-dependently reduced mRNA levels of pro-inflammatory cytokines including inos , cox-2 , il-1β , tnf-α , and il-6 in LPS-stimulated macrophages. Pseudane-VII also diminished iNOS protein levels and IL-1β secretion. In addition, Pseudane-VII elicited anti-inflammatory effects by inhibiting ERK, JNK, p38, and nuclear factor (NF)-κB-p65 phosphorylation. Consistently, pseudane-VII was also shown to inhibit the LPS-stimulated release of IL-1β and expression of iNOS in mice. These results suggest that pseudane-VII exerted anti-inflammatory effects on LPS-stimulated macrophage activation via inhibition of ERK, JNK, p38 MAPK phosphorylation, and pro-inflammatory gene expression. These findings may provide new approaches in the effort to develop anti-inflammatory therapeutics.

  5. Evaluation of the biological differences of canine and human factor VIII in gene delivery: Implications in human hemophilia treatment

    Science.gov (United States)

    The canine is the most important large animal model for testing novel hemophilia A(HA) treatment. It is often necessary to use canine factor VIII (cFIII) gene or protein for the evaluation of HA treatment in the canine model. However, the different biological properties between cFVIII and human FVII...

  6. ENDF/B-VII.1 versus ENDF/B-VII.0: What's Different?

    International Nuclear Information System (INIS)

    Cullen, D.E.

    2012-01-01

    Recently the new ENDF/B-VII.1 library was released; this completely replaces the earlier ENDF/B-VII.0 library. One of the first questions we ask about a new library is: What's Different? Here I attempt to at least partially answer this question. I present results in both tabulated form (so you can quickly determine if any evaluations of interest to you have changed), and graphic form (so that you can see how much evaluations have changed and in what energy ranges). For the table I have compared what I refer to as the ENDF neutron data, namely MF=1 through 6. Here I did a character-by-character comparison of the same sections (MF/MT) that appear I both ENDF/B-VII.0 and VII.1; here I found differences in 170 evaluations. For the plots I have only compared the total cross sections for all evaluations that are common to both libraries, and I found that of the 423 evaluations in ENDF/B-VII.1, 120 of these have total cross sections that differ by 1% or more from the evaluation of the same isotope in ENDF/B-VII.0. This should be considered only a preliminary comparison; obviously there can be more subtle important differences that do not effect of total cross sections. Here I present plots comparing the total cross section of these 120 isotopes. The plots are only broad overviews of the total cross sections over their entire energy range. If you have interest in more detailed plots for specific evaluations, you can download the evaluations (1,2) and the PREPRO (3) codes I used to prepare and view the data. This is all I needed to do my comparisons, and is all you should need to do any more detailed comparisons to meet your individual needs.

  7. Frederik VII og folkets kærlighed

    DEFF Research Database (Denmark)

    Perlt, Michael; Vinding, Niels Valdemar

    2013-01-01

    I den turbulente tid mellem de to slesvigske krige drog kong Frederik VII under en rejse til Jylland i 1857 i procession op på højene i Jelling for at modtage folkets hyldest. På det historiske sted lod Frederik VII sig fejre som danskernes konge under en stor folkefest med bønder og deres familier...

  8. Nuclear energy and astrophysics applications of ENDF/B-VII.1 evaluated nuclear library

    International Nuclear Information System (INIS)

    Pritychenko, B.

    2012-01-01

    Recently released ENDF/B-VII.1 evaluated nuclear library contains the most up-to-date evaluated neutron cross section and covariance data. These data provide new opportunities for nuclear science and astrophysics application development. The improvements in neutron cross section evaluations and more extensive utilization of covariance files, by the Cross Section Evaluation Working Group (CSEWG) collaboration, allowed users to produce neutron thermal cross sections, Westcott factors, resonance integrals, Maxwellian-averaged cross sections and astrophysical reaction rates, and provide additional insights on the currently available neutron-induced reaction data. Nuclear reaction calculations using the ENDF/B-VII.1 library and current computer technologies will be discussed and new results will be presented

  9. TEH võrgustik - viis aastat Eestis / Marika Kusnets

    Index Scriptorium Estoniae

    Kusnets, Marika

    2005-01-01

    Eestis on tervist edendavate haiglate (TEH) võrgustik tegutsenud juba viis aastat, sellega on liitunud 22 haiglat. Tänavust konverentsi peeti teemal "Tervise edendamine ja kvaliteedi tagamine haiglas: standardid ja praktika"

  10. Faktor-faktor Yang Memengaruhi Produksi Gula PTPN VII (Persero)

    OpenAIRE

    Savitri, Rizky; Widyastutik, Widyastutik

    2013-01-01

    This study aimed to analyze the influence of the level of sugar cane yield, labor, production process period, and supporting materials on the production of PTPN VII (Persero) PG. Cinta Manis, as well as analyzing the elasticity of production and business scale of PTPN VII (Persero) PG. Cinta Manis. The method used to analyze the data were quantitative analysis of Cobb Douglas production function with ordinary least square method to observe variable influences of PG. Cinta Manis sugar product...

  11. Separation of Rhenium (VII) from Tungsten (VI)

    International Nuclear Information System (INIS)

    Vucina, J.; Lukic, D.; Stoiljkovic, M.; Milosevic, M.; Orlic, M.

    2004-01-01

    Examined were the conditions for an effective separation of tungsten (VI) and rhenium (VII) on alumina if the solution of 0.20 mol dm -3 NaCl, ph=2.6 is used as the aqueous phase. Under the given experimental conditions alumina was found to be much better adsorbent for tungsten than for rhenium. The breakthrough and saturation capacities of alumina at pH=2 are 24 and 78 mg W/g Al 2 O 3 , respectively. With the increase of pH these values decrease. So, at pH=6 they are only 4 and 13 mg W/g Al 2 O 3 respectively. The elution volume for rhenium for the given column dimensions and quantity of the adsorbent is about 16 ml. These results were confirmed by the experiments of the radiological separations. Tungsten-187 remains firmly bound to the alumina. The radionuclide purity of the eluted 186'188 Re at pH=2 is very high. (authors)

  12. Analysis of the ZPPR-15 Critical Experiments with ENDF/B-V.2 and ENDF/B-VII.0 Data

    International Nuclear Information System (INIS)

    Kim, Sang Ji; Yang, Won Sik; Lee, Changho

    2008-01-01

    This paper presents the analysis results for the ZPPR-15 critical experiments. Using the ENDF/B-V.2 and ENDF/B-VII.0 data, three loading configurations of the ZPPR-15 Phase A experiments were analyzed with the ANL code suite for a fast reactor neutronics analysis, including the recently updated MC 2 -2 code. For the VIM Monte Carlo analyses with 3-D as-built models, the ENDF/B-VII.0 data improved the core multiplication factors by 0.21 to 0.37 %Δk, relative to the ENDF/B-V.2 data. With the plate heterogeneity effects taken into account by the SDX 1-D unit cell calculations, the DIF3D nodal transport solutions with the ENDF/B-V.2 data showed a good agreement for the core multiplication factors with the VIM Monte Carlo results to within 0.12 %Δk, but those with the ENDF/B-VII.0 data showed relatively larger deviations. Sensitivity studies based on the RZ models with homogenized cells showed excellent agreement for the core multiplication factors between the deterministic and Monte Carlo calculations to within 0.1 %Δk for both ENDF/B data. These results indicate that the MC 2 -2 methods are adequate for generating the multigroup cross sections for a fast reactor analysis, but the SDX process to account for the heterogeneity effect needs to be improved for the ENDF/B-VII.0 data. (authors)

  13. Experimental evidence for competitive growth advantage of genotype VII over VI: implications for foot-and-mouth disease virus serotype A genotype turnover in nature.

    Science.gov (United States)

    Mohapatra, J K; Subramaniam, S; Singh, N K; Sanyal, A; Pattnaik, B

    2012-04-01

    In India, systematic genotype replacement has been observed for serotype A foot-and-mouth disease virus. After a decade of co-circulation of genotypes VI and VII, genotype VII emerged as the single dominant genotype since 2001. To derive possible explanations for such epochal evolution dynamics, in vitro intergenotype growth competition experiments involving both co- and superinfection regimes were conducted. Coinfection of BHK-21 cells demonstrated abrupt loss in the genotype VI viral load with commensurate increase in the load of genotype VII as measured by the genotype differentiating ELISA, RT-PCR and real-time RT-PCR. The superinfection dynamics was shaped by temporal spacing of infection, where the invading genotype VII took more number of passages than coinfection to eventually overtake the resident genotype VI. It was speculated that such superior replicative fitness of genotype VII could have been a possible factor for the ultimate dominance of genotype VII in nature. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Benchmarking ENDF/B-VII.0

    International Nuclear Information System (INIS)

    Marck, Steven C. van der

    2006-01-01

    The new major release VII.0 of the ENDF/B nuclear data library has been tested extensively using benchmark calculations. These were based upon MCNP-4C3 continuous-energy Monte Carlo neutronics simulations, together with nuclear data processed using the code NJOY. Three types of benchmarks were used, viz., criticality safety benchmarks (fusion) shielding benchmarks, and reference systems for which the effective delayed neutron fraction is reported. For criticality safety, more than 700 benchmarks from the International Handbook of Criticality Safety Benchmark Experiments were used. Benchmarks from all categories were used, ranging from low-enriched uranium, compound fuel, thermal spectrum ones (LEU-COMP-THERM), to mixed uranium-plutonium, metallic fuel, fast spectrum ones (MIX-MET-FAST). For fusion shielding many benchmarks were based on IAEA specifications for the Oktavian experiments (for Al, Co, Cr, Cu, LiF, Mn, Mo, Si, Ti, W, Zr), Fusion Neutronics Source in Japan (for Be, C, N, O, Fe, Pb), and Pulsed Sphere experiments at Lawrence Livermore National Laboratory (for 6 Li, 7 Li, Be, C, N, O, Mg, Al, Ti, Fe, Pb, D 2 O, H 2 O, concrete, polyethylene and teflon). For testing delayed neutron data more than thirty measurements in widely varying systems were used. Among these were measurements in the Tank Critical Assembly (TCA in Japan) and IPEN/MB-01 (Brazil), both with a thermal spectrum, and two cores in Masurca (France) and three cores in the Fast Critical Assembly (FCA, Japan), all with fast spectra. In criticality safety, many benchmarks were chosen from the category with a thermal spectrum, low-enriched uranium, compound fuel (LEU-COMP-THERM), because this is typical of most current-day reactors, and because these benchmarks were previously underpredicted by as much as 0.5% by most nuclear data libraries (such as ENDF/B-VI.8, JEFF-3.0). The calculated results presented here show that this underprediction is no longer there for ENDF/B-VII.0. The average over 257

  15. (111)Indium Labelling of Recombinant Activated Coagulation Factor VII

    DEFF Research Database (Denmark)

    Nalla, Amarnadh; Buch, Inge; Sigvardt, Maibritt

    2012-01-01

    The aim of this study is to investigate whether (111)Indium-labelled recombinant FVIIa (rFVIIa) could be a potential radiopharmaceutical for localization of bleeding sources. DTPA-conjugated rFVIIa was radiolabelled with (111)In chloride. In vitro binding efficiency of (111)In-DTPA-rFVIIa to F1A2...

  16. Recombinant activated factor VII for uncontrolled bleeding postcardiac surgery

    Directory of Open Access Journals (Sweden)

    Aly Makram Habib

    2016-10-01

    Conclusion: In this analysis, rFVIIa succefully reduced the chest tube bleeding and blood products transfused during severe post cardiac surgical bleeding. However, safety of rFVIIa remains unclear. Prospective controlled trials are still needed to confirm the role of rFVIIa.

  17. VII International Congress of Engineering Physics

    Science.gov (United States)

    2015-01-01

    In the frame of the fortieth anniversary celebration of the Universidad Autónoma Metropolitana and the Physics Engineering career, the Division of Basic Science and Engineering and its Departments organized the "VII International Congress of Physics Engineering". The Congress was held from 24 to 28 November 2014 in Mexico City, Mexico. This congress is the first of its type in Latin America, and because of its international character, it gathers experts on physics engineering from Mexico and all over the globe. Since 1999, this event has shown research, articles, projects, technological developments and vanguard scientists. These activities aim to spread, promote, and share the knowledge of Physics Engineering. The topics of the Congress were: • Renewable energies engineering • Materials technology • Nanotechnology • Medical physics • Educational physics engineering • Nuclear engineering • High precision instrumentation • Atmospheric physics • Optical engineering • Physics history • Acoustics This event integrates lectures on top trending topics with pre-congress workshops, which are given by recognized scientists with an outstanding academic record. The lectures and workshops allow the exchange of experiences, and create and strengthen research networks. The Congress also encourages professional mobility among all universities and research centres from all countries. CIIF2014 Organizing and Editorial Committee Dr. Ernesto Rodrigo Vázquez Cerón Universidad Autónoma Metropolitana - Azcapotzalco ervc@correo.azc.uam.mx Dr. Luis Enrique Noreña Franco Universidad Autónoma Metropolitana - Azcapotzalco lnf@correo.azc.uam.mx Dr. Alberto Rubio Ponce Universidad Autónoma Metropolitana - Azcapotzalco arp@correo.azc.uam.mx Dr. Óscar Olvera Neria Universidad Autónoma Metropolitana - Azcapotzalco oon@correo.azc.uam.mx Professor Jaime Granados Samaniego Universidad Autónoma Metropolitana - Azcapotzalco jgs@correo.azc.uam.mx Dr. Roberto Tito Hern

  18. Factor Xa generation by computational modeling: an additional discriminator to thrombin generation evaluation.

    Directory of Open Access Journals (Sweden)

    Kathleen E Brummel-Ziedins

    Full Text Available Factor (fXa is a critical enzyme in blood coagulation that is responsible for the initiation and propagation of thrombin generation. Previously we have shown that analysis of computationally generated thrombin profiles is a tool to investigate hemostasis in various populations. In this study, we evaluate the potential of computationally derived time courses of fXa generation as another approach for investigating thrombotic risk. Utilizing the case (n = 473 and control (n = 426 population from the Leiden Thrombophilia Study and each individual's plasma protein factor composition for fII, fV, fVII, fVIII, fIX, fX, antithrombin and tissue factor pathway inhibitor, tissue factor-initiated total active fXa generation was assessed using a mathematical model. FXa generation was evaluated by the area under the curve (AUC, the maximum rate (MaxR and level (MaxL and the time to reach these, TMaxR and TMaxL, respectively. FXa generation was analyzed in the entire populations and in defined subgroups (by sex, age, body mass index, oral contraceptive use. The maximum rates and levels of fXa generation occur over a 10- to 12- fold range in both cases and controls. This variation is larger than that observed with thrombin (3-6 fold in the same population. The greatest risk association was obtained using either MaxR or MaxL of fXa generation; with an ∼2.2 fold increased risk for individuals exceeding the 90(th percentile. This risk was similar to that of thrombin generation(MaxR OR 2.6. Grouping defined by oral contraceptive (OC use in the control population showed the biggest differences in fXa generation; a >60% increase in the MaxR upon OC use. FXa generation can distinguish between a subset of individuals characterized by overlapping thrombin generation profiles. Analysis of fXa generation is a phenotypic characteristic which may prove to be a more sensitive discriminator than thrombin generation among all individuals.

  19. Perturbation fields in W VII-AS and Helias configurations

    International Nuclear Information System (INIS)

    Harmeyer, E.; Kisslinger, J.; Montvai, A.; Rau, F.; Wobig, H.

    1988-01-01

    Effects of pertubed topologies of the W VII-AS vacuum fields on the configuration with rational and irrational rotational transform are illustrated. Even small perturbation fields are unacceptable at rational values of the rotational transform. For example at a rotational transform = 1/2 in W VII-AS, when exceeding an effective homogeneous Bx/B = 3 x 10 -4 , the size of the rotational transform = 1/2 = 5/10 islands is doubled. At irrational values a Bx/B = 1/2% shows tolerable effects, for both W VII-AS and HS4-12. At rational values of the rotational transform = 1 near the edge, Bx/B values = 1/4 to 1/8% show a rather large increase of the aspect ratio, so an edge value of rotational transform = 1 should be avoided

  20. Amino acid sequence and posttranslational modifications of human factor VIIa from plasma and transfected baby hamster kidney cells

    International Nuclear Information System (INIS)

    Thim, L.; Bjoern, S.; Christensen, M.; Nicolaisen, E.M.; Lund-Hansen, T.; Pedersen, A.H.; Hedner, U.

    1988-01-01

    Blood coagulation factor VII is a vitamin K dependent glycoprotein which in its activated form, factor VII a , participates in the coagulation process by activating factor X and/or factor IX in the presence of Ca 2+ and tissue factor. Three types of potential posttranslational modifications exist in the human factor VII a molecule, namely, 10 γ-carboxylated, N-terminally located glutamic acid residues, 1 β-hydroxylated aspartic acid residue, and 2 N-glycosylated asparagine residues. In the present study, the amino acid sequence and posttranslational modifications of recombinant factor VII a as purified from the culture medium of a transfected baby hamster kidney cell line have been compared to human plasma factor VII a . By use of HPLC, amino acid analysis, peptide mapping, and automated Edman degradation, the protein backbone of recombinant factor VII a was found to be identical with human factor VII a . Asparagine residues 145 and 322 were found to be fully N-glycosylated in human plasma factor VII a . In the recombinant factor VII a , asparagine residue 322 was fully glycosylated whereas asparagine residue 145 was only partially (approximately 66%) glycosylated. Besides minor differences in the sialic acid and fucose contents, the overall carbohydrate compositions were nearly identical in recombinant factor VII a and human plasma factor VII a . These results show that factor VII a as produced in the transfected baby hamster kidney cells is very similar to human plasma factor VII a and that this cell line thus might represent an alternative source for human factor VII a

  1. Plasmodium falciparum ookinete expression of plasmepsin VII and plasmepsin X.

    Science.gov (United States)

    Li, Fengwu; Bounkeua, Viengngeun; Pettersen, Kenneth; Vinetz, Joseph M

    2016-02-24

    Plasmodium invasion of the mosquito midgut is a population bottleneck in the parasite lifecycle. Interference with molecular mechanisms by which the ookinete invades the mosquito midgut is one potential approach to developing malaria transmission-blocking strategies. Plasmodium aspartic proteases are one such class of potential targets: plasmepsin IV (known to be present in the asexual stage food vacuole) was previously shown to be involved in Plasmodium gallinaceum infection of the mosquito midgut, and plasmepsins VII and plasmepsin X (not known to be present in the asexual stage food vacuole) are upregulated in Plasmodium falciparum mosquito stages. These (and other) parasite-derived enzymes that play essential roles during ookinete midgut invasion are prime candidates for transmission-blocking vaccines. Reverse transcriptase PCR (RT-PCR) was used to determine timing of P. falciparum plasmepsin VII (PfPM VII) and plasmepsin X (PfPM X) mRNA transcripts in parasite mosquito midgut stages. Protein expression was confirmed by western immunoblot and immunofluorescence assays (IFA) using anti-peptide monoclonal antibodies (mAbs) against immunogenic regions of PfPM VII and PfPM X. These antibodies were also used in standard membrane feeding assays (SMFA) to determine whether inhibition of these proteases would affect parasite transmission to mosquitoes. The Mann-Whitney U test was used to analyse mosquito transmission assay results. RT-PCR, western immunoblot and immunofluorescence assay confirmed expression of PfPM VII and PfPM X in mosquito stages. Whereas PfPM VII was expressed in zygotes and ookinetes, PfPM X was expressed in gametes, zygotes, and ookinetes. Antibodies against PfPM VII and PfPM X decreased P. falciparum invasion of the mosquito midgut when used at high concentrations, indicating that these proteases play a role in Plasmodium mosquito midgut invasion. Failure to generate genetic knockouts of these genes limited determination of the precise role of

  2. PERANCANGAN SISTEM INFORMASI DI PTAIS KOPERTAIS WILAYAH VII SUMATERA SELATAN

    Directory of Open Access Journals (Sweden)

    Fenny Purwani

    2015-12-01

    Full Text Available Relations and information technology today closely related. One technology that is widely used and very popular on the Internet is a website. The website is agood means to facilitate and share information as much to college. However, the college today togetthe informationisnot maximized. This study aimstobuildawebsite on Kopertais SUMBAGSEL region VII. This website was developed using Macromedia Dreamweaver CS3 software, PHP, and MySQL, and method development using RAD (Rapid Application Development, and the purpose of this website serves to facilitate the college to receiver elevant information about online Kopertais VII region and terupdates.

  3. 40 CFR Appendix Vii to Part 268 - LDR Effective Dates of Surface Disposed Prohibited Hazardous Wastes

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 26 2010-07-01 2010-07-01 false LDR Effective Dates of Surface Disposed Prohibited Hazardous Wastes VII Appendix VII to Part 268 Protection of Environment ENVIRONMENTAL... VII to Part 268—LDR Effective Dates of Surface Disposed Prohibited Hazardous Wastes Table 1—Effective...

  4. 76 FR 31892 - Recordkeeping and Reporting Requirements Under Title VII, the ADA, and GINA

    Science.gov (United States)

    2011-06-02

    ... Requirements Under Title VII, the ADA, and GINA AGENCY: Equal Employment Opportunity Commission. ACTION: Notice... Civil Rights Act of 1964 (Title VII) and the Americans with Disabilities Act (ADA) to entities covered... the same record retention requirements under GINA that are imposed under Title VII and the ADA, i.e...

  5. 76 FR 79065 - Recordkeeping and Reporting Requirements Under Title VII, the ADA and GINA

    Science.gov (United States)

    2011-12-21

    ... Reporting Requirements Under Title VII, the ADA and GINA CFR Correction In Title 29 of the Code of Federal... title VII or section 107 of the ADA'' and add in their place the words ``section 709(c) of title VII, section 107 of the ADA, or section 207(a) of GINA'' wherever they appear in the following sections...

  6. Photosynthetic pigments of oceanic Chlorophyta belonging to prasinophytes clade VII.

    Science.gov (United States)

    Lopes Dos Santos, Adriana; Gourvil, Priscillia; Rodríguez, Francisco; Garrido, José Luis; Vaulot, Daniel

    2016-02-01

    The ecological importance and diversity of pico/nanoplanktonic algae remains poorly studied in marine waters, in part because many are tiny and without distinctive morphological features. Amongst green algae, Mamiellophyceae such as Micromonas or Bathycoccus are dominant in coastal waters while prasinophytes clade VII, yet not formerly described, appear to be major players in open oceanic waters. The pigment composition of 14 strains representative of different subclades of clade VII was analyzed using a method that improves the separation of loroxanthin and neoxanthin. All the prasinophytes clade VII analyzed here showed a pigment composition similar to that previously reported for RCC287 corresponding to pigment group prasino-2A. However, we detected in addition astaxanthin for which it is the first report in prasinophytes. Among the strains analyzed, the pigment signature is qualitatively similar within subclades A and B. By contrast, RCC3402 from subclade C (Picocystis) lacks loroxanthin, astaxanthin, and antheraxanthin but contains alloxanthin, diatoxanthin, and monadoxanthin that are usually found in diatoms or cryptophytes. For subclades A and B, loroxanthin was lowest at highest light irradiance suggesting a light-harvesting role of this pigment in clade VII as in Tetraselmis. © 2015 Phycological Society of America.

  7. Statistics and Title VII Proof: Prima Facie Case and Rebuttal.

    Science.gov (United States)

    Whitten, David

    1978-01-01

    The method and means by which statistics can raise a prima facie case of Title VII violation are analyzed. A standard is identified that can be applied to determine whether a statistical disparity is sufficient to shift the burden to the employer to rebut a prima facie case of discrimination. (LBH)

  8. Extended analyses of Se VII and Se VIII

    International Nuclear Information System (INIS)

    Vankleef, Th.A.M.; Joshi, Y.N.

    1984-01-01

    Joshi et al. (1984) have conducted an analysis of the 3d8 4s-3d8 4p transitions in As VII. The present investigation is concerned with an analysis of similar transitions in Se VIII. The selenium spectrum was photographed in the 400-1200-A wavelength region on a variety of normal-incidence spectrographs. Attention is given to least-squares-fit (LSF) and Hartree-Fock (HF) parameter values for the 3d9 4d configuration of Se VII, LSF and HF parameter values for the 3d8 4s and 3d8 4p configurations of Se VIII, the energy and composition of the levels of the 3d9 4d configuration of Se VII, classified lines in Se VII, energy levels and composition of the 3d8 4s configuration and the revised and newly determined levels of the 3d8 4p configuration of Se VIII, and newly classified lines of Se VIII. 15 references

  9. Viis aastakümmet raamatukogunduse radadel / Anne Veinberg

    Index Scriptorium Estoniae

    Veinberg, Anne

    2008-01-01

    Arvustus: Kikas, Konrad. Verba volant, scripta manent : viis aastakümmet raamatukogunduse ja infoteaduse radadel = Verba volant, scripta manent : five decades on the field of librarianship and information science. - Tallinn : Tallinna Tehnikaülikooli Kirjastus, 2008. - 366 lk. : ill. portr. - (Tallinna Tehnikaülikooli Raamatukogu töid. A ; 5)

  10. Viis armastuslugu suurel ekraanil / Tristan Priimägi

    Index Scriptorium Estoniae

    Priimägi, Tristan, 1976-

    2008-01-01

    Viis näidet filmiajaloost, kus režissööri ja staari vahel on tunded : Roger Vadim ja Tema Naised, Werner Herzog ja Klaus Kinski, Federico Fellini ja Anita Ekberg, Quentin Tarantino ja Uma Thurman, Rainer Werner Fassbinder ja Mr/Mrs X

  11. 40 CFR Appendix Vii to Part 266 - Health-Based Limits for Exclusion of Waste-Derived Residues*

    Science.gov (United States)

    2010-07-01

    ... Waste-Derived Residues* VII Appendix VII to Part 266 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) STANDARDS FOR THE MANAGEMENT OF SPECIFIC HAZARDOUS WASTES AND SPECIFIC TYPES OF HAZARDOUS WASTE MANAGEMENT FACILITIES Pt. 266, App. VII Appendix VII to Part 266—Health...

  12. Human Recombinant Factor VIIa is Neuroprotective in a Model of Traumatic Brain Injury and Secondary Hypoxemia

    National Research Council Canada - National Science Library

    Bauman, R. A; Long, J. B; Ketchum, L. H; Macdonald, V. W

    2004-01-01

    .... In the untraumatized brain, TF is physically isolated from FVII. However, traumatic brain injury (TBI) frequently results in the disruption of the vascular endothelium and resultant exposure of FVII to subendothelial TF...

  13. Modifying EPA radiation risk models based on BEIR VII

    International Nuclear Information System (INIS)

    Pawel, D.; Puskin, J.

    2007-01-01

    This paper summarizes a 'draft White Paper' that provides details on proposed changes in EPA's methodology for estimating radiogenic cancer risks. Many of the changes are based on the contents of a recent National Academy of Sciences (NAS) report (BEIR VII), that addresses cancer and genetic risks from low doses of low-LET radiation. The draft White Paper was prepared for a meeting with the EPA's Science Advisory Board's Radiation Advisory Committee (RAC) in September for seeking advice on the application of BEIR VII and on issues relating to these modifications and expansions. After receiving the Advisory review, we plan to implement the changes by publishing the new methodology in an EPA report, which we expect to submit to the RAC for final review. The revised methodology could then be applied to update the cancer risk coefficients for over 800 radionuclides that are published in EPA's Federal Guidance Report 13. (author)

  14. Star formation and abundances in the nearby irregular galaxy VII ZW 403

    Science.gov (United States)

    Tully, R. B.; Boesgaard, A. M.; Dyck, H. M.; Schempp, W. V.

    1981-05-01

    Photometry in J, H, and K bands reveals that there is an unresolved source of infrared emission associated with the brightest H II region in VII Zw 403, and the colors suggest the presence of a substantial number of K and M supergiants in addition to the hot O stars that must be present to account for the ionized gas. Spectrophotometry of this emission region indicates that reddening is substantial, and that the interpretation of the observed Balmer decrement in terms of reddening is not straightforward. The primary nucleosynthesis products O, S, and Ne are underabundant compared with the sun by a factor of 15; N is underabundant compared with the sun by a factor of 160; and the helium abundance suggests that either there could have been only a small number of star formation episodes or the galaxy is younger than the time scale of the process that deposits N in the interstellar medium.

  15. Activity of recombinant factor VIIa under different conditions in vitro

    DEFF Research Database (Denmark)

    Bladbjerg, Else-Marie; Jespersen, Jørgen

    2008-01-01

    Recombinant activated factor VII (NovoSeven; Novo Nordisk A/S, Måløv, Denmark) is an effective drug for treatment of bleeding in patients with haemophilia A or B and inhibitors. Little is known about physiological conditions influencing the efficacy of recombinant activated factor VII. We...... investigated the in-vitro effects of pH, temperature, and haemodilution on the activity of recombinant activated factor VII. Samples from eight healthy volunteers were spiked with recombinant activated factor VII (final concentration 1.7 microg/ml) and adjusted to pH 6.0, 6.5, 7.0, and 7.4 or analysed at 30......, 33, 37, and 40 degrees C, or diluted 0, 10, 20, 40, and 60% with dextran before analysis. Samples were analysed as rotational thromboelastometry in whole blood (clotting time, clot formation time, and maximum clot firmness) with and without Innovin (tissue factor), and as factor VII coagulant...

  16. Probing the Role of Loops & Domains in Regulating Coagulation Factor VIIa Allostery and Specificity

    DEFF Research Database (Denmark)

    Sørensen, Anders Bundgård

    2016-01-01

    The front-page illustrates the protease domain of factor VII in complex with tissue factor, the structure was solved during this dissertation (pdb id 5feo).......The front-page illustrates the protease domain of factor VII in complex with tissue factor, the structure was solved during this dissertation (pdb id 5feo)....

  17. 29 CFR 1604.8 - Relationship of title VII to the Equal Pay Act.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Relationship of title VII to the Equal Pay Act. 1604.8... GUIDELINES ON DISCRIMINATION BECAUSE OF SEX § 1604.8 Relationship of title VII to the Equal Pay Act. (a) The... based on the Equal Pay Act may be raised in a proceeding under title VII. (c) Where such a defense is...

  18. Collagen VII deficient mice show morphologic and histologic corneal changes that phenotypically mimic human dystrophic epidermolysis bullosa of the eye.

    Science.gov (United States)

    Chen, Vicki M; Shelke, Rajani; Nyström, Alexander; Laver, Nora; Sampson, James F; Zhiyi, Cao; Bhat, Najma; Panjwani, Noorjahan

    2018-06-16

    Absence of collagen VII causes blistering of the skin, eyes and many other tissues. This disease is termed dystrophic epidermolysis bullosa (DEB). Corneal fibrosis occurs in up to 41% and vision loss in up to 64% of patients. Standard treatments are supportive and there is no cure. The immune-histologic and morphologic changes in the corneas of the mouse model for this disease have not been described in the literature. Our purpose is to characterize the eyes of these mice to determine if this is an appropriate model for study of human therapeutics. Western blot analysis (WB) and immunohistochemistry (IHC) were performed to assess the relative collagen VII protein levels and its location within the cornea. Additional IHC for inflammatory and fibrotic biomarkers alpha-smooth muscle actin (α-SMA), transforming growth factor-beta (TGF-β), connective tissue growth factor (CTGF), proteinase 3, tenascin C and collagen III were performed. Clinical photographs documenting opacification of the corneas of animals of differing ages were assessed and scored independently by 2 examiners. Histology was then used to investigate morphologic changes. IHC and WB confirmed that these mice are deficient in collagen VII production at the level of the basement membrane when compared with wild-types. IHC showed anomalous deposition of collagen III throughout the stroma. Of the 5 biomarkers tested, TGF-β showed the strongest and most consistently staining. Photographs documented corneal opacities only in mice older than 10 weeks, opacities were not seen in younger animals. Histology showed multiple abnormalities, including epithelial hyperplasia, ulceration, fibrosis, edema, dysplasia, neovascularization and bullae formation. The collagen VII hypomorphic mouse shows reduced collagen VII production at the level of the corneal basement membrane. Corneal changes are similar to pathology seen in humans with this disease. The presence of anomalous stromal collagen III and TGF-β appear to be

  19. Gene disruption reveals a dispensable role for plasmepsin VII in the Plasmodium berghei life cycle.

    Science.gov (United States)

    Mastan, Babu S; Kumari, Anchala; Gupta, Dinesh; Mishra, Satish; Kumar, Kota Arun

    2014-06-01

    Plasmepsins (PM), aspartic proteases of Plasmodium, comprises a family of ten proteins that perform critical functions in Plasmodium life cycle. Except VII and VIII, functions of the remaining plasmepsin members have been well characterized. Here, we have generated a mutant parasite lacking PM VII in Plasmodium berghei using reverse genetics approach. Systematic comparison of growth kinetics and infection in both mosquito and vertebrate host revealed that PM VII depleted mutants exhibited no defects in development and progressed normally throughout the parasite life cycle. These studies suggest a dispensable role for PM VII in Plasmodium berghei life cycle. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Uudised : Baltimaade suurim, XII "Jazzkaar". VII rahvusvaheline koorifestival. Leipzigis improviseeriti edukalt

    Index Scriptorium Estoniae

    2001-01-01

    23.-29. apr. toimuvast festivalist "Jazzkaar 2001". VII rahvusvahelisest koorifestivalist "Tallinn "2001". 6. ja 7. apr. Leipzigis toimunud V rahvusvahelisest improvisatsioonikonkursist, kus osalesid ka eesti interpreedid

  1. Extended analysis of six-times ionized barium (Ba VII)

    International Nuclear Information System (INIS)

    Sharma, M.K.; Tauheed, A.; Rahimullah, K.

