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Sample records for anti-factor xa activity

  1. 体积排阻色谱法测定低分子量肝素抗凝血因子Xa的活性%An assay for anti-factor Xa activity of low molecular weight heparins by high performance liquid size exclusion chromatography

    Institute of Scientific and Technical Information of China (English)

    张倩倩; 康经武

    2013-01-01

    发展了一种基于体积排阻色谱测定低分子量肝素(LMWH)抗凝血活性的方法.利用肝素与抗凝血酶Ⅲ(ATⅢ)结合后可增强ATⅢ对凝血因子Xa (FXa)抑制作用的原理,通过测定加入LMWH后FXa水解其生色底物产生对硝基苯胺(pNA)这一反应的抑制程度确定LMWH的活性.首先将含有一定浓度LMWH的缓冲溶液与ATⅢ溶液混合,然后依次加入FXa和生色底物,分别孵育一段时间.底物被FXa水解,产生游离的pNA.体积排阻色谱可将小分子产物pNA与其他大分子分离开,因而可以在pNA的最大吸收波长下得到高灵敏度的测定,并且不再受其他成分的干扰.该方法重复性好,灵敏度高,极大地减少了样品的消耗量,降低了成本,并且还可进行各种复杂样品(如血浆)中LMWH抗FXa活性的监测.%The "gold standard" assay for monitoring low molecular weight heparins (LMWHs) activity is the chromogenic-based anti-factor Xa assay.The methodology of an anti-factor Xa assay is that LMWH is added to a known amount of excess factor Xa and excess antithrombin.It will bind to antithrombin and form a triplet complex with factor Xa,inhibiting the activity of factor Xa.However,the residual factor Xa can still hydrolyze chromogenic peptide substrate,releasing the chromophore for photometric detection.The absorbance is inversely proportional to the amount of heparin/LMWH.The results are given in anticoagulant concentration in units/ mL of anti-factor Xa,such that high values indicate high levels of anticoagulation and low values indicate low levels of anticoagulation.Herein,a novel assay method for anti-FXa activity of LMWHs using high performance liquid size exclusion chromatography (SEC) is reported,in which antithrombin m (AT m) was diluted by the buffer solution contained LMWHs.Subsequently,exogenous FXa and p-nitroaniline coupled peptide substrate were added and incubated for a period,separately.The resulting mixture was separated based on size by SEC

  2. Development of a fluorescent anti-factor Xa assay to monitor unfractionated and low molecular weight heparins.

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    Harris, Leanne F; Castro-López, Vanessa; Hammadi, Nissrin; O'Donnell, James S; Killard, Anthony J

    2010-06-15

    Fluorogenic assays have many potential advantages over traditional clot-based and chromogenic assays such as the absence of interference from a range of factor deficiencies as well as offering the possibility of assays in platelet rich plasma or whole blood. A fluorogenic anti-factor Xa (anti-FXa) assay has been developed for the determination of unfractionated heparin (UFH), low molecular weight heparins (LMWHs), namely enoxaparin and tinzaparin, and the synthetic heparinoid danaparoid, in commercial human pooled plasma. The assay was based on the complexation of heparin-spiked plasmas with exogenous FXa at a concentration of 4nM in the presence of 0.9microM of the fluorogenic substrate methylsulfonyl-D-cyclohexylalanyl-glycyl-arginine-7-amino-4-methylcoumarin acetate (Pefafluor FXa). Pooled plasma samples were spiked with concentrations of anticoagulants in the range 0-1.6U/ml. The assay was capable of the measurement of UFH and danaparoid in the range 0-1U/ml, and enoxaparin and tinzaparin in the range 0-0.8 and 0-0.6U/ml, respectively. Correlation coefficients generated by linear regression of the log/lin data analysis were between 0.93 and 0.96 for the anticoagulants tested. Assay percentage coefficients of variation were typically below 7%. PMID:20441964

  3. Monitoring low molecular weight heparins at therapeutic levels: dose-responses of, and correlations and differences between aPTT, anti-factor Xa and thrombin generation assays.

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    Owain Thomas

    Full Text Available Low molecular weight heparins (LMWH's are used to prevent and treat thrombosis. Tests for monitoring LMWH's include anti-factor Xa (anti-FXa, activated partial thromboplastin time (aPTT and thrombin generation. Anti-FXa is the current gold standard despite LMWH's varying affinities for FXa and thrombin.To examine the effects of two different LMWH's on the results of 4 different aPTT-tests, anti-FXa activity and thrombin generation and to assess the tests' concordance.Enoxaparin and tinzaparin were added ex-vivo in concentrations of 0.0, 0.5, 1.0 and 1.5 anti-FXa international units (IU/mL, to blood from 10 volunteers. aPTT was measured using two whole blood methods (Free oscillation rheometry (FOR and Hemochron Jr (HCJ and an optical plasma method using two different reagents (ActinFSL and PTT-Automat. Anti-FXa activity was quantified using a chromogenic assay. Thrombin generation (Endogenous Thrombin Potential, ETP was measured on a Ceveron Alpha instrument using the TGA RB and more tissue-factor rich TGA RC reagents.Methods' mean aPTT at 1.0 IU/mL LMWH varied between 54s (SD 11 and 69s (SD 14 for enoxaparin and between 101s (SD 21 and 140s (SD 28 for tinzaparin. ActinFSL gave significantly shorter aPTT results. aPTT and anti-FXa generally correlated well. ETP as measured with the TGA RC reagent but not the TGA RB reagent showed an inverse exponential relationship to the concentration of LMWH. The HCJ-aPTT results had the weakest correlation to anti-FXa and thrombin generation (Rs0.62-0.87, whereas the other aPTT methods had similar correlation coefficients (Rs0.80-0.92.aPTT displays a linear dose-response to LMWH. There is variation between aPTT assays. Tinzaparin increases aPTT and decreases thrombin generation more than enoxaparin at any given level of anti-FXa activity, casting doubt on anti-FXa's present gold standard status. Thrombin generation with tissue factor-rich activator is a promising method for monitoring LMWH's.

  4. Peculiaridades da terapia trombolítica na síndrome nefrótica pediátrica: monitorização do fator anti-Xa Particularities of thrombolytic therapy in pediatric nephrotic syndrome: anti-factor Xa monitoring

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    Patrícia Zambi Meirelles

    2008-06-01

    respiratory discomfort. Pulmonary ventilation/perfusion cintilography scan demonstrated high probability of PTE and the doppler ultrasonography showed obstruction of the left internal jugular vein. Oxygen support as well as enoxaparin, at a dose of 2mg/kg/day, were prescribed. Six days later, the patient developed transitory cerebrovascular symptoms without alterations in the cranial CT. The serum anti-Xa factor level was lower than the therapeutic range and enoxaparin was increased to 3mg/kg/day. The edema and the pulmonary symptoms improved and the boy was discharged at the 33rd day of stay. COMMENTS: Although PTE is rare in children, nephrotic syndrome is a prothrombotic condition amenable to this complication. LMWH can be considered for treatment and for secondary prophylaxis of PTE. Anti-factor Xa serum level monitoring is necessary to adjust LMWH dosage and to promote an effective and safe treatment.

  5. A novel prothrombin time assay for assessing the anticoagulant activity of oral factor Xa inhibitors.

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    Barrett, Yu Chen; Wang, Zhaoqing; Knabb, Robert M

    2013-09-01

    Conventional prothrombin time (PT) assays have limited sensitivity and dynamic range in monitoring the anticoagulant activity of direct factor Xa inhibitors. Hence, new assays are needed. We modified a PT assay by adding calcium chloride (CaCl2) to the thromboplastin reagent to increase assay dynamic range and improve sensitivity. Effects of calcium and sodium ion concentrations, and sample handling, were evaluated to optimize assay performance. Increasing concentrations of calcium ions produced progressive increases in PT across the factor Xa inhibitor concentrations of 0 to 2500 nmol/L for razaxaban and apixaban. The greatest effect was seen when the thromboplastin reagent was diluted 1:2.25 with 100 mmol/L CaCl2 (thus selected for routine use). The optimized assay showed an interassay precision of 1.5 to 9.3 percentage coefficient of variation (%CV) for razaxaban and 3.1 to 4.6 %CV for apixaban. We conclude that the modified PT assay is likely to be suitable as a pharmacodynamic marker for activity at therapeutic concentrations of factor Xa inhibitors.

  6. Clinical Scenarios for Discordant Anti-Xa

    OpenAIRE

    Jesus Vera-Aguilera; Hindi Yousef; Diego Beltran-Melgarejo; Teng Hugh Teng; Ramos Jan; Mary Mok; Carlos Vera-Aguilera; Eduardo Moreno-Aguilera

    2016-01-01

    Anti-Xa test measures the activity of heparin against the activity of activated coagulation factor X; significant variability of anti-Xa levels in common clinical scenarios has been observed. Objective. To review the most common clinical settings in which anti-Xa results can be bias. Evidence Review. Guidelines and current literature search: we used PubMed, Medline, Embase, and MEDION, from 2000 to October 2013. Results. Anti-Xa test is widely used; however the assay underestimates heparin co...

  7. Hysteresis-like binding of coagulation factors X/Xa to procoagulant activated platelets and phospholipids results from multistep association and membrane-dependent multimerization.

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    Podoplelova, Nadezhda A; Sveshnikova, Anastasia N; Kurasawa, James H; Sarafanov, Andrey G; Chambost, Herve; Vasil'ev, Sergey A; Demina, Irina A; Ataullakhanov, Fazly I; Alessi, Marie-Christine; Panteleev, Mikhail A

    2016-06-01

    Binding of coagulation factors X (fX) and Xa (fXa) to activated platelets is required for the formation of membrane-dependent enzymatic complexes of intrinsic tenase and prothrombinase. We carried out an in-depth characterization of fX/fXa binding to phospholipids and gel-filtered, thrombin-activated platelets. Flow cytometry, surface plasmon resonance, and computational modeling were used to investigate interactions of fX/fXa with the membranes. Confocal microscopy was employed to study fXa binding to platelet thrombi formed in flowing whole blood under arterial conditions. Binding of fX/fXa to either vesicles or procoagulant platelets did not follow a traditional one-step reversible binding model. Their dissociation was a two-step process resulting in a plateau that was up to 10-fold greater than the saturation value observed in the association experiments. Computational modeling and experimental evidence suggested that this was caused by a combination of two-step association (mainly for fX) and multimerization on the membrane (mainly for fXa). Importantly, fX formed multimers with fXa, thereby improving its retention. The same binding/dissociation hysteresis was observed for annexin V known to form trimers on the membranes. Experiments with platelets from gray syndrome patients showed that alpha-granular factor Va provided an additional high-affinity binding site for fXa that did not affect the hysteresis. Confocal microscopy observation of fXa binding to platelet thrombi in a flow chamber and its wash-out confirmed that this phenomenon persisted under physiologically relevant conditions. This suggests its possible role of "locking" coagulation factors on the membrane and preventing their inhibition in plasma and removal from thrombi by flow.

  8. Daboxin P, a Major Phospholipase A2 Enzyme from the Indian Daboia russelii russelii Venom Targets Factor X and Factor Xa for Its Anticoagulant Activity

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    Iyer, Janaki Krishnamurthy; Shih, Norrapat; Majumder, Munmi; Mattaparthi, Venkata Satish Kumar; Mukhopadhyay, Rupak; Doley, Robin

    2016-01-01

    In the present study a major protein has been purified from the venom of Indian Daboia russelii russelii using gel filtration, ion exchange and Rp-HPLC techniques. The purified protein, named daboxin P accounts for ~24% of the total protein of the crude venom and has a molecular mass of 13.597 kDa. It exhibits strong anticoagulant and phospholipase A2 activity but is devoid of any cytotoxic effect on the tested normal or cancerous cell lines. Its primary structure was deduced by N-terminal sequencing and chemical cleavage using Edman degradation and tandem mass spectrometry. It is composed of 121 amino acids with 14 cysteine residues and catalytically active His48 -Asp49 pair. The secondary structure of daboxin P constitutes 42.73% of α-helix and 12.36% of β-sheet. It is found to be stable at acidic (pH 3.0) and neutral pH (pH 7.0) and has a Tm value of 71.59 ± 0.46°C. Daboxin P exhibits anticoagulant effect under in-vitro and in-vivo conditions. It does not inhibit the catalytic activity of the serine proteases but inhibits the activation of factor X to factor Xa by the tenase complexes both in the presence and absence of phospholipids. It also inhibits the tenase complexes when active site residue (His48) was alkylated suggesting its non-enzymatic mode of anticoagulant activity. Moreover, it also inhibits prothrombinase complex when pre-incubated with factor Xa prior to factor Va addition. Fluorescence emission spectroscopy and affinity chromatography suggest the probable interaction of daboxin P with factor X and factor Xa. Molecular docking analysis reveals the interaction of the Ca+2 binding loop; helix C; anticoagulant region and C-terminal region of daboxin P with the heavy chain of factor Xa. This is the first report of a phospholipase A2 enzyme from Indian viper venom which targets both factor X and factor Xa for its anticoagulant activity. PMID:27089306

  9. Daboxin P, a Major Phospholipase A2 Enzyme from the Indian Daboia russelii russelii Venom Targets Factor X and Factor Xa for Its Anticoagulant Activity.