    2013-01-01

    The seventh spectrum of barium (Ba VII) has been investigated using experimental recordings made on a 3-m normal incidence vacuum spectrograph in Canada in the wavelength region 300–2000 Å. The data below 350 Å was supplemented from the spectrograms recorded on a 10.7-m grazing incidence spectrograph of NIST laboratory USA. The sources used to excite the spectra in both the cases were triggered spark. Previously reported levels of 5s 2 5p 2 , 5s5p 3 , 5s 2 5p5d and 5s 2 5p6s in Ba VII have been confirmed except the 1 P 1 level of 5s 2 5p5d. The analysis has been extended considerably to include new configurations 5s 2 5p6d and 5s 2 5p7s in odd parity configuration and doubly excited configurations 5s 2 5p6p, 5s 2 5p4f, 5s 2 5p5f, 5p 4 , 5s5p 2 5d and 5s5p 2 6s in even parity configuration. The 3 F 4 level of 5s 2 5p5d configuration has now been established through the identification of transitions from 5s 2 5p6p. In all, one hundred twenty-two levels have been established in this spectrum out of which ninety-two are new. A configuration interaction Hartree–Fock calculation supports the analysis. -- Highlights: ► The spectrum of Ba was recorded on a 3-m spectrograph with triggered spark source. ► Atomic transitions for Ba VII were identified to established new energy levels. ► CI calculations with relativistic corrections were made for theoretical predictions. ► Weighted oscillator strength (gf) and transition probabilities (gA) were calculated

  2. Neutron flux measurements at the Wendelstein VII-A stellarator

    International Nuclear Information System (INIS)

    Weller, A.; Maassberg, H.

    1985-10-01

    In addition to charge exchange analysis (CX) and charge exchange recombination spectroscopy (CXRS), the time evolution of the central ion temperature during neutral beam heated plasma discharges in the Wendelstein VII-A stellarator is derived from the neutron flux from thermal D-D reactions. In general, good quantitative agreement between the different methods is obtained. Neutron flux measurements also permit to investigate the slowing down of fast D + -ions from neutral beam injection (NBI). The results agree well with the predictions based on the assumption of a collisional slowing down mechanism. (orig.)

  3. Proceedings of the 2. Workshop on Wendelstein VII-X

    International Nuclear Information System (INIS)

    Rau, F.; Leotta, G.G.

    1988-01-01

    The specification and final concept of W VII-X were discussed. Plasma equilibrium; plasma stability; transport; bootstrap current; plasma parameter prediction methods; boundary regions; heating; the coil system; and mechanical engineering aspects were considered. A Helias configuration with five field periods (rather than the four previously suggested) is advocated. The major radius is increased to 6.5m to alleviate plasma-wall interaction effects due to the increased number of field periods. The magnetic field is reduced from 4 to 3T, to keep the amount of superconducting material needed for coils fixed

  4. Technical progress report on Wendelstein VII-AS

    International Nuclear Information System (INIS)

    Sapper, J.

    1985-01-01

    The modification of the WENDELSTEIN experiment at Garching into an advanced version with modular design was approved in 1982, after a planning time of one and a half year. The essential components /1,2/ of the new WENDELSTEIN VII-AS device are: - A modular field system instead of a helix and TF-system, consisting of 45 nonplanar coils. - A modular vacuum vessel, adapted to the coil system. - An additional TF-system for t-variation, consisting of 10 plane coils. - A structure shell for the modular field coils so that the vessel is free of coil forces

  5. Weighted oscillator strengths and lifetimes for the S VII spectrum

    International Nuclear Information System (INIS)

    Borges, F.O.; Cavalcanti, G.H.; Trigueiros, A.G.; Jupen, C.

    2004-01-01

    The weighted oscillator strengths (gf) and the lifetimes presented in this work were carried out in a multiconfiguration Hartree-Fock relativistic approach. In this calculation, the electrostatic parameters were optimized by a least-squares procedure, in order to improve the adjustment to experimental energy levels. This method produces gf-values that are in better agreement with intensity observations and lifetime values that are closer to the experimental ones. In this work, we presented all the experimentally known electric dipole S VII spectral lines

  6. Evaluated Nuclear Data Covariances: The Journey From ENDF/B-VII.0 to ENDF/B-VII.1

    International Nuclear Information System (INIS)

    Smith, Donald L.

    2011-01-01

    Recent interest from data users on applications that utilize the uncertainties of evaluated nuclear reaction data has stimulated the data evaluation community to focus on producing covariance data to a far greater extent than ever before. Although some uncertainty information has been available in the ENDF/B libraries since the 1970's, this content has been fairly limited in scope, the quality quite variable, and the use of covariance data confined to only a few application areas. Today, covariance data are more widely and extensively utilized than ever before in neutron dosimetry, in advanced fission reactor design studies, in nuclear criticality safety assessments, in national security applications, and even in certain fusion energy applications. The main problem that now faces the ENDF/B evaluator community is that of providing covariances that are adequate both in quantity and quality to meet the requirements of contemporary nuclear data users in a timely manner. In broad terms, the approach pursued during the past several years has been to purge any legacy covariance information contained in ENDF/B-VI.8 that was judged to be subpar, to include in ENDF/B-VII.0 (released in 2006) only those covariance data deemed then to be of reasonable quality for contemporary applications, and to subsequently devote as much effort as the available time and resources allowed to producing additional covariance data of suitable scope and quality for inclusion in ENDF/B-VII.1. Considerable attention has also been devoted during the five years since the release of ENDF/B-VII.0 to examining and improving the methods used to produce covariance data from thermal energies up to the highest energies addressed in the ENDF/B library, to processing these data in a robust fashion so that they can be utilized readily in contemporary nuclear applications, and to developing convenient covariance data visualization capabilities. Other papers included in this issue discuss in considerable

  7. BEIR VII: What's old, What's new, and What challenges remain?

    International Nuclear Information System (INIS)

    Douple, E.; Jostes, R.

    2007-01-01

    The Biological Effects of Ionizing Radiation (BEIR VII) Committee reviewed evidence since the 1990 BEIR V report and developed BEIR VII risk estimates, including a linear, no-threshold dose-response relationship between exposure to ionizing radiation and the development of cancer in humans for exposures up to 0.1 Sv, quantifying the lifetime risks for both cancer mortality and incidence as a function of age at exposure and sex, primarily based on the Japanese atomic-bomb survivor data. If 100 people with an age distribution typical of the U.S. population receive an acute exposure of 0.1 Sv, one person would be expected to eventually develop cancer from this exposure, while 42 of the 100 people would be expected to develop cancer from other causes. The committee estimated the risk following radiation exposure for both incidence and mortality for 11 specific cancer sites. The total risk of heritable genetic diseases from parents exposed prior to conception was 3,000 to 4,700 cases per million progeny per Sv, 0.4-0.6% compared to an estimated baseline risk of 738,000 cases per million. Noncancer diseases such as cardiovascular disease can result from exposures to high doses of radiation, but the data available at this time are not sufficient to develop reliable estimates of risk for these noncancer outcomes at low doses of radiation. Twelve specific recommendations were presented as needs for future research. (author)

  8. Endf/B-VII.0 Based Library for Paragon - 313

    International Nuclear Information System (INIS)

    Huria, H.C.; Kucukboyaci, V.N.; Ouisloumen, M.

    2010-01-01

    A new 70-group library has been generated for the Westinghouse lattice physics code PARAGON using the ENDF/B-VII.0 nuclear data files. The new library retains the major features of the current library, including the number of energy groups and the reduction in the U-238 resonance integral. The upper bound for the up-scattering effects in the new library, however, has been moved to 4.0 eV from 2.1 eV for better MOX fuel predictions. The new library has been used to analyze standard benchmarks and also to compare the measured and predicted parameters for different types of Westinghouse and Combustion Engineering (CE) type operating reactor cores. Results indicate that the new library will not impact the reactivity, power distribution and the temperature coefficient predictions over a wide range of physics design parameters; however, will improve the MOX core predictions. In other words, the ENDF/B-VI.3 and ENDF/B-VII.0 produce similar results for reactor core calculations. (authors)

  9. Verification OFENDF/B-VII.0, ENDF/B-VII.1 and JENDL-4.0 nuclear data libraries for criticality calculations using NEA/NSC benchmarks

    International Nuclear Information System (INIS)

    Bouhaddane, A.; Farkas, G.; Hascik, J.; Slugen, V.

    2015-01-01

    The paper presents verification of selected nuclear data libraries with the aim to apply them to fast reactor calculations. More precise results were achieved for thermal neutrons calculations. This corresponds with the demand for more precise nuclear data for fast reactors. However, fast neutron calculations show some consistency, in particular between ENDF-B/VII.1 and JENDL-4.0 nuclear data libraries. The results support the idea to prefer using newer ENDF-B/VII.1 instead of the previous version ENDF-B/VII.0. Certainly, there are still some issues to be addressed and there is potential to gain more conclusive results. Although, application of ENDF-B/VII.1 and JENDL-4.0 is expected for further calculations. (authors)

  10. 76 FR 57013 - Recordkeeping and Reporting Requirements Under Title VII, the ADA, and GINA

    Science.gov (United States)

    2011-09-15

    ... EQUAL EMPLOYMENT OPPORTUNITY COMMISSION 29 CFR Part 1602 RIN 3046-AA89 Recordkeeping and Reporting Requirements Under Title VII, the ADA, and GINA AGENCY: Equal Employment Opportunity Commission. ACTION... under title VII, the ADA, and GINA. (76 FR 31892, June 2, 2011). No requests to present oral testimony...

  11. Specific DNA binding of a potential transcriptional regulator, inosine 5'-monophosphate dehydrogenase-related protein VII, to the promoter region of a methyl coenzyme m reductase I-encoding operon retrieved from Methanothermobacter thermautotrophicus strain DeltaH.

    Science.gov (United States)

    Shinzato, Naoya; Enoki, Miho; Sato, Hiroaki; Nakamura, Kohei; Matsui, Toru; Kamagata, Yoichi

    2008-10-01

    Two methyl coenzyme M reductases (MCRs) encoded by the mcr and mrt operons of the hydrogenotrophic methanogen Methanothermobacter thermautotrophicus DeltaH are expressed in response to H(2) availability. In the present study, cis elements and trans-acting factors responsible for the gene expression of MCRs were investigated by using electrophoretic mobility shift assay (EMSA) and affinity particle purification. A survey of their operator regions by EMSA with protein extracts from mrt-expressing cultures restricted them to 46- and 41-bp-long mcr and mrt upstream regions, respectively. Affinity particle purification of DNA-binding proteins conjugated with putative operator regions resulted in the retrieval of a protein attributed to IMP dehydrogenase-related protein VII (IMPDH VII). IMPDH VII is predicted to have a winged helix-turn-helix DNA-binding motif and two cystathionine beta-synthase domains, and it has been suspected to be an energy-sensing module. EMSA with oligonucleotide probes with unusual sequences showed that the binding site of IMPDH VII mostly overlaps the factor B-responsible element-TATA box of the mcr operon. The results presented here suggest that IMPDH VII encoded by MTH126 is a plausible candidate for the transcriptional regulator of the mcr operon in this methanogen.

  12. Convenient synthesis of bis(alkoxy)rhenium(VII) complexes

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Z.; Al-Ajlouni, A.M.; Espenson, J.H. [Iowa State Univ., Ames, IA (United States)

    1996-02-28

    The study of high-oxidation-state organorhenium compounds has been a field of continuing activity, thanks to the success of methylrhenium trioxide (CH{sub 3}ReO{sub 3} or MTO) in catalytic processes. This catalyst is effective in oxidations, olefin metathesis, the olefination of aldehydes, and the preparation of other compounds with three-membered rings. The syntheses of some rhenium compounds derived form MTO have been reported. Epoxide formation is a key reaction, and it bears directly on these findings reported here. Re(VII) complexes containing a chelated bis(diolate) ligand can be synthesized by refluxing MTO with 2,3-dimethyl-2,3-diol. Here, the authors report a more convenient method for this preparation. A different series of related compounds consists of chelated bis(diolates) of the Cp*Re-oxo series, Cp*ReO-(diolate).

  13. Discovery of the type VII ESX-1 secretion needle?

    Science.gov (United States)

    Ates, Louis S; Brosch, Roland

    2017-01-01

    Mycobacterium tuberculosis, the etiological agent of human tuberculosis, harbours five ESAT-6/type VII secretion (ESX/T7S) systems. The first esx gene clusters were identified during the genome-sequencing project of M. tuberculosis H37Rv. Follow-up studies revealed additional genes playing important roles in ESX/T7S systems. Among the latter genes, one can find those that encode Pro-Glu (PE) and Pro-Pro-Glu (PPE) proteins as well as a gene cluster that is encoded >260 kb upstream of the esx-1 locus and encodes ESX-1 secretion-associated proteins EspA (Rv3616c), EspC (Rv3615c) and EspD (Rv3614c). The espACD cluster has been suggested to have an important function in ESX-1 secretion since EspA-EspC and EsxA-EsxB are mutually co-dependent on each other for secretion. However, the molecular mechanism of this co-dependence and interaction between the substrates remained unknown. In this issue of Molecular Microbiology, Lou and colleagues show that EspC forms high-molecular weight polymerization complexes that resemble selected components of type II, III and/or IV secretion systems of Gram-negative bacteria. Indeed, EspC-multimeric complexes form filamentous structures that could well represent a secretion needle of ESX-1 type VII secretion systems. This exciting observation opens new avenues for research to discover and characterize ESX/T7S components and elucidates the co-dependence of EsxA/B secretion with EspA/C. © 2016 John Wiley & Sons Ltd.

  14. Extensive small-angle X-ray scattering studies of blood coagulation factor VIIa reveal interdomain flexibility

    DEFF Research Database (Denmark)

    Mosbæk, Charlotte Rode; Nolan, David; Persson, Egon

    2010-01-01

    Blood coagulation factor VIIa (FVIIa) is used in the treatment of replacement therapy resistant hemophilia patients, and FVIIa is normally activated upon complex formation with tissue factor (TF), potentially in context with structural rearrangements. The solution behavior of uncomplexed FVIIa...... is important for understanding the mechanism of activation and for the stability and activity of the pharmaceutical product. However, crystal structures of FVIIa in complex with TF and of truncated free FVIIa reveal different overall conformations while previous small-angle scattering studies suggest FVIIa...... causing resistance to activation, thereby emphasizing the connection between the distribution of different conformations of FVII and the mechanism of activation....

  15. (99)Tc(VII) Retardation, Reduction, and Redox Rate Scaling in Naturally Reduced Sediments.

    Science.gov (United States)

    Liu, Yuanyuan; Liu, Chongxuan; Kukkadapu, Ravi K; McKinley, James P; Zachara, John; Plymale, Andrew E; Miller, Micah D; Varga, Tamas; Resch, Charles T

    2015-11-17

    An experimental and modeling study was conducted to investigate pertechnetate (Tc(VII)O4(-)) retardation, reduction, and rate scaling in three sediments from Ringold formation at U.S. Department of Energy's Hanford site, where (99)Tc is a major contaminant in groundwater. Tc(VII) was reduced in all the sediments in both batch reactors and diffusion columns, with a faster rate in a sediment containing a higher concentration of HCl-extractable Fe(II). Tc(VII) migration in the diffusion columns was reductively retarded with retardation degrees correlated with Tc(VII) reduction rates. The reduction rates were faster in the diffusion columns than those in the batch reactors, apparently influenced by the spatial distribution of redox-reactive minerals along transport paths that supplied Tc(VII). X-ray computed tomography and autoradiography were performed to identify the spatial locations of Tc(VII) reduction and transport paths in the sediments, and results generally confirmed the newly found behavior of reaction rate changes from batch to column. The results from this study implied that Tc(VII) migration can be reductively retarded at Hanford site with a retardation degree dependent on reactive Fe(II) content and its distribution in sediments. This study also demonstrated that an effective reaction rate may be faster in transport systems than that in well-mixed reactors.

  16. The Effect of Neonatal Gene Therapy on Skeletal Manifestations in Mucopolysaccharidosis VII Dogs after a Decade

    Science.gov (United States)

    Xing, Elizabeth M.; Knox, Van W.; O'Donnell, Patricia A.; Sikura, Tracey; Liu, Yuli; Wu, Susan; Casal, Margret L.; Haskins, Mark E.; Ponder, Katherine P.

    2013-01-01

    Mucopolysaccharidosis (MPS) VII is a lysosomal storage disease due to deficient activity of β-glucuronidase (GUSB), and results in glycosaminoglycan accumulation. Skeletal manifestations include bone dysplasia, degenerative joint disease, and growth retardation. One gene therapy approach for MPS VII involves neonatal intravenous injection of a gamma retroviral vector expressing GUSB, which results in stable expression in liver and secretion of enzyme into blood at levels predicted to be similar or higher to enzyme replacement therapy. The goal of this study was to evaluate the long-term effect of neonatal gene therapy on skeletal manifestations in MPS VII dogs. Treated MPS VII dogs could walk throughout their lives, while untreated MPS VII dogs could not stand beyond 6 months and were dead by 2 years. Luxation of the coxofemoral joint and the patella, dysplasia of the acetabulum and supracondylar ridge, deep erosions of the distal femur, and synovial hyperplasia were reduced, and the quality of articular bone was improved in treated dogs at 6 to 11 years of age compared with untreated MPS VII dogs at 2 years or less. However, treated dogs continued to have osteophyte formation, cartilage abnormalities, and an abnormal gait. Enzyme activity was found near synovial blood vessels, and there was 2% as much GUSB activity in synovial fluid as in serum. We conclude that neonatal gene therapy reduces skeletal abnormalities in MPS VII dogs, but clinically-relevant abnormalities remain. Enzyme replacement therapy will probably have similar limitations long-term. PMID:23628461

  17. VII National Congress of Spanish Radiotherapy and Oncology Association, Sevilla 20-22 October 1993 Abstracts

    International Nuclear Information System (INIS)

    1993-01-01

    This special issue of Oncology Journal presents the 142 abstracts of VII National Congress of Spanish Radiotherapy and Oncology Association. The lectures were distributed into 3 groups: a) Radiochemotherapy b) Lymphoma c) Paliative radiotherapy and quality of life

  18. Vehicle infrastructure integration (VII) based road-condition warning system for highway collision prevention.

    Science.gov (United States)

    2009-05-01

    As a major ITS initiative, the Vehicle Infrastructure Integration (VII) program is to revolutionize : transportation by creating an enabling communication infrastructure that will open up a wide range of : safety applications. The road-condition warn...

  19. Biological and phylogenetic characterization of a genotype VII Newcastle disease virus from Venezuela: Efficacy of vaccination

    Science.gov (United States)

    Here we describe the characterization a virulent genotype VII Newcastle disease virus (NDV) from Venezuela and evaluate the efficacy of heterologous genotype commercial vaccination under field and controlled rearing conditions. Biological pathotyping and molecular analysis were applied. Results sh...

  20. Viis raamatutäit poola näidendeid / Riina Mägi

    Index Scriptorium Estoniae

    Mägi, Riina, 1957-

    2006-01-01

    Tõlkija Hendrik Lindepuult ilmus viies tõlkekogumik poola dramaturgia tippteoseid tutvustavast sarjast. Seekord said kaante vahele Tadeusz Rozewiczi näidendid "Valge abielu", "Lõks" ja "Vana naine haub"

  1. The Financial Regulations of the Agency. Amendment of Articles V, VI and VII

    International Nuclear Information System (INIS)

    1960-01-01

    On 13 January 1960 the Board of Governors made certain changes in Articles V, VI and VII of the Financial Regulations. The Articles thus amended are reproduced in this document for the information of all Members of the Agency

  2. The Financial Regulations of the Agency. Amendment of Articles V, VI and VII

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1960-03-24

    On 13 January 1960 the Board of Governors made certain changes in Articles V, VI and VII of the Financial Regulations. The Articles thus amended are reproduced in this document for the information of all Members of the Agency.

  3. Treatment of lysosomal storage disease in MPS VII mice using a recombinant adeno-associated virus.

    Science.gov (United States)

    Watson, G L; Sayles, J N; Chen, C; Elliger, S S; Elliger, C A; Raju, N R; Kurtzman, G J; Podsakoff, G M

    1998-12-01

    Mucopolysaccharidosis type VII (MPS VII) is a lysosomal storage disease caused by a genetic deficiency of beta-glucuronidase (GUS). We used a recombinant adeno-associated virus vector (AAV-GUS) to deliver GUS cDNA to MPS VII mice. The route of vector administration had a dramatic effect on the extent and distribution of GUS activity. Intramuscular injection of AAV-GUS resulted in high, localized production of GUS, while intravenous administration produced low GUS activity in several tissues. This latter treatment of MPS VII mice reduced glycosaminoglycan levels in the liver to normal and reduced storage granules dramatically. We show that a single administration of AAV-GUS can provide sustained expression of GUS in a variety of cell types and is sufficient to reverse the disease phenotype at least in the liver.

  4. MICROX-2 cross section library based on ENDF/B-VII

    International Nuclear Information System (INIS)

    Hou, J.; Ivanov, K.; Choi, H.

    2012-01-01

    New cross section libraries of a neutron transport code MICROX-2 have been generated for advanced reactor design and fuel cycle analyses. A total of 386 nuclides were processed, including 10 thermal scattering nuclides, which are available in ENDF/B-VII release 0 nuclear data. The NJOY system and MICROR code were used to process nuclear data and convert them into MICROX-2 format. The energy group structure of the new library was optimized for both the thermal and fast neutron spectrum reactors based on Contributon and Point-wise Cross Section Driven (CPXSD) method, resulting in a total of 1173 energy groups. A series of lattice cell level benchmark calculations have been performed against both experimental measurements and Monte Carlo calculations for the effective/infinite multiplication factor and reaction rate ratios. The results of MICROX-2 calculation with the new library were consistent with those of 15 reference cases. The average errors of the infinite multiplication factor and reaction rate ratio were 0.31% δk and 1.9%, respectively. The maximum error of reaction rate ratio was 8% for 238 U-to- 235 U fission of ZEBRA lattice against the reference calculation done by MCNP5. (authors)

  5. The Freedom to Believe and the Freedom to Practice: Title VII, Muslim Women, and Hijab

    OpenAIRE

    Benson, Kristina

    2014-01-01

    Although Title VII of the Civil Rights Act nominally affirmed employees’ right to wear hijab in the workplace, the courts have taken an increasingly narrow view of the term “religion” and failed to uphold the right to wear hijab in both private and public sector settings on several occasions. This is because Title VII and its attendant protections are grounded in a framework that presumes Christianity as normative, and religiously mandated accoutrements as communicative in function. The manne...

  6. Pengaruh Penerapan Pembelajaran Arias Dipadu Mind Map terhadap Hasil Belajar Kognitif Siswa Kelas VII

    OpenAIRE

    Leliavia, Leliavia; Al Muhdhar, Mimien Henie Irawati; Suwono, Hadi

    2017-01-01

    This research was to determine the effect of differences ARIAS combined mind map learning and ARIAS learning to cognitive learning outcomes grade VII SMPN 1 Tempunak. This research with quasy research experiment design approach with the design of pretest-posttest. Data were analyzed using descriptive statistics and inferensial to test the hypothesis that analysis of covariance (ANCOVA) using SPSS 23 for windows with a significance level of 0,05. The study was conducted at the grade VII SMPN 1...

  7. PENINGKATAN KEMAMPUAN PEMECAHAN MASALAH DAN PENGEMBANGAN KARAKTER PADA SISWA KELAS VII MELALUI MODEL PBL BERBANTUAN SCAFFOLDING

    OpenAIRE

    Novy Kris Zaini; Wuryanto Wuryanto; Hery Sutarto

    2016-01-01

    Tujuan penelitian ini adalah untuk mengetahui (1) apakah kemampuan pemecahan masalah matematika peserta didik yang diajar dengan model PBL berbantuan scaffolding pada materi pokok segiempat kelas VII dapat mencapai KKM yang ditetapkan, (2) apakah pembelajaran matematika dengan model PBL berbantuan scaffolding pada materi pokok segiempat kelas VII dapat meningkatkan kemampuan pemecahan masalah peserta didik pilihan, (3) apakah pembelajaran matematika dengan model PBL berbantuan scaffolding pad...

  8. Addition to the analysis of the Sr VI and Sr VII spectra

    International Nuclear Information System (INIS)

    Wyart, J.F.

    1989-01-01

    Fifty-six lines of multicharged strontium are measured with an improved wavelength accuracy, or interpreted for the first time. They are 4p-4s, 4p-5s and 4p-4d transitions in Sr VII and 4p-5s transitions in Sr VI. The revision of the singlet-triplet connection in Sr VII is supported by theoretical survey of the ground configuration in Ge-like ions. (orig.)

  9. GANGGUAN CEMAS PADA MAHASISWA SEMESTER I DAN VII PROGRAM STUDI PENDIDIKAN DOKTER FAKULTAS KEDOKTERAN UNIVERSITAS UDAYANA

    Directory of Open Access Journals (Sweden)

    Dyah Chandratika

    2015-05-01

    Full Text Available Penting untuk dilakukan penelitian mengenai gangguan cemas pada mahasiswa kedokteran karena tingginya tingkat stres mahasiswa terutama pada tahun pertama perkuliahan. Tujuan penelitian ini adalah untuk mengetahui prevalensi dan perbedaan skor  gangguan  cemas  pada mahasiswa  semester  I dan  VII serta untuk  mengetahui perbedaan skor gangguan cemas antara mahasiswa laki-laki dan perempuan di Fakultas Kedokteran Universitas Udayana. Desain penelitian ini adalah cross sectional analitik. Pengambilan sampel dilakukan secara random sampling. Sampel mengisi identitas, kuesioner L-MMPI, kuesioner Hamilton Anxiety Rating Scale (HARS. Kemudian dihitung prevalensi gangguan cemas tiap kelompok serta data dianalisis menggunakan uji t-independen. Terdapat 15 orang (25,0% mahasiswa semester I dan 7 orang (11,7% mahasiswa semester VII yang mengalami gangguan cemas. Dari hasil uji t-independen antara skor gangguan cemas mahasiswa semester I dan VII diperoleh nilai p = 0,001 (<0,05. Sedangkan diperoleh p = 0,080 antara mahasiswa laki-laki dan perempuan pada semester I dan p = 0,744 antara mahasiswa laki-laki dan perempuan pada semester VII. Prevalensi gangguan cemas pada mahasiswa semester I yaitu 25,0% sedangkan 11,7% pada mahasiswa semester VII. Terdapat perbedaan bermakna antara skor gangguan cemas mahasiswa semester I dan VII. Tidak ditemukan perbedaan bermakna skor gangguan cemas antara laki-laki dan perempuan.   

  10. Structural incorporation of MgCl2 into ice VII at room temperature

    Science.gov (United States)

    Watanabe, Mao; Komatsu, Kazuki; Noritake, Fumiya; Kagi, Hiroyuki

    2017-05-01

    Raman spectra and X-ray diffraction patterns were obtained from 1:100 and 1:200 \\text{MgCl}2:\\text{H}2\\text{O} solutions (in molar ratio) at pressures up to 6 GPa using diamond anvil cells (DACs) and compared with those of pure water. The O-H stretching band from ice VII crystallized from the 1:200 solution was approximately 10 cm-1 higher than that of pure ice VII. The phase boundaries between ice VII and VIII crystallized from the MgCl2 solutions at 4 GPa were 2 K lower than those of pure ice VII and VIII. These observations indicate that ice VII incorporates MgCl2 into its structure. The unit cell volumes of ice VII crystallized from pure water and the two solutions coincided with each other within the experimental error, and salt incorporation was not detectable from the cell volume. Possible configurations of ion substitution and excess volume of ice VIII were simulated on the basis of density functional theory (DFT) calculations.

  11. United Nations Charter, Chapter VII, Article 43: Now or Never.

    Science.gov (United States)

    Burkle, Frederick M

    2018-04-25

    For more than 75 years, the United Nations Charter has functioned without the benefit of Chapter VII, Article 43, which commits all United Nations member states "to make available to the Security Council, on its call, armed forces, assistance, facilities, including rights of passage necessary for the purpose of maintaining international peace and security." The consequences imposed by this 1945 decision have had a dramatic negative impact on the United Nation's functional capacity as a global body for peace and security. This article summarizes the struggle to implement Article 43 over the decades from the onset of the Cold War, through diplomatic attempts during the post-Cold War era, to current and often controversial attempts to provide some semblance of conflict containment through peace enforcement missions. The rapid growth of globalization and the capability of many nations to provide democratic protections to their populations are again threatened by superpower hegemony and the development of novel unconventional global threats. The survival of the United Nations requires many long overdue organizational structure and governance power reforms, including implementation of a robust United Nations Standing Task Force under Article 43. (Disaster Med Public Health Preparedness. 2018;page 1 of 8).

  12. In silico dissection of Type VII Secretion System components across bacteria: New directions towards functional characterization.

    Science.gov (United States)

    Das, Chandrani; Ghosh, Tarini Shankar; Mande, Sharmila S

    2016-03-01

    Type VII Secretion System (T7SS) is one of the factors involved in virulence of Mycobacterium tuberculosis H37Rv. Numerous research efforts have been made in the last decade towards characterizing the components of this secretion system. An extensive genome-wide analysis through compilation of isolated information is required to obtain a global view of diverse characteristics and pathogenicity-related aspects of this machinery. The present study suggests that differences in structural components (of T7SS) between Actinobacteria and Firmicutes, observed earlier in a few organisms, is indeed a global trend. A few hitherto uncharacterized T7SS-like clusters have been identified in the pathogenic bacteria Enterococcus faecalis, Saccharomonospora viridis, Streptococcus equi, Streptococcus gordonii and Streptococcus sanguinis. Experimental verification of these clusters can shed lights on their role in bacterial pathogenesis. Similarly, verification of the identified variants of T7SS clusters consisting additional membrane components may help in unraveling new mechanism of protein translocation through T7SS. A database of various components of T7SS has been developed to facilitate easy access and interpretation of T7SS related data.

  13. ECRH experiments on the W VII-A stellarator

    International Nuclear Information System (INIS)

    Whilelm, R.; Erckmann, V.; Janzen, G.; Mueller, G.; Schueller, P. G.; Schwoerer, K.; Thumm, H.

    1985-01-01

    Plasma build-up and heating of a ''currentless'' plasma by means of ECR wave irradiation were studied at the Garching W VII-A stellarator. The experiments were performed at 28 GHz with approx. 200 kW RF power and a pulse duration 02 mode corresponding to a 50% O-mode and 50% X-mode mixture) was launched directly into the plasma from the low field side. In a second step the radiation was converted into the almost linearly polarized TE 11 mode and irradiated in O-mode orientation (E-tilde parallel to B-barsub(o), k-bar perpendicular to B-barsub(o)) into the torus, the nonabsorbed part of the RF power was reflected into the plasma in the X-mode by a focussing polarization twist reflector mounted to the inner torus wall. As a main result the heating efficiency has been slightly improved by the transition from ''simple'' to ''advanced'' wave launching (up to 50% instead of approx. 40%). The central electron temperatures were remarkably increased from approx. 700 eV to 1200 eV due to the well localized O-mode absorption of the TE 11 beam, however. The X-mode from the mirror on the other hand does not contribute to the total plasma energy as expected. This is explained by a local absorption of the arising Bernstein waves due to a macroscopically turbulent behaviour of the plasma in the outer regions. Possibly as a result of wave decay into lower hybrid waves pronounced ion tail heating was observed. For both kinds of wave irradiation toroidal plasma currents were generated. This seems to be caused by asimmetrically confined co- and counter-streaming fast electrons

  14. Impurity transport in the Wendelstein VII-A stellarator

    International Nuclear Information System (INIS)

    1985-01-01

    Impurity radiation losses in net-current-free neutral-beam-heated plasmas in the Wendelstein W VII-A stellarator are the combined effect of particularly strong impurity sources and improved particle confinement as compared with ohmically heated tokamak-like plasma discharges. Experiments are described and conclusions are drawn about the impurity species, their origin and their transport behaviour. The impurity transport is modelled by a 1-D impurity transport and radiation code. The evolution of the total radiation in time and space deduced from soft-X-ray and bolometer measurements can be fairly well simulated by the code. Experimentally, oxygen was found to make the main contribution to the radiation losses. In the calculations, an influx of cold oxygen desorbed from the walls of the order of 10 13 -10 14 cm -2 .s -1 and a rate of fast injected oxygen corresponding to a 1% impurity content of the neutral beams in combination with neoclassical impurity transport leads to quantitative agreement between the simulation and the observed radiation. The transport of A1 trace impurities injected by the laser blow-off technique was experimentally studied by soft-X-ray measurements using a differential method allowing extraction of the time evolution of A1 XII, XIII radial profiles. These are compared with code predictions, together with additional spectroscopic measurements. The main features of the impurity transport are consistent with neoclassical predictions, which explain particularly the central impurity accumulation. Some details, however, seem to require additional 'anomalous' transport. Such an enhancement is correlated with distortions of the magnetic configuration around resonant magnetic surfaces. (author)

  15. Plattlet atmosphere - study of factors 2 and 7 - modifications brought about by X-rays

    International Nuclear Information System (INIS)

    Hollard, D.; Darnault, J.; Rambaud, F.; Suscillon, M.; Marcille, G.