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    Maitreyee Sharma

    Full Text Available In the present study a major protein has been purified from the venom of Indian Daboia russelii russelii using gel filtration, ion exchange and Rp-HPLC techniques. The purified protein, named daboxin P accounts for ~24% of the total protein of the crude venom and has a molecular mass of 13.597 kDa. It exhibits strong anticoagulant and phospholipase A2 activity but is devoid of any cytotoxic effect on the tested normal or cancerous cell lines. Its primary structure was deduced by N-terminal sequencing and chemical cleavage using Edman degradation and tandem mass spectrometry. It is composed of 121 amino acids with 14 cysteine residues and catalytically active His48 -Asp49 pair. The secondary structure of daboxin P constitutes 42.73% of α-helix and 12.36% of β-sheet. It is found to be stable at acidic (pH 3.0 and neutral pH (pH 7.0 and has a Tm value of 71.59 ± 0.46°C. Daboxin P exhibits anticoagulant effect under in-vitro and in-vivo conditions. It does not inhibit the catalytic activity of the serine proteases but inhibits the activation of factor X to factor Xa by the tenase complexes both in the presence and absence of phospholipids. It also inhibits the tenase complexes when active site residue (His48 was alkylated suggesting its non-enzymatic mode of anticoagulant activity. Moreover, it also inhibits prothrombinase complex when pre-incubated with factor Xa prior to factor Va addition. Fluorescence emission spectroscopy and affinity chromatography suggest the probable interaction of daboxin P with factor X and factor Xa. Molecular docking analysis reveals the interaction of the Ca+2 binding loop; helix C; anticoagulant region and C-terminal region of daboxin P with the heavy chain of factor Xa. This is the first report of a phospholipase A2 enzyme from Indian viper venom which targets both factor X and factor Xa for its anticoagulant activity.

  10. Inhibition of the alternative complement activation pathway in traumatic brain injury by a monoclonal anti-factor B antibody: a randomized placebo-controlled study in mice

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    Holers V Michael

    2007-05-01

    Full Text Available Abstract Background The posttraumatic response to traumatic brain injury (TBI is characterized, in part, by activation of the innate immune response, including the complement system. We have recently shown that mice devoid of a functional alternative pathway of complement activation (factor B-/- mice are protected from complement-mediated neuroinflammation and neuropathology after TBI. In the present study, we extrapolated this knowledge from studies in genetically engineered mice to a pharmacological approach using a monoclonal anti-factor B antibody. This neutralizing antibody represents a specific and potent inhibitor of the alternative complement pathway in mice. Methods A focal trauma was applied to the left hemisphere of C57BL/6 mice (n = 89 using a standardized electric weight-drop model. Animals were randomly assigned to two treatment groups: (1 Systemic injection of 1 mg monoclonal anti-factor B antibody (mAb 1379 in 400 μl phosphate-buffered saline (PBS at 1 hour and 24 hours after trauma; (2 Systemic injection of vehicle only (400 μl PBS, as placebo control, at identical time-points after trauma. Sham-operated and untreated mice served as additional negative controls. Evaluation of neurological scores and analysis of brain tissue specimens and serum samples was performed at defined time-points for up to 1 week. Complement activation in serum was assessed by zymosan assay and by murine C5a ELISA. Brain samples were analyzed by immunohistochemistry, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL histochemistry, and real-time RT-PCR. Results The mAb 1379 leads to a significant inhibition of alternative pathway complement activity and to significantly attenuated C5a levels in serum, as compared to head-injured placebo-treated control mice. TBI induced histomorphological signs of neuroinflammation and neuronal apoptosis in the injured brain hemisphere of placebo-treated control mice for up to 7 days. In contrast, the

  11. Clinical Scenarios for Discordant Anti-Xa

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    Vera-Aguilera, Jesus; Yousef, Hindi; Beltran-Melgarejo, Diego; Teng, Teng Hugh; Jan, Ramos; Mok, Mary; Vera-Aguilera, Carlos; Moreno-Aguilera, Eduardo

    2016-01-01

    Anti-Xa test measures the activity of heparin against the activity of activated coagulation factor X; significant variability of anti-Xa levels in common clinical scenarios has been observed. Objective. To review the most common clinical settings in which anti-Xa results can be bias. Evidence Review. Guidelines and current literature search: we used PubMed, Medline, Embase, and MEDION, from 2000 to October 2013. Results. Anti-Xa test is widely used; however the assay underestimates heparin concentration in the presence of significant AT deficiency, pregnancy, end stage renal disease, and postthrombolysis and in patients with hyperbilirubinemia; limited published data evaluating the safety and effectiveness of anti-Xa assays for managing UH therapy is available. Conclusions and Relevance. To our knowledge this is the first paper that summarizes the most common causes in which this assay can be affected, several “day to day” clinical scenarios can modify the outcomes, and we concur that these rarely recognized scenarios can be affected by negative outcomes in the daily practice. PMID:27293440

  12. Clinical Scenarios for Discordant Anti-Xa

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    Jesus Vera-Aguilera

    2016-01-01

    Full Text Available Anti-Xa test measures the activity of heparin against the activity of activated coagulation factor X; significant variability of anti-Xa levels in common clinical scenarios has been observed. Objective. To review the most common clinical settings in which anti-Xa results can be bias. Evidence Review. Guidelines and current literature search: we used PubMed, Medline, Embase, and MEDION, from 2000 to October 2013. Results. Anti-Xa test is widely used; however the assay underestimates heparin concentration in the presence of significant AT deficiency, pregnancy, end stage renal disease, and postthrombolysis and in patients with hyperbilirubinemia; limited published data evaluating the safety and effectiveness of anti-Xa assays for managing UH therapy is available. Conclusions and Relevance. To our knowledge this is the first paper that summarizes the most common causes in which this assay can be affected, several “day to day” clinical scenarios can modify the outcomes, and we concur that these rarely recognized scenarios can be affected by negative outcomes in the daily practice.

  13. Lyso-Sulfatide Binds Factor Xa and Inhibits Thrombin Generation by the Prothrombinase Complex.

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    Subramanian Yegneswaran

    Full Text Available Blood coagulation reactions are strongly influenced by phospholipids, but little is known about the influence of sphingolipids on coagulation mechanisms. Lysosulfatide (lyso-SF (sulfogalactosyl sphingosine prolonged factor Xa (fXa 1-stage plasma clotting assays, showing it had robust anticoagulant activity. In studies using purified clotting factors, lyso-SF inhibited >90% of prothrombin (II activation for reaction mixtures containing fXa/factor Va (fVa/II, and also inhibited II activation generation by fXa/ phospholipids and by Gla-domainless-fXa/fVa/phospholipids. When lyso-SF analogs were tested, results showed that N-acetyl-sulfatide was not anticoagulant, implying that the free amine group was essential for the anticoagulant effects of lyso-SF. Lyso-SF did not inhibit fXa enzymatic hydrolysis of small peptide substrates, showing it did not directly inhibit the fXa activity. In surface plasmon resonance studies, lyso-SF bound to immobilized inactivated fXa as well as inactivated Gla-domainless-fXa. Confirming this lyso-SF:fXa interaction, fluorescence studies showed that fluorescently-labeled-fXa in solution bound to lyso-SF. Thus, lyso-SF is an anticoagulant lipid that inhibits fXa when this enzyme is bound to either phospholipids or to fVa. Mechanisms for inhibition of procoagulant activity are likely to involve lyso-SF binding to fXa domain(s that are distinct from the fXa Gla domain. This suggests that certain sphingolipids, including lyso-SF and some of its analogs, may down-regulate fXa activity without inhibiting the enzyme's active site or binding to the fXa Gla domain.

  14. Complement inhibitory and anticoagulant activities of fractionated heparins

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    Hennink, W.E.; Klerx, J.P.A.M.; Dijk, H. van; Feijen, J.

    1984-01-01

    Almost monodisperse heparin fractions (w/n < 1.1) were obtained by gel filtration of a commercial heparin. These fractions were assayed for anticoagulant activity (thrombin times and APTT), chromogenic anti-factor Xa activity, inhibitory activity for the human classical complement pathway, carboxyl

  15. Basis for the Specificity and Activation of the Serpin Protein Z-dependent Proteinase Inhibitor (ZPI) as an Inhibitor of Membrane-associated Factor Xa

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Xin; Dementiev, Alexey; Olson, Steven T.; Gettins, Peter G.W. (UIC)

    2012-12-13

    The serpin ZPI is a protein Z (PZ)-dependent specific inhibitor of membrane-associated factor Xa (fXa) despite having an unfavorable P1 Tyr. PZ accelerates the inhibition reaction {approx}2000-fold in the presence of phospholipid and Ca{sup 2+}. To elucidate the role of PZ, we determined the x-ray structure of Gla-domainless PZ (PZ{sub {Delta}GD}) complexed with protein Z-dependent proteinase inhibitor (ZPI). The PZ pseudocatalytic domain bound ZPI at a novel site through ionic and polar interactions. Mutation of four ZPI contact residues eliminated PZ binding and membrane-dependent PZ acceleration of fXa inhibition. Modeling of the ternary Michaelis complex implicated ZPI residues Glu-313 and Glu-383 in fXa binding. Mutagenesis established that only Glu-313 is important, contributing {approx}5-10-fold to rate acceleration of fXa and fXIa inhibition. Limited conformational change in ZPI resulted from PZ binding, which contributed only {approx}2-fold to rate enhancement. Instead, template bridging from membrane association, together with previously demonstrated interaction of the fXa and ZPI Gla domains, resulted in an additional {approx}1000-fold rate enhancement. To understand why ZPI has P1 tyrosine, we examined a P1 Arg variant. This reacted at a diffusion-limited rate with fXa, even without PZ, and predominantly as substrate, reflecting both rapid acylation and deacylation. P1 tyrosine thus ensures that reaction with fXa or most other arginine-specific proteinases is insignificant unless PZ binds and localizes ZPI and fXa on the membrane, where the combined effects of Gla-Gla interaction, template bridging, and interaction of fXa with Glu-313 overcome the unfavorability of P1 Tyr and ensure a high rate of reaction as an inhibitor.

  16. Effects of Water Soluble Phosphotidylserine on Bovine Factor Xa: Functional and Structural Changes Plus Dimerization

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    Majumder, Rinku; Wang, Jianfang; Lentz, Barry R.

    2003-01-01

    Previous work has shown that two molecules of a soluble form of phosphatidylserine, C6PS, bind to human and bovine factor Xa. Activity measurements along with the fluorescence of active-site-labeled human factor Xa showed that two linked sites specifically regulate the active site conformation and proteolytic activity of the human enzyme. These results imply, but cannot demonstrate, a C6PS-induced factor Xa conformational change. The purpose of this paper is to extend these observations to bo...

  17. Expressional and Biochemical Characterization of Rice Disease Resistance Gene Xa3/Xa26 Family

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    Songjie Xu; Yinglong Cao; Xianghua Li; Shiping Wang

    2007-01-01

    The rice (Oryza sativa L.) Xa3/Xa26 gene, conferring race-specific resistance to bacterial blight disease and encoding a leucine-rich repeat (LRR) receptor kinase-like protein, belongs to a multigene family consisting of tandem clustered homologous genes, colocalizing with several uncharacterized genes for resistance to bacterial blight or fungal blast. To provide more information on the expressional and biochemical characteristics of the Xa3/Xa26 family, we analyzed the family members. Four Xa3/Xa26 family members in the indica rice variety Teqing, which carries a bacterial blight resistance gene with a chromosomal location tightly linked to Xa3/Xa26, and five Xa3/Xa26 family members in the japonica rice variety Nipponbare, which carries at least one uncharacterized blast resistance gene, were constitutively expressed in leaf tissue. The result suggests that some of the family members may be candidates of these uncharacterized resistance genes. At least five putative N-glycosylation sites in the LRR domain of XA3/XA26 protein are not glycosylated. The XA3/XA26 and its family members MRKa and MRKc all possess the consensus sequences of paired cysteines, which putatively function in dimerization of the receptor proteins for signal transduction, immediately before the first LRR and immediately after the last LRR. However, no homo-dimer between the XA3/XA26 molecules or hetero-dimer between XA3/XA26 and MRKa or MRKc were formed, indicating that XA3/XA26 protein might function either as a monomer or a hetero-dimer formed with other protein outside of the XA3/XA26 family. These results provide valuable information for further extensive investigation into this multiple protein family.