    1966-01-01

    After a quantitative measure of factor II and VII adsorbed at the platelet surface, the authors study the comportment of these factors opposite to: un-numerous washes, irradiations of 0 to 70000 R. It appears that these factors are not solidly fixed at the platelet as: 10 washes are sufficient to get rid of each of the 2 factors; 1500 R overthrow factor VII; 40000 R are necessary to suppress F II. (author) [fr

  16. Studies on normal-conducting coils for Wendelstein VII-X

    International Nuclear Information System (INIS)

    Harmeyer, E.; Kisslinger, J.; Rau, F.; Sapper, J.; Wobig, H.

    1990-08-01

    For Wendelstein VII-X, the next step stellarator experiment at IPP Garching, a Helias configuration has been chosen. The goals of Wendelstein VII-X are to continue the development of the modular stellarator and to demonstrate the reactor capability of this stellarator line. The main data of the selected HS5-10 configuration with five field periods are: major radius R 0 = 5.5 m, magnetic induction B 0 = 3 T and stored magnetic energy W ≅ 0.6 GJ. For comparison with the superconducting coil system which is foreseen for Wendelstein VII-X, a pulsed water-cooled normal-conducting version has been designed in order to explore the limitations and restrictions of this approach. Limitations are the high ohmic power dissipated in the coils and the electric energy currently available at IPP. Normal-conducting coils would allow to apply the well-known techniques in manufactoring these coils, as successful in use in the Wendelstein VII-AS experiment. But these techniques are applicable also for the conductor proposed for the superconducting coils of Wendelstein VII-X. In this report the time-dependent current and resistance of the coil system circuit is considered; the electric power needed, the total dissipated energy, and the temperature rise of the coil copper is calculated. Scaling laws are derived and parameter studies are made by varying the geometrical dimensions of the system. (orig.)

  17. Stabilization of the (2,1) tearing mode and of the current disruption in the W VII-A stellarator

    International Nuclear Information System (INIS)

    Bartlett, D.V.; Cannici, G.; Cattanei, G.

    1980-01-01

    A numerical code based on a Δ'-analysis is applied to calculate the saturated amplitude of tearing modes dependent on the current density profile. The only stellarator effect included is the additional, shearless external rotational transform in the safety factor profile q(r). In this way, the stellarator field shifts the resonant q=2 surface toward the outside, where the current density gradient is smaller, and stabilizes the (2,1) mode as observed experimentally. Also the measured dependence of the (2,1) mode amplitude on electron density and plasma current can be absolutely predicted by the calculations. - In addition to stabilizing the (2,1) tearing mode, the current disruption is suppressed in Ohmically heated W VII-A discharges for approximately >0.15. The experimental findings, together with the calculated island widths, are compared with the predictions of a theoretical model proposed by several authors to explain the current disruption. (author)

  18. A search for the millimetre lines of HCN in Comets Wilson 1987 VII and Machholz 1988 XV

    Science.gov (United States)

    Crouvisier, J.; Despois, D.; Bockelee-Morvan, D.; Gerard, E.; Paubert, G.; Johansson, L. E. B.; Ekelund, L.; Winnberg, A.; Ge, W.; Irvine, W. M.; Kinzel, W. M.; Schloerb, F. P.

    1990-08-01

    The J(1-0) lines of HCN at 89 GHz were searched for in Comet Wilson 1987 VII, with the FCRAO, the SEST and the IRAM radio telescopes between February and June 1987. There was no firm detection, but significant upper limits were obtained, which put severe constraints on the HCN production rate in that comet. A direct comparison with the observations of P/Halley suggests that the HCN abundance relative to water might be smaller in Comet Wilson by at least a factor of two. The J(1-0) and J(3-2) lines of HCN at 89 and 266 GHz were searched for in Comet Machholz 1988 XV when it was close to perihelion at 0.17 AU from the sun. There was no detection. At that moment, the comet was probably no longer active.

  19. The interaction of Np(V), Pu(VI) and Tc(VII) with metal in alkaline solutions

    International Nuclear Information System (INIS)

    Silin, V.I.; Kareta, A.V.

    1998-01-01

    The interaction of Np(V), Pu(VI) and Tc(VII) with metal reductants Zn, Cr, Sn and their alloys was investigated in 0.5-4 mol l -1 NaOH solutions in static and dynamic conditions (by filtration of solutions through the column filled with grains of metal). In this paper, it was found that the reduction and succeeding precipitation hydroxides of these elements, on the surface of metal grains from 0.5 to 4 mol l -1 NaOH solutions, gives a decontamination factor (DF) from 1.1 to 67. The best result was achieved for Pu (DF=67) on Cr grains after 2.5 h contact at 60 C with 0.5 mol l -1 NaOH solution containing Pu(VI). Increasing the NaOH concentration, and the addition of chromate ions and complex-forming agents to alkaline solution results in a decrease of the decontamination factor (DF). A better result for Np sorption from 1 mol l -1 NaOH solutions was achieved after longer contact, than for Pu, with Cr and Zn grains. The maximum DF=8.9 was achieved for Tc on a column with Zn grains after filtration with a 3.5 mol l -1 NaOH solution containing Tc(VII). Washing out of Np and Pu, sorbed on the Cr grain surfaces, was achieved using an acid solution (1 mol l -1 HNO 3 ). The technetium was desorbed from metal surface by 10% H 2 O 2 solution. (orig.)

  20. Ice-VII inclusions in diamonds: Evidence for aqueous fluid in Earth’s deep mantle

    Science.gov (United States)

    Tschauner, O.; Huang, S.; Greenberg, E.; Prakapenka, V. B.; Ma, C.; Rossman, G. R.; Shen, A. H.; Zhang, D.; Newville, M.; Lanzirotti, A.; Tait, K.

    2018-03-01

    Water-rich regions in Earth’s deeper mantle are suspected to play a key role in the global water budget and the mobility of heat-generating elements. We show that ice-VII occurs as inclusions in natural diamond and serves as an indicator for such water-rich regions. Ice-VII, the residue of aqueous fluid present during growth of diamond, crystallizes upon ascent of the host diamonds but remains at pressures as high as 24 gigapascals; it is now recognized as a mineral by the International Mineralogical Association. In particular, ice-VII in diamonds points toward fluid-rich locations in the upper transition zone and around the 660-kilometer boundary.

  1. Verification and validation of ACE-format library created from ENDF/B-VII.0

    International Nuclear Information System (INIS)

    Chen Chaobin; Hu Zehua; Zhang Benai; Chen Yixue; Wu Jun

    2009-01-01

    ENDF/B-VII.0, released by the USA Cross Section Evaluation Working Group(CSEWG) in December 2006, was developed in five years since the previous release of ENDF/B-VI.8 and was demonstrated to contain much better physical representations of the data and to perform much better than previus ENDF evaluations over a broad range of applications. We generated ACE-format pointwise cross section library from the ENDF/B-VII.0 neutron reaction sublibrary with the processing code NJOY. The paper provides an overview of ENDF/B-VII.0, a summary of the ACE-format files producing process and a detail description of the validation of the ACE-format library. The conclusion is that the ACE-format library produced is correct. (authors)

  2. Dove sta andando l'analisi musicale? Riflessioni sul VII EuroMac

    Directory of Open Access Journals (Sweden)

    Mario Baroni

    2014-01-01

    Full Text Available Come tutti i lettori della Rivista ormai sapranno, si è svolto a Roma dal 29 settembre al 2 ottobre di quest’anno, presso il Conservatorio di S. Cecilia, il settimo convegno europeo di analisi musicale (VII European Music Analysis Conference ossia VII EuroMac. Nel convegno, organizzato dal GATM e diretto da Giorgio Sanguinetti, sono state presentate 197 relazioni e svolti otto laboratori. Tutti i materiali sono stati riassunti in un volume (Programme and Abstract Book, Iter Edizioni di Subiaco curato da Egidio Pozzi e Antonio Cascelli.

  3. Employment discrimination implications of genetic screening in the workplace under Title VII and the Rehabilitation Act.

    Science.gov (United States)

    Canter, E F

    1984-01-01

    The emergence of genetic screening techniques will permit employers to exclude hypersusceptible individuals from potentially hazardous workplace environments. The denial of employment opportunities to these individuals, however, may constitute discrimination. This Note analyzes genetic screening cases with respect to currently available remedies contained in Title VII of the Civil Rights Act of 1964 and the Rehabilitation Act of 1973. The Note concludes that Title VII claims may succeed but only in limited circumstances and that Rehabilitation Act claims will encounter numerous obstacles to relief. Additionally, the Note discusses some of the implications of the use of genetic screening in the workplace.

  4. Confinement of Stellarator plasmas with neutral beam and RF heating in W VII-A

    International Nuclear Information System (INIS)

    Grieger, G.; Cattanei, G.; Dorst, D.

    1986-01-01

    WENDELSTEIN VII-A has been operated for ten years. It is a low-shear, high-aspect-ratio device. The confinement properties have been thoroughly studied for both ohmically heated and net-current free plasmas. For the latter case, NBI- and ECF-maintained plasmas were of particular importance. It was found that under optimized conditions the core of high-pressure, net-current free plasmas is mainly governed by collisional effects. The experiment will now be shut down for upgrading it into the Advanced Stellarator WEDNDELSTEIN VII-AS. (author)

  5. VII International scientific conference Radiation-thermal effects and processes in inorganic materials. Proceedings

    International Nuclear Information System (INIS)

    2010-01-01

    In the collection there are the reports of the VII International scientific conference and the VII All-Russian school-conference Radiation-thermal effects and processes in inorganic materials which were conducted on October 2-10, 2010, in Tomsk. The reports deal with new developments of charged particles high-intensity beam sources, high-temperature metrology of high-current beams and work materials, radiation-thermal stimulated effects and processes in inorganic materials, physical basics of technological processes, radiation-thermal technologies and equipment for their realization, allied branches of science and technology, specifically, nanotechnologies [ru

  6. Newcastle disease outbreaks in recent years in Western Europe were caused by an old (VI) and a novel genotype (VII)

    DEFF Research Database (Denmark)

    Lomniczi, B.; Wehmann, E.; Herczeg, J.

    1998-01-01

    and Greece in the late 1960's and in Hungary in the early 1980's. In contrast, viruses that caused epizootics in Germany, Belgium, The Netherlands, Spain and Italy could be classified into a novel genotype (provisionally termed VII), hitherto undetected in Europe. It is possible that the genotype VII viruses...

  7. Conserved water-mediated hydrogen bond network between TM-I, -II, -VI, and -VII in 7TM receptor activation

    DEFF Research Database (Denmark)

    Nygaard, Rie; Hansen, Louise Valentin; Mokrosinski, Jacek

    2010-01-01

    Five highly conserved polar residues connected by a number of structural water molecules together with two rotamer micro-switches, TrpVI:13 and TyrVII:20, constitute an extended hydrogen bond network between the intracellular segments of TM-I, -II, -VI, and -VII of 7TM receptors. Molecular dynamics...... to apparently function as a catching trap for water molecules. Mutational analysis of the beta2-adrenergic receptor demonstrated that the highly conserved polar residues of the hydrogen bond network were all important for receptor signaling but served different functions, some dampening constitutive activity...... (AsnI:18, AspII:10, and AsnVII:13), whereas others (AsnVII:12 and AsnVII:16) located one helical turn apart and sharing a water molecule were shown to be essential for agonist-induced signaling. It is concluded that the conserved water hydrogen bond network of 7TM receptors constitutes an extended...

  8. Demonstration of resonant photopumping of Mo VII by Mo XII for a VUV laser near 600 Angstrom

    International Nuclear Information System (INIS)

    Ilcisin, K.J.; Aumayr, F.; Schwob, J.L.; Suckewer, S.

    1993-09-01

    We present data of experiments on the resonant photopumping of Mo VII by Mo XII as a method of generating a coherent VUV source near 600 angstrom. The experiment is based on a scheme proposed by Feldman and Reader in which the 4p 6 -- 4p 5 6s transition in Mo VII in resonantly photopumped by the 5s 2 S 1/2 -- 4p 2 P 1/2 transition in Mo XII. Results of the laser produced plasma experiments show the successful enhancement of the population of the Mo VII 4p 5 6s upper lasing level when pumped by an adjacent Mo VII plasma. No enhancement was seen in a control experiment where the Mo VII plasma was pumped by a Zr X plasma. Improvements of the intensity of the Mo XII pump source, achieved using an additional pump laser, lead to the generation of a population inversion for the VUV transition

  9. Development and verification of a 281-group WIMS-D library based on ENDF/B-VII.1

    International Nuclear Information System (INIS)

    Dong, Zhengyun; Wu, Jun; Ma, Xubo; Yu, Hui; Chen, Yixue

    2016-01-01

    Highlights: • A new WIMS-D library based on SHEM 281 energy structures is developed. • The method for calculating the lambda factor is illustrated and parameters are discussed. • The results show the improvements of this library compared with other libraries. - Abstract: The WIMS-D library based on WIMS 69 or XMAS 172 energy group structures is widely used in thermal reactor research. Otherwise, the resonance overlap effect is not taken into account in the two energy group structure, which limits the accuracy of resonance treatment. The SHEM 281 group structure is designed by the French to avoid the resonance overlap effect. In this study, a new WIMS-D library with SHEM 281 mesh is developed by using the NJOY nuclear data processing system based on the latest Evaluated Nuclear Data Library ENDF/B-VII.1. The parameters such as the thermal cut-off energy and lambda factor that depend on group structure are discussed. The lambda factor is calculated by Neutron Resonance Spectrum Calculation System and the effect of this factor is analyzed. The new library is verified through the analysis of various criticality benchmarks by using DRAGON code. The values of multiplication factor are consistent with the experiment data and the results also are improved in comparison with other WIMS libraries.

  10. FAKTOR-FAKTOR YANG MEMPENGARUHI KESULITAN BELAJAR IPS TERPADU KELAS VII DI SMP NEGERI 1 PLANTUNGAN KABUPATEN KENDAL

    Directory of Open Access Journals (Sweden)

    Lina Maftukhah,

    2012-10-01

    Full Text Available Kesulitan belajar dipengaruhi oleh berbagai macam faktor, baik faktor intern maupun faktor ekstern. Berdasarkan hasil observasi dari data nilai UAS IPS Terpadu sebagian besar siswa kelas VII SMP Negeri 1 Plantungan mendapat nilai rendah dan menyebabkan tidak lulus KKM. Hal ini dapat dijadikan indikasi bahwa siswa mengalami kesulitan belajar IPS Terpadu. Permasalahan yang dikaji dalam penelitian ini adalah apa saja faktor-faktor yang mempengaruhi kesulitan belajar mata pelajaran IPS Terpadu Siswa Kelas VII dan faktor apakah yang lebih dominan mempengaruhi kesulitan belajar mata pelajaran IPS Terpadu Siswa Kelas VII SMP Negeri 1 Plantungan Kabupaten Kendal Tahun Ajaran 2011/2012. Penelitian ini bertujuan untuk mengetahui faktor-faktor apa saja yang mempengaruhi kesulitan belajar mata pelajaran IPS Terpadu dan faktor apakah yang lebih dominan mempengaruhi kesulitan belajar mata pelajaran IPS Terpadu. Penelitian ini dilakukan di SMP N egeri 1 Plantungan Kabupaten Kendal. Populasi penelitian ini adalah siswa kelas VII sebanyak 131 siswa. Pengambilan sampel dilakukan secara proposional claster random sampling dan didapat sampel sebanyak 100 siswa. Variabel dalam penelitian ini adalah faktor-faktor yang mempengaruhi kesulitan belajar IPS Terpadu kelas VII SMP Negeri 1 Plantungan Kabupaten Kendal. Metode pengumpulan data yang digunakan adalah metode kuesioner dan dokumentasi. Sedangkan untuk analisis data yang digunakan adalah analisis faktor dan deskriptif persentase. Berdasarkan analisis faktor terdapat 5 komponen yang akan membentuk 5 faktor baru. Adapun tingkat kesulitan belajar siswa dari 5 faktor baru berdasarkan uji Deskripsi Persentase sebagai berikut : (a kemampuan siswa 61,55%, (b kemampuan guru 66,75%, (c sarana penunjang 77,00%, (d dukungan sekolah 72,67%, (e dukungan keluarga 62,00%. Dari kelima faktor yang ada, faktor kemampuan siswa merupakan pengaruh yang paling dominan dengan koefisien varian sebesar 61,55% dengan kategori menghambat

  11. Computational analysis of neutronic parameters for TRIGA Mark-II research reactor using evaluated nuclear data libraries ENDF/B-VII.0 and JENDL-3.3

    International Nuclear Information System (INIS)

    Altaf, M.H.; Badrun, N.H.; Chowdhury, M.T.

    2015-01-01

    Highlights: • SRAC-PIJ code and SRAC-CITATION have been utilized to model the core. • Most of the simulated results show no significant differences with references. • Thermal peak flux varies a bit due to up condition of TRIGA. • ENDF/B-VII.0 and JENDL-3.3 libraries perform well for neutronics analysis of TRIGA. - Abstract: Important kinetic parameters such as effective multiplication factor, k eff , excess reactivity, neutron flux and power distribution, and power peaking factors of TRIGA Mark II research reactor in Bangladesh have been calculated using the comprehensive neutronics calculation code system SRAC 2006 with the evaluated nuclear data libraries ENDF/B-VII.0 and JENDL-3.3. In the code system, PIJ code was employed to obtain cross section of the core cells, followed by the integral calculation of neutronic parameters of the reactor conducted by CITATION code. All the analyses were performed using the 7-group macroscopic cross section library. Results were compared to the experimental data, the safety analysis report (SAR) of the reactor provided by General Atomic as well as to the simulated values by numerically benchmarked MCNP4C, WIMS-CITATION and SRAC-CITATION codes. The maximum power densities at the hot spot were found to be 169.7 W/cc and 170.1 W/cc for data libraries ENDF/B-VII.0 and JENDL-3.3, respectively. Similarly, the total peaking factors based on ENDF/B-VII.0 and JENDL-3.3 were calculated as 5.68 and 5.70, respectively, which were compared to the original SAR value of 5.63, as well as to MCNP4C, WIMS-CITATION and SRAC-CITATION results. It was found in most cases that the calculated results demonstrate a good agreement with our experiments and published works. Therefore, this analysis benchmarks the code system and will be helpful to enhance further neutronics and thermal hydraulics study of the reactor

  12. Presidendi teenetemärgi pälvis viis spordiinimest

    Index Scriptorium Estoniae

    2008-01-01

    Vt. ka Linnaleht : Tartu 7. veebr., lk. 7. Eesti riigile osutatud teenete eest pälvisid president Toomas Hendrik Ilveselt teenetemärgi viis spordieluga seotud inimest: jalgpallikoondise ekstreenerid Jelle Goes ja Arno Pijpers, kergejõustikutreener Vésteinn Hafsteinsson, sõudetreener Tatjana Jaanson ning spordielu edendaja Nora Kutti. Juuresoleval fotol Jelle Goes

  13. Chemical Analysis of the Moon at the Surveyor VII Landing Site: Preliminary Results.

    Science.gov (United States)

    Turkevich, A L; Franzgrote, E J; Patterson, J H

    1968-10-04

    The alpha-scattering experiment aboard Surveyor VII has provided a chemical analysis of the moon in the area of the crater Tycho. The preliminary results indicate a chemical composition similar to that already found at two mare sites, but with a lower concentration of elements of the iron group (titanium through copper).

  14. The measurement and interpretation of Ne VII spectral line intensity ratios

    International Nuclear Information System (INIS)

    Lang, J.

    1983-03-01

    Results are presented for the measurement, using the branching ratios calibration method, of the spectral intensities of Ne VII lines emitted from a theta-pinch plasma whose electron temperature and density have been found by laser scattering and alternate techniques. (author)

  15. Law School Faculty Hiring under Title VII: How a Judge Might Decide a Disparate Impact Case.

    Science.gov (United States)

    Redlich, Norman

    1991-01-01

    A judicial opinion concerning law school violations of Title VII of the Civil Rights Act of 1964 in faculty hiring is presented. The case concerns a black candidate rejected for an entry-level tenure-track position. Issues cited include the law school's mission and stated reasons for not hiring the candidate. (MSE)

  16. Investigation of current drive possibilities with the present ICRH system in Wendelstein VII-AS

    International Nuclear Information System (INIS)

    Chiu, S.C.

    1990-01-01

    With the double antenna configuration, designed for first heating tests on W VII-AS, a maximum driven current of 390 A/MW coupled can be expected when using a frequency of 75 MHz and a phasing of π/2. (orig.)

  17. CASMO5 JENDL-4.0 and ENDF/B-VII.1beta4 libraries

    International Nuclear Information System (INIS)

    Rhodes, J.; Gheorghiu, N.; Ferrer, R.

    2012-01-01

    This paper details the generation of neutron data libraries for the CASMO5 lattice physics code based on the recently released JENDL-4.0 and ENDF/B-VII.1beta4 nuclear data evaluations. This data represents state-of-the-art nuclear data for late-2011. The key features of the new evaluations are briefly described along with the procedure for processing of this data into CASMO5, 586-energy group neutron data libraries. Finally some CASMO5 results for standard UO 2 and MOX critical experiments for the two new libraries and the current ENDF/B-VII.0 CASMO5 library are presented including the B and W 1810 series, DIMPLE S06A, S06B, TCA reflector criticals with iron plates and the PNL-30-35 MOX criticals. The results show that CASMO5 with the new libraries is performing well for these criticals with a very slight edge in results to the JENDL-4.0 nuclear data evaluation over the ENDF/B-VII.1beta4 evaluation. Work is currently underway to generate a CASMO5 library based on the final ENDF/B-VII.R1 evaluation released Dec. 22, 2011. (authors)

  18. Analysis of time series for postal shipments in Regional VII East Java Indonesia

    Science.gov (United States)

    Kusrini, DE; Ulama, B. S. S.; Aridinanti, L.

    2018-03-01

    The change of number delivery goods through PT. Pos Regional VII East Java Indonesia indicates that the trend of increasing and decreasing the delivery of documents and non-documents in PT. Pos Regional VII East Java Indonesia is strongly influenced by conditions outside of PT. Pos Regional VII East Java Indonesia so that the prediction the number of document and non-documents requires a model that can accommodate it. Based on the time series plot monthly data fluctuations occur from 2013-2016 then the model is done using ARIMA or seasonal ARIMA and selected the best model based on the smallest AIC value. The results of data analysis about the number of shipments on each product sent through the Sub-Regional Postal Office VII East Java indicates that there are 5 post offices of 26 post offices entering the territory. The largest number of shipments is available on the PPB (Paket Pos Biasa is regular package shipment/non-document ) and SKH (Surat Kilat Khusus is Special Express Mail/document) products. The time series model generated is largely a Random walk model meaning that the number of shipment in the future is influenced by random effects that are difficult to predict. Some are AR and MA models, except for Express shipment products with Malang post office destination which has seasonal ARIMA model on lag 6 and 12. This means that the number of items in the following month is affected by the number of items in the previous 6 months.

  19. Correction of murine mucopolysaccharidosis VII by a human. beta. -glucuronidase transgene

    Energy Technology Data Exchange (ETDEWEB)

    Kyle, J.W.; Vogler, C.; Hoffmann, J.W.; Sly, W.S. (St. Louis Univ. School of Medicine, MO (USA)); Birkenmeier, E.H.; Gwynn, B. (Jackson Laboratory, Bar Harbor, ME (USA))

    1990-05-01

    The authors recently described a murine model for mucopolysaccharidosis VII in mice that have an inherited deficiency of {beta}-glucuronidase. Affected mice, of genotype gus{sup mps}/gus{sup mps}, present clinical manifestations similar to those of humans with mucopolysaccharidosis VII (Sly syndrome) and are shown here to have secondary elevations of other lysosomal enzymes. The mucopolysaccharidosis VII phenotype in both species includes dwarfism, skeletal deformities, and premature death. Lysosome storage is visualized within enlarged vesicles and correlates biochemically with accumulation of undegraded and partially degraded glycosaminoglycans. In this report they describe the consequences of introducing the human {beta}-glucuronidase gene, GUSB, into gus{sup mps}/gus{sup mps} mice that produce virtually no murine {beta}-glucuronidase. Transgenic mice homozygous for the mucopolysaccharidosis VII mutation expressed high levels of human {beta}-glucuronidase activity in all tissues examined and were phenotypically normal. Biochemically, both the intralysosomal storage of glycosaminoglycans and the secondary elevation of other acid hydrolases were corrected. These findings demonstrate that the GUSB transgene is expressed in gus{sup mps}/gus{sup mps} mice and that human {beta}-glucuronidase corrects the murine mucopolysaccharidosis storage disease.

  20. Vittorio De Sica viis meistritööd / Aare Ermel

    Index Scriptorium Estoniae

    Ermel, Aare, 1957-2013

    2008-01-01

    DVD-st "Vittorio De Sica Masterpiece Collection", kus on peal itaalia filmirežissööri Vittorio De Sica viis teost: "Jalgratavargad" ("Ladri di biciclette", 1948), "Ime Milanos" ("Miraclo a milano", 1951), "Umberto D." (1952), "Eile täna, homme" ("Ieri, oggi, domani", 1963), "Ajatu filmikunst" ("Cinema senza tempo: Cosi e la vita", 2001)

  1. Sarah J. Hale High School Project SABER. ESEA Title VII. Final Evaluation Report, 1979-80.

    Science.gov (United States)

    New York City Board of Education, Brooklyn, NY. Office of Educational Evaluation.

    This is an evaluation of a Title VII Bilingual Program conducted at a New York City High School in 1979-80. The report contains information on the program goals and objectives, the school site, and the student characteristics. Aspects of the instructional component discussed include programming, mainstreaming, and program funding.…

  2. VVER-440 and VVER-1000 reactor dosimetry benchmark - BUGLE-96 versus ALPAN VII.0

    International Nuclear Information System (INIS)

    Duo, J. I.

    2011-01-01

    Document available in abstract form only, full text of document follows: Analytical results of the vodo-vodyanoi energetichesky reactor-(VVER-) 440 and VVER-1000 reactor dosimetry benchmarks developed from engineering mockups at the Nuclear Research Inst. Rez LR-0 reactor are discussed. These benchmarks provide accurate determination of radiation field parameters in the vicinity and over the thickness of the reactor pressure vessel. Measurements are compared to calculated results with two sets of tools: TORT discrete ordinates code and BUGLE-96 cross-section library versus the newly Westinghouse-developed RAPTOR-M3G and ALPAN VII.0. The parallel code RAPTOR-M3G enables detailed neutron distributions in energy and space in reduced computational time. ALPAN VII.0 cross-section library is based on ENDF/B-VII.0 and is designed for reactor dosimetry applications. It uses a unique broad group structure to enhance resolution in thermal-neutron-energy range compared to other analogous libraries. The comparison of fast neutron (E > 0.5 MeV) results shows good agreement (within 10%) between BUGLE-96 and ALPAN VII.O libraries. Furthermore, the results compare well with analogous results of participants of the REDOS program (2005). Finally, the analytical results for fast neutrons agree within 15% with the measurements, for most locations in all three mockups. In general, however, the analytical results underestimate the attenuation through the reactor pressure vessel thickness compared to the measurements. (authors)

  3. Dos Idiomas, Un Mundo. Dual Language Project. Title VII Biennial Evaluation Report, 1995-97.

    Science.gov (United States)

    Ernest, Harishini M.; Gonzalez, Rosa M.

    This is an evaluation of the first 2 years of a 5-year comprehensive Bilingual Education grant funded by Title VII Part A of the Improving America's Schools Act of 1994 in the Austin Independent School District (AISD) (Texas). The grant awarded to the AISD funds a program of Developmental Bilingual Education at two elementary schools where more…

  4. Safety and Equality at Odds: OSHA and Title VII Clash over Health Hazards in the Workplace.

    Science.gov (United States)

    Crowell, Donald R.; Copus, David A.

    1978-01-01

    Discusses the legal problems presented by job health hazards which have a different effect on men and women. Where methods of eliminating or minimizing exposure, as required by the Occupational Safety and Health Act, affect only one sex, the provisions of Title VII of the Civil Rights Act may be violated. (MF)

  5. "Põrgu wärk" võitis Balti teatrifestivalil viis auhinda

    Index Scriptorium Estoniae

    2006-01-01

    Balti teatrifestivalil "OmaDraama 2006" nähtud etendustest said viis auhinda eestlased - Mart Kivastik näidendi "Põrgu Wärk" eest, Hendrik Toompere lavastuse eest, Harriet Toompere naisosatäitmise eest, Jan Uuspõld Wiiralti kehastamise eest ning Margus Prangel Tuglase osa eest. Ka teistest festivalil auhinnasaajatest

  6. Eesti lavastus "Põrgu wärk" võitis Balti teatrifestivalil viis auhinda

    Index Scriptorium Estoniae

    2006-01-01

    Balti teatrifestivalil "OmaDraama 2006" nähtud etendustest said viis auhinda eestlased - Mart Kivastik näidendi "Põrgu Wärk" eest, Hendrik Toompere lavastuse eest, Harriet Toompere naisosatäitmise eest, Jan Uuspõld Wiiralti kehastamise eest ning Margus Prangel Tuglase osa eest

  7. Neutron Thermal Cross Sections, Westcott Factors, Resonance Integrals, Maxwellian Averaged Cross Sections and Astrophysical Reaction Rates Calculated from the ENDF/B-VII.1, JEFF-3.1.2, JENDL-4.0, ROSFOND-2010, CENDL-3.1 and EAF-2010 Evaluated Data Libraries

    Science.gov (United States)

    Pritychenko, B.; Mughabghab, S. F.

    2012-12-01

    We present calculations of neutron thermal cross sections, Westcott factors, resonance integrals, Maxwellian-averaged cross sections and astrophysical reaction rates for 843 ENDF materials using data from the major evaluated nuclear libraries and European activation file. Extensive analysis of newly-evaluated neutron reaction cross sections, neutron covariances, and improvements in data processing techniques motivated us to calculate nuclear industry and neutron physics quantities, produce s-process Maxwellian-averaged cross sections and astrophysical reaction rates, systematically calculate uncertainties, and provide additional insights on currently available neutron-induced reaction data. Nuclear reaction calculations are discussed and new results are presented. Due to space limitations, the present paper contains only calculated Maxwellian-averaged cross sections and their uncertainties. The complete data sets for all results are published in the Brookhaven National Laboratory report.

  8. Pengembangan LKS Untuk Melatih Kemampuan Berpikir Kritis dalam Mata Pelajaran Matematika di Kelas VII SMP

    Directory of Open Access Journals (Sweden)

    Puji Astuti

    2017-10-01

    Full Text Available Tujuan pembelajaran matematika adalah untuk melatih siswa berpikir kritis. Oleh karena itu, perlu dikembangkan Lembar Kerja Siswa (LKS untuk melatih kemampuan berpikir kritis siswa. Penelitian ini bertujuan untuk menghasilkan LKS yang berkarakteristik untuk melatih kemampuan berpikir kritis siswa kelas VII SMP. Sampel pada penelitian ini adalah kelas VII7 berjumlah 30 siswa semester II SMP Negeri 9 Palembang. Metode penelitian yang digunakan adalah metode penelitian pengembangan yang terdiri dari analisis, desain, evaluasi dan revisi. Pengumpulan data dilakukan dengan cara prototyping.  Prototyping dilakukan untuk mengetahui bagaimana karakteristik LKS untuk melatih kemampuan berpikir kritis siswa kelas VII SMP. Hasil penelitian ini adalah karakteristik LKS untuk melatih kemampuan berpikir kritis siswa kelas VII SMP. Kata kunci: Kemampuan berpikir kritis, Lembar Kerja Siswa    Mathematics learning aims to develop students critical thinking. Therefore, it is necessary to develop Student Worksheet to train students' critical thinking skills. This research aims to develop student worksheet that has characteristics of critical thinking skill for 7th grade Junior High School students (SMP. The sample in this research is VII7 class with 30 students of the second semester of SMP Negeri 9 Palembang. The research method used is a development research method that consists of analysis, design, evaluation and revision. Data collection is done by prototyping. Prototyping was used to find out how the characteristics of student worksheet to develop critical thinking ability of grade  7th students. The result of this research is characteristic of student worksheet to develop critical thinking ability of 7th grade Junior High School student. Keywords: critical thinking ability, student worksheet

  9. Tissue factor-dependent activation of tritium-labeled factor IX and factor X in human plasma

    International Nuclear Information System (INIS)

    Morrison, S.A.; Jesty, J.