  18. Evaluation of Factor Xa-Specific Chromogenic Substrate Assays and the Determination of Pharmacokinetics of Fondaparinux.

    Science.gov (United States)

    Yuri, Maiko; Tabe, Yoko; Tsuchiya, Koji; Sadatsuki, Ryo; Aoki, Jun; Horii, Takashi; Iba, Toshiaki; Ohsaka, Akimichi

    2016-07-01

    Fondaparinux (FPX), a synthesized factor Xa inhibitor, is one of the most popular anticoagulants for the prevention of postoperative venous thromboembolism (VTE). Although routine monitoring is not required, the bleeding adverse events cannot be neglected, and the measurement of anti-Xa activity is expected to be monitored. The primary purpose of this study is to evaluate the performances of 2 chromogenic assays for the detection of anti-Xa activity. Furthermore, the pharmacokinetics of FPX was examined using chromogenic assays. Anti-Xa activity was measured using 2 FPX-based chromogenic substrates (S2222 and STA-Liquid Anti-Xa). The reproducibility, detection limits, linearity, and correlations between the substrates were examined using normal plasma doped with low and high concentrations of FPX formulation. In addition, anti-Xa activity in 235 clinical samples from 164 cases treated was measured, and the pharmacokinetics of FPX was evaluated. Both of the tested substrates were capable of accurately measuring the anti-Xa activity of FPX, with a lower limit of 0.05 μg/mL and a coefficient of variation of less than 10%. The repeated administration of FPX induced a gradual but significant increase in the anti-Xa activity, which was negatively correlated with body weight and estimated glomerular filtration rate. No significant correlation between the anti-Xa activity and the occurrence of postoperative VTE or bleeding event was observed. Anti-Xa activity can be successfully determined using 2 chromogenic assays and automated biochemical analyzers. The clinical significance of anti-Xa activity monitoring should be examined in the future study. PMID:26177660

  19. [Roles of coagulation pathway and factor Xa in chronic kidney disease (CKD)].

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    Ono, Takahiko

    2012-01-01

    Considering that fibrin deposition is observed in glomerulonephritis as well as in diabetic nephropathy, we performed studies to clarify the roles of the coagulation pathway and the active type of coagulation factor X (factor Xa) in the development of chronic kidney disease (CKD) using animal models. Factor Xa activates various cell types through protease-activated receptor 2 (PAR2). Several in vitro studies have demonstrated that PAR2 can mediate factor Xa signaling, but not thrombin signaling. Coagulation processes proceed together with the extracellular matrix (ECM) accumulation through factor V expression in rat Thy-1 nephritis. DX-9065a, a factor Xa inhibitor, suppresses this type of glomerulonephritis. The factor Xa inhibitor danaparoid ameliorated proteinuria, cellular proliferation, and fibrin deposition in lipopolysaccharide (LPS)-triggered activation of High IgA (HIGA) strain of ddY mice. Another factor Xa inhibitor, fondaparinux, suppressed urinary protein, glomerular hypertrophy, and connective tissue growth factor (CTGF), and ECM protein deposition together with angiogenesis in diabetic db/db mice. Finally, in the model of peritoneal fibrosis, fondaparinux treatment decreased the thickness of submesothelial fibrotic tissue and angiogenesis. In consideration of the results to potential human therapy, factor Xa regulation may be promising for the treatment of the aggravation in glomerulonephritis and of the early phase of diabetic nephropathy. In the near future, novel factor Xa inhibitors with the characteristics of oral administration and biliary elimination may appear in the clinical use for treatment of cardiovascular diseases. PMID:22465921

  20. Evaluation of a Heparin-Calibrated Antifactor Xa Assay for Measuring the Anticoagulant Effect of Oral Direct Xa Inhibitors.

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    Beyer, Jacob; Trujillo, Toby; Fisher, Sheila; Ko, Ann; Lind, Stuart E; Kiser, Tyree H

    2016-07-01

    The introduction of oral direct anti-Xa anticoagulants apixaban and rivaroxaban has significantly impacted the treatment and prevention of thromboembolic disease. Clinical scenarios exist in which a quantitative assessment for degree of anticoagulation due to these agents would aid management. The purpose of this work was to evaluate the chromogenic antifactor Xa assay calibrated with heparin standards at our institution for assessment of intensity of anticoagulation with rivaroxaban or apixaban in addition to its current use for unfractionated heparin or low-molecular-weight heparin. We also aimed to propose expected steady state peak and trough antifactor Xa activities for these agents based upon dosing regimens approved for nonvalvular atrial fibrillation. Antifactor Xa activity correlated very strongly with apixaban and rivaroxaban concentration in both spiked samples and treated patient plasma samples (r (2) = .99, P < .001). This correlation was observed over a broad range (20-500 ng/mL) of drug concentrations, as sample dilution with pooled normal plasma significantly extended the range of quantitative assessment. Based on drug concentrations previously published in pharmacokinetic studies, the expected steady state peak and trough antifactor Xa activity ranges for apixaban are 1.80 to 2.20 IU/mL and 0.70 to 1.10 IU/mL, respectively. For rivaroxaban, these ranges are 3.80 to 6.20 IU/mL and 0.60 to 1.00 IU/mL, respectively. In conclusion, our findings demonstrate that heparin-calibrated antifactor Xa activity correlates strongly with apixaban and rivaroxaban concentration. The dilution of samples allowed for this correlation to be extended over the majority of on-therapy drug concentrations. PMID:26842561

  1. Blood coagulation factor Xa as an emerging drug target

    NARCIS (Netherlands)

    K. Borensztajn; C.A. Spek

    2011-01-01

    Introduction: Factor (F) Xa is well-known as an important player in the coagulation cascade responsible for thrombin generation. More recently, FXa emerged as an essential player in cell biology via activation of proteaseactivated receptors (PAR)-1 and -2. This pleiotropic role of FXa forms the basi

  2. Rice XB15, a protein phosphatase 2C, negatively regulates cell death and XA21-mediated innate immunity.

    Directory of Open Access Journals (Sweden)

    Chang-Jin Park

    2008-09-01

    Full Text Available Perception of extracellular signals by cell surface receptors is of central importance to eukaryotic development and immunity. Kinases that are associated with the receptors or are part of the receptors themselves modulate signaling through phosphorylation events. The rice (Oryza sativa L. XA21 receptor kinase is a key recognition and signaling determinant in the innate immune response. A yeast two-hybrid screen using the intracellular portion of XA21, including the juxtamembrane (JM and kinase domain as bait, identified a protein phosphatase 2C (PP2C, called XA21 binding protein 15 (XB15. The interaction of XA21 and XB15 was confirmed in vitro and in vivo by glutathione-S-transferase (GST pull-down and co-immunoprecipitation assays, respectively. XB15 fusion proteins purified from Escherichia coli and from transgenic rice carry PP2C activity. Autophosphorylated XA21 can be dephosphorylated by XB15 in a temporal- and dosage-dependent manner. A serine residue in the XA21 JM domain is required for XB15 binding. Xb15 mutants display a severe cell death phenotype, induction of pathogenesis-related genes, and enhanced XA21-mediated resistance. Overexpression of Xb15 in an XA21 rice line compromises resistance to the bacterial pathogen Xanthomonas oryzae pv. oryzae. These results demonstrate that Xb15 encodes a PP2C that negatively regulates the XA21-mediated innate immune response.

  3. Anti Xa monitoring during treatment with low molecular weight heparin or danaparoid: inter-assay variability.

    Science.gov (United States)

    Kitchen, S; Iampietro, R; Woolley, A M; Preston, F E

    1999-10-01

    If laboratory monitoring of low molecular weight heparin (LMWH) therapy is required the test of choice is the anti Xa activity assay. The relationship between anti Xa results obtained using different techniques is unknown. The aim of the present study was to compare anti Xa results obtained with eight different commercially available anti Xa activity assays (five chromogenic and three clotting based assays) in samples from patients receiving either therapeutic or prophylactic LMWH (enoxaparin or dalteparin) or danaparoid. We have demonstrated that highly significant differences exist between results obtained using different techniques. The mean anti Xa activity in patients receiving treatment or prophylaxis with enoxaparin ranged from 0.28 to 0.64 iu/ml. A similar relationship was present in samples from patients treated with dalteparin, mean anti Xa results ranging from 0.43 to 0.69 iu/ml. The Heptest clotting assay as used here in combination with the Automated Coagulation Laboratory instrument, was associated with lower results than other clotting or chromogenic techniques. In patients receiving danaparoid for heparin induced thrombocytopaenia (HIT) mean results with three clotting based assays were 0.30 to 0.36 u/ml, compared to mean results of 0.47 to 0.65 u/ml for chromogenic assays. Our data clearly indicate that the selection of anti Xa assay method could influence patient management since the dose required to achieve the therapeutic range would differ according to the assay employed. This is particularly important since the frequency of haemorrhagic side effects has been shown by others to be dose dependent, irrespective of the concomitant anti Xa activity results. In danaparoid therapy the clotting assays studied here should not be employed for monitoring without a modified target range, unless it can be demonstrated that the higher doses required to achieve the therapeutic range are safe. PMID:10544915

  4. Structure-guided creation of AcAP5-derived and platelet targeted factor Xa inhibitors.

    Science.gov (United States)

    Zhu, Yuanjun; Lin, Yuan; Liu, Aihua; Shui, Mengyang; Li, Ruyi; Liu, Xiaoyan; Hu, Wenhui; Wang, Yinye

    2015-06-15

    Anticoagulants and anti-platelet agents are simultaneously administrated in clinical practice (i.e. percutaneous coronary intervention), which cause significant risk of systemic bleeding. Targeted delivery of anticoagulants to the activated platelets at sites of vascular injuries may condense the site-specific anticoagulant effect and reduce the hemorrhage side effects in uninjured vessels. To this end, we prepared three ancylostoma caninum anticoagulant peptide 5 (AcAP5) variants NR1, NR2 and NR3 engineered with a platelet-binding Arg-Gly-Asp (RGD) motif and evaluated their anti-Factor Xa (FXa) and platelet-binding effects. These RGD-containing AcAP5 variants were capable of interacting with platelet receptor αIIbβ3 as shown in computational analysis. All variants, especially NR2 and NR3, retained entirely the anti-FXa function of parent AcAP5. Moreover, they prevented the formation of occlusive thrombi in rat carotid artery injury model, suggesting that they inhibit platelet aggregation in vivo. Further functional investigation of NR3 demonstrated that NR3 inhibited platelet aggregation in vitro and FXa activity in vivo, and prolonged the coagulation time, all in a dose-dependent manner. Through flow cytometry assay, we confirmed the binding of NR3 to αIIbβ3 receptor. In mouse model of carotid artery endothelium injury, NR3-treated mice showed less tail bleeding time than AcAP5-treated mice, and aspirin plus NR3 treatment exhibited moderate reduction of blood loss compared with aspirin plus AcAP5 treatment. These results indicate the feasibility to engineer a novel FXa inhibitor specifically targeting the activated platelets, which centralizes its anticoagulation efficacy in the injured vascular endothelium and reduces the risk of systemic bleeding. PMID:25887920

  5. Factor Xa : at the crossroads between coagulation and signaling in physiology and disease

    NARCIS (Netherlands)

    Borensztajn, Keren; Peppelenbosch, Maikel P.; Spek, C. Arnold

    2008-01-01

    Activated factor Xa (FXa) is traditionally known as an important player in the coagulation cascade responsible for thrombin generation. Long considered a passive bystander, it is now evident that FXa exerts direct effects on a wide variety of cell types via activation of its two main receptors, prot

  6. The role of structural information in the discovery of direct thrombin and factor Xa inhibitors.

    Science.gov (United States)