    1984-01-01

    A comparism was made of the tissue factor-dependent activation of tritium-labeled factor IX and factor X in a human plasma system and a study was made of the role of proteases known to stimulate factor VII activity. Plasma was defibrinated by heating and depleted of its factors IX and X by passing it through antibody columns. Addition of human brain thromboplastin, Ca2+, and purified 3H-labeled factor X to the plasma resulted, after a short lag, in burst-like activation of the factor X, measured as the release of radiolabeled activation peptide. The progress of activation was slowed by both heparin and a specific inhibitor of factor Xa but factor X activation could not be completely abolished by such inhibitors. In the case of 3H-factor IX activation, the rate also increased for approximately 3 min after addition of thromboplastin, but was not subsequently curtailed. A survey of proteases implicated as activators of factor VII in other settings showed that both factor Xa and factor IXa could accelerate the activation of factor IX. However, factor Xa was unique in obliterating activation when present at concentrations greater than approximately 1 nM. Heparin inhibited the tissue factor-dependent activation of factor IX almost completely, apparently through the effect of antithrombin on the feedback reactions of factors Xa and IXa on factor VII. These results suggest that a very tight, biphasic control of factor VII activity exists in human plasma, which is modulated mainly by factor Xa. At saturation of factor VIIa/tissue factor, factor IX activation was significantly more rapid than was previously found in bovine plasma under similar conditions. The activation of factor X at saturation was slightly more rapid than in bovine plasma, despite the presence of heparin

  10. Oxidation of triclosan by permanganate (Mn(VII)): importance of ligands and in situ formed manganese oxides.

    Science.gov (United States)

    Jiang, Jin; Pang, Su-Yan; Ma, Jun

    2009-11-01

    Experiments were conducted to examine permanganate (Mn(VII); KMnO(4)) oxidation of the widely used biocide triclosan (one phenolic derivative) in aqueous solution at pH values of 5-9. Under slightly acidic conditions, the reactions displayed autocatalysis, suggesting the catalytic role of in situ formed MnO(2). This was further supported by the promoting effects of the addition of preformed MnO(2) colloids on Mn(VII) oxidations of triclosan and two other selected phenolics (i.e., phenol and 2,4-dichlorophenol), as well as p-nitrophenol which otherwise showed negligible reactivity toward Mn(VII) and MnO(2) colloids, respectively. Surprisingly, phosphate buffer significantly enhanced Mn(VII) oxidation of triclosan, as well as phenol and 2,4-dichlorophenol over a wide pH range. Further, several other selected ligands (i.e., pyrophosphate, EDTA, and humic acid) also exerted oxidation enhancement, supporting a scenario where highly active aqueous manganese intermediates (Mn(INT)(aq)) formed in situ upon Mn(VII) reduction might be stabilized to a certain extent in the presence of ligands and subsequently involved in further oxidation of target phenolics, whereas without stabilizing agents Mn(INT)(aq) autodecomposes or disproportionates spontaneously. The effectiveness of Mn(VII) for the oxidative removal of triclosan in natural water and wastewater was confirmed. Their background matrices were also found to accelerate Mn(VII) oxidation of phenolics.

  11. COINCIDENCES BETWEEN O VI AND O VII LINES: INSIGHTS FROM HIGH-RESOLUTION SIMULATIONS OF THE WARM-HOT INTERGALACTIC MEDIUM

    International Nuclear Information System (INIS)

    Cen Renyue

    2012-01-01

    With high-resolution (0.46 h –1 kpc), large-scale, adaptive mesh-refinement Eulerian cosmological hydrodynamic simulations we compute properties of O VI and O VII absorbers from the warm-hot intergalactic medium (WHIM) at z = 0. Our new simulations are in broad agreement with previous simulations with ∼40% of the intergalactic medium being in the WHIM. Our simulations are in agreement with observed properties of O VI absorbers with respect to the line incidence rate and Doppler-width-column-density relation. It is found that the amount of gas in the WHIM below and above 10 6 K is roughly equal. Strong O VI absorbers are found to be predominantly collisionally ionized. It is found that (61%, 57%, 39%) of O VI absorbers of log N(O VI) cm 2 = (12.5-13, 13-14, > 14) have T 5 K. Cross correlations between galaxies and strong [N(O VI) > 10 14 cm –2 ] O VI absorbers on ∼100-300 kpc scales are suggested as a potential differentiator between collisional ionization and photoionization models. Quantitative prediction is made for the presence of broad and shallow O VI lines that are largely missed by current observations but will be detectable by Cosmic Origins Spectrograph observations. The reported 3σ upper limit on the mean column density of coincidental O VII lines at the location of detected O VI lines by Yao et al. is above our predicted value by a factor of 2.5-4. The claimed observational detection of O VII lines by Nicastro et al., if true, is 2σ above what our simulations predict.

  12. Hypoxia induces cancer-associated cAMP/PKA signalling through HIF-mediated transcriptional control of adenylyl cyclases VI and VII.

    Science.gov (United States)

    Simko, Veronika; Iuliano, Filippo; Sevcikova, Andrea; Labudova, Martina; Barathova, Monika; Radvak, Peter; Pastorekova, Silvia; Pastorek, Jaromir; Csaderova, Lucia

    2017-08-31

    Hypoxia is a phenomenon often arising in solid tumours, linked to aggressive malignancy, bad prognosis and resistance to therapy. Hypoxia-inducible factor-1 has been identified as a key mediator of cell and tissue adaptation to hypoxic conditions through transcriptional activation of many genes involved in glucose metabolism and other cancer-related processes, such as angiogenesis, cell survival and cell invasion. Cyclic adenosine 3'5'-monophosphate is one of the most ancient and evolutionarily conserved signalling molecules and the cAMP/PKA signalling pathway plays an important role in cellular adaptation to hypoxia. We have investigated possible new mechanisms behind hypoxic activation of the cAMP/PKA pathway. For the first time, we have shown that hypoxia induces transcriptional up-regulation of the system of adenylyl cyclases, enzymes responsible for cAMP production, in a panel of carcinoma cell lines of various origin. Our data prove functional relevance of the hypoxic increase of adenylyl cyclases VI and VII at least partially mediated by HIF-1 transcription factor. We have identified adenylyl cyclase VI and VII isoforms as mediators of cellular response to hypoxia, which led to the elevation of cAMP levels and enhanced PKA activity, with an impact on cell migration and pH regulation.

  13. Complex diagnostic approaches in metastases of tumors in skeleton. VII

    International Nuclear Information System (INIS)

    Bek, V.; Stepan, J.; Hausner, P.; Vosecky, M.; Konopasek, B.; Novy, F.

    1987-01-01

    In addition to the current methods of imaging the skeleton and of histomorphological and cytomorphological examinations of the bone marrow and the bone tissue, an ever growing attention is devoted to humoral factors affecting the metabolism of the skeleton. Prostaglandins, or in a broader sense, eicosanoids are in the forefront of the attention. Their relations is studied to immune and endocrine mechanisms and to growth factors (TGF (transforming growth factor), EDF (epidermal growth factor), PDGF (platelet derived growth factor)). Specific monoclonal antibodies to the membrane and cytoplasma structures of malignant cells represent an important shift towards improved detection of disseminated tumor cells in the bone marrow. Computerized tomography and nuclear magnetic resonance contribute to improved definition in bone diagnosis. The condition of bone metabolism can be assessed by whole-body retention using technetium-labelled phosphate complexes. The methods offering information on the state of blood supply for the skeleton are also important. Common tests of bone marrow metastasis detection combine with the determination of the presence of tumor markers (CEA (carcinoembryonic antigen), TPA (tissue polypeptide antigen), plasminogen activator, polyamine, etc.). Upon heterogeneity of cell populations in the tumor, an urgent need arises for the clinician to penetrate down to the cellular and the subcellular levels of the malignant growth with the aim of identifying biological potency of the individual cell clones, including their capability of produce and proliferate metastases. We are approaching this desirable target through the flow cytometry method. (author). 30 refs

  14. Planck early results. VII. The Early Release Compact Source Catalogue

    DEFF Research Database (Denmark)

    Ade, P. A. R.; Aghanim, N.; Arnaud, M.

    2011-01-01

    .28, 0.25, 0.47 and 0.82 Jy at each of the nine frequencies between 30 and 857 GHz. Sources which are up to a factor of 2 fainter than this limit, and which are present in "clean" regions of the Galaxy where the sky background due to emission from the interstellar medium is low, are included in the ERCSC...

  15. Department of Neurosurgery, Seth Gordhandas Sunderdas Medical College and King Edward VII Memorial (K.E.M.) Hospital, Mumbai.

    Science.gov (United States)

    Pandya, Sunil; Goel, Atul

    2017-01-01

    Seth Gordhandas Sunderdas Medical College and King Edward VII Memorial (K.E.M.) Hospital, Mumbai were inaugurated in 1925. This article traces its illustrious history and of the eminent neurosurgeons who shaped its destiny.

  16. DNA and factor VII-activating protease protect against the cytotoxicity of histones

    NARCIS (Netherlands)

    Marsman, Gerben; von Richthofen, Helen; Bulder, Ingrid; Lupu, Florea; Hazelzet, Jan; Luken, Brenda M.; Zeerleder, Sacha

    2017-01-01

    Circulating histones have been implicated as major mediators of inflammatory disease because of their strong cytotoxic effects. Histones form the protein core of nucleosomes; however, it is unclear whether histones and nucleosomes are equally cytotoxic. Several plasma proteins that neutralize

  17. Determinación del estado de salud bucal en pacientes discapacitados del Área VII en Cienfuegos

    Directory of Open Access Journals (Sweden)

    Ana Belkys Hernández Millán

    2014-10-01

    Full Text Available Fundamento: la discapacidad constituye una preocupación social, sin embargo, se cuenta con pocos estudios sobre el estado de salud bucal de los pacientes discapacitados. Objetivo: determinar el estado de salud bucal en pacientes discapacitados del Área VII de la provincia Cienfuegos. Métodos: se realizó un estudio descriptivo, de serie de casos, del Área VII del municipio de Cienfuegos, en el periodo de enero-diciembre de 2013. Se estudiaron 192 discapacitados que acudieron a consulta estomatológica o fueron visitados en terreno. Las variables analizadas fueron: edad, sexo, nivel de escolaridad, tipo de discapacidad, clasificación epidemiológica en cuanto al estado de salud bucal, enfermedades sistémicas, factores de riesgo a tener en cuenta para las enfermedades bucales, estado de salud bucal, periodontopatías, maloclusiones, lesiones premalignas, necesidad de prótesis total o parcial y necesidad de tratamiento en Atención Primaria o Secundaria. La información se recogió en historia clínica individual, planilla de clasificación de discapacidad. Los resultados se presentan en número y porcentaje. Resultados: el género femenino fue el más afectado, y la edad más representativa la de 35-59 años, predominaron las enfermedades crónicas degenerativas, los enfermos en la clasificación epidemiológica según estado de salud bucal, la hipertensión arterial entre las enfermedades sistémicas. Antecedentes de caries fue el factor de riesgo más relevante, resultando la gingivitis crónica edematosa, con un mayor porcentaje. Conclusiones: se determinó que la salud bucal en el grupo estudiado fue deficiente y existen dificultades por parte del Estomatólogo General Integral para tratar a estos pacientes a pesar de existir programas de atención a discapacitados.

  18. Sobre el envío de tropas de la Legio VII Gemina al limes africano

    Directory of Open Access Journals (Sweden)

    Juan José PALAO VICENTE

    2010-02-01

    Full Text Available RESUMEN: Las relaciones entre Hispania y Africa en época romana fueron corrientes en todos los campos, incluyendo el militar. Este artículo intenta analizar la presencia en territorio africano de tropas de la Legio VII Gemina, tratando de conocer cuáles fueron los verdaderos motivos de dicha estancia. El estudio del material amplía la visión tradicional de las posibles funciones allí desempeñadas por estos destacamentos, que posiblemente abarcaron aspectos administrativos y logísticos.ABSTRACT: The relationship between Hispania and Africa in the Roman world were very strong in alls fields incluiding the military, too. This paper purposes to analize the presence of legio VII Gemina's troops in African territories, attempting to know the true reasons of this presence.The study of material presents a new vision about the mission of those troops, which undertake possibly administratives and logistics works.

  19. PENGARUH KEMANDIRIAN BELAJAR DAN PENGGUNAAN UANG SAKU TERHADAP PRESTASI BELAJAR KOMPETENSI DASAR EKONOMI KELAS VII DAN VIII

    OpenAIRE

    Apri Dwi Astuti

    2012-01-01

    Kemandirian belajar membantu siswa untuk bertanggung jawab dan menumbuhkan kesadaran belajar. Penggunaan uang saku menumbuhkan jiwa mandiri, jujur dan komitmen. Adapun hasil observasi awal menunjukkan masih ada siswa kels VII dan VIII SMP Semesta untuk kompetensi dasar ekonomi dibawah KKM. Tujuan penelitian ini untuk mengetahui pengaruh kemandirian belajar dn penggunaan uang saku terhadap prestasi belajar kompetensi dasar ekonomi kelas VII dan VIII SMP Semesta. Populasi penelitian ini adalah ...

  20. 29 CFR 1620.27 - Relationship to the Equal Pay Act of title VII of the Civil Rights Act.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Relationship to the Equal Pay Act of title VII of the Civil... OPPORTUNITY COMMISSION THE EQUAL PAY ACT § 1620.27 Relationship to the Equal Pay Act of title VII of the Civil... equal pay under the Equal Pay Act has no relationship to whether the employee is in the lower paying job...

  1. PENGEMBANGAN BAHAN AJAR MEMBACA PEMAHAMAN BERDASARKAN STRATEGI PLAN (PREDICT, LOCATE, ADD, NOTE) UNTUK SISWA KELAS VII

    OpenAIRE

    Sudiati Sudiati; Nurhidayah Nurhidayah

    2017-01-01

    Abstract This study aims to produce reading comprehension learning materials based on the PLAN strategy and to find out the appropriateness for Grade VII students. This was a design and development study. The stages were taken from those of Borg and Gall. The data were qualitative and quantitative in nature. The data trustworthiness was assessed in terms of credibility, transferability, dependability, and confirmability. The research instruments were an interview guide and ...

  2. Redox reactions of Tc{sup VII} with magnetite and mackinawite. Solving an old enigma

    Energy Technology Data Exchange (ETDEWEB)

    Yalcintas, E.; Gaona, X.; Altmeier, M. [Karlsruhe Institute of Technology (KIT), Karlsruhe (Germany). Inst. for Nuclear Waste Disposal; Scheinost, Andreas C. [Helmholtz-Zentrum Dresden-Rossendorf e.V., Dresden (Germany). Molecular Structures

    2017-06-01

    While the reduction of heptavalent technetium, Tc(VII), by magnetite and mackinawite under anoxic conditions is well known, the identification of the resulting Tc(IV) species shows substantial disagreement between different studies. Here we use a systematic variation of initial Tc concentration, loading and pH to decipher the Tc species by EXAFS spectroscopy and to shine light on their formation pathways.

  3. Elmo Bumpy Torus proof of principle, Phase II: Title 1 report. Volume VII. Cryogenic system

    International Nuclear Information System (INIS)

    Poteat, T.J.

    1982-01-01

    This document, Volume VII EBT-P Cryogenic System Title I Design Report, describes the system that resulted from the Title I Preliminary Design effort. It is a self-contained document that can be read apart from the other Volumes comprising the EBT-P Title I Report. This document is a contract deliverable item and provides the detail necessary to support the Cryogenic System design contained in the EBT-P Baseline Design Data Book

  4. Japanese contributions to IAEA INTOR workshop, phase two A, part 2 chapter VII: technical benefit

    International Nuclear Information System (INIS)

    Itoh, Shin-ichi; Iida, Hiromasa; Tomabechi, Ken; Tone, Tatsuzo; Fujisawa, Noboru.

    1985-07-01

    This report corresponds to Chapter VII of Japanese contribution report to IAEA INTOR Workshop, Phase Two A, Part 2. The purpose of technical benefit study is to examine the implications of having different manufacturers fabricate components of a major system of INTOR. A systematic examinations of advantages and disadvantages of designing and fabricating major INTOR components in the frame of one international joint projects is performed. (author)

  5. Desain Pembelajaran Materi Belah Ketupat Menggunakan Kain Jumputan Palembang untuk Siswa Kelas VII

    Directory of Open Access Journals (Sweden)

    Fauziyah Fauziyah

    2016-06-01

    Full Text Available Desain pembelajaran materi belah ketupat menggunakan kain Jumputan Palembang untuk siswa kelas VII. Penelitian ini bertujuan untuk melihat bagaimana penggunaan kain Jumputan Palembang dalam membangun pemahaman siswa mengenai belah ketupat. Siswa akan membandingkan luas daerah dua buah kain Jumputan, merancang dan membuat belah ketupat kemudian menggunting serta menyusunnya kembali menjadi suatu bentuk baru, menentukan luas daerah belah ketupat, membandingkan keliling dua buah kain Jumputan dan menentukan keliling belah ketupat. Subjek penelitian ini adalah 30 siswa kelas VII SMP Pusri Palembang. Penelitian ini menggunakan design research yang terdiri dari tiga tahap : preparing for the experiment, experiment in the classroom (pilot experiment dan  teaching experiment, dan retrospective analysis. Pada tahap preparing for the experiment, beberapa aktifitas dibuat menggunakan pendekatan Pendidikan Matematika Realistik Indonesia (PMRI. Hasil dari penelitian menunjukkan kain Jumputan Palembang dapat digunakan sebagai starting point dalam pembelajaran belah ketupat untuk siswa kelas VII SMP.The design learning rhombus using kain Jumputan Palembang for VII grade students. This research aims to investigate how to use Kain Jumputan Palembang to build student’s understanding on rhombus. Students were required to comparing the area of two cloths, designing and making rhombus then reshaping to new shapes, determining the area of rhombus, comparing the perimeter of two cloths and determining the perimeter of rhombus. Subjects were 30 first grade students of SMP Pusri Palembang. The study used a design research method consisting of three stages : preparing for the experiment, experiment in the classroom (pilot experiment and teaching experiment, and retrospective analysis. During the preparing for the experiment stage, instructional activities was designing utilizing of Indonesian Realistic Mathematics Education (PMRI approach. The result of experiments

  6. Release of the ENDF/B-VII.1 Evaluated Nuclear Data File

    Energy Technology Data Exchange (ETDEWEB)

    Brown, David

    2012-06-30

    The Cross Section Evaluation Working Group (CSEWG) released the ENDF/B-VII.1 library on December 22, 2011. The ENDF/B-VII.1 library is CSEWG's latest recommended evaluated nuclear data file for use in nuclear science and technology applications, and incorporates advances made in the five years since the release of ENDF/B-VII.0, including: many new evaluation in the neutron sublibrary (423 in all and over 190 of these contain covariances), new fission product yields and a greatly improved decay data sublibrary. This summary barely touches on the five years worth of advances present in the ENDF/B-VII.1 library. We expect that these changes will lead to improved integral performance in reactors and other applications. Furthermore, the expansion of covariance data in this release will allow for better uncertainty quantification, reducing design margins and costs. The ENDF library is an ongoing and evolving effort. Currently, the ENDF data community embarking on several parallel efforts to improve library management: (1) The adoption of a continuous integration system to provide evaluators 'instant' feedback on the quality of their evaluations and to provide data users with working 'beta' quality libraries in between major releases. (2) The transition to new hierarchical data format - the Generalized Nuclear Data (GND) format. We expect GND to enable new kinds of evaluated data which cannot be accommodated in the legacy ENDF format. (3) The development of data assimilation and uncertainty propagation techniques to enable the consistent use of integral experimental data in the evaluation process.

  7. Immobilization of 99-Technetium (VII) by Fe(II)-Goethite and Limited Reoxidation

    Energy Technology Data Exchange (ETDEWEB)

    W Um; H Chang; J Icenhower; W Lukens; R Serne; N Qafoku; J Westsik Jr.; E Buck; S Smith

    2011-12-31

    During the nuclear waste vitrification process volatilized {sup 99}Tc will be trapped by melter off-gas scrubbers and then washed out into caustic solutions, and plans are currently being contemplated for the disposal of such secondary waste. Solutions containing pertechnetate [{sup 99}Tc(VII)O{sub 4}{sup -}] were mixed with precipitating goethite and dissolved Fe(II) to determine if an iron (oxy)hydroxide-based waste form can reduce Tc(VII) and isolate Tc(IV) from oxygen. The results of these experiments demonstrate that Fe(II) with goethite efficiently catalyzes the reduction of technetium in deionized water and complex solutions that mimic the chemical composition of caustic waste scrubber media. Identification of the phases, goethite + magnetite, was performed using XRD, SEM and TEM methods. Analyses of the Tc-bearing solid products by XAFS indicate that all of the Tc(VII) was reduced to Tc(IV) and that the latter is incorporated into goethite or magnetite as octahedral Tc(IV). Batch dissolution experiments, conducted under ambient oxidizing conditions for more than 180 days, demonstrated a very limited release of Tc to solution (2-7 {micro}g Tc/g solid). Incorporation of Tc(IV) into the goethite lattice thus provides significant advantages for limiting reoxidation and curtailing release of Tc disposed in nuclear waste repositories.

  8. PENINGKATAN KEMAMPUAN PEMECAHAN MASALAH DAN PENGEMBANGAN KARAKTER PADA SISWA KELAS VII MELALUI MODEL PBL BERBANTUAN SCAFFOLDING

    Directory of Open Access Journals (Sweden)

    Novy Kris Zaini

    2016-04-01

    Full Text Available Tujuan penelitian ini adalah untuk mengetahui (1 apakah kemampuan pemecahan masalah matematika peserta didik yang diajar dengan model PBL berbantuan scaffolding pada materi pokok segiempat kelas VII dapat mencapai KKM yang ditetapkan, (2 apakah pembelajaran matematika dengan model PBL berbantuan scaffolding pada materi pokok segiempat kelas VII dapat meningkatkan kemampuan pemecahan masalah peserta didik pilihan, (3 apakah pembelajaran matematika dengan model PBL berbantuan scaffolding pada materi pokok segiempat kelas VII dapat meningkatkan karakter rasa ingin tahu peserta didik pilihan. Desain penelitian ini adalah concurrent triangulation (campuran kuatitatif dan kualitatif secara seimbang, menggabungkan antara metode kuantitatif dan metode kualitatif untuk digunakan secara bersama-sama dalam suatu kegiatan penelitian, sehingga diperoleh data yang lebih komprehensif, valid, reliabel dan obyektif. Penentuan sumber data dalam penelitian ini menggunakan teknik triangulasi, yaitu menggabungkan dari berbagai teknik pengumpulan data dan sumber data yang telah ada. Data diperoleh dengan observasi, wawancara, dan dokumentasi yang kemudian dianalisis menggunakan analisis kualitatif, sedangkan tes dan observasi dianalisis menggunakan analisis kuantitatif dan analisis gain untuk mengukur peningkatan. Analisis kualitatif menunjukkan karakter rasa ingin tahu dan kemampuan pemecahan masalah peserta didik meningkat, serta kemampuan pemecahan masalah peserta didik mencapai KKM melalui model pembelajaran PBL

  9. MENDF71x. Multigroup Neutron Cross Section Data Tables Based upon ENDF/B-VII.1

    International Nuclear Information System (INIS)

    Conlin, Jeremy Lloyd; Parsons, Donald Kent; Gardiner, Steven J.; Gray, Mark Girard; Lee, Mary Beth; White, Morgan Curtis

    2015-01-01

    A new multi-group neutron cross section library has been released along with the release of NDI version 2.0.20. The library is named MENDF71x and is based upon the evaluations released in ENDF/B-VII.1 which was made publicly available in December 2011. ENDF/B-VII.1 consists of 423 evaluations of which ten are excited states evaluations and 413 are ground state evaluations. MENDF71x was created by processing the 423 evaluations into 618-group, downscatter only NDI data tables. The ENDF/B evaluation files were processed using NJOY version 99.393 with the exception of 35 Cl and 233 U. Those two isotopes had unique properties that required that we process the evaluation using NJOY version 2012. The MENDF71x library was only processed to room temperature, i.e., 293.6 K. In the future, we plan on producing a multi-temperature library based on ENDF/B-VII.1 and compatible with MENDF71x.

  10. KEEFEKTIFAN MODEL PEMBELAJARAN KOOPERATIF TIPE SQ3R TERHADAP KEMAMPUAN PEMECAHAN MASALAH SISWA SMP KELAS VII

    Directory of Open Access Journals (Sweden)

    Dian Teguh Firmansyah

    2012-10-01

    Full Text Available This study aims to determine the effectiveness of cooperative learning model types Survey Question Read Recite Review (SQ3R to mathematical problem solving abilities of students in the junior high school grade VII of material relationships between angles. The population in this study is students of grade VII SMP N 1 Pagerbarang school year 2011/2012. The samples taken by cluster random sampling technique so namely studentsinclassVIIB as control group and studentsinclass VIIC as experiment group. Design used in this research is true experimental design posttest only control type. Results showed that the averagetest scores mathematical problem solving abilities of students in class taught by cooperative learning model types SQ3Rof material relationships between angles achieve minimal completeness criteria(KKM applies in SMP N 1 Pagerbarang, with many students who achieve KKM is more than equal 75%, and average test scores mathematical problem solving abilities of students in classtaught by cooperative learning model typesSQ3Rof material relationships between anglesmore than the average test scoresmathematical problem solving abilities of students in class taught by expository model. Based on the research results can be concluded that the cooperative learning model types SQ3R is effective to improve students problem solving skills students grade VII to the material relationships between angles.

  11. Monte Carlo analysis of KRITZ-2 critical benchmarks on the reactivity temperature coefficient using ENDF/B-VII.1 and JENDL-4.0 nuclear data libraries

    International Nuclear Information System (INIS)

    El Ouahdani, S.; Boukhal, H.; Erradi, L.; Chakir, E.; El Bardouni, T.; Hajjaji, O.; Boulaich, Y.; Benaalilou, K.; Kaddour, M.

    2016-01-01

    Highlights: • A set of KRITZ-2 experiments with UO 2 and MOX LWR lattices, at room and elevated temperatures, have been analysed using the MCNP6.1 code with the libraries: JENDL-4 and ENDF/B-VII.1. • The detailed comparisons of the calculations and measurements demonstrate a good agreement between calculations and measurements. • To investigate better the influence of cross sections differences on the reactivity temperature coefficient, we break it down into its components using a pin cell model. - Abstract: A set of KRITZ-2 experiments light water moderated lattices with uranium oxide and mixed-oxide fuel rods, at room and elevated temperatures, performed in the early 1970’s have been assessed. Using the MCNP6.1 code with the most recent cross section libraries: JENDL-4 and ENDF/B-VII.1, the critical experiments KRITZ: 2-1, KRITZ: 2-13, and KRITZ: 2-19 achieved in the Sweden reactor KRITZ were analyzed. We have used the ENDF/B-VII.1 data provided with the MCNP6.1.1 version in ACE format and the Makxsf utility to handle the data in the specific temperatures not available in the MCNP6.1.1 original data. The JENDL-4 evaluations were processed using NJOY99 (update 364) to the temperatures of interest. The detailed comparisons of the calculated and measured (Benchmark, 2005) effective multiplication factors and pin power distributions for UO2 and MOX fuelled cores presented in this work demonstrate a good agreement between calculation and measurements. The maximum deviation of the calculation from the experimental data for k eff , is 0.58% (absolute value) obtained for the KRITZ 2:1 at 248.5 °C using ENDF/B-VII.1 data. To investigate better the influence of cross sections differences on the reactivity and temperature coefficient, we break down the infinite multiplication factor into its components using a pin cell model. Using this simple model we evaluated the temperature effect on the infinite multiplication factor and the effect on its components. We have

  12. Particle orbits in W VII-X configurations

    International Nuclear Information System (INIS)

    Wobig, H.

    1987-01-01

    It is shown that magnetic coordinates are very convenient for describing particle orbits and neoclassical losses in stellarator studies. In the configurations considered (WVII-A and AS, Helias, Heliac, and BSX) plateau losses can be reduced by a factor of 3-4 compared with an equivalent tokamak. It is possible to reduce plateau losses and bootstrap current simultaneously. The bootstrap current can be made negligibly small. The Heliac configuration shows larger plateau losses than the equivalent tokamak. It is possible to localize trapped particles in a region of minimum radial drift velocity. The Er fields strongly reduce localized particle losses

  13. ZZ POINT-2007, linearly interpolable ENDF/B-VII.0 data for 14 temperatures

    International Nuclear Information System (INIS)

    Cullen, Dermott E.

    2007-01-01

    A - Description or function: The ENDF/B data library, ENDF/B-VII.0 was processed into the form of temperature dependent cross sections. The original evaluated data include cross sections represented in the form of a combination of resonance parameters and/or tabulated energy dependent cross sections, nominally at 0 Kelvin temperature. For use in applications, these ENDF/B-VII.0 data were processed into the form of temperature dependent cross sections at eight temperatures: 0, 300, 600, 900, 1200, 1500, 1800 and 2100 Kelvin. It has also been processed to six astrophysics like temperatures: 0.1, 1, 10, 100 eV, 1 and 10 keV. At each temperature the cross sections are tabulated and linearly interpolable in energy with a tolerance of 0.1 %. POINT 2007 contains all of the evaluations in the ENDF/B-VII general purpose library, which contains 78 new evaluations + 315 old ones: total 393 nuclides. It also includes 16 new elemental evaluations replaced by isotopic evaluations + 19 old ones. No special purpose ENDF/B-VII libraries, such as fission products, thermal scattering, photon interaction data are included. These evaluations include all cross sections over the energy range 10 e-5 eV to at least 20 MeV. The list of nuclides is indicated. B - Methods: The PREPRO 2007 code system was used to process the ENDF/B data. Listed below are the steps, including the PREPRO2007 codes, which were used to process the data in the order in which the codes were run. 1) Linearly interpolable, tabulated cross sections (LINEAR) 2) Including the resonance contribution (RECENT) 3) Doppler broaden all cross sections to temperature (SIGMA1) 4) Check data, define redundant cross sections by summation (FIXUP) 5) Update evaluation dictionary in MF/MT=1/451 (DICTIN) C - Restrictions: Due to recent changes in ENDF-6 Formats and Procedures only the latest version of the ENDF/B Pre-processing codes, namely PREPRO 2007, can be used to accurately process all current ENDF/B-VII evaluations. The use of

  14. Keefektivan PMRI Berbantuan Alat Peraga Terhadap Kemampuan Pemecahan Masalah Serupa PISA Pada Kelas VII

    Directory of Open Access Journals (Sweden)

    Riyanto Riyanto

    2014-06-01

    Full Text Available AbstrakTujuan penelitian ini untuk mengetahui keefektivan pembelajaran dengan metode Pendidi-kan Matematika Realistik Indonesia (PMRI berbantuan alat peraga terhadap kemampuan pemecahan masalah serupa PISA siswa pada materi segiempat. Populasi dalam penelitian ini adalah siswa kelas VII SMP Negeri 3 Ungaran tahun pelajaran 2012/2013. Pemilihan sampel dengan cara random sampling, diperoleh siswa kelas VII-I dan siswa kelas VII-J se-bagai kelas eksperimen dan kelas kontrol. Kelas eksperimen diajar dengan metode PMRI berbantuan alat peraga, sedangkan kelas kontrol diajar dengan metode ekspositori. Data di-peroleh dengan metode observasi untuk mengamati aktivitas belajar guru dan metode tes untuk menentukan hasil belajar siswa yang kemudian dianalisis dengan uji ketuntasan dan uji perbedaan rata-rata: uji satu pihak (pihak kanan. Hasil penelitian adalah (1 hasil be-lajar siswa kelas eksperimen belum mencapai kriteria ketuntasan klasikal, (2 rata-rata ke-mampuan pemecahan masalah serupa PISA kelas eksperimen lebih baik dari kelas kontrol, dan (3 skor rata-rata aktivitas guru kelas ekperimen dan kelas kontrol memiliki kategori baik. Kata kunci:       Kualitas Pembelajaran; PISA; PMRI.  AbstractThe purpose of this research was to determine the effectiveness of learning by Teams Pendidikan Matematika Realistik Indonesia (PMRI assisted on figure tools to the problem solving skills PISA student on quadrilateral material. The population in this study is student of VIIth grade class of 3 Ungaran junior high school on period 2012/2013. The selection of the sample is done by random sampling which is gotten students class VII-I and students class VII-J as the experimental class and the controlling class. Experimental class was taught by PMRI assisted on figure tools, while the controlling class was taught with the expository method. Data obtained by the observation method to observe the activities of teacher learning and test methods for determining

  15. Human Adenovirus Infection Causes Cellular E3 Ubiquitin Ligase MKRN1 Degradation Involving the Viral Core Protein pVII.

    Science.gov (United States)

    Inturi, Raviteja; Mun, Kwangchol; Singethan, Katrin; Schreiner, Sabrina; Punga, Tanel

    2018-02-01

    Human adenoviruses (HAdVs) are common human pathogens encoding a highly abundant histone-like core protein, VII, which is involved in nuclear delivery and protection of viral DNA as well as in sequestering immune danger signals in infected cells. The molecular details of how protein VII acts as a multifunctional protein have remained to a large extent enigmatic. Here we report the identification of several cellular proteins interacting with the precursor pVII protein. We show that the cellular E3 ubiquitin ligase MKRN1 is a novel precursor pVII-interacting protein in HAdV-C5-infected cells. Surprisingly, the endogenous MKRN1 protein underwent proteasomal degradation during the late phase of HAdV-C5 infection in various human cell lines. MKRN1 protein degradation occurred independently of the HAdV E1B55K and E4orf6 proteins. We provide experimental evidence that the precursor pVII protein binding enhances MKRN1 self-ubiquitination, whereas the processed mature VII protein is deficient in this function. Based on these data, we propose that the pVII protein binding promotes MKRN1 self-ubiquitination, followed by proteasomal degradation of the MKRN1 protein, in HAdV-C5-infected cells. In addition, we show that measles virus and vesicular stomatitis virus infections reduce the MKRN1 protein accumulation in the recipient cells. Taken together, our results expand the functional repertoire of the HAdV-C5 precursor pVII protein in lytic virus infection and highlight MKRN1 as a potential common target during different virus infections. IMPORTANCE Human adenoviruses (HAdVs) are common pathogens causing a wide range of diseases. To achieve pathogenicity, HAdVs have to counteract a variety of host cell antiviral defense systems, which would otherwise hamper virus replication. In this study, we show that the HAdV-C5 histone-like core protein pVII binds to and promotes self-ubiquitination of a cellular E3 ubiquitin ligase named MKRN1. This mutual interaction between the pVII and

  16. Combination of recombinant factor VIIa and fibrinogen corrects clot formation in primary immune thrombocytopenia at very low platelet counts

    DEFF Research Database (Denmark)

    Larsen, Ole H; Stentoft, Jesper; Radia, Deepti

    2013-01-01

    Haemostatic treatment modalities alternative to platelet transfusion are desirable to control serious acute bleeds in primary immune thrombocytopenia (ITP). This study challenged the hypothesis that recombinant activated factor VII (rFVIIa) combined with fibrinogen concentrate may correct whole b...