    Nar, Herbert

    2012-05-01

    The quest for novel medications to treat thromboembolic disorders such as venous thrombosis, pulmonary embolism and stroke received a boost when the 3D structures of two major players in the blood coagulation cascade were determined in 1989 and 1993. Structure-guided design of inhibitors of thrombin (factor IIa, fIIa) and factor Xa (fXa) eventually led to the discovery of potent, selective, efficacious, orally active and safe compounds that proved successful in clinical studies. In 2008, the direct thrombin inhibitor dabigatran etexilate developed by Boehringer Ingelheim became the first novel antithrombotic molecular entity to enter the market in 50 years. Additional compounds targeting factor Xa were subsequently granted marketing authorization or are in late-stage clinical studies. In this review, I use selected case studies to describe the discovery of novel fIIa and fXa inhibitors, with a particular emphasis on the pre-eminent role that structural information played in this process. PMID:22503439

  7. The new factor Xa inhibitor: Apixaban

    Directory of Open Access Journals (Sweden)

    Sangeeta Bhanwra

    2014-01-01

    Full Text Available Cardiovascular diseases are still the most important cause of morbidity and mortality worldwide and anti-thrombotic treatment is widely used as a result. The currently used drugs include heparin and its derivatives, vitamin K antagonists, though efficacious, have their own set of limitations like unpredictable pharmacokinetic profile, parenteral route (with heparin and its derivatives only, narrow therapeutic window, and constant laboratory monitoring for their efficacy and safety. This lead to the development of novel factor Xa inhibitors which could be given orally, have predictable dose response relationship and are associated with lesser hemorrhagic complications. They include rivaroxaban, apixaban, and edoxaban among others. Apixaban has currently been approved for use in patients undergoing total knee or hip replacement surgery and to prevent stroke in patients with atrial fibrillation. Many trials are ongoing for apixaban to firmly establish its place in future, among the anti-thrombotic drugs.

  8. AcAP5蛋白N端片段的表达、纯化与活性评价%Expression, purification and evaluation of N-terminal domain of AcAP5 with Factor Xa inhibitory activity

    Institute of Scientific and Technical Information of China (English)

    刘爱华; 朱元军; 刘晓岩; 王银叶

    2013-01-01

    Ancylostoma anticoagulant peptide 5 (AcAP5) is a strong inhibitor of human coagulation factor Xa (FXa).The N-terminal residues (N40) of AcAP5 contains a domain that could combine with FXa.In order to determine whether N40 protein has FXa inhibitory effect,we cloned,expressed and purified the protein for activity evaluation.The DNA fragment coding N40 was amplified by PCR,cloned into pET-30a to construct recombinant plasmid pET30a-N40,and subsequently transformed into E.coli.BL21 (DE3).Expression of N40 was induced by isopropyl β-D-l-thiogalactopyranoside (IPTG),and the interest protein was identified by SDS-PAGE and purified using one-step nickel (Ni) affinity chromatography.Under the optimal expression condition (0.05 mM IPTG for 6 h at 37 ℃),the purity of N40 reached 90%.We also evaluated the inhibition activity of N40 protein on FXa,finding the IC50 was 4.58× 10 5 mol/L.This study suggests the N40 of AcAP5 could combine with FXa to inhibit FXa activity.%犬钩虫抗凝肽5 (Ancylostoma anticoagulant peptide 5,AcAP5)N端40个氨基酸片段(N40)含有与FXa结合的结构域.为研究N40的FXa抑制作用,我们克隆、表达和纯化了N40,并检测其生物活性.用PCR扩增N40基因;将PCR产物克隆至原核表达载体pET-30a中,构建质粒pET30a-N40;将其转化入大肠杆菌E.coli.BL21 (DE3)中,IPTG诱导目的蛋白表达,SDS-PAGE电泳鉴定,经过镍柱亲和层析纯化,用BCA法进行蛋白定量,测定该蛋白抑制FXa的活性.限制性酶切鉴定和基因测序结果显示重组质粒构建成功;SDS-PAGE结果显示目的蛋白在E.coli.BL21(DE3)中为可溶性表达,亲和层析纯化后获得了纯度约90%的蛋白,经活性鉴定该蛋白确有抑制FXa的活性.

  9. 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.

  10. Characterization of Xanthomonas oryzae-Responsive cis-Acting Element in the Promoter of Rice Race-Specific Susceptibility Gene Xa13

    Institute of Scientific and Technical Information of China (English)

    Ting Yuan; Xianghua Li; Jinghua Xiao; Shiping Wang

    2011-01-01

    The rice Xa13 gene,whose promoter harbors a UPT (up-regulated by transcription activator-like [TAL] effector) box,UPTPthXo1,plays a pivotal role in the race-specific pathogenicity caused by Xanthomonas oryzae pv. Oryzae (Xoo) strain PXO99. PXO99 causes rice disease by inducing Xa13. It is unknown,however,whether the UPTPthXo1 box is the only PXO99-responsive c/s-regulating elements in the activation of Xa13 expression. We analyzed the expression of a series of end- and site-truncated and site-mutated Xa 13 promoters in rice and the binding of PXO99 protein to the intact,partial,or site-mutated UPTPthXo1 boxes. In the Xa13 promoter,UPTPthXo1 box is the only Xoo-responsive cis-acting element that results in PXO99-induced Xa13 expression. The 5'-terminal second,third,and fourth nucleotides of the box are important for bacterial protein binding and gene activation;mutation of any one of these sites abolished PXO99-induced gene expression. Furthermore,the 3'-half of the UPTPthXo1 box is also required for protein binding and gene activation. These findings will enhance our understanding of the molecular mechanism of the interaction of rice and Xoo via UPT boxes and TAL effectors.