  17. Structure of EspB from the ESX-1 type VII secretion system and insights into its export mechanism.

    Science.gov (United States)

    Solomonson, Matthew; Setiaputra, Dheva; Makepeace, Karl A T; Lameignere, Emilie; Petrotchenko, Evgeniy V; Conrady, Deborah G; Bergeron, Julien R; Vuckovic, Marija; DiMaio, Frank; Borchers, Christoph H; Yip, Calvin K; Strynadka, Natalie C J

    2015-03-03

    Mycobacterium tuberculosis (Mtb) uses the ESX-1 type VII secretion system to export virulence proteins across its lipid-rich cell wall, which helps permeabilize the host's macrophage phagosomal membrane, facilitating the escape and cell-to-cell spread of Mtb. ESX-1 membranolytic activity depends on a set of specialized secreted Esp proteins, the structure and specific roles of which are not currently understood. Here, we report the X-ray and electron microscopic structures of the ESX-1-secreted EspB. We demonstrate that EspB adopts a PE/PPE-like fold that mediates oligomerization with apparent heptameric symmetry, generating a barrel-shaped structure with a central pore that we propose contributes to the macrophage killing functions of EspB. Our structural data also reveal unexpected direct interactions between the EspB bipartite secretion signal sequence elements that form a unified aromatic surface. These findings provide insight into how specialized proteins encoded within the ESX-1 locus are targeted for secretion, and for the first time indicate an oligomerization-dependent role for Esp virulence factors. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Modulated crystal structures of VII and V phases in (NH4)3H(SO4)2. I. Neutron Laue diffraction

    International Nuclear Information System (INIS)

    McIntyre, G.; Smirnov, L.S.; Baranov, A.I.; Dolbinina, V.V.; Frontas'eva, M.V.; Pavlov, S.S.; Pankratova, Yu.S.

    2010-01-01

    The study of crystal structures of VII and V phases of (NH 4 ) 3 H(SO 4 ) 2 by means of neutron Laue diffraction is carried out at temperatures from 5 to 300 K. It is found that crystal structures of VII and V phases have incommensurate modulation with different periods, and phase transition from phase VII to phase V is transition of the first type

  19. Type VII Collagen is Enriched in the Enamel Organic Matrix Associated with the Dentin-Enamel Junction of Mature Human Teeth

    OpenAIRE

    McGuire, Jacob D.; Walker, Mary P.; Mousa, Ahmad; Wang, Yong; Gorski, Jeff P.

    2014-01-01

    The inner enamel region of erupted teeth is known to exhibit higher fracture toughness and crack growth resistance than bulk phase enamel. However, an explanation for this behavior has been hampered by the lack of compositional information for the residual enamel organic matrix. Since enamel-forming ameloblasts are known to express type VII collagen and type VII collagen null mice display abnormal amelogenesis, the aim of this study was to determine whether type VII collagen is a component of...

  20. PENGARUH PENGGUNAAN MODUL KONTEKSTUAL BERPENDEKATAN SETS TERHADAP HASIL BELAJAR DAN KEMANDIRIAN PESERTA DIDIK KELAS VII SMP

    Directory of Open Access Journals (Sweden)

    Desy Ria Pratama

    2017-02-01

    Full Text Available Abstrak _________________________________________________________________________________________________________________ Kebutuhan terhadap bahan ajar yang dapat meningkatkan kemandirian belajar dan hasil belajar peserta didik menuntut guru untuk dapat membuat bahan ajar yang ideal. Bahan ajar yang dapat mengaitkan materi dengan fenomena dalam kehidupan sehari-hari dapat memudahkan peserta didik dalam memahami materi. Kebermaknaan dalam pembelajaran juga dibutuhkan dalam mata pelajaran IPA agar peserta didik dapat mengetahui manfaat pembelajaran yang dilakukan. SETS merupakan pendekatan yang mengaitkan materi dengan aspek sains, lingkungan, teknologi, dan masyarakat dalam pembelajaran. Penerapan pendekatan SETS pada bahan ajar sangat ideal untuk memudahkan peserta didik dalam memahami materi serta belajar menyelesaikan permasalahan dalam pembelajaran secara mandiri. Penelitian ini bertujuan untuk mengetahui adanya pengaruh modul kontekstual berpendekatan SETS terhadap hasil belajar dan kemandirian peserta didik kelas VII SMP. Populasi pada penelitian ini adalah kelas VII A-VII H SMP Negeri 10 Semarang tahun pelajaran 2015/2016, sedangkan sampel diambil dengan menggunakan teknik purposive sampling sehingga diperoleh kelas VII C sebagai kelas eksperimen dan kelas VII D sebagai kelas kontrol. Desain penelitian yang digunakan adalah nonequivalent control group design. Hasil penelitian menunjukkan bahwa penggunaan modul berpengaruh terhadap hasil belajar dan kemandirian peserta didik. Hal tersebut dilihat dari hasil korelasi yang menunjukkan korelasi penggunaan modul dengan kemandirian, hasil belajar afektif, dan hasil belajar psikomotorik dalam kategori kuat, dan dalam kategori sangat kuat pada hasil belajar kognitif. Besar pengaruh penggunaan modul terhadap kemandirian sebesar 60,22% berdasarkan data observasi, dan 47,61% berdasarkan data angket. Sedangkan besar pengaruh penggunaan modul terhadap hasil belajar kognitif adalah sebesar 82

  1. Differences among KERMA or DPA data calculated from JENDL-4.0, ENDF/B-VII.1, JEFF-3.2 and FENDL-3.1b with NJOY

    International Nuclear Information System (INIS)

    Konno, C.

    2016-01-01

    KERMA factors and DPA cross-section data below 20 MeV in the official ACE files of JENDL-4.0, ENDF/B-VII.1, JEFF-3.2 and FENDL-3.1b were compared in detail. As a result, it was found out that the KERMA and DPA data of a lot of nuclei were different among the nuclear data libraries. Reasons of most of the differences were successfully categorized to the nuclear data and NJOY issues. The KERMA factors and DPA cross-section data in the ACE files with the problems should be revised. (author)

  2. Tissue factor-factor VIIa-specific up-regulation of IL-8 expression in MDA-MB-231 cells is mediated by PAR-2 and results in increased cell migration

    DEFF Research Database (Denmark)

    Hjortoe, Gertrud M; Petersen, Lars C; Albrektsen, Tatjana

    2004-01-01

    Tissue factor (TF), the cellular receptor for factor VIIa (FVIIa), besides initiating blood coagulation, is believed to play an important role in tissue repair, inflammation, angiogenesis, and tumor metastasis. Like TF, the chemokine interleukin-8 (IL-8) is shown to play a critical role...... in these processes. To elucidate the potential mechanisms by which TF contributes to tumor invasion and metastasis, we investigated the effect of FVIIa on IL-8 expression and cell migration in a breast carcinoma cell line, MDA-MB-231, a cell line that constitutively expresses abundant TF. Expression of IL-8 m......RNA in MDA-MB-231 cells was markedly up-regulated by plasma concentrations of FVII or an equivalent concentration of FVIIa (10 nM). Neither thrombin nor other proteases involved in hemostasis were effective in stimulating IL-8 in these cells. Increased transcriptional activation of the IL-8 gene...

  3. Optimizing Cr(VI) and Tc(VII) remediation through nano-scale biomineral engineering

    International Nuclear Information System (INIS)

    Cutting, R.S.; Coker, V.S.; Telling, N.D.; Kimber, R.L.; Pearce, C.I.; Ellis, B.; Lawson, R; van der Laan, G.; Pattrick, R.A.D.; Vaughan, D.J.; Arenholz, E.; Lloyd, J.R.

    2009-01-01

    To optimize the production of biomagnetite for the bioremediation of metal oxyanion contaminated waters, the reduction of aqueous Cr(VI) to Cr(III) by two biogenic magnetites and a synthetic magnetite was evaluated under batch and continuous flow conditions. Results indicate that nano-scale biogenic magnetite produced by incubating synthetic schwertmannite powder in cell suspensions of Geobacter sulfurreducens is more efficient at reducing Cr(VI) than either biogenic nano-magnetite produced from a suspension of ferrihydrite 'gel' or synthetic nano-scale Fe 3 O 4 powder. Although X-ray Photoelectron Spectroscopy (XPS) measurements obtained from post-exposure magnetite samples reveal that both Cr(III) and Cr(VI) are associated with nanoparticle surfaces, X-ray Magnetic Circular Dichroism (XMCD) studies indicate that some Cr(III) has replaced octahedrally coordinated Fe in the lattice of the magnetite. Inductively Coupled Plasma-Atomic Emission Spectrometry (ICP-AES) measurements of total aqueous Cr in the associated solution phase indicated that, although the majority of Cr(III) was incorporated within or adsorbed to the magnetite samples, a proportion (∼10-15 %) was released back into solution. Studies of Tc(VII) uptake by magnetites produced via the different synthesis routes also revealed significant differences between them as regards effectiveness for remediation. In addition, column studies using a γ-camera to obtain real time images of a 99m Tc(VII) radiotracer were performed to visualize directly the relative performances of the magnetite sorbents against ultra-trace concentrations of metal oxyanion contaminants. Again, the magnetite produced from schwertmannite proved capable of retaining more (∼20%) 99m Tc(VII) than the magnetite produced from ferrihydrite, confirming that biomagnetite production for efficient environmental remediation can be fine-tuned through careful selection of the initial Fe(III) mineral substrate supplied to Fe

  4. POINT 2011: ENDF/B-VII.1 Beta2 Temperature Dependent Cross Section Library

    Energy Technology Data Exchange (ETDEWEB)

    Cullen, D E

    2011-04-07

    This report is one in the series of 'POINT' reports that over the years have presented temperature dependent cross sections for the then current version of ENDF/B. In each case I have used my personal computer at home and publicly available data and codes. I have used these in combination to produce the temperature dependent cross sections used in applications and presented in this report. I should mention that today anyone with a personal computer can produce these results. The latest ENDF/B-VII.1 beta2 data library was recently and is now freely available through the National Nuclear Data Center (NNDC), Brookhaven National Laboratory. This release completely supersedes all preceding releases of ENDF/B. As distributed the ENDF/B-VII.1 data includes cross sections represented in the form of a combination of resonance parameters and/or tabulated energy dependent cross sections, nominally at 0 Kelvin temperature. For use in our applications the ENDF/B-VII.1 library has been processed into cross sections at eight neutron reactor like temperatures, between 0 and 2100 Kelvin, in steps of 300 Kelvin (the exception being 293.6 Kelvin, for exact room temperature at 20 Celsius). It has also been processed to five astrophysics like temperatures, 1, 10, 100 eV, 1 and 10 keV. For reference purposes, 300 Kelvin is approximately 1/40 eV, so that 1 eV is approximately 12,000 Kelvin. At each temperature the cross sections are tabulated and linearly interpolable in energy. All results are in the computer independent ENDF-6 character format [R2], which allows the data to be easily transported between computers. In its processed form the POINT 2011 library is approximately 16 gigabyte in size and is distributed on one compressed DVDs (see, below for the details of the contents of each DVD).

  5. PENGEMBANGAN LKS BERBASIS PROJECT BASED LEARNING UNTUK PEMBELAJARAN MATERI SEGITIGA DI KELAS VII

    Directory of Open Access Journals (Sweden)

    Dian Novita

    2016-06-01

    Full Text Available Penelitian ini merupakan penelitian pengembangan yang bertujuan untuk (1mengetahui karakteristik LKS berbasis Project Based Learning (PjBL yang valid dan praktis dalam pembelajaran materi segitiga di kelas VII; (2mengetahui efek potensial penggunaan LKS berbasis PjBL terhadap hasil belajar siswa dalam pembelajaran materi segitiga di kelas VII. Metode penelitian pengembangan yang digunakan adalah model  ADDIE (Analysis, Design, Development, Implementation, and Evaluation. Teknik pengumpulan data yang digunakan adalah walkthrough, tes hasil belajar dan angket. Dari tes hasil belajar, diperoleh bahwa sebesar 82,5% siswa telah mencapai kategori tuntas dan 17,5% belum tuntas dengan KKM 75. Hasil angket respon siswa menunjukkan bahwa untuk pelaksanaan pembelajaran menggunakan LKS berbasis PjBL telah mencapai kriteria kepraktisan. Kemudian untuk LKS berbasis PjBL yang telah didesain, divalidasi oleh beberapa pakar, kemudian direvisi berdasarkan saran dari para pakar tersebut. LKS yang telah direvisi tersebut dianggap telah memenuhi kriteria kevalidan dan kepraktisan sehingga dapat digunakan dalam pembelajaran materi segitiga di kelas VII. Kesimpulan dari penelitian ini adalah (1 LKS bebasis PjBL yang dikembangkan valid, tergambar dari konten (sesuai dengan kurikulum untuk materi segitiga, konstruk (sesuai dengan prinsip PjBL, dan bahasa (sesuai dengan ejaan yang disempurnakan (EYD. Kepraktisan tergambar dari proses kerja siswa dalam melaksanakan LKS dan hasil angket respon siswa terhadap pembelajaran menggunakan LKS berbasis PjBL; (2 dari hasil latihan yang dikerjakan oleh siswa, LKS berbasis PjBL memiliki efek potensial terhadap hasil belajar, yakni sebanyak 33 siswa termasuk kategori tuntas (82,5% dan 7 orang belum tuntas (17,5%, dengan KKM 75. Kata Kunci : LKS, Project Based Learning DOI: http://dx.doi.org/10.22342/jpm.10.2.3626.1-12

  6. Optimizing Cr(VI) and Tc(VII) remediation through nano-scale biomineral engineering

    Energy Technology Data Exchange (ETDEWEB)

    Cutting, R. S.; Coker, V. S.; Telling, N. D.; Kimber, R. L.; Pearce, C. I.; Ellis, B.; Lawson, R; van der Laan, G.; Pattrick, R.A.D.; Vaughan, D.J.; Arenholz, E.; Lloyd, J. R.

    2009-09-09

    To optimize the production of biomagnetite for the bioremediation of metal oxyanion contaminated waters, the reduction of aqueous Cr(VI) to Cr(III) by two biogenic magnetites and a synthetic magnetite was evaluated under batch and continuous flow conditions. Results indicate that nano-scale biogenic magnetite produced by incubating synthetic schwertmannite powder in cell suspensions of Geobacter sulfurreducens is more efficient at reducing Cr(VI) than either biogenic nano-magnetite produced from a suspension of ferrihydrite 'gel' or synthetic nano-scale Fe{sub 3}O{sub 4} powder. Although X-ray Photoelectron Spectroscopy (XPS) measurements obtained from post-exposure magnetite samples reveal that both Cr(III) and Cr(VI) are associated with nanoparticle surfaces, X-ray Magnetic Circular Dichroism (XMCD) studies indicate that some Cr(III) has replaced octahedrally coordinated Fe in the lattice of the magnetite. Inductively Coupled Plasma-Atomic Emission Spectrometry (ICP-AES) measurements of total aqueous Cr in the associated solution phase indicated that, although the majority of Cr(III) was incorporated within or adsorbed to the magnetite samples, a proportion ({approx}10-15 %) was released back into solution. Studies of Tc(VII) uptake by magnetites produced via the different synthesis routes also revealed significant differences between them as regards effectiveness for remediation. In addition, column studies using a {gamma}-camera to obtain real time images of a {sup 99m}Tc(VII) radiotracer were performed to visualize directly the relative performances of the magnetite sorbents against ultra-trace concentrations of metal oxyanion contaminants. Again, the magnetite produced from schwertmannite proved capable of retaining more ({approx}20%) {sup 99m}Tc(VII) than the magnetite produced from ferrihydrite, confirming that biomagnetite production for efficient environmental remediation can be fine-tuned through careful selection of the initial Fe(III) mineral

  7. Aspectos literarios de la obra de don Joan de Castellanos : Capítulo VII

    Directory of Open Access Journals (Sweden)

    Mario Germán Romero

    1966-02-01

    Full Text Available Capitulo VII. Los discursos de Colón Es sabido que los escritores antiguos; principalmente los historiógrafos, introducían supuestos discursos en sus obras. Salustio consigna cuatro en sus Historias. Tito Livio los elabora con perfección y los pone en boca de políticos y generales importantes; en los treinta y cinco libros que se conservan de este autor encontramos unos cuatrocientos discursos, breves o extensos, que como los de Salustio fueron recopilados y editados para fines retóricos.

  8. Studies on the reduction of technetate(VII) by 1,2 bis(diphenylphosphino)ethane

    International Nuclear Information System (INIS)

    Muenze, R.; Seifert, S.; Kloetzer, D.; Maeding, P.; Goerner, W.

    1984-01-01

    The reduction of technetate(VII) by using 1,2 bis(diphenylphosphino)ethane (DPPE) has been investigated as a model for the preparation of new myotropic technetium compounds. Phosphino complexes were isolated and characterized which contain technetium in the oxidation state V([TcO 2 DPPE 2 ][TcO 4 ]), IV([TcCl 2 DPPE 2 ][TcCl 6 ]), III ([TcCl 3 DPPE 2 ] 0 ), ([TcCl 2 DPPE 2 ]Cl, and II ([TcCl 2 DPPE 2 ] 0 ) dependent on the reaction conditions, in particular Tc/DPPE and Tc/HCl ratios. (author)

  9. Underground Test Area Subproject Phase I Data Analysis Task. Volume VII - Tritium Transport Model Documentation Package

    Energy Technology Data Exchange (ETDEWEB)

    None

    1996-12-01

    Volume VII of the documentation for the Phase I Data Analysis Task performed in support of the current Regional Flow Model, Transport Model, and Risk Assessment for the Nevada Test Site Underground Test Area Subproject contains the tritium transport model documentation. Because of the size and complexity of the model area, a considerable quantity of data was collected and analyzed in support of the modeling efforts. The data analysis task was consequently broken into eight subtasks, and descriptions of each subtask's activities are contained in one of the eight volumes that comprise the Phase I Data Analysis Documentation.

  10. Current driven drift instability in the W VII-A stellarator

    International Nuclear Information System (INIS)

    Deutsch, R.; Wobig, H.

    1978-12-01

    The instability region and growth rates of current driven drift modes in the W VII-A stellarator are calculated. Several theoretical results are evaluated for specific temperature and density profiles. It is found that in the outer region of the plasma-column (r > 6 cm) collisional drift waves with wavelengths (k 2 x + K 2 y)sup(-1/2) = 0.13 - 0.3 cm exist. In this region also the electron thermal conductivity determined experimentally appears to be large. (orig./GG) [de

  11. Multiconfiguration Dirac-Hartree-Fock calculations of energy levels and radiative rates of Fe VII

    Science.gov (United States)

    Li, Yang; Xu, Xiaokai; Li, Bowen; Jönsson, Per; Chen, Ximeng

    2018-06-01

    Detailed calculations are performed for 134 fine-structure levels of the 3p63d2, 3p63d4s, 3p53d3 and 3p63d4p configurations in Fe VII using the multiconfiguration Dirac-Hartree-Fock (MCDHF) and relativistic configuration interaction (RCI) methods. Important electron correlation effects are systematically accounted for through active space (AS) expansions. Our results compare well with experimental measurements, emphasizing the importance of a careful treatment of electron correlation, and provide some missing data in the NIST atomic database. The data obtained are expected to be useful in astrophysical applications, particularly for the research of the solar coronal plasma.

  12. Vacuum magnetic field and modular coil system of the advanced stellarator Wendelstein VII-AS

    International Nuclear Information System (INIS)

    Rau, F.; Kisslinger, J.; Wobig, H.

    1982-06-01

    The vacuum field and the modular coils of the advanced stellarator WENDELSTEIN VII-AS are described. Each of the five field periods contains 9 different twisted coils, one of them with increased dimensions and current in order to provide sufficient access. The standard vacuum field configuration (B=3 T, t=0.39, aspect ratio approx. equal to 10, low shear, and magnetic well) can be varied by toroidal and vertical fields, or by changing independently the current in the large special coils. From a study of magnetic field perturbations some estimates are derived for the admissible coil tolerances. (orig.)

  13. Evolution of radiation losses and importance of charge exchange between plasma impurities and injection beam neutrals in the W VII-A stellarator

    International Nuclear Information System (INIS)

    Smeulders, P.

    1981-01-01

    In certain discharges during Neutral Injection (N.I.) (84 0 CO-injection) in the 1 = 2, m = 5 WENDELSTEIN VII-A Stellarator impurity accumulation in the plasma center seems to occur as seen by bolometric, spectroscopic and ultra soft X-ray (USX) measurement. The time evolution of the radiation losses is shown. Three possible sources of the impurities which are responsible for the high central radiation losses are: - Beam injected impurities. - Plasma wall interaction. - Molybdenum protection plates. Possible mechanisms that can be responsible for the central impurity accumulations are: - An inward flow of the plasma or beam impurities. - An increased peaking of the depostion of the beam impurities. Various factors influencing the behaviour of the central radiation are mentioned. (orig./AH)

  14. In vitro amylolysis of pulse and hylon VII starches explained in terms of their composition, morphology, granule architecture and interaction between hydrolysed starch chains.

    Science.gov (United States)

    Maaran, S; Hoover, R; Vamadevan, V; Waduge, R N; Liu, Q

    2016-02-01

    The objective of this study was to understand the factors underlying the susceptibility of pulse (lablab bean, navy bean, rice bean, tepary bean, velvet bean, and wrinkled pea) and hylon VII starches towards in vitro hydrolysis by the combined action of pancreatin and amyloglucosidase. The time taken to reach an equivalent level of hydrolysis (50%) varied significantly among the starches. Changes to molecular order, crystallinity, double helical content, radial orientation of starch chains (polarized light), enthalpy and apparent amylose content during the progress of hydrolysis showed that rate and extent of hydrolysis were influenced both by the structure of the native starches at different levels (molecular, mesoscopic, microscopic) of granule organization, and by the extent of retrogradation between hydrolysed starch chains. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Atherosclerosis VII

    International Nuclear Information System (INIS)

    Fidge, N.H.; Nestel, P.J.; Flinders Univ., Adelaide

    1986-01-01

    In these proceedings the major themes of the conference have been preserved and comprise epidemiology, lipoproteins, pathogenesis, and clinical, therapeutic and nutritional aspects. The diet-lipidcoronary artery disease hypothesis has been strengthened significantly. Several long-awaited trials, reviewed here, have provided very strong support for the rationale for treating hyperlipidemia. A strategy for the prevention of atherosclerosis was defined at the conference. The genesis of atherosclerosis was shown to be more firmly grounded in the influx of lipoprotein into the arterial wall. The regulation of these processes and the rapid advances made possible by new technology were detailed in several sessions. Important new developments in the clinical area and in pharmacology give promise of greatly improved management of established disease. However, the possibility of mounting large-scale preventive measures in the near future, was given credence in the epidemiology and nutrition workshops. (Auth.)

  16. Effect of octanols structure on their extraction ability as regards to rhenium(VII) in sulfuric acid solutions

    International Nuclear Information System (INIS)

    Kasikov, A.G.; Petrova, A.M.

    2007-01-01

    It is established that extraction ability of octanols as regards to rhenium(VII) and sulfuric acid depends on the structure of alcohol, but if in passage from octanol-1 to octanol-3 as regard to rhenium(VII) it rises, then for H 2 SO 4 it falls. Dependence of the distribution function of rhenium from the concentration of the acid has maximums at 4-7 mol l 1- that the most distinctly it becomes apparent for secondary alcohols. Decreasing the extraction ability of octyl alcohols with the growth of H 2 SO 4 concentration more than 7 mol l 1- is connected with the change of extractant composition and forms of rhenium(VII) being in the solution [ru

  17. Preparation and Characterisation of tri-n-octylamine Microcapsule (TOA-MC) as Selective Separation of Re (VII)

    International Nuclear Information System (INIS)

    Tsai, T.L.; Mimura, H.; Syed, M.R.; Yin, X.B.; Lee, C.P.; Tsai, S.C.

    2015-01-01

    Much attention has been paid on the selective separation and effective utilisation of 99 Tc from high level radioactive liquid waste (HLLW). TOA-MC was developed as an absorbent for Re (VII), a substitute for Tc (VII) due to their similarities of chemical behaviour in this study. The uptake (%), normally above 95% of Re (VII) for TOA-MC in the presence of dilute HNO 3 (0.01∼0.1 M) was strongly retained and decreased with higher HNO 3 concentration by batch method. The surface morphology and thermal stability of microcapsules were characterised by scanning electron microscopy (SEM) and thermogravimetric analysis (TGA), respectively. The diameters in the range of 700-800 μm and size distribution of the microcapsules were examined using digital microscope (DM). The chemical structures of the synthesised microcapsules and two starting materials of TOA and sodium alginate (NaALG) were performed using Fourier transform infrared spectroscopy (FTIR). (authors)

  18. New Neutron, Proton, and S(α,β) MCNP Data Libraries Based on ENDF/B-VII

    International Nuclear Information System (INIS)

    Little, Robert C.; Trellue, Holly R.; MacFarlane, Robert E.; Kahler, A.C.; Lee, Mary Beth; White, Morgan C.

    2008-01-01

    The general-purpose Evaluated Nuclear Data File ENDF/B-VII.0 was released in December 2006. A number of sub-libraries were included in ENDF/B-VII.0 such that data were provided for incident neutrons, photons, and charged particles. This paper describes the creation of MCNP data libraries at Los Alamos National Laboratory based on three ENDF/B-VII.0 sub-libraries: neutrons, protons, and thermal scattering. An ACE-formatted continuous-energy neutron data library called ENDF70 for MCNP has been produced. This library provides data for 390 materials at five temperatures: 293.6, 600, 900, 1200, and 2500 K. The library was processed primarily with Version 248 of NJOY99. Extensive checking and quality-assurance tests were applied to the data. Improvements to the processing code were made and certain evaluations were modified as a result of these tests. ENDF/B-VII.0 included proton evaluations for 48 target materials. Forty-seven proton evaluations (all except for 13 C) were processed at room temperature and combined into the MCNP library ENDF70PROT. Neutron thermal S(α,β) scattering data exist for twenty different materials in ENDF/B-VII.0. All twenty of these evaluations were processed at all applicable temperatures (these vary for each evaluation), and combined into the MCNP library ENDF70SAB. All of these ENDF/B-VII.0 based MCNP libraries (ENDF70, ENDF70PROT, and ENDF70SAB) are available as part of the MCNP5 1.50 release. (authors)

  19. Magnetic surfaces and localized perturbations in the Wendelstein VII-A stellarator

    International Nuclear Information System (INIS)

    Wobig, H.

    1986-09-01

    The critical dependence of plasma confinement in low-shear stellarators, such as Wendelstein VII-A, on the external rotational transform can be explained on the basis of magnetic surface destruction. External symmetry-breaking perturbations generate islands on the low order rational magnetic surfaces. The islands are largest at t=1/2 and t=1/3. Confinement is optimum in close proximity to these values. In order to study the structure of surfaces under the influence of perturbations, a mapping procedure is used instead of field line integration. It is found that the neighbourhood of low- order rational surfaces is particularly robust against surface destruction. The reason is that in this vicinity only rational surfaces with large m and n exist (t=m/n). On these surfaces the external perturbation only generates small islands. In W VII-A the current leads to the helical windings are one symmetry- breaking perturbation, and there might also be others. It is possible to avoid field errors of this kind in future stellarators. (orig.)

  20. Y-12 Construction/Demolition Landfill VII: Permit application: Part 1 and 2

    International Nuclear Information System (INIS)

    1992-04-01

    The United States Department of Energy (DOE) has three major operating facilities on the DOE Oak Ridge Reservation (ORR) at Oak Ridge, Tennessee: the Y-12 Plant, the K-25 Site, and the Oak Ridge National Laboratory (ORNL). Operations associated with the DOE energy research and production facilities at Oak Ridge result in the production of several types of waste materials. Disposal of solid waste (as defined in the Solid Waste Processing and Disposal Rules for Tennessee) in disposal facilities operated by the Y-12 Plant is the responsibility of Y-12 Waste Management Division (MWD). The WMD is proposing to develop a facility that will include two new disposal units: one for construction/demolition waste and spoil and one for industrial solid waste. This manual describes the closure and post-closure plans for the construction/demolition waste and spoil disposal unit. This disposal unit is referred to as the Y-12 Construction/Demolition Landfill VII (CD-VII) and is to be operated by the Y-12 Plant for the DOE. This will be a Tennessee Department of Environment and Conservation/Division of Solid Waste Management (TDEC/DSWM) Class IV disposal unit

  1. Phase transitions of antibiotic clarithromycin forms I, IV and new form VII crystals.

    Science.gov (United States)

    Ito, Masataka; Shiba, Rika; Watanabe, Miteki; Iwao, Yasunori; Itai, Shigeru; Noguchi, Shuji

    2018-06-01

    Metastable crystal form I of the antibiotic clarithromycin has a pharmaceutically valuable characteristic that its crystalline phase transition can be applied for its sustained release from tablets. The phase transition of form I was investigated in detail by single crystal and powder X-ray analyses, dynamic vapor sorption analysis and thermal analysis. The single crystal structure of form I revealed that form I was not an anhydrate crystal but contained a partially occupied water molecule in the channel-like void space. Dynamic vapor sorption (DVS) analysis demonstrated that form I crystals reversibly sorbed water molecules in two steps when the relative humidity (RH) increased and finally transited to hydrate form IV at 95% RH. DVS analysis also showed that when the RH decreased form IV crystals lost water molecules at 40% RH and transited to the newly identified anhydrate crystal form VII. Form VII reversibly transited to form IV at lower RH than form I, suggesting that form I is more suitable for manufacturing a sustained-release tablet of CAM utilizing the crystalline phase transition. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Neutral gas transport and particle recycling in the W VII-AS stellarator

    International Nuclear Information System (INIS)

    Sardei, F.; Ringler, H.; Dodhy, A.; Kuehner, G.

    1990-01-01

    Neutral gas transport simulations with the 3D DEGAS code were applied to model plasmas before the W VII-AS operation was started. For a source of neutrals due to limiter recycling the calculated neutral density distribution is strongly affected by the asymmetries of the magnetic flux surfaces, limiter and wall structures. For a typical ECF heated deuterium discharge from the first months of W VII-AS operation the time histories of H α signals at five toroidal positions provide information about the neutral fluxes due to limiter and wall recycling and to gas puffing. The H α signals are used to scale the calculated 3D distributions of the neutrals and the radial profiles of the ion sources as obtained from the DEGAS code. By comparing the results for the three different neutral sources the limiter is found to provide more than 80% of the plasma refuelling, with a recycling coefficient of about 95%. The calculated total particle fluxes resulting from the integrated ion sources are consistent with neoclassical predictions in the temperature gradient region. Near the plasma edge, however, the fluxes are strongly anomalous. The diffusion coefficient estimated from the fluxes and the measured density gradients (with z eff approx. 3) is about 1/10 - 1/20 of the electron heat conductivity. (author). 6 refs, 10 figs

  3. A comparison of reaction rate calculations using Endf/B-VII with critical assembly measurements

    International Nuclear Information System (INIS)

    Wilkerson, C.; Mac Innes, M.; Barr, D.; Trellue, H.; MacFarlane, R.; Chadwick, M.

    2008-01-01

    We present critical assembly reaction rate data, and modeling of the same using the recently released Endf/B-VII library. While some of the experimental measurements were performed as long as 50 years ago, the results have not been widely used/available outside of Los Alamos. Over the years, a variety of target foils were fabricated and placed in differing neutron spectrum/fluence environments within critical assemblies. Neutron-induced reactions such as (n,γ), (n,2n), and (n,f) on these targets were measured, typically referenced to 235 U(n,f) or 239 Pu(n,f). Because the cross section for the latter reactions are now well known, these experiments provide a rich data set for testing evaluated cross sections. Due to the large variety of critical assemblies that were historically available at Los Alamos, it was possible to make measurements in spectral environments ranging from hard (Pu Jezebel, center of Pu Flattop) through intermediate (Big Ten) to degraded (reflector region of Flattop). This broad range of configurations allows us to test both the cross section magnitudes and their energy dependencies. We will present data, along with reaction rate predictions using primarily MCNP5 in conjunction with Endf/B-VII, for a number of target nuclei, including iridium, isotopes of uranium (e.g., 233, 235, 237, 238), neptunium (237), plutonium (239), and americium (241). (authors)

  4. Expression and localization of tissue factor pathway inhibitor-2 in normal and atherosclerotic human vessels

    NARCIS (Netherlands)

    Crawley, James T. B.; Goulding, David A.; Ferreira, Valérie; Severs, Nicholas J.; Lupu, Florea

    2002-01-01

    Tissue factor pathway inhibitor-2 (TFPI-2) is a Kunitz-type, serine protease inhibitor with inhibitory activity toward activated factor XI, plasma kallikrein, plasmin, certain matrix metalloproteinases, and the tissue factor:activated factor VII complex. In this study, we investigated TFPI-2

  5. Low sensitivity of type VII collagen enzyme-linked immunosorbent assay in epidermolysis bullosa acquisita : serration pattern analysis on skin biopsy is required for diagnosis

    NARCIS (Netherlands)

    Terra, J. B.; Jonkman, M. F.; Diercks, G. F. H.; Pas, H. H.

    BackgroundThe type VII collagen (coll VII) enzyme-linked immunosorbent assay (ELISA) has been reported to have high sensitivity (>93%) and specificity (>96%) for diagnosing epidermolysis bullosa acquisita (EBA) in patients who are seropositive on indirect immunofluorescence on salt-split skin (SSS).

  6. PENGARUH MOTIVASI BELAJAR DAN KOMPETENSI PROFESIONAL GURU TERHADAP PRESTASI BELAJAR MATA PELAJARAN IPS EKONOMI SISWA KELAS VII SMP NEGERI 3 MAGELANG TAHUN PELAJARAN 2011/2012

    Directory of Open Access Journals (Sweden)

    Yunik Sulistyowati,

    2012-10-01

    Full Text Available Prestasi belajar merupakan indikator yang penting untuk mengukur keberhasilan proses belajar mengajar. Prestasi belajar dipengaruhi oleh banyak faktor, di antaranya motivasi belajar dan kompetensi profesional guru. Permasalahan dalam penelitian ini adalah adakah pengaruh motivasi belajar dan kompetensi profesional guru terhadap prestasi belajar IPS ekonomi siswa kelas VII SMP Negeri 3 Magelang Tahun Ajaran 2011/2012 baik secara simultan maupun parsial.Populasi penelitian ini adalah siswa kelas VII SMP Negeri 3 Magelang dengan sampel berjumlah 133 siswa. Variabel penelitian terdiri dari variabel bebas yaitu motivasi belajar (X1 dan kompetensi profesional guru (X2, dan variabel terikat yaitu prestasi belajar (Y. Metode pengumpulan data menggunakan angket dan dokumentasi. Hasil penelitian deskriptif persentase menunjukkan bahwa motivasi belajar siswa dalam kategori tinggi, kompetensi profesional guru� dalam kategori baik, dan prestasi belajar siswa dalam kategori tuntas. Hasil penelitian diperoleh persamaan regresi yaitu ?= 48,387 + 0,607(X1 + 0,101(X2. Dari hasil uji F diperoleh nilai signifikan sebesar 0,000 dan menunjukkan bahwa secara simultan ada pengaruh yang signifikan antara motivasi belajar dan kompetensi profesional guru terhadap prestasi belajar IPS ekonomi sebesar 47,7% sedangkan sisanya 52,3% dipengaruhi oleh faktor lain yang tidak dikaji dalam penelitian ini. Secara parsial menunjukkan bahwa ada pengaruh antara motivasi belajar terhadap prestasi belajar sebesar 22,09%, dan ada pengaruh kompetensi profesional guru terhadap prestasi belajar sebesar 28,40%. Learning achievement is an indicator that it is important to measure the success of the process of teaching and learning. Learning achievement are influenced by many factors, such as learning motivation and teacher�s professional competence.The problem in this study is whether there is influence of learning motivation and teacher�s professional competence toward learning

  7. Comparative sensitivity study of some criticality safety benchmark experiments using JEFF-3.1.2, JEFF-3.2T and ENDF/B-VII.1

    International Nuclear Information System (INIS)

    Kooyman, Timothee; Messaoudia, Nadia

    2014-01-01

    A sensitivity study on a set of evaluated criticality benchmarks with two versions of the JEFF nuclear data library, namely JEFF-3.1.2 and JEFF-3.2T, and ENDF/B-VII.1 was performed using MNCP(X) 2.6.0. As these benchmarks serve to estimate the upper safety limit for criticality risk analysis at SCK.CEN the sensitivity of their results to nuclear data is an important parameter to asses. Several nuclides were identified as being responsible for an evident change in the effective multiplication factor k eff : 235 U, 239 Pu, 240 Pu, 54 Fe, 56 Fe, 57 Fe and 208 Pb. A high sensitivity was found to the fission cross-section of all the fissile material in the study. Additionally, a smaller sensitivity to inelastic and capture cross-section of 235 U and 240 Pu was also found. Sensitivity to the scattering law for non-fissile material was postulated. The biggest change in the k eff due to non-fissile material was due to 208 Pb evaluation (±700 pcm), followed by 56 Fe (±360 pcm) for both versions of the JEFF library. Changes due to 235 U (±300 pcm) and Pu isotopes (±120 pcm for 239 Pu and ±80 pcm for 240 Pu) were found only with JEFF-3.1.2. 238 U was found to have no effect on the k eff . Significant improvements were identified between the two versions of the JEFF library. No further differences were found between the JEFF-3.2T and the ENDF/B-VII.1 calculations involving 235 U or Pu. (authors)

  8. Idiopathic Acquired Hemophilia A with Undetectable Factor VIII Inhibitor

    Directory of Open Access Journals (Sweden)

    Nicholas B. Abt

    2014-01-01

    Full Text Available Objective. We present the case of a 73-year-old female, with no family or personal history of a bleeding disorder, who had a classic presentation for acquired hemophilia A. Factor VIII activity was low but detectable and a factor VIII inhibitor was undetectable. Methods. The patient’s plasma was comprehensively studied to determine the cause of the acquired coagulopathy. Using the Nijmegen modification of the Bethesda assay, no factor VIII autoantibody was measureable despite varying the incubation time from 1 to 3 hours. Results. The aPTT was prolonged at 46.8 seconds, which did not correct in the 4 : 1 mix but did with 1 : 1 mix. Using a one stage factor VIII activity assay, the FVIII activity was 16% and chromogenic FVIII activity was also 16%. The patient was treated with recombinant FVII and transfusion, significantly reducing bleeding. Long-term therapy was initiated with cyclophosphamide and prednisone with normalization of FVIII activity. Conclusions. Physicians can be presented with the challenging clinical picture of an acquired factor VIII inhibitor without a detectable inhibitor by the Bethesda assay. Standard therapy for an acquired hemophilia A should be considered.

  9. An Inter-Rater Comparison of DoD Human Factors Analysis and Classification System (HFACS) and Human Factors Analysis and Classification System-Maritime (HFACS-M)

    Science.gov (United States)

    2013-09-01

    LEFT BLANK vii TABLE OF CONTENTS I.  INTRODUCTION ............................................................................................. 1...Adams, Brent DeVore, John Zuzich, and Cory Blaser. xviii THIS PAGE INTENTIONALLY LEFT BLANK 1 I. INTRODUCTION A. OVERVIEW Human error has...Behavioral Factors Perceptual Factors Condition of Individuals Crew Resource Mangement Self Imposed Stress Personnel Factors PRECONDITIONS Figure 7

  10. The role of stress hormones in the relationship between resting blood pressure and coagulation activity.

    Science.gov (United States)

    Wirtz, Petra H; Ehlert, Ulrike; Emini, Luljeta; Rüdisüli, Katharina; Groessbauer, Sara; Mausbach, Brent T; von Känel, Roland

    2006-12-01

    Systemic hypertension confers a hypercoagulable state. We hypothesized that resting mean blood pressure (MBP) interacts with stress hormones in predicting coagulation activity at rest and with acute mental stress. We measured plasma clotting factor VII activity (FVII:C), FVIII:C, fibrinogen, D-dimer, epinephrine and norepinephrine, and saliva cortisol in 42 otherwise healthy normotensive and hypertensive medication-free men (mean age 43 +/- 14 years) at rest, immediately after stress, and twice during 60 min of recovery from stress. At rest, the MBP-by-epinephrine interaction predicted FVII:C (beta = -0.33, P AUC) predicted D-dimer AUC (beta = 0.34, P = 0.04) independent of MBP. The MBP-by-epinephrine AUC interaction predicted FVII:C AUC (beta = 0.28) and fibrinogen AUC (beta = -0.30), and the MBP-by-norepinephrine AUC interaction predicted FVIII:C AUC (beta = -0.28), all with borderline significance (Ps < 0.09) and independent of age and BMI. MBP significantly altered the association between stress hormones and coagulation activity at rest and, with borderline significance, across the entire stress and recovery interval. Independent of MBP, catecholamines were associated with procoagulant effects and cortisol reactivity dampened the acute procoagulant stress response.

  11. Equal Employment in Postsecondary HPERD. Administrative Guidelines for Compliance with Title VII and the Equal Pay Act.

    Science.gov (United States)

    Nursall, John G.

    1989-01-01

    Outlined are key provisions, relevant to education, of Title VII of the Civil Rights Act of 1964 and the Equal Pay Act of 1963. Administrative guidelines to insure compliance are presented, as well as preventive measures that reduce vulnerability to charges of discrimination in hiring, promotion, and compensation. (IAH)

  12. 75 FR 36099 - Legislative Changes to Primary Care Loan Program Authorized Under Title VII of the Public Health...

    Science.gov (United States)

    2010-06-24

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Health Resources and Services Administration Legislative Changes to Primary Care Loan Program Authorized Under Title VII of the Public Health Service Act AGENCY... changes Section 723 of the Public Health Service Act (PHSA) regarding administration of the PCL program...

  13. Title VII Enhancement Project for Compartiendo Culturas/Sharing Cultures 1995-96. Research Report on Educational Programs.

    Science.gov (United States)

    Houston Independent School District, TX. Dept. of Research and Evaluation.

    Compartiendo Culturas/Sharing Cultures, a Title VII Two-Way Developmental Bilingual Education Program at the Gary L. Herod Elementary School in the Houston Independent School District (Texas) was designed to end the isolation typically experienced by language minority students in traditional bilingual education and to provide language majority…

  14. 75 FR 51429 - Definitions Contained in Title VII of Dodd-Frank Wall Street Reform and Consumer Protection Act

    Science.gov (United States)

    2010-08-20

    ... VII of Dodd-Frank Wall Street Reform and Consumer Protection Act AGENCY: Securities and Exchange... comments. SUMMARY: The Dodd-Frank Wall Street Reform and Consumer Protection Act (the ``Dodd-Frank Act... requirements. \\1\\ Dodd-Frank Wall Street Reform and Consumer Protection Act, Public Law No. 111-203, 124 Stat...

  15. LAWS ON SEX DISCRIMINATION IN EMPLOYMENT--FEDERAL CIVIL RIGHTS ACT, TITLE VII. STATE FAIR EMPLOYMENT PRACTICES LAWS.

    Science.gov (United States)

    Women's Bureau (DOL), Washington, DC.

    TITLE VII OF THE FEDERAL CIVIL RIGHTS ACT (1964) PROHIBITS DISCRIMINATION ON THE BASIS OF SEX IN ADDITION TO THE USUAL GROUNDS OF RACE, COLOR, RELIGION, AND NATIONAL ORIGIN. IT COVERS PRIVATE EMPLOYMENT AND LABOR ORGANIZATIONS ENGAGED IN INDUSTRIES AFFECTING COMMERCE, AS WELL AS EMPLOYMENT AGENCIES. IT IS UNLAWFUL FOR EMPLOYERS TO REFUSE TO HIRE,…

  16. 78 FR 36711 - Food and Drug Administration Safety and Innovation Act Title VII-Drug Supply Chain; Standards for...

    Science.gov (United States)

    2013-06-19

    ... inspections, and drive safety and quality throughout the supply chain. Implementation of these authorities... authorities granted to FDA under Title VII and their importance in ensuring drug safety, effectiveness, and.... FDA-2013-N-0683, FDA-2013-N-0684, and FDA-2013-N-0685] Food and Drug Administration Safety and...

  17. Incoherent inelastic neutron scattering measurements on ice VII: Are there two kinds of hydrogen bonds in ice?

    International Nuclear Information System (INIS)

    Klotz, S.; Strassle, Th.; Philippe, J.; Salzmann, C.G.; Parker, S.F.

    2005-01-01

    We report the vibrational spectrum of recovered ice VII measured by inelastic incoherent neutron scattering and compare this to similar data of its fully hydrogen-ordered form, ice VIII, under exactly the same conditions (15 K, 1 bar). The spectra of the two phases have their principal features at similar energies, in both the translational and vibrational bands, with a substantial disorder-related broadening in ice VII. In particular, we find no evidence for a peak at 49 meV in ice VII which earlier was associated with the possible existence of two kinds of hydrogen bonds. Additional Raman measurements in ice VII and ice VIII show that the O-H stretching frequencies in the two phases are almost identical. Therefore, the presence of split molecular-optic bands in ice phases, including ordinary ice Ih, is likely related to an incomplete description of the phonon dispersion rather than to a fundamentally new feature in the nature of the hydrogen bond. (authors)

  18. Electron density profile reconstruction by maximum entropy method with multichannel HCN laser interferometer system on SPAC VII

    International Nuclear Information System (INIS)

    Kubo, S.; Narihara, K.; Tomita, Y.; Hasegawa, M.; Tsuzuki, T.; Mohri, A.

    1988-01-01

    A multichannel HCN laser interferometer system has been developed to investigate the plasma electron confinement properties in SPAC VII device. Maximum entropy method is applied to reconstruct the electron density profile from measured line integrated data. Particle diffusion coefficient in the peripheral region of the REB ring core spherator was obtained from the evolution of the density profile. (author)

  19. ENDF/B-VII.1 Nuclear Data for Science and Technology: Cross Sections, Covariances, Fission Product Yields and Decay Data

    International Nuclear Information System (INIS)

    Palmiotti, G.

    2011-01-01

    The ENDF/B-VII.1 library is our latest recommended evaluated nuclear data file for use in nuclear science and technology applications, and incorporates advances made in the five years since the release of ENDF/B-VII.0. These advances focus on neutron cross sections, covariances, fission product yields and decay data, and represent work by the US Cross Section Evaluation Working Group (CSEWG) in nuclear data evaluation that utilizes developments in nuclear theory, modeling, simulation, and experiment. The principal advances in the new library are: (1) An increase in the breadth of neutron reaction cross section coverage, extending from 393 nuclides to 418 nuclides; (2) Covariance uncertainty data for 185 of the most important nuclides, as documented in companion papers in this edition; (3) R-matrix analyses of neutron reactions on light nuclei, including isotopes of He, Li, and Be; (4) Resonance parameter analyses at lower energies and statistical high energy reactions at higher energies for isotopes of F, Cl, K, Ti, V, Mn, Cr, Ni, Zr and W; (5) Modifications to thermal neutron reactions on fission products (isotopes of Mo, Tc, Rh, Ag, Cs, Nd, Sm, Eu) and neutron absorber materials (Cd, Gd); (6) Improved minor actinide evaluations for isotopes of U, Np, Pu, and Am (we are not making changes to the major actinides 235,238U and 239Pu at this point, except for delayed neutron data, and instead we intend to update them after a further period of research in experiment and theory), and our adoption of JENDL-4.0 evaluations for isotopes of Cm, Bk, Cf, Es, Fm, and some other minor actinides; (7) Fission energy release evaluations; (8) Fission product yield advances for fission-spectrum neutrons and 14 MeV neutrons incident on 239Pu; and (9) A new Decay Data sublibrary. Integral validation testing of the ENDF/B-VII.1 library is provided for a variety of quantities: For nuclear criticality, the VII.1 library maintains the generally-good performance seen for VII.0 for a wide

  20. Heavy impurity collection at the plasma edge of the stellarator W VII A

    International Nuclear Information System (INIS)

    Schou, J.

    1981-12-01

    The presence of impurities at the plasma edge of the Wendelstein VII-A stellarator was studied by means of carbon probes that were exposed to up to 200 plasma discharges in helium. The probes were subsequently analysed with 1 MeV 4 He + Rutherford Backscattering. The average impurity deposition for Ti, Mo and wall components (Fe, Cr, Ni) was 2-4 x 10 12 atoms/cm 2 , 6 x 10 10 atoms/cm 2 and 1 x 10 11 atoms/cm 2 per discharge, respectively. With the exception of Ti this impurity deposition is more than one order of magnitude smaller than the corresponding results from comparable tokamaks. (orig.)

  1. First startup of the Siemens SL prototype magnets W VII in the IPP

    International Nuclear Information System (INIS)

    Amenda, W.; Kullmann, D.; Krueger, P.; Pillsticker, M.

    The first test results with a big superconductive prototype coil developed for the Garching Stellarator W VII are reported. Flux jumping at low currents did not start quenching. The critical current of the Nb-Ti coil reaches 91 percent of the short sample value. The stored energy at quenching is 1.83 MJ and the maximum value of the magnetic field in the winding region is 61.5 kG. The mechanical stresses did not damage the windings. Degradation was not observed. A training of the coil was not necessary. Altogether the test was successful, as important technical problems were satisfactorily solved. Only parts of cryogenic systems should be improved in order to reduce the helium losses. (U.S.)

  2. Benchmarking ENDF/B-VII.1, JENDL-4.0 and JEFF-3.1

    International Nuclear Information System (INIS)

    Van Der Marck, S. C.

    2012-01-01

    Three nuclear data libraries have been tested extensively using criticality safety benchmark calculations. The three libraries are the new release of the US library ENDF/B-VII.1 (2011), the new release of the Japanese library JENDL-4.0 (2011), and the OECD/NEA library JEFF-3.1 (2006). All calculations were performed with the continuous-energy Monte Carlo code MCNP (version 4C3, as well as version 6-beta1). Around 2000 benchmark cases from the International Handbook of Criticality Safety Benchmark Experiments (ICSBEP) were used. The results were analyzed per ICSBEP category, and per element. Overall, the three libraries show similar performance on most criticality safety benchmarks. The largest differences are probably caused by elements such as Be, C, Fe, Zr, W. (authors)

  3. Spectrum and energy levels of six-times ionized yttrium (Y VII)

    Science.gov (United States)

    Reader, Joseph

    2018-03-01

    The spectrum of six-times ionized yttrium, Y VII, was photographed with a sliding-spark discharge on 10.7 m normal- and grazing-incidence spectrographs. The region of observation was 157-824 Å. The observations extend the known configurations 4s24p3, 4s4p4, 4p5, 4s24p25s, 4s24p26s to the nearly complete 4s24p24d configuration. Our results for 4s24p24d significantly revise results of Rahimullah et al (1978 Phys. Scr. 18 96); Ateqad et al (1984 J. Phys. B: At. Mol. Phys. 17 4617). A total of 168 lines and 56 energy levels are now known for this ion. The observed configurations were interpreted with Hartree-Fock calculations and least-squares fits of the energy parameters to the observed levels. Transition probabilities for all classified lines were calculated with the fitted parameters.

  4. KETERAMPILAN PROSES SAINS SISWA KELAS VII DENGAN PEMBELAJARAN MODEL LEVELS OF INQUIRY

    Directory of Open Access Journals (Sweden)

    Fitri Fatimah

    2016-09-01

    Banyak penelitian yang mengkaji tentang keterampilan proses sains namun masih diteliti secara terpisah antara keterampilan proses dasar dan keterampilan terintegrasi. Oleh karena itu, perlu dilakukan penelitian tentang keterampilan proses sains yang menggabungkan keterampilan dasar dan terintegrasi dengan menggunakan Levels of Inquiry pada materi ciri-ciri dan klasifikasi makhluk hidup. Penelitian ini menggunakan mixed methods desain embedded terhadap siswa kelas VII SMPN 9 Pontianak. Data dianalisis secara kuantitatif dan kualitatif. Hasil analisis data menunjukkan pembelajaran model Levels of Inquiry dapat melatih dan mengembangkan keterampilan proses sains siswa mulai dari kurang terampil sampai menjadi sangat terampil. Hasil pretes dan postes memperlihatkan peningkatan hasil dengan N-gain sebesar 0.67 berada pada kriteria sedang.

  5. VII Seminario Internacional de Investigación en Odontología

    Directory of Open Access Journals (Sweden)

    Carolina Torres Rodríguez

    2016-07-01

    Full Text Available El VII Seminario de investigación en odontología, organizado por el programa de Maestría en Odontología, es un espacio de encuentro de estudiantes, investigadores nacionales e internacionales y asistentes, con el fin de compartir conocimientos y entablar redes de colaboración. También es una estrategia de comunicación, difusión, apropiación y transferencia de conocimiento y de los resultados de la investigación de los diferentes grupos con la comunidad científica nacional y/o internacional y un método para dar a conocer, promover e impulsar la investigación a nivel nacional, todo esto con el fin de brindar soluciones a las diferentes problemáticas de la profesión y de la salud oral y general.

  6. Rietveld refinement of Y2O3 using the pearson VII profile shape function

    International Nuclear Information System (INIS)

    Smrcok, L.

    1989-01-01

    Very good agreement between the observed and the calculated intensities was obtained using the Pearson VII profile shape function. The variable exponent m could be refined only in the damped iterations involving exclusively the profile parameters. Simultaneous refinement of the m with the positional and/or thermal parameters has led to large oscillations of the shifts of almost all parameters. Precision of the refined atomic coordinates is better than those from previously published Rietveld refinement and is comparable with single crystal results. The degree of serial correlation in residuals has been determined by the use of the Durbin-Watson d statistic. Normal probability plot based on δR i has been almost linear with the slope greater than one. The weighting scheme with w i = 1/y oi has proved to be good first approximation. (author)

  7. A Pearson VII distribution function for fast calculation of dechanneling and angular dispersion of beams

    International Nuclear Information System (INIS)

    Shao Lin; Peng Luohan

    2009-01-01

    Although multiple scattering theories have been well developed, numerical calculation is complicated and only tabulated values have been available, which has caused inconvenience in practical use. We have found that a Pearson VII distribution function can be used to fit Lugujjo and Mayer's probability curves in describing the dechanneling phenomenon in backscattering analysis, over a wide range of disorder levels. Differentiation of the obtained function gives another function to calculate angular dispersion of the beam in the frameworks by Sigmund and Winterbon. The present work provides an easy calculation of both dechanneling probability and angular dispersion for any arbitrary combination of beam and target having a reduced thickness ≥0.6, which can be implemented in modeling of channeling spectra. Furthermore, we used a Monte Carlo simulation program to calculate the deflection probability and compared them with previously tabulated data. A good agreement was reached.

  8. The transitions 4p-5s in Y VI, Zr VII, Nb VIII and Mo IX

    International Nuclear Information System (INIS)

    Chaghtai, M.S.Z.; Rahimullah, K.; Khatoon, S.

    1976-01-01

    With the help of the spectra recorded in the Physics Department of Lund University, Y VI, Zr VII, Nb VIII and Mo IX are freshly analysed. The five 4s 2 4p 4 ground levels and the ten 4s 2 4p 3 5s levels of previous analyses are confirmed in the first three spectra, except for revising in Y VI the 4p 4 1 S 0 and 4p 3 5s( 4 Ssub(3/2)) 2 levels and interchanging 5s( 2 Dsub(3/2)) 1 with 5s( 2 Dsub(3/2)) 2 . All level values are improved due to the new measurements. A new analysis of Mo IX establishing all the 4p 4 and 4p 3 5s levels is being reported. (Auth.)

  9. Keefektifan Strategi Pembelajaran React Pada Kemampuan Siswa Kelas VII Aspek Komunikasi Matematis

    Directory of Open Access Journals (Sweden)

    A.T. Arifin

    2014-06-01

    Full Text Available AbstrakTujuan penelitian ini adalah mengetahui pembelajaran dengan strategi REACT efektif ter-hadap kemampuan komunikasi matematis siswa. Metode pengumpulan data dilakukan de-ngan metode dokumentasi, tes, dan observasi. Hasil uji proporsi menunjukkan bahwa hasil belajar siswa kelas eksperimen pada aspek kemampuan komunikasi matematis telah men-capai ketuntasan klasikal, mencapai lebih dari 80 % yaitu sebesar 96,7%. Dilihat dari nilai rata-rata tes kemampuan komunikasi matematis kelas eksperimen  adalah 83,61 sedangkan kelas kontrol adalah 73,79 dapat disimpulkan bahwa kemampuan komunikasi matematis siswa kelas eksperimen lebih baik daripada kemampuan komunikasi matematis siswa kon-trol. Hasil penelitian menunjukkan bahwa penerapan strategi pembelajaran REACT efektif terhadap kemampuan komunikasi matematis siswa materi segiempat kelas VII SMP Negeri 1 Gembong. Kata kunci:      keefektifan, kemampuan komunikasi matematis, Relating Experiencing Applying Cooperating Transferring (REACT  AbstractThe purpose of this study was to determine the effectiveness of the application of REACT learning strategy approach to mathematic communication ability of students. Methods of data collection is done by the method of documentation, testing, and observation. The test results showed that the proportion of student learning outcomes in the experimental class with the aspects of mathematic communication ability has reached the classical completeness, reached more than 80% is equal to 96.7%. Judging from the value of the average test learners' ability to mathematic communication experimental class was 83.61 while the control class is 73.79 it can be concluded that the mathematic communication skills of learners experimental classes are better than mathematic communication abilities of learners control class. The results showed that the application of REACT learning strategy approach effective to mathematic communication abilities of students of class VII

  10. XMM-Newton Survey of Local O VII Absorption Lines in the Spectra of Galactic X-Ray Sources

    Science.gov (United States)

    Luo, Yang; Fang, Taotao; Ma, Renyi

    2018-04-01

    The detection of highly ionized metal absorption lines in the X-ray spectra of the Galactic X-ray binaries (XRBs) implies the distribution of hot gas along the sightline toward the background sources. However, the origin of this hot gas is still unclear: it can arise in the hot interstellar medium (ISM), or is intrinsic to the XRBs. In this paper, we present an XMM-Newton survey of the O VII absorption lines in the spectra of Galactic XRBs. A total of 33 XRBs were selected, with 29 low-mass XRBs and 4 high-mass XRBs. At a more than 3σ threshold, O VII absorption line was detected in 16 targets, among which 4 were newly discovered in this work. The average line equivalent width is centered around ∼20 mÅ. Additionally, we do not find strong correlations between the O VII EWs and the Galactic neutral absorption N H, the Galactic coordinates, or the distance of background targets. Such non-correlation may suggest contamination of the circumstellar material, or a lack of constraints on the line Doppler-b parameter. We also find that regardless of the direction of the XRBs, the O VII absorption lines are always detected when the flux of the background XRBs reaches a certain level, suggesting a uniform distribution of this hot gas. We estimate a ratio of 0.004–0.4 between the hot and neutral phases of the ISM. This is the second paper in the series following Fang et al. (2015), in which we focused on the local O VII absorption lines detected in the background AGN spectra. Detailed modeling of the hot ISM distribution will be investigated in a future paper.

  11. Large proteoglycan complexes and disturbed collagen architecture in the corneal extracellular matrix of mucopolysaccharidosis type VII (Sly syndrome).

    Science.gov (United States)

    Young, Robert D; Liskova, Petra; Pinali, Christian; Palka, Barbara P; Palos, Michalis; Jirsova, Katerina; Hrdlickova, Enkela; Tesarova, Marketa; Elleder, Milan; Zeman, Jiri; Meek, Keith M; Knupp, Carlo; Quantock, Andrew J

    2011-08-24

    Deficiencies in enzymes involved in proteoglycan (PG) turnover underlie a number of rare mucopolysaccharidoses (MPS), investigations of which can considerably aid understanding of the roles of PGs in corneal matrix biology. Here, the authors analyze novel pathologic changes in MPS VII (Sly syndrome) to determine the nature of PG-collagen associations in stromal ultrastructure. Transmission electron microscopy and electron tomography were used to investigate PG-collagen architectures and interactions in a cornea obtained at keratoplasty from a 22-year-old man with MPS VII, which was caused by a compound heterozygous mutation in the GUSB gene. Transmission electron microscopy showed atypical morphology of the epithelial basement membrane and Bowman's layer in MPS VII. Keratocytes were packed with cytoplasmic vacuoles containing abnormal glycosaminoglycan (GAG) material, and collagen fibrils were thinner than in normal cornea and varied considerably throughout anterior (14-32 nm), mid (13-42 nm), and posterior (17-39 nm) regions of the MPS VII stroma. PGs viewed in three dimensions were striking in appearance in that they were significantly larger than PGs in normal cornea and formed highly extended linkages with multiple collagen fibrils. Cellular changes in the MPS VII cornea resemble those in other MPS. However, the wide range of collagen fibril diameters throughout the stroma and the extensive matrix presence of supranormal-sized PG structures appear to be unique features of this disorder. The findings suggest that the accumulation of stromal chondroitin-, dermatan-, and heparan-sulfate glycosaminoglycans in the absence of β-glucuronidase-mediated degradation can modulate collagen fibrillogenesis.

  12. Type VII collagen is enriched in the enamel organic matrix associated with the dentin-enamel junction of mature human teeth.

    Science.gov (United States)

    McGuire, Jacob D; Walker, Mary P; Mousa, Ahmad; Wang, Yong; Gorski, Jeff P

    2014-06-01

    The inner enamel region of erupted teeth is known to exhibit higher fracture toughness and crack growth resistance than bulk phase enamel. However, an explanation for this behavior has been hampered by the lack of compositional information for the residual enamel organic matrix. Since enamel-forming ameloblasts are known to express type VII collagen and type VII collagen null mice display abnormal amelogenesis, the aim of this study was to determine whether type VII collagen is a component of the enamel organic matrix at the dentin-enamel junction (DEJ) of mature human teeth. Immunofluorescent confocal microscopy of demineralized tooth sections localized type VII collagen to the organic matrix surrounding individual enamel rods near the DEJ. Morphologically, immunoreactive type VII collagen helical-bundles resembled the gnarled-pattern of enamel rods detected by Coomassie Blue staining. Western blotting of whole crown or enamel matrix extracts also identified characteristic Mr=280 and 230 kDa type VII dimeric forms, which resolved into 75 and 25 kDa bands upon reduction. As expected, the collagenous domain of type VII collagen was resistant to pepsin digestion, but was susceptible to purified bacterial collagenase. These results demonstrate the inner enamel organic matrix in mature teeth contains macromolecular type VII collagen. Based on its physical association with the DEJ and its well-appreciated capacity to complex with other collagens, we hypothesize that enamel embedded type VII collagen fibrils may contribute not only to the structural resilience of enamel, but may also play a role in bonding enamel to dentin. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Cardiovascular risk factors and mortality in children with chronic ...

    African Journals Online (AJOL)

    Traditional and non-traditional cardiovascular risk factors. (CVRFs) play an ..... to other causes of anaemia in CKD such as declining production of erythropoietin .... Care 2008;35(2):329-. 344, vii. https:/doi.org/10.1016/j.pop.2008.01.008. 2.

  14. Brain-derived neurotrophic factor and early-life stress

    Indian Academy of Sciences (India)

    2016-10-24

    Oct 24, 2016 ... The brain-derived neurotrophic factor (BDNF) is a key regulator of neural development and ... forms are produced by splicing individual non-coding ..... VII and. IX m. RNA. ↑. mBDNF. ↓. (MS). 5. BDNF expression was unch;.

  15. ENDF/B-VII.1 Neutron Cross Section Data Testing with Critical Assembly Benchmarks and Reactor Experiments

    Energy Technology Data Exchange (ETDEWEB)

    Kahler, A.C.; Herman, M.; Kahler,A.C.; MacFarlane,R.E.; Mosteller,R.D.; Kiedrowski,B.C.; Frankle,S.C.; Chadwick,M.B.; McKnight,R.D.; Lell,R.M.; Palmiotti,G.; Hiruta,H.; Herman,M.; Arcilla,R.; Mughabghab,S.F.; Sublet,J.C.; Trkov,A.; Trumbull,T.H.; Dunn,M.

    2011-12-01

    The ENDF/B-VII.1 library is the latest revision to the United States Evaluated Nuclear Data File (ENDF). The ENDF library is currently in its seventh generation, with ENDF/B-VII.0 being released in 2006. This revision expands upon that library, including the addition of new evaluated files (was 393 neutron files previously, now 423 including replacement of elemental vanadium and zinc evaluations with isotopic evaluations) and extension or updating of many existing neutron data files. Complete details are provided in the companion paper [M. B. Chadwick et al., 'ENDF/B-VII.1 Nuclear Data for Science and Technology: Cross Sections, Covariances, Fission Product Yields and Decay Data,' Nuclear Data Sheets, 112, 2887 (2011)]. This paper focuses on how accurately application libraries may be expected to perform in criticality calculations with these data. Continuous energy cross section libraries, suitable for use with the MCNP Monte Carlo transport code, have been generated and applied to a suite of nearly one thousand critical benchmark assemblies defined in the International Criticality Safety Benchmark Evaluation Project's International Handbook of Evaluated Criticality Safety Benchmark Experiments. This suite covers uranium and plutonium fuel systems in a variety of forms such as metallic, oxide or solution, and under a variety of spectral conditions, including unmoderated (i.e., bare), metal reflected and water or other light element reflected. Assembly eigenvalues that were accurately predicted with ENDF/B-VII.0 cross sections such as unmoderated and uranium reflected {sup 235}U and {sup 239}Pu assemblies, HEU solution systems and LEU oxide lattice systems that mimic commercial PWR configurations continue to be accurately calculated with ENDF/B-VII.1 cross sections, and deficiencies in predicted eigenvalues for assemblies containing selected materials, including titanium, manganese, cadmium and tungsten are greatly reduced. Improvements are also

  16. ENDF/B-VII.0: Next Generation Evaluated Nuclear Data Library for Nuclear Science and Technology

    Energy Technology Data Exchange (ETDEWEB)

    Chadwick, M B; Oblozinsky, P; Herman, M; Greene, N M; McKnight, R D; Smith, D L; Young, P G; MacFarlane, R E; Hale, G M; Haight, R C; Frankle, S; Kahler, A C; Kawano, T; Little, R C; Madland, D G; Moller, P; Mosteller, R; Page, P; Talou, P; Trellue, H; White, M; Wilson, W B; Arcilla, R; Dunford, C L; Mughabghab, S F; Pritychenko, B; Rochman, D; Sonzogni, A A; Lubitz, C; Trumbull, T H; Weinman, J; Brown, D; Cullen, D E; Heinrichs, D; McNabb, D; Derrien, H; Dunn, M; Larson, N M; Leal, L C; Carlson, A D; Block, R C; Briggs, B; Cheng, E; Huria, H; Kozier, K; Courcelle, A; Pronyaev, V; der Marck, S

    2006-10-02

    We describe the next generation general purpose Evaluated Nuclear Data File, ENDF/B-VII.0, of recommended nuclear data for advanced nuclear science and technology applications. The library, released by the U.S. Cross Section Evaluation Working Group (CSEWG) in December 2006, contains data primarily for reactions with incident neutrons, protons, and photons on almost 400 isotopes. The new evaluations are based on both experimental data and nuclear reaction theory predictions. The principal advances over the previous ENDF/B-VI library are the following: (1) New cross sections for U, Pu, Th, Np and Am actinide isotopes, with improved performance in integral validation criticality and neutron transmission benchmark tests; (2) More precise standard cross sections for neutron reactions on H, {sup 6}Li, {sup 10}B, Au and for {sup 235,238}U fission, developed by a collaboration with the IAEA and the OECD/NEA Working Party on Evaluation Cooperation (WPEC); (3) Improved thermal neutron scattering; (4) An extensive set of neutron cross sections on fission products developed through a WPEC collaboration; (5) A large suite of photonuclear reactions; (6) Extension of many neutron- and proton-induced reactions up to an energy of 150 MeV; (7) Many new light nucleus neutron and proton reactions; (8) Post-fission beta-delayed photon decay spectra; (9) New radioactive decay data; and (10) New methods developed to provide uncertainties and covariances, together with covariance evaluations for some sample cases. The paper provides an overview of this library, consisting of 14 sublibraries in the same, ENDF-6 format, as the earlier ENDF/B-VI library. We describe each of the 14 sublibraries, focusing on neutron reactions. Extensive validation, using radiation transport codes to simulate measured critical assemblies, show major improvements: (a) The long-standing underprediction of low enriched U thermal assemblies is removed; (b) The {sup 238}U, {sup 208}Pb, and {sup 9}Be reflector

  17. ENDF/B-VII.0: Next Generation Evaluated Nuclear Data Library for Nuclear Science and Technology

    International Nuclear Information System (INIS)

    Chadwick, M.B.; Oblozinsky, P.; Herman, M.