  11. Transcriptional Characteristics of Xa21-mediated Defense Responses in Rice

    Institute of Scientific and Technical Information of China (English)

    Qiang Gan; Hui Bai; Xianfeng Zhao; Yong Tao; Haipan Zeng; Yuning Han; Wenyuan Song; Lihuang Zhu; Guozhen Liu

    2011-01-01

    Bacterial blight, caused by Xanthomonas oryzae pv. oryzae (Xoo), is the most destructive bacterial disease of rice. The cloned rice gene Xa21 confers resistance to a broad spectrum of Xoo races. To identify genes involved in Xa21-mediated immunity, a whole-genome oligonucleotide microarray of rice was used to profile the expression of rice genes between incompatible interactions and mock treatments at 0, 4, 8, 24, 72 and 120 h post inoculation (hpi) or between incompatible and compatible interactions at 4 hpi, respectively. A total of 441 differentially expressed genes, designated as XDGs (Xa21 mediated differentially expressed genes), were identified. Based on their functional annotations, the XDGs were assigned to 14 categories, including defense-related, signaling, transcriptional regulators. Most of the defense-related genes belonged to the pathogenesis-related gene family, which was induced dramatically at 72 and 120 hpi. Interestingly, most signaling and transcriptional regulator genes were downregulated at 4 and 8 hpi, suggesting that negative regulation of cellular signaling may play a role in the Xa21-mediated defense response. Comparison of expression profiles between Xa21- and other R gene-mediated defense systems revealed interesting common responses. Representative XDGs with supporting evidences were also discussed.

  12. Coagulation factor Xa drives tumor cells into apoptosis through BH3-only protein Bim up-regulation

    NARCIS (Netherlands)

    Borensztajn, Keren S.; Bijlsma, Maarten F.; Groot, Angelique P.; Bruggemann, Lois W.; Versteeg, Henri H.; Reitsma, Pieter H.; Peppelenbosch, Maikel P.; Spek, C. Arnold

    2007-01-01

    Coagulation Factor (F)Xa is a serine protease that plays a crucial role during blood coagulation by converting prothrombin into active thrombin. Recently, however, it emerged that besides this role in coagulation, FXa induces intracellular signaling leading to different cellular effects. Here, we sh

  13. Comparative nutritional compositions and proteomics analysis of transgenic Xa21 rice seeds compared to conventional rice.

    Science.gov (United States)

    Gayen, Dipak; Paul, Soumitra; Sarkar, Sailendra Nath; Datta, Swapan K; Datta, Karabi

    2016-07-15

    Transgenic rice expressing the Xa21 gene have enhanced resistant to most devastating bacterial blight diseases caused by Xanthomonas oryzae pv. oryzae (Xoo). However, identification of unintended modifications, owing to the genetic modification, is an important aspect of transgenic crop safety assessment. In this study, the nutritional compositions of seeds from transgenic rice plants expressing the Xa21 gene were compared against non-transgenic rice seeds. In addition, to detect any changes in protein translation levels as a result of Xa21 gene expression, rice seed proteome analyses were also performed by two-dimensional gel electrophoresis. No significant differences were found in the nutritional compositions (proximate components, amino acids, minerals, vitamins and anti-nutrients) of the transgenic and non-transgenic rice seeds. Although gel electrophoresis identified 11 proteins that were differentially expressed between the transgenic and non-transgenic seed, only one of these (with a 20-fold up-regulation in the transgenic seed) shows nutrient reservoir activity. No new toxins or allergens were detected in the transgenic seeds. PMID:26948618

  14. Marker-aided Incorporation of Xa38, a Novel Bacterial Blight Resistance Gene, in PB1121 and Comparison of its Resistance Spectrum with xa13 + Xa21.

    Science.gov (United States)

    Ellur, Ranjith K; Khanna, Apurva; S, Gopala Krishnan; Bhowmick, Prolay K; Vinod, K K; Nagarajan, M; Mondal, Kalyan K; Singh, Nagendra K; Singh, Kuldeep; Prabhu, Kumble Vinod; Singh, Ashok K

    2016-01-01

    Basmati rice is preferred internationally because of its appealing taste, mouth feel and aroma. Pusa Basmati 1121 (PB1121) is a widely grown variety known for its excellent grain and cooking quality in the international and domestic market. It contributes approximately USD 3 billion to India's forex earning annually by being the most traded variety. However, PB1121 is highly susceptible to bacterial blight (BB) disease. A novel BB resistance gene Xa38 was incorporated in PB1121 from donor parent PR114-Xa38 using a modified marker-assisted backcross breeding (MABB) scheme. Phenotypic selection prior to background selection was instrumental in identifying the novel recombinants with maximum recovery of recurrent parent phenome. The strategy was effective in delimiting the linkage drag to <0.5 mb upstream and <1.9 mb downstream of Xa38 with recurrent parent genome recovery upto 96.9% in the developed NILs. The NILs of PB1121 carrying Xa38 were compared with PB1121 NILs carrying xa13 + Xa21 (developed earlier in our lab) for their resistance to BB. Both NILs showed resistance against the Xoo races 1, 2, 3 and 6. Additionally, Xa38 also resisted Xoo race 5 to which xa13 + Xa21 was susceptible. The PB1121 NILs carrying Xa38 gene will provide effective control of BB in the Basmati growing region. PMID:27403778

  15. Comparative study of Factor Xa fluorogenic substrates and their influence on the quantification of LMWHs.

    Science.gov (United States)

    Castro-López, Vanessa; Harris, Leanne F; O'Donnell, James S; Killard, Anthony J

    2011-01-01

    Low molecular weight heparins (LMWHs) are recognised as the preferred anticoagulants in the prevention and treatment of venous thromboembolism. Anti-Factor Xa (anti-FXa) levels are used to monitor the anticoagulant effect of LMWHs and such assays are routinely employed in hospital diagnostic laboratories. In this study, a fluorogenic anti-FXa assay was developed using a commercially available fluorogenic substrate with an attached 6-amino-1-naphthalene-sulfonamide (ANSN) fluorophore and was used for the determination of two LMWHs, enoxaparin and tinzaparin and the heparinoid, danaparoid. The assay was based on the complexation of heparinised plasma with 100 nM exogenous FXa and 25 μM of the fluorogenic substrate Mes-D-LGR-ANSN (C(2)H(5))(2) (SN-7). The assay was tested with pooled plasma samples spiked with anticoagulant concentrations in the range 0-1.6 U mL(-1). The statistically sensitive assay range was 0-0.4 U mL(-1) for enoxaparin and tinzaparin and 0-0.2 U mL(-1) for danaparoid, with assay variation typically below 10.5%. This assay was then compared with a previously published fluorogenic anti-FXa assay developed with the peptide substrate, methylsulfonyl-D: -cyclohexylalanyl-glycyl-arginine-7-amino-4-methylcoumarin acetate (Pefafluor FXa). Both assays were compared in terms of fluorescence intensity, lag times and sensitivity to anticoagulants. PMID:20972772

  16. Data of evolutionary structure change: 1C4XA-2OG1B [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1C4XA