    2006-01-01

    We describe the next generation general purpose Evaluated Nuclear Data File, ENDF/B-VII.0, of recommended nuclear data for advanced nuclear science and technology applications. The library, released by the U.S. Cross Section Evaluation Working Group (CSEWG) in December 2006, contains data primarily for reactions with incident neutrons, protons, and photons on almost 400 isotopes, based on experimental data and theory predictions. The principal advances over the previous ENDF/B-VI library are the following: (1) New cross sections for U, Pu, Th, Np and Am actinide isotopes, with improved performance in integral validation criticality and neutron transmission benchmark tests; (2) More precise standard cross sections for neutron reactions on H, 6 Li, 10 B, Au and for 235,238 U fission, developed by a collaboration with the IAEA and the OECD/NEA Working Party on Evaluation Cooperation (WPEC); (3) Improved thermal neutron scattering; (4) An extensive set of neutron cross sections on fission products developed through a WPEC collaboration; (5) A large suite of photonuclear reactions; (6) Extension of many neutron- and proton-induced evaluations up to 150 MeV; (7) Many new light nucleus neutron and proton reactions; (8) Post-fission beta-delayed photon decay spectra; (9) New radioactive decay data; (10) New methods for uncertainties and covariances, together with covariance evaluations for some sample cases; and (11) New actinide fission energy deposition. The paper provides an overview of this library, consisting of 14 sublibraries in the same ENDF-6 format as the earlier ENDF/B-VI library. We describe each of the 14 sublibraries, focusing on neutron reactions. Extensive validation, using radiation transport codes to simulate measured critical assemblies, show major improvements: (a) The long-standing underprediction of low enriched uranium thermal assemblies is removed; (b) The 238 U and 208 Pb reflector biases in fast systems are largely removed; (c) ENDF/B-VI.8 good

  18. The Application Model of Learning Cycle 5e in Subject Matter of Magnitude and Derivative at Class VII Junior High School 1 Sengah Temila

    Directory of Open Access Journals (Sweden)

    Ira Nofita Sari

    2016-10-01

    Penelitian ini bertujuan untuk mengetahui penerapan model learning cycle 5 e pada materi besaran pokok dan turunankelas VII SMP Negeri 1 Sengah Temila. Penelitian ini termasuk penelitian quasi eksperiment dengan rancangan posttest only design control design. Alat pengumpul data yang digunakan adalah tes pilihan jamak. Hipotesis diuji menggunakanuji t satu pihak. Berdasarkan hasil analisis data disimpulkan bahwa: (1 hasil belajar siswa setelah diterapkan model learning cycle 5 e pada materi besaran pokok dan turunan kelas VII SMP Negeri 1 Sengah Temilatergolong baik, (2 hasil belajar siswa setelah diterapkan model learning cycle 5 e pada materi besaran pokok dan turunan kelas VII SMP Negeri 1 Sengah Temilatergolong kurang, dan (3 hasil belajar siswa setelah diterapkan model learning cycle 5 e lebih baik daripada hasil belajar siswa setelah diterapkan model pembelajaran konvensional pada materi besaran pokok dan turunan kelas VII SMP Negeri 1 Sengah Temila. Kata kunci: besaran pokok dan turunan, hasil belajar, model learning cycle 5e

  19. PENGARUH KEMANDIRIAN BELAJAR DAN PENGGUNAAN UANG SAKU TERHADAP PRESTASI BELAJAR KOMPETENSI DASAR EKONOMI KELAS VII DAN VIII

    Directory of Open Access Journals (Sweden)

    Apri Dwi Astuti

    2012-10-01

    Full Text Available Kemandirian belajar membantu siswa untuk bertanggung jawab dan menumbuhkan kesadaran belajar. Penggunaan uang saku menumbuhkan jiwa mandiri, jujur dan komitmen. Adapun hasil observasi awal menunjukkan masih ada siswa kels VII dan VIII SMP Semesta untuk kompetensi dasar ekonomi dibawah KKM. Tujuan penelitian ini untuk mengetahui pengaruh kemandirian belajar dn penggunaan uang saku terhadap prestasi belajar kompetensi dasar ekonomi kelas VII dan VIII SMP Semesta. Populasi penelitian ini adalah semua siswa kelas VII dan VIII SMP Semesta Boarding School Semarang. Variabel penelitian ini adalah kemandirian belajar dan penggunaan uang saku sebagai variabel bebas, sedangkan untuk� variabel terikat adalah prestasi belajar kompetensi dasar ekonomi. Data diambil dengan metode wawancara, kuesioner dan dokumentasi guru. Analisis data menggunakan analisis regresi linear berganda.Berdasarkan penelitian secara simultan menunjukkan adanya pengaruh antara kemandirian belajar dan penggunaan uang saku terhadap prestasi belajar kompetensi dasar ekonomi sebesar 51,3%. Secara parsial, pengaruh kemandirian belajar terhadap prestasi belajar kompetensi dasar ekonomi sebesar 66,2% dan pengaruh penggunaan uang saku terhadap prestasi belajar kompetensi dasar ekonomi sebesar 62,5%.Berdasarkan hasil penelitian diatas disimpulkan bahwa kemandirian belajar dan penggunaan uang saku berpengaruh positif baik secara simultan maupun parsial terhadap prestasi belajar kompetensi dasar ekonomi kelas VII dan VIII SMP Semesta Boarding school semarang tahun pelajaran 2011/2012. Saran yang berkaitan dengan penelitian ini yaitu : 1 Sekolah disarankan untuk memberikan batasan siswa pulang ke rumah agar dapat membantu siswa beradaptasi dengan cepat dan mudah tinggal di asrama. 2 Orang tua disarankan untuk memberikan uang saku yang disesuaikan dengan kebutuhan siswa. 3 Siswa disarankan untuk meningkatkan kemandirian dalam aspek belajar terutama bagi mata pelajaran yang masih kurang dari

  20. Theoretical emission line ratios for [Fe III] and [Fe VII] applicable to the optical and infrared spectra of gaseous nebulae.

    Science.gov (United States)

    Keenan, F P; Aller, L H; Ryans, R S; Hyung, S

    2001-08-14

    Recent calculations of electron impact excitation rates and Einstein A-coefficients for transitions among the 3d(6) levels of Fe III and among the 3d(2) levels of Fe VII are used to derive theoretical emission line ratios applicable to the optical and infrared spectra of gaseous nebulae. Results for [Fe III] are generated for electron temperatures T(e) = 7,000-20,000 K and densities N(e) = 10(2)-10(8) cm(-3), whereas those for [Fe VII] are provided for T(e) = 10,000-30,000 K and N(e) = 10(2)-10(8) cm(-3). The theoretical line ratios are significantly different in some instances from earlier calculations and resolve discrepancies between theory and observation found for the planetary nebulae IC 4997 and NGC 7027.

  1. Influence of Discussion Rating in Cooperative Learning Type Numbered Head Together on Learning Results Students VII MTSN Model Padang

    Science.gov (United States)

    Sasmita, E.; Edriati, S.; Yunita, A.

    2018-04-01

    Related to the math score of the first semester in class at seventh grade of MTSN Model Padang which much the score that low (less than KKM). It because of the students who feel less involved in learning process because the teacher don't do assessment the discussions. The solution of the problem is discussion assessment in Cooperative Learning Model type Numbered Head Together. This study aims to determine whether the discussion assessment in NHT effect on student learning outcomes of class VII MTsN Model Padang. The instrument used in this study is discussion assessment and final tests. The data analysis technique used is the simple linear regression analysis. Hypothesis test results Fcount greater than the value of Ftable then the hypothesis in this study received. So it concluded that the assessment of the discussion in NHT effect on student learning outcomes of class VII MTsN Model Padang.

  2. ENDF/B-VII.1 Nuclear Data for Science and Technology: Cross Sections, Covariances, Fission Product Yields and Decay Data

    Energy Technology Data Exchange (ETDEWEB)

    Chadwick, M.B.; Herman, M.; Author(s): Chadwick,M.B.; Herman,M.; Oblozinsky,P.; Dunn,M.E.; Danon,Y.; Kahler,A.C.; Smith,D.L.; Pritychenko,B.; Arbanas,G.; Arcilla,R.; Brewer,R.; Brown,D.A.; Capote,R.; Carlson,A.D.; Cho,Y.S.; Derrien,H.; Guber,K.; Hale,G.M.; Hoblit,S.; Holloway,S.: Johnson,T.D.; Kawano,T.; Kiedrowski,B.C.; Kim,H.; Kunieda,S.; Larson,N.M.; Leal,L.; Lestone,J.P.; Little,R.C.; McCutchan,E.A.; MacFarlane,R.E.; MacInnes,M.; Mattoon,C.M.; McKnight,R.D.; Mughabghab,S.F.; Nobre,G.P.A.; Palmiotti,G.; Palumbo,A.; Pigni,M.T.; Pronyaev,V.G.; Sayer,R.O.; Sonzogni,A.A.; Summers,N.C.; Talou,P.; Thompson,I.J.; Trkov,A.; Vogt,R.L.; van der Marck,S.C.; Wallner,A.; White,M.C.; Wiarda,D.; Young,P.G.

    2011-12-01

    The ENDF/B-VII.1 library is our latest recommended evaluated nuclear data file for use in nuclear science and technology applications, and incorporates advances made in the five years since the release of ENDF/B-VII.0. These advances focus on neutron cross sections, covariances, fission product yields and decay data, and represent work by the US Cross Section Evaluation Working Group (CSEWG) in nuclear data evaluation that utilizes developments in nuclear theory, modeling, simulation, and experiment. The principal advances in the new library are: (1) An increase in the breadth of neutron reaction cross section coverage, extending from 393 nuclides to 423 nuclides; (2) Covariance uncertainty data for 190 of the most important nuclides, as documented in companion papers in this edition; (3) R-matrix analyses of neutron reactions on light nuclei, including isotopes of He, Li, and Be; (4) Resonance parameter analyses at lower energies and statistical high energy reactions for isotopes of Cl, K, Ti, V, Mn, Cr, Ni, Zr and W; (5) Modifications to thermal neutron reactions on fission products (isotopes of Mo, Tc, Rh, Ag, Cs, Nd, Sm, Eu) and neutron absorber materials (Cd, Gd); (6) Improved minor actinide evaluations for isotopes of U, Np, Pu, and Am (we are not making changes to the major actinides {sup 235,238}U and {sup 239}Pu at this point, except for delayed neutron data and covariances, and instead we intend to update them after a further period of research in experiment and theory), and our adoption of JENDL-4.0 evaluations for isotopes of Cm, Bk, Cf, Es, Fm, and some other minor actinides; (7) Fission energy release evaluations; (8) Fission product yield advances for fission-spectrum neutrons and 14 MeV neutrons incident on {sup 239}Pu; and (9) A new decay data sublibrary. Integral validation testing of the ENDF/B-VII.1 library is provided for a variety of quantities: For nuclear criticality, the VII.1 library maintains the generally-good performance seen for VII.0

  3. Pseudane-VII Isolated from Pseudoalteromonas sp. M2 Ameliorates LPS-Induced Inflammatory Response In Vitro and In Vivo

    OpenAIRE

    Mi Eun Kim; Inae Jung; Jong Suk Lee; Ju Yong Na; Woo Jung Kim; Young-Ok Kim; Yong-Duk Park; Jun Sik Lee

    2017-01-01

    The ocean is a rich resource of flora, fauna, food, and biological products. We found a wild-type bacterial strain, Pseudoalteromonas sp. M2, from marine water and isolated various secondary metabolites. Pseudane-VII is a compound isolated from the Pseudoalteromonas sp. M2 metabolite that possesses anti-melanogenic activity. Inflammation is a response of the innate immune system to microbial infections. Macrophages have a critical role in fighting microbial infections and inflammation. Recent...

  4. Proceedings of VII International Symposium on Nuclear and Related Techniques. XIII Workshop on Nuclear Physics. WONP-NURT 2011

    International Nuclear Information System (INIS)

    2012-06-01

    This year 2012, the VII International Workshop held Tecnolaser 2012 alongside the Third International Meeting Optics, Life and Heritage organized by the Center of Technological Applications and Nuclear Development from 10 to 13 April at the National Museum of Fine Arts. Tecnolaser has been held since 1997 and has contributed to the exchange between professionals from various countries of the world in the fields of optics and laser applications. The papers submitted to this event are presented in this CD-ROM.

  5. Self-diffusion of protons in H{sub 2}O ice VII at high pressures: Anomaly around 10 GPa

    Energy Technology Data Exchange (ETDEWEB)

    Noguchi, Naoki, E-mail: noguchi-n@okayama-u.ac.jp; Okuchi, Takuo [Institute for Planetary Materials, Okayama University, Misasa, Tottori 682-0193 (Japan)

    2016-06-21

    The self-diffusion of ice VII in the pressure range of 5.5–17 GPa and temperature range of 400–425 K was studied using micro Raman spectroscopy and a diamond anvil cell. The diffusion was monitored by observing the distribution of isotope tracers: D{sub 2}O and H{sub 2}{sup 18}O. The diffusion coefficient of hydrogen reached a maximum value around 10 GPa. It was two orders of magnitude greater at 10 GPa than at 6 GPa. Hydrogen diffusion was much faster than oxygen diffusion, which indicates that protonic diffusion is the dominant mechanism for the diffusion of hydrogen in ice VII. This mechanism is in remarkable contrast to the self-diffusion in ice I{sub h} that is dominated by an interstitial mechanism for the whole water molecule. An anomaly around 10 GPa in ice VII indicates that the rate-determining process for the proton diffusion changes from the diffusion of ionic defects to the diffusion of rotational defects, which was suggested by proton conductivity measurements and molecular dynamics simulations.

  6. The discovery of an O VII emission line in the ASCA spectrum of the Seyfert galaxy NGC 3783

    Science.gov (United States)

    George, I. M.; Turner, T. J.; Netzer, H.

    1995-01-01

    We report the first observation of an O VII 0.57 keV emission line in a Seyfert 1 galaxy. NGC 3783 was observed by ASCA twice over a period of 4 days in 1993 December. The source exhibited a approximately 30% change in intensity between the two observations, with most of the variability taking place as a result of steepening of the continuum less than or approximately equal to 1 keV. Spectra from both observations show intense absorption features in the 0.5-1.5 keV band, which can be well fitted by an ionized absorber model of solar composition, column density of 10(exp 22.2)/sq cm and ionization parameter of approximately 7-8; the strongest absorption features being due to O VII and O VIII. Two emission features are also seen in the spectra which we identify as O VII 0.57 keV (equivalent width approximately equals 36 eV) and O VIII 0.65 keV (equivalent width approximately equals 11 eV). We also show that the 3-6 keV continuum of the source is well fitted by a Gamma = 1.3-1.4 power-law continuum, a narrow neutral iron K-shell fluorescence line and a strong iron K-shell absorption edge, possibly corresponding to highly ionized iron.

  7. A case of linear IgA bullous dermatosis with IgA anti-type VII collagen autoantibodies.

    Science.gov (United States)

    Hashimoto, T; Ishiko, A; Shimizu, H; Tanaka, T; Dodd, H J; Bhogal, B S; Black, M M; Nishikawa, T

    1996-02-01

    In this study we present a patient with the sublamina densa type of linear IgA bullous dermatosis (LABD), with IgA autoantibodies reactive with the 290-kDa type VII collagen (the epidermolysis bullosa acquisita (EBA) antigen) and with immunoblotting of normal human dermal extracts. The clinical and histological features of the present case were compatible with those of LABD but quite different from those of EBA. Although EBA sera reacted with the bacterial fusion protein of the N-terminal globular (NC1) domain of type VII collagen, this patient's serum did not show reactivity. Furthermore, ultrastructural localization of target epitopes on the anchoring fibrils in this patient was considerably different from EBA. These results indicate that, whereas EBA antibodies react with the NC1 domain of type VII collagen, the epitope in this case is different from that of EBA (and is most likely on the central triple helical domain). This difference may be responsible for the clinical presentation in this patient being distinct from that of EBA.

  8. Prediction of the Sodium Void Reactivity in the Metal-fueled SFR Using the ENDF/B-VII.0 Library

    Energy Technology Data Exchange (ETDEWEB)

    Yun, Sunghwan; Lim, Jae-Yong [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2016-10-15

    The SVR (Sodium Void Reactivity) is one of the most important parameters in SFR (Sodium-cooled Fast Reactor) safety analysis. In this paper, to estimate the error of the SVR in metal-fueled SFR, three physics experiments named as BFS-75-1, BFS-109-2A, and BFS-84-1 were examined using recent cross-section library, ENDF/B-VII.0 and the MCNP code. In the MCNP6 calculation, two million histories/generation with 50 inactive/300 active generations are used with the continuous-energy ENDF/B-VII.0 library. We expect that accuracy of total cross-section of the sodium may play a dominant role in errors of SVRs at core peripheral and sodium plenum regions, whereas accuracy of capture cross-section of the sodium may play a dominant role for the results in errors of SVRs at core central region. In addition, capture cross-sections of the sodium in the ENDF/B-VII.0, the JEFF-3.2, and the JENDL-4.0 libraries show significant differences between each other, while total cross-sections of sodium in three libraries show good agreement.

  9. Mathematical Communication Ability by Grade VII Students Using a Themed Problem Based Learning with Scaffolding on Rectangle Materials

    Directory of Open Access Journals (Sweden)

    Didik Adi Saputro

    2017-08-01

    Full Text Available The aim of research to test students' mathematical communication used themed of PBL with scaffolding, themed of PBL and PBL achieve mastery learning;to test students' mathematical communication that used the themed of PBL with scaffolding, themed of PBL and PBL; and to test students' mathematical communication for the low, medium group, and a high-group themed of PBL with scaffolding, themed of PBL and PBL. This type of research is quantitative research. The Population is seventh grade students of SMPN 22 Semarang and the sample class VII E, F and VII VII G. Used normality test, homogenity test, equality test on average, the proportion of one-party test, one way anova test, and scheffe test. The results showed that (1 Student’s mathematical communication ability using themed of PBLwith Scaffolding strategy,themed of PBL, and PBL achieve the completeness of learning, (2 there is a difference in the classroom using the themed of PBL with scaffolding, themed of PBL, as well as PBL, (3 For the low, medium, high and there is a difference in the classroom using the themed of PBL with scaffolding, themed of PBL and PBL.

  10. PENGEMBANGAN MEDIA PEMBELAJARAN KOSAKATA BAHASA INGGRIS BERBANTUAN KOMPUTER UNTUK SISWA SMP KELAS VII

    Directory of Open Access Journals (Sweden)

    Bastani Bastani

    2014-05-01

    Full Text Available Penelitian ini bertujuan: (1 menghasilkan media pembelajaran kosakata bahasa Inggris berbantuan komputer untuk siswa SMP kelas VII; dan (2 mengetahui kelayakan media pada aspek materi, pemrograman, dan tampilan. Penelitian ini adalah penelitian dan pengembangan dengan menggunakan model pengembangan Borg & Gall dan Alessi & Trollip’s yang telah dimodifikasi. Penelitian ini dilaksanakan melalui tiga tahap, yaitu perencanaan, desain, dan pengembangan. Tahap perencanaan meliputi penetapan tujuan dan penganalisisan kebutuhan. Tahap desain meliputi penyelenggaraan focus group discussion, pembuatan flowchart, storyboard, penyiapan materi, dan bahan pendukung. Tahap pengembangan meliputi pembuatan aplikasi berdasarkan flowchart dan storyboard, validasi ahli dan validasi pengguna. Instrumen penelitian yang digunakan adalah kuesioner/angket dan tes. Hasil penelitian dan pengembangan ini adalah: (1 produk media pembelajaran kosakata bahasa Inggris berbantuan komputer dalam bentuk CD pembelajaran dan print out produk; dan (2 kelayakan media ditinjau dari aspek materi termasuk kriteria sangat layak dengan rata-rata skor 4,47 pada skala lima, aspek pemrograman termasuk kriteria sangat layak dengan rata-rata skor 4,21 dan aspek tampilan termasuk kriteria sangat layak dengan rata-rata skor 4,44. Kata kunci: pengembangan, media pembelajaran, kosakata, pembelajaran berbantuan komputer.

  11. Reflectometry observations of density fluctuations in Wendelstein VII-AS stellarator

    International Nuclear Information System (INIS)

    Sanchez, J.; Hartfuss, H.J.; Anabitarte, E.; Navarro, A.P.

    1991-01-01

    In the almost shearless stellarator Wendelstein VII-AS strong correlation between the confinement properties and the rotational transform iota has been found. Reduced confinement was observed for the low order rational values 1/2 and 1/3. In their vicinity best confinement is observed. In general optimum confinement is obtained in the low shear configuration if the 'resonant' iota values can be excluded from the plasma column. The iota profile inside the plasma is affected by toroidal currents and beta effects. Although the global net current can be kept at zero level using a small OH induced current opposed to the gradient driven bootstrap current, the different currents flow at different radial positions affecting the iota profile. Tools for configuration control inside the plasma are besides OH current vertical fields and the currents driven by the NBI and most promising the ECH heating systems. In this context experimental information on the iota profile is highly needed. The localization of rational surfaces by reflectometry seems possible. Radially resolved density fluctuation measurements have been carried out by means of a simple microwave reflectometry system. The method is based on the reflection of microwave radiation in the millimeter range at the plasma cutoff layer. (orig./AH)

  12. The oxidation of hydroxylamine by nitric and nitrous acids in the presence of technetium (VII)

    International Nuclear Information System (INIS)

    Koltunov, V.S.; Gomonova, T.V.; Savilova, O.A.; Zhuravleva, G.I.

    2000-01-01

    The oxidation of hydroxylamine by nitric acid in the presence of technetium ions at temperatures above ∝60 C is an autocatalytic process comprising an induction period and then a catalysed reaction involving HNO 2 , which has accumulated in the solution. Tc ions have no appreciable effect on the reaction rate, which is governed only by the nitric and nitrous acid oxidation reactions of hydroxylamine, but the presence of Tc ions does extend the initial induction period. The rate of hydroxylamine oxidation by HNO 3 in the presence of HNO 2 , that is, after the induction period, was found to be: -d[NH 3 OH + ]/dt = k[NH 3 OH + ][HNO 2 ][HNO 3 ] 3.5 where k = 120 ± 10 l 4.5 mol -4.5 min -1 at T = 80 C, μ = 2 and [H + ] ≤ 2 M. Under these conditions, the reaction apparently has a high activation energy of 160-180 kJ mol -1 . At low temperatures (20-40 C) hydroxylamine is effectively stable in solutions of HNO 3 up to concentrations of ∝2 M, whether or not Tc(VII) ions are present. Tc(V) was also observed to form at least one complex on reduction with excess hydroxylamine with an absorption maximum between 467 and 480 nm dependent on the solution acidity. (orig.)

  13. PERMAINAN TRADISIONAL “GAPREK KEMPUNG” SEBAGAI MEDIA PEMBELAJARAN PADA MATA PELAJARAN EKONOMI KELAS VII

    Directory of Open Access Journals (Sweden)

    Fera Wulandari

    2017-03-01

    Full Text Available The purpose of this study is (1 to produce a media product of social science learning traditional game Gaprek Kempung by utilizing the existing facilities in the surrounding environment, (2 to determine the effectiveness of the development of instructional media of social science traditional games Gaprek Kempung to improve learning outcomes on economic subjects grade VII SMP N 1 Tumpang. Based on the analysis testing the effectiveness of instructional media traditional game Gaprek Kempung by using software IBM SPSS 24 with the formula t-test, t-hitung obtained from posttest control class and experimental class SMP N 1 Tumpang amounted to 2,763 with t-table value is 2.005 thus t-hitung> t-tabel which means an increase in the economic value of learning outcomes experimental class is better than the control class. Furthermore, gained a significance value of 0.007 t-tabel yang berarti peningkatan nilai hasil belajar ekonomi kelas eksperimen lebih baik daripada kelas kontrol. Selanjutnya, didapatkan nilai signifikansi sebesar 0,007<α (0,05 yang menunjukkan bahwa H1 diterima artinya kelas eksperimen lebih baik dari pada kelas kontrol. Penelitian ini menunjukkan bahwa media pembelajaran permainan tradisional Gaprek Kempung lebih meningkatkan nilai hasil belajar ekonomi siswa dibandingkan tanpa menggunakan media pembelajaran. Hal ini berarti media pembelajaran permainan tradisional Gaprek Kempung layak digunakan untuk meningkatkan hasil belajar siswa dan media pembelajaran permainan tradisional Gaprek Kempung efektif untuk meningkatkan hasil belajar siswa.

  14. PENGEMBANGAN SOAL MATEMATIKA MODEL TIMSS UNTUK MENDUKUNG PEMBELAJARAN MATEMATIKA SMP KELAS VII KURIKULUM 2013

    Directory of Open Access Journals (Sweden)

    M. Andy Rudhito

    2016-02-01

    DEVELOPING THE TIMSS MATH PROBLEM MODEL TO SUPPORT THE MATHEMATICS LEARNING IN GRADE VII USING THE 2013 CURRICULUM Abstract: This study was aimed to produce a valid and practical TIMMS math problem model for junior high school students using the 2013 curriculum. The study used the research and development design. The design process of the problems as assessment instruments was carried out through prototyping involving two stages. Prototype I was the design product and the problem development done by the researchers themselves, while Prototype II was the revision of Prototype I based on the feedback provided by experts, colleagues, and Mathematics teachers in the form of validators’ notes and the minutes taken from discussions. The findings showed that the book of math problems was written by grouping the chapters following the materials domains as those in TIMSS, that is, numbers, geometry, algebra, data, and probability. For the student book, it was not nsecessary to write the materials domain, the essential topics, and the cognitive domain. The feedback from the FGD was that the problems should be arranged from the easiest ones to the most difficult ones. The multiple choice items should not be written in the form of questions, but in the form of incomplete sentences with the blanks in the middle or the end of the sentences. The items should not ask about implication. Keywords: Development of problems, junior high school mathematics, TIMSS, Curriculum 2013

  15. Immobilization of 99-Technetium (VII) by Fe(II)-Goethite and Limited Reoxidation

    International Nuclear Information System (INIS)

    Um, Wooyong; Chang, Hyun-Shik; Icenhower, Jonathan P.; Lukens, Wayne W.; Serne, R. Jeffrey; Qafoku, Nikolla; Westsik, Joseph H.; Buck, Edgar C.; Smith, Steven C.

    2011-01-01

    Synthesized goethite was successfully used with addition of Fe(II) to sequester Tc present in both deionized water and simulated off-gas scrubber waste solutions. Pertechnetate concentration in solution decreased immediately when the pH was raised above 7 by addition of sodium hydroxide. Removal of Tc(VII) from solution occurred most likely as a result of heterogeneous surface-catalyzed reduction to Tc(IV) and subsequent co-precipitation onto the goethite. The final Tc-bearing solid was identified as goethite-dominated Fe(III)-(oxy)hydroxide based on XRD analysis, confirming the widespread observation of its characteristic acicular habit by TEM/SEM images. Analysis of the solid precipitate by XAFS showed that the dominant oxidation state of Tc was Tc(IV) and was in octahedral coordination with Tc-O, Fe-O, and Tc-Fe bond distances that are consistent with direct substitution of Tc for Fe in the goethite structure. In some experiments the final Tc-goethite product was subsequently armored with additional layers of freshly precipitated goethite. Successful incorporation of Tc(IV) within the goethite mineral lattice and subsequent goethite armoring can limit re-oxidation of Tc(IV) and its subsequent release from Tc-goethite waste forms, even when the final product is placed in oxidizing environments that typify shallow waste burial facilities.

  16. VII International Symposium and Young Scientists School “Modern Problems of Laser Physics”

    International Nuclear Information System (INIS)

    2017-01-01

    General Information This volume of the Journal is devoted to the VII International Symposium and Young Scientists School “Modern Problems of Laser Physics” (MPLP-2016). I was held in Novosibirsk Akademgorodok, Russia, 22–28 August 2016. Akademgorodok is the well-known Siberian Scientific Centre of Russian Academy of Sciences (RAS). It was founded in 1957. Since that time it is the place of many international scientific meetings, because it reflects the unique and fruitful symbiosis of many research institutions and Novosibirsk State University at one territory. Since the first MPLP meeting in 1995 the Symposium usually gathers scientists from many countries, carrying out their investigations at the forefront of laser physics, quantum metrology and high-resolution spectroscopy, physics of ultracold atoms, molecules and ions, atom optics, ultrafast phenomena and attoscience, quantum optics and information, nonlinear optics and applications of laser radiation from THz to UV radiation ranges in medicine, geophysics, chemistry and microbiology. Traditionally the Symposium is the place where scientists can discuss new trends in modern laser physics, generate new ideas as well as initiate further collaborations. (paper)

  17. Spectrum and energy levels of six-times-ionized molybdenum (Mo VII)

    International Nuclear Information System (INIS)

    Reader, J.

    1990-01-01

    The spectrum of the kryptonlike ion Mo VII was observed from 140 to 2274 A with sliding-spark discharges on 10.7-m normal- and grazing-incidence spectrographs. Experimental energies were determined for all levels of the 4s 2 4p 6 , 4s 2 4p 5 4d, 4f, 5s, 5p, 5d, 5f, 5g, and 4s4p 6 4d configurations. A few levels of the 4s 2 4p 4 4d 2 configuration were also found. A total of 399 lines were classified as transitions between 86 observed levels. The observed configurations were theoretically interpreted. The energy parameters determined by least-squares fits to the observed levels are compared with Hartree--Fock calculations. A revised value of the ionization energy was obtained by using the energy of the 4p 5 5g configuration together with an isoelectronically extrapolated value of the effective quantum number n(5g). The adopted limit is 1 013 340±200 cm -1 (125.64±0.02 eV)

  18. Flotillin scaffold activity contributes to type VII secretion system assembly in Staphylococcus aureus.

    Directory of Open Access Journals (Sweden)

    Benjamin Mielich-Süss

    2017-11-01

    Full Text Available Scaffold proteins are ubiquitous chaperones that promote efficient interactions between partners of multi-enzymatic protein complexes; although they are well studied in eukaryotes, their role in prokaryotic systems is poorly understood. Bacterial membranes have functional membrane microdomains (FMM, a structure homologous to eukaryotic lipid rafts. Similar to their eukaryotic counterparts, bacterial FMM harbor a scaffold protein termed flotillin that is thought to promote interactions between proteins spatially confined to the FMM. Here we used biochemical approaches to define the scaffold activity of the flotillin homolog FloA of the human pathogen Staphylococcus aureus, using assembly of interacting protein partners of the type VII secretion system (T7SS as a case study. Staphylococcus aureus cells that lacked FloA showed reduced T7SS function, and thus reduced secretion of T7SS-related effectors, probably due to the supporting scaffold activity of flotillin. We found that the presence of flotillin mediates intermolecular interactions of T7SS proteins. We tested several small molecules that interfere with flotillin scaffold activity, which perturbed T7SS activity in vitro and in vivo. Our results suggest that flotillin assists in the assembly of S. aureus membrane components that participate in infection and influences the infective potential of this pathogen.

  19. THE EVALUATION OF BSE BAHASA INGGRIS FOR GRADE VII: WHEN ENGLISH RINGS A BELL

    Directory of Open Access Journals (Sweden)

    Doddy Dwi Wahyuwono

    2017-12-01

    Full Text Available Coursebooks are core parts of any curriculum as the unique contributors to content learning (Demir & Ertas, 2014. Currently, in Indonesian curriculum, K13, the government develops coursebooks that can be used by students nationally. The developed coursebooks, Buku Sekolah Elektronik (BSE, vary for different level of education, starting from elementary schools up to senior and vocational high schools. In developing the coursebooks, the government needs to implement the coursebooks to the real life situation and also evaluate them. In this paper, the researchers try to evaluate a coursebook used in English class for Junior High School students grade VII. The evaluation is done through two ways, the theory-based analysis and checklist-based analysis. The used evaluative theories are made by Cunningsworth and the Checklist is made by Mukundan, Nimehchisalem, and Hajimohammadi. The findings show that the coursebook has met the requirements of learners‘ needs stated in the K13; however, there are still some aspects that can use some further improvement, such as the design, materials‘ authenticity, and so on. Ergo, in corresponding to the findings, the suggestions can be given to two parties, the developers and the teachers. The developers are hoped to take the evaluation results into account as the crucial points for future improvement and the teachers are hoped to not solely depend on the coursebook itself, but creatively look for extra materials.

  20. Outer Children Marriages Status After Constitutional Court Decision No: 46/PUU-VII/2010

    Directory of Open Access Journals (Sweden)

    Sri Budi Purwaningsih

    2014-01-01

    Full Text Available The decision of the Constitutional Court of the Republic of Indonesia No.46/PUU-VIII / 2010 dated 17 February 2012, granted the judicial review of Article 43 (1 of Law No. 1 of 1974 on Marriage by deciding that the article should read "Children who are born outside of marriage just had a civil relationship with her mother and her mother's family as well as with men as a father who can be proved based on science and technology and / or evidence, has blood ties according to law, including a civil relationship with his father's family". This Indonesian Constitutional Court's decision bring Juridical consequence that illegitimate children not only have a legal relationship with her mother, but also has a legal relationship with the father (biological and his father's family, as long as it is proven with science and technology. The Constitutional Court's decision is a starting point in the legal protection of illegitimate children, namely the "right alignment" between the illegitimate child with the legitimate son. Illegitimate children have the rights to demand their civil rights toward their father (biological as the same rights obtained by the legitimate son. How To Cite: Purwaningsih, S. (2016. Outer Children Marriages Status After Constitutional Court Decision No: 46/PUU-VII/2010. Rechtsidee, 1(1, 119-130. doi:http://dx.doi.org/10.21070/jihr.v1i1.99

  1. FREQUENCY DEFORMITY SCOLIOSIS AND FLAT FEET IN PUPILS III, V.VII GRADE SCHOOL

    Directory of Open Access Journals (Sweden)

    Dejаn Gojković

    2013-07-01

    Full Text Available Scoliosis is a lateral deviation of the spine or the angular deviation of the normal position of one or more segmenata.Funkcional curve can be fully corrected until the internal structural scoliosis are bone disorders, muscle nerve elements that support the spine, and complete correction is impossible. Static role is reflected in the foot taking kisses body weight through the bones pop and transmission and distribution of weight on the main point of support of the foot and therefore subject to various changes in the normal foot status.Dinamic role is reflected in walking, running and jumping in different forms. Because of this, the percentage of foot disorders is particularly large in the form of lowering the testing we arche.Perform o.š.Pale Pale deformities in scoliosis and flat feet in students III, V, VII grade. Our aim was to verify the extent to which physical education classes take appropriate measures in the detection and removal of poor posture and physical deformities. For testing we used: clinical method for scoliosis, a method for flat feet -Thomson method.

  2. Fast ion loss and radial electric field in Wendelstein VII-Λ stellarator

    International Nuclear Information System (INIS)

    Itoh, K.; Sanuki, H.; Itoh, S.

    1991-10-01

    Theoretical model is developed to determine the radial electric field and the fast ion loss simultaneously in stellarators, and is applied to the Wendelstein VII-A stellarator. The predicted value of the radial electric field is more closer to experiments than the purely neoclassical calculation. The loss rate, which is determined simultaneously, is in the range of experimental observations. The partition of the injection energy by the bulk heating, direct orbit loss and shine through is estimated by using the self consistent electric field profile. The orbit loss become noticeable as the injection energy increases. The influence of the neutral particles is also studied. Neutral particles enhances the negative radial electric field, and reduces the direct orbit loss by the expense of the charge exchange loss. The impact of the increased radial electric field on the neoclassical ion thermal energy loss is compared to the direct loss of fast ions. The reduction of the neoclassical loss is much smaller than the orbit loss. (author)

  3. Mode and sawtooth behaviour during neutral beam injection in the W VII-A stellarator

    International Nuclear Information System (INIS)

    Grieger, G.; Renner, H.; Sapper, J.; Wobig, H.; Dorst, D.; Cattanei, G.; Javel, P.; Rau, F.; Zippe, M.; Jaeckel, H.

    1980-02-01

    The mode behaviour during Neutral Beam Injection in the WENDELSTEIN VII-A stellarator is presented. The analysis is mainly relying on soft X-ray measurements. Two types of discharges were found during Neutral Beam Injection with plasma currents >= 20 kA. The first type is dominated by large, regular and long sawteeth, which are caused by a (m,n) = (1,1) mode. In the second type the sawteeth disappear completely. Later in the discharge a local disruption causes a transition to the first type; this disruption has a (3,2) mode precursor. A new mode (2,2) is found and phase coupled to the (3,2) mode. Even at a high external rotational transform (t 0 = 0.23) a large (2,1) mode is found after the (3,2) mode has caused the local disruption. At slightly lower external rotational transform values major current disruptions may even occur. This is mainly due to the enhanced edge heating by the Neutral Beam Injection. Results of simulations of the mode structures are also presendet. (orig./GG)

  4. Holographic fermions at strong translational symmetry breaking: a Bianchi-VII case study

    Energy Technology Data Exchange (ETDEWEB)

    Bagrov, A. [Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, Nijmegen 6525 AJ (Netherlands); Kaplis, N.; Krikun, A.; Schalm, K.; Zaanen, J. [Institute Lorentz ITP, Leiden University, PO Box 9506, Leiden 2300 RA (Netherlands)

    2016-11-09

    It is presently unknown how strong lattice potentials influence the fermion spectral function of the holographic strange metals predicted by the AdS/CFT correspondence. This embodies a crucial test for the application of holography to condensed matter experiments. We show that for one particular momentum direction this spectrum can be computed for arbitrary strength of the effective translational symmetry breaking potential of the so-called Bianchi-VII geometry employing ordinary differential equations. Deep in the strange metal regime we find rather small changes to the single-fermion response computed by the emergent quantum critical IR, even when the potential becomes relevant in the infra-red. However, in the regime where holographic quasi-particles occur, defining a Fermi surface in the continuum, they acquire a finite lifetime at any finite potential strength. At the transition from irrelevancy to relevancy of the Bianchi potential in the deep infra-red the quasi-particle remnants disappear completely and the fermion spectrum exhibits a purely relaxational behaviour.

  5. Peningkatan Kemampuan Menulis Cerita Pendek Melalui Pendekatan Kontekstual Pada Siswa SMP Kelas VII

    Directory of Open Access Journals (Sweden)

    Jatuh Padmi

    2017-05-01

    The objective of this research was to improve the short story writing ability at grade VII student of one private junior high school in Jakarta of the 2014/2015 Academic Year through contextual approach, both process and outcomes of learning. It was an action research with mix-method research.(qualitative and quantitative. It used Kemmis & Taggart’s action research model  which consists of four stages, namely planning, action, observation, and reflection and held in 3 cycles. The data were collected through short stories written tests, observation, interview, student’s journaling, and documentation. Qualitatf data was analyzed by describing the process of action research and the quality of student’s ability in short stories writing through contextual approach, while qualitative data was analyzed using the percentage of the normal distribution. The results showed an increase in the short stories writing ability through contextual approach ranging from pre-action, cycle 1, cycle 2 and cycle 3 seen from the average score, categorization, and the average score of short stories aspects of assessment.

  6. MT71x: Multi-Temperature Library Based on ENDF/B-VII.1

    Energy Technology Data Exchange (ETDEWEB)

    Conlin, Jeremy Lloyd [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Parsons, Donald Kent [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Gray, Mark Girard [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Lee, Mary Beth [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); White, Morgan Curtis [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-12-16

    The Nuclear Data Team has released a multitemperature transport library, MT71x, based upon ENDF/B-VII.1 with a few modifications as well as additional evaluations for a total of 427 isotope tables. The library was processed using NJOY2012.39 into 23 temperatures. MT71x consists of two sub-libraries; MT71xMG for multigroup energy representation data and MT71xCE for continuous energy representation data. These sub-libraries are suitable for deterministic transport and Monte Carlo transport applications, respectively. The SZAs used are the same for the two sub-libraries; that is, the same SZA can be used for both libraries. This makes comparisons between the two libraries and between deterministic and Monte Carlo codes straightforward. Both the multigroup energy and continuous energy libraries were verified and validated with our checking codes checkmg and checkace (multigroup and continuous energy, respectively) Then an expanded suite of tests was used for additional verification and, finally, verified using an extensive suite of critical benchmark models. We feel that this library is suitable for all calculations and is particularly useful for calculations sensitive to temperature effects.

  7. Physics and Algorithm Enhancements for a Validated MCNP/X Monte Carlo Simulation Tool, Phase VII

    International Nuclear Information System (INIS)

    McKinney, Gregg W.

    2012-01-01

    Currently the US lacks an end-to-end (i.e., source-to-detector) radiation transport simulation code with predictive capability for the broad range of DHS nuclear material detection applications. For example, gaps in the physics, along with inadequate analysis algorithms, make it difficult for Monte Carlo simulations to provide a comprehensive evaluation, design, and optimization of proposed interrogation systems. With the development and implementation of several key physics and algorithm enhancements, along with needed improvements in evaluated data and benchmark measurements, the MCNP/X Monte Carlo codes will provide designers, operators, and systems analysts with a validated tool for developing state-of-the-art active and passive detection systems. This project is currently in its seventh year (Phase VII). This presentation will review thirty enhancements that have been implemented in MCNPX over the last 3 years and were included in the 2011 release of version 2.7.0. These improvements include 12 physics enhancements, 4 source enhancements, 8 tally enhancements, and 6 other enhancements. Examples and results will be provided for each of these features. The presentation will also discuss the eight enhancements that will be migrated into MCNP6 over the upcoming year.

  8. ENDF/B-VII.1 Neutron Cross Section Data Testing with Critical Assembly Benchmarks and Reactor Experiments

    Energy Technology Data Exchange (ETDEWEB)

    Kahler, A. [Los Alamos National Laboratory (LANL); Macfarlane, R E [Los Alamos National Laboratory (LANL); Mosteller, R D [Los Alamos National Laboratory (LANL); Kiedrowski, B C [Los Alamos National Laboratory (LANL); Frankle, S C [Los Alamos National Laboratory (LANL); Chadwick, M. B. [Los Alamos National Laboratory (LANL); Mcknight, R D [Argonne National Laboratory (ANL); Lell, R M [Argonne National Laboratory (ANL); Palmiotti, G [Idaho National Laboratory (INL); Hiruta, h [Idaho National Laboratory (INL); Herman, Micheal W [Brookhaven National Laboratory (BNL); Arcilla, r [Brookhaven National Laboratory (BNL); Mughabghab, S F [Brookhaven National Laboratory (BNL); Sublet, J C [Culham Science Center, Abington, UK; Trkov, A. [Jozef Stefan Institute, Slovenia; Trumbull, T H [Knolls Atomic Power Laboratory; Dunn, Michael E [ORNL

    2011-01-01

    The ENDF/B-VII.1 library is the latest revision to the United States' Evaluated Nuclear Data File (ENDF). The ENDF library is currently in its seventh generation, with ENDF/B-VII.0 being released in 2006. This revision expands upon that library, including the addition of new evaluated files (was 393 neutron files previously, now 423 including replacement of elemental vanadium and zinc evaluations with isotopic evaluations) and extension or updating of many existing neutron data files. Complete details are provided in the companion paper [1]. This paper focuses on how accurately application libraries may be expected to perform in criticality calculations with these data. Continuous energy cross section libraries, suitable for use with the MCNP Monte Carlo transport code, have been generated and applied to a suite of nearly one thousand critical benchmark assemblies defined in the International Criticality Safety Benchmark Evaluation Project's International Handbook of Evaluated Criticality Safety Benchmark Experiments. This suite covers uranium and plutonium fuel systems in a variety of forms such as metallic, oxide or solution, and under a variety of spectral conditions, including unmoderated (i.e., bare), metal reflected and water or other light element reflected. Assembly eigenvalues that were accurately predicted with ENDF/B-VII.0 cross sections such as unrnoderated and uranium reflected (235)U and (239)Pu assemblies, HEU solution systems and LEU oxide lattice systems that mimic commercial PWR configurations continue to be accurately calculated with ENDF/B-VII.1 cross sections, and deficiencies in predicted eigenvalues for assemblies containing selected materials, including titanium, manganese, cadmium and tungsten are greatly reduced. Improvements are also confirmed for selected actinide reaction rates such as (236)U; (238,242)Pu and (241,243)Am capture in fast systems. Other deficiencies, such as the overprediction of Pu solution system critical

  9. ENDF/B-VII.1 Nuclear Data for Science and Technology: Cross Sections, Covariances, Fission Product Yields and Decay Data

    Energy Technology Data Exchange (ETDEWEB)

    Chadwick, M. B. [Los Alamos National Laboratory (LANL); Herman, Micheal W [Brookhaven National Laboratory (BNL); Oblozinsky, Pavel [Brookhaven National Laboratory (BNL); Dunn, Michael E [ORNL; Danon, Y. [Rensselaer Polytechnic Institute (RPI); Kahler, A. [Los Alamos National Laboratory (LANL); Smith, Donald L. [Argonne National Laboratory (ANL); Pritychenko, B [Brookhaven National Laboratory (BNL); Arbanas, Goran [ORNL; Arcilla, r [Brookhaven National Laboratory (BNL); Brewer, R [Los Alamos National Laboratory (LANL); Brown, D A [Brookhaven National Laboratory (BNL); Capote, R. [International Atomic Energy Agency (IAEA); Carlson, A. D. [National Institute of Standards and Technology (NIST); Cho, Y S [Korea Atomic Energy Research Institute; Derrien, Herve [ORNL; Guber, Klaus H [ORNL; Hale, G. M. [Los Alamos National Laboratory (LANL); Hoblit, S [Brookhaven National Laboratory (BNL); Holloway, Shannon T. [Los Alamos National Laboratory (LANL); Johnson, T D [Brookhaven National Laboratory (BNL); Kawano, T. [Los Alamos National Laboratory (LANL); Kiedrowski, B C [Los Alamos National Laboratory (LANL); Kim, H [Korea Atomic Energy Research Institute; Kunieda, S [Los Alamos National Laboratory (LANL); Larson, Nancy M [ORNL; Leal, Luiz C [ORNL; Lestone, J P [Los Alamos National Laboratory (LANL); Little, R C [Los Alamos National Laboratory (LANL); Mccutchan, E A [Brookhaven National Laboratory (BNL); Macfarlane, R E [Los Alamos National Laboratory (LANL); MacInnes, M [Los Alamos National Laboratory (LANL); Matton, C M [Lawrence Livermore National Laboratory (LLNL); Mcknight, R D [Argonne National Laboratory (ANL); Mughabghab, S F [Brookhaven National Laboratory (BNL); Nobre, G P [Brookhaven National Laboratory (BNL); Palmiotti, G [Idaho National Laboratory (INL); Palumbo, A [Brookhaven National Laboratory (BNL); Pigni, Marco T [ORNL; Pronyaev, V. G. [Institute of Physics and Power Engineering (IPPE), Obninsk, Russia; Sayer, Royce O [ORNL; Sonzogni, A A [Brookhaven National Laboratory (BNL); Summers, N C [Lawrence Livermore National Laboratory (LLNL); Talou, P [Los Alamos National Laboratory (LANL); Thompson, I J [Lawrence Livermore National Laboratory (LLNL); Trkov, A. [Jozef Stefan Institute, Slovenia; Vogt, R L [Lawrence Livermore National Laboratory (LLNL); Van der Marck, S S [Nucl Res & Consultancy Grp, Petten, Netherlands; Wallner, A [University of Vienna, Austria; White, M C [Los Alamos National Laboratory (LANL); Wiarda, Dorothea [ORNL; Young, P C [Los Alamos National Laboratory (LANL)

    2011-01-01

    The ENDF/B-VII.1 library is our latest recommended evaluated nuclear data file for use in nuclear science and technology applications, and incorporates advances made in the five years since the release of ENDF/B-VII.0. These advances focus on neutron cross sections, covariances, fission product yields and decay data, and represent work by the US Cross Section Evaluation Working Group (CSEWG) in nuclear data evaluation that utilizes developments in nuclear theory, modeling, simulation, and experiment. The principal advances in the new library are: (1) An increase in the breadth of neutron reaction cross section coverage, extending from 393 nuclides to 423 nuclides; (2) Covariance uncertainty data for 190 of the most important nuclides, as documented in companion papers in this edition; (3) R-matrix analyses of neutron reactions on light nuclei, including isotopes of He; Li, and Be; (4) Resonance parameter analyses at lower energies and statistical high energy reactions for isotopes of Cl; K; Ti, V, Mn, Cr, Ni, Zr and W; (5) Modifications to thermal neutron reactions on fission products (isotopes of Mo, Tc, Rh, Ag, Cs, Nd, Sm, Eu) and neutron absorber materials (Cd, Gd); (6) Improved minor actinide evaluations for isotopes of U, Np, Pu, and Am (we are not making changes to the major actinides (235,238)U and (239)Pu at this point, except for delayed neutron data and covariances, and instead we intend to update them after a further period of research in experiment and theory), and our adoption of JENDL-4.0 evaluations for isotopes of Cm, Bk, Cf, Es; Fm; and some other minor actinides; (7) Fission energy release evaluations; (8) Fission product yield advances for fission-spectrum neutrons and 14 MeV neutrons incident on (239)Pu; and (9) A new decay data sublibrary. Integral validation testing of the ENDF/B-VII.1 library is provided for a variety of quantities: For nuclear criticality, the VII.1 library maintains the generally-good performance seen for VII.0 for a wide

  10. Speciation of Mn(II), Mn(VII) and total manganese in water and food samples by coprecipitation-atomic absorption spectrometry combination

    International Nuclear Information System (INIS)

    Citak, Demirhan; Tuzen, Mustafa; Soylak, Mustafa

    2010-01-01

    A speciation procedure based on the coprecipitation of manganese(II) with zirconium(IV) hydroxide has been developed for the investigation of levels of manganese species. The determination of manganese levels was performed by flame atomic absorption spectrometry (FAAS). Total manganese was determined after the reduction of Mn(VII) to Mn(II) by ascorbic acid. The analytical parameters including pH, amount of zirconium(IV), sample volume, etc., were investigated for the quantitative recoveries of manganese(II). The effects of matrix ions were also examined. The recoveries for manganese(II) were in the range of 95-98%. Preconcentration factor was calculated as 50. The detection limit for the analyte ions based on 3 sigma (n = 21) was 0.75 μg L -1 for Mn(II). The relative standard deviation was found to be lower than 7%. The validation of the presented procedure was performed by analysis of certified reference material having different matrices, NIST SRM 1515 (Apple Leaves) and NIST SRM 1568a (Rice Flour). The procedure was successfully applied to natural waters and food samples.

  11. Contextos cerámicos de los siglos V-VII en Cartagena

    Directory of Open Access Journals (Sweden)

    Ramallo Asensio, Sebastián F.

    1996-12-01

    Full Text Available The excavations realized in the Roman theatre of Cartagena have documented a wide stratigraphie sequence with covers levels from IInd century B.C. to today. The material contexts of Vth to VIIth B.C. are specially interesting because they were associated with considerable removals of the town planning. The construction of a comercial site in the second half of the Vth century, markets and stores, built on a big exedra with portico and 15 divisions in line, represents the total use of the theatre, the structures of which became fossilized, in part, in a new shape. A village of Byzantin age was built over both constructions, characterized with quadrangular rooms which alternates with opened public spaces and irregular streets adjusted to the artificial and inclined topography dependent on the precedent constructions.Las excavaciones realizadas en el teatro romano de Cartagena han documentado una amplia secuencia estratigráfica que abarca desde niveles del siglo II a. de C. hasta nuestros días. Especialmente interesantes son los contextos materiales de los siglos V al VII, asociados a profundas remociones de carácter urbanístico. La construcción en la segunda mitad del siglo V de un complejo comercial, mercado/almacén, estructurado sobre una gran exedra porticada y una serie de 15 compartimentos alineados, representa la amortización total del edificio del teatro cuyas estructuras en parte fosiliza el nuevo conjunto. Encima de ambas construcciones se construyó un barrio de época bizantina caracterizado por habitaciones de forma cuadrangular que alternan con espacios comunes abiertos y calles de trazado irregular adaptadas a la topografía artificial y en pendiente impuesta por las construcciones precedentes.

  12. Considerations on ECFH current drive and bootstrap current for W VII-X

    International Nuclear Information System (INIS)

    Gasparino, U.; Maassberg, H.

    1988-01-01

    Low shear is the characteristic of all proposed Wendelstein VII-X configurations. To avoid low harmonic rational numbers within the rotational transform profile, the current contribution to the rotational transform, Δt a α I/B, should be typically less than 10%. This leads to an upper limit of 50 kA (at B = 2.5 T) for the tolerable net toroidal current. A considerable net toroidal current (bootstrap current) is expected by neoclassical theory in the plateau and the low-collisionality regimes. Both radial transport as well as the bootstrap current densities depend sensitively on the magnetic configuration (see A. Montvai, this workshop). In case of an axisymmetric configuration with dimension and plasma parameters as predicted for the high- regime of WVII-X ( ∼ 5%), this current (∼ 0.5/1 MA) would dominate the rotational transform profile. This requires a reduction of magnitude of the bootstrap current to some % of the value of an equivalent tokamak. This reduction must act on the current profile itself and should not be merely obtained by having two channels of currents of different sign at different radii. Due to the possibility of controlling absorbed power and driven current profiles, electron cyclotron waves are a natural candidate for current profile control. Linear calculations show the possibility to drive a counteracting current with a profile similar to the bootstrap one. For ∼ 5% conditions, however, the optimium current drive efficiency (η ∼ 10 kA per MW) is far too low to make ECF-current drive suitable

  13. Electron cyclotron resonance heating on the W VII A-stellarator

    International Nuclear Information System (INIS)

    Wilhelm, R.; Erckmann, V.; Janzen, G.

    1985-01-01

    Plasma build-up and heating of OH-current free plasmas by ECR-wave irradiation were investigated on the WENDELSTEIN VII-A stellarator using three kinds of wave launching: direct irradiation of the gyrotron modes from the low field side, or advanced wave launching in 0-mode polarization from the low field side, the nonabsorbed fraction being reflected back to the plasma from the high field side in X-mode polarization. An increase of the central electron temperature from 0.7 keV (TE 02 mode) to 1.2 keV (TE 11 , HE 11 mode) was observed which is explained by the narrow and well centred power deposition profiles for TE 11 , HE 11 modes. However, there is only a slight increase of the heating efficiency from 40% to 50%. The reflected X-mode fraction does not contribute to bulk plasma heating via Bernstein wave conversion and absorption as expected. The reason seems to be local absorption of the arising electron Bernstein waves due to a macroscopically turbulent structure around the upper hybrid resonance layer. Correlated with X-mode irradiation direct ion heating was observed (500 eV ion tail), possibly due to low frequency decay waves. In all ECRH experiments a toroidal plasma current was generated due to asymmetrically confined fast electrons. Optimum confinement in the shearless l=2 configuration was achieved at most irrational values of the rotational transform with small toroidal net current. It can be concluded from a numerical 1D-transport analysis that neoclassical electron confinement seems to be dominant in the hot central plasma core

  14. In Vitro Effect of Activated Recombinant Factor VII (rFVIIa) on Coagulation Properties of Human Blood at Hypothermic Temperatures

    Science.gov (United States)

    2007-11-01

    is co- agulopathy, particularly when it is associated with metabolic acidosis and hypothermia, often referred to as the “lethal triad”.3–5 Substantial...that rFVIIa may be able to improve early survival of mas- sively bleeding trauma patients.27 It is also suggested that the correction of acidosis and...ratio and clotting time was measured. Fibrinogen in plasma was also determined based on a clotting assay in which a large excess of bovine thrombin (50

  15. Analysis of the 4d9-(4d86p + 4p54d10) transitions of Sb VII and the strongest transitions of the 4d9-4d84f array of Sb VII and Te VIII

    International Nuclear Information System (INIS)

    Kildiyarova, R.R.; Churilov, S.S.; Joshi, Y.N.; Ryabtsev, A.N.

    1995-01-01

    The spectra of antimony and tellurium were photographed in the 100-200 A region on grazing incidence spectrographs at Moscow, Russia and NIST, U.S.A. laboratories. The 4d 9 -[4d 8 6p + 4p 5 4d 10 ] transition array of Sb VII was analyzed. 31 levels in Sb VII were established. 41 new lines in Sb VII belonging to the 4d 9 -(4p 5 4d 10 + 4d 8 6p) transition array have been classified. Seven lines each in Sb VII and Te VIII belonging to the 4d 9 -4d 8 4f transition array have been classified. Parametric least-squares-fitted calculations involving configuration interaction have been carried out to interpret the spectrum satisfactorily. (orig.)

  16. Magnetic anomaly patterns over crustal blocks of the King Edward VII Peninsula, Marie Byrd Land, West Antarctica

    Directory of Open Access Journals (Sweden)

    M. Spano

    2000-06-01

    Full Text Available Within the framework of the GITARA II project an aeromagnetic survey was performed during the GANOVEXVII expedition (1992/1993 over the King Edward VII Peninsula in northwestern Marie Byrd Land (West Antarctica. This region which may represent the eastern flank of the Ross Sea rift system had previously been explored only at reconnaissance level. New total field and upward continued (10 km magnetic anomaly maps are produced and interpreted here to map and discuss the crustal structure of the Edward VII Peninsula. Tworound-shaped, high-amplitude magnetic anomalies are recognised over the Alexandra Mountains block. The anomalies are difficult to interpret since susceptibility data indicate the prevalence of non-magnetic rocks at the surface. A possible interpretation is that the anomalies are due to Cretaceous mafic intrusives distinct from weakly magnetic Byrd Coast Granite of the adjacent Rockefeller Mountains block. Alternatively the anomalies could be related to buried pluton-sized Devonian Ford Granodiorite intruded by dikes. If Cretaceous in age, the former intrusives revealed from the magnetics could also be responsible for contact metamorphism of the adjacent Alexandra Mountains migmatites. Lower amplitude circular anomalies over the Central Plateau and Prestrud Inlet are likely to be caused by unexposed Devonian Ford Granodiorite which crops out in the Ford Ranges. Elongated high-frequency anomalies of the Sulzberger Bay are similar to those recognised over seismically constrained Cenozoic rift-related volcanics of the Ross Sea. A broad magnetic low over the Sulzberger Ice Shelf may be indicative of a fault bounded graben-like basin with sedimentary infill. Overall recognition of magnetic anomaly patterns and trends reveals segmentation of the Edward VII Peninsula and of the adjacent marine areas in distinct crustal blocks. Faults may separate these blocks and they are interpreted to reflect multiple Cretaceous and maybe Cenozoic crustal

  17. Comparison of student's learning achievement through realistic mathematics education (RME) approach and problem solving approach on grade VII

    Science.gov (United States)

    Ilyas, Muhammad; Salwah

    2017-02-01

    The type of this research was experiment. The purpose of this study was to determine the difference and the quality of student's learning achievement between students who obtained learning through Realistic Mathematics Education (RME) approach and students who obtained learning through problem solving approach. This study was a quasi-experimental research with non-equivalent experiment group design. The population of this study was all students of grade VII in one of junior high school in Palopo, in the second semester of academic year 2015/2016. Two classes were selected purposively as sample of research that was: year VII-5 as many as 28 students were selected as experiment group I and VII-6 as many as 23 students were selected as experiment group II. Treatment that used in the experiment group I was learning by RME Approach, whereas in the experiment group II by problem solving approach. Technique of data collection in this study gave pretest and posttest to students. The analysis used in this research was an analysis of descriptive statistics and analysis of inferential statistics using t-test. Based on the analysis of descriptive statistics, it can be concluded that the average score of students' mathematics learning after taught using problem solving approach was similar to the average results of students' mathematics learning after taught using realistic mathematics education (RME) approach, which are both at the high category. In addition, It can also be concluded that; (1) there was no difference in the results of students' mathematics learning taught using realistic mathematics education (RME) approach and students who taught using problem solving approach, (2) quality of learning achievement of students who received RME approach and problem solving approach learning was same, which was at the high category.

  18. EFEKTIVITAS PENGGUNAAN LINGKUNGAN SEBAGAI SUMBER BELAJAR MATERI IPA POKOK BAHASAN EKOSISTEM PADA KELAS VII SMP N 2 PRINGAPUS KABUPATEN SEMARANG TERHADAP HASIL BELAJAR SISWA

    Directory of Open Access Journals (Sweden)

    miftakhul jannah

    2016-02-01

    Penelitian ini bertujuan untuk mengetahui efektivitas pembelajaran IPA khususnya kelas VII   menggunakan lingkungan langsung   sebagai sumber belajar  terhadap hasil belajar siswa kelas VII  SMP N 2 Pringapus Kabupaten Semarang  pada poko bahasan  materi  ekosistem. Hasil pene- litian ini  merupakan penelitian kuantitatif dengan metode penelitian eks- perimen terpola bentuk posttest control design. Populasi dalam penelitian ini adalah peserta didik kelas VII SMP N 2 Pringapus Semarang, yaitu kelas VII A sebagai kelas eksperimen dan kelas VII C sebagai kelas kontrol. Pen- gumpulan data dalam penelitian ini menggunakan metode tes, observasi dan demonstrasi. Data penelitian yang terkumpul digunakan analisis uji t-test.Berdasarkan hasil t-test, dihasilkan bahwa t hitung = 2,947 dan ttabel  = 1,68 dengan taraf nyata 5% Karena t hitung > ttabel maka data tersebut signifikan. Sedangkan untuk uji hipotesis pihak kanan dibandingkan dengan KKM diperoleh thitung  = 9,2876 dan ttabel  = 1,714 maka penggunaan lingkun- gan sebagai sumber belajar dapat  mencapai  KKM yang  telah ditentukan yaitu 70. Dengan demikian pembelajaran IPA menggunakan lingkungan sebagai sumber belajar efektif terhadap hasil belajar siswa Kelas VII  SMP N 2 Pringapus   Kabupaten   Semarang pada mata pelajaran IPA   pokok bahasan.

  19. The positive expression of genotype VII Newcastle disease virus (Malaysian isolate in Japanese quails (Coturnix coturnix japonica

    Directory of Open Access Journals (Sweden)

    Lizma Felisha Mazlan

    2017-05-01

    Full Text Available Aim: Genotype VII Newcastle disease virus (NDV is the most predominant NDV strains that circulating in Malaysia; thus, this study was aimed to determine the susceptibility of Japanese quails toward genotype VII NDV. Clinical signs, gross pathological lesions of organs, positive detection of virus in organs and cloacal swabs, as well as the expression of the antibody titer, were used as parameters to assess the susceptibility of Japanese quails following infection of genotype VII NDV. Materials and Methods: About 20 quails were divided into three groups (n=8 for Groups A and B; n=4 for the control group. The quails in the Groups A and B were infected via intraocular route with 0.03 ml of 103.5 ELD50 and 107.0 ELD50 of NDV strain IBS 002, respectively, while the control group received 1x phosphate-buffered saline. Cloacal swabs and necropsy were taken on day 7 post-infection for all quails were subjected to one-step reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR for detection of virus and examination for gross pathological lesion, respectively. Blood serums of infected quails were taken on day 10, 14, and 21 post-day infections and were subjected for hemagglutination inhibition (HI assay. Results: Depression and ruffled feathers, trachea rales, leg paralysis, and torticollis were shown in some of the quails in both infected groups. Based on statistical analysis, there was no significant difference (p>0.05 in clinical signs between the infected groups. The results for RT-qPCR were found to be negative for all groups, and no gross pathological lesions of organs observed for quails in both infected groups. Trachea, proventriculus, and cecal tonsil were taken for the detection of NDV by RT-qPCR, and some of the organ samples showed positive detection of virus in both infected groups. HI assay showed an increase in mean titers of antibody across time and between infected groups. Conclusion: In summary, Japanese quails

  20. Fuerzas Militares de Colombia Ejército Nacional VII División : el conflicto armado en las regiones

    OpenAIRE

    Sandoval M., Jairo Martin; Álvarez Bahena, Eyesid; Roldan Villa, Ana María; Consuegra, Claudia Patricia; Restrepo Marín, Janeth del Carmen; Gómez Yepes, William Arvey; Cardona Ángel, Yised; Zuluaga Parodi, David; Parada Contreras, Javier Antonio; López, Diana María; Blanco Mejia, Oscar; Flórez Giraldo, Lina Patricia; Martiínez Berdugo, Nathalia; Díaz Sáenz, María Juliana; Yunda Martínez, Alfonso

    2017-01-01

    El presente documento de investigación es resultado de un ejercicio de investigación de construcción de memoria histórica de la VII División del Ejército Nacional que hace parte de una serie nacional de diez tomos de contexto regional. Este ejercicio es desarrollado con el propósito de identificar y describir el desempeño que las unidades del Ejército Nacional tuvieron en el marco del desarrollo del conflicto armado en la región. El marco temporal e interpretativo que guió la construcción del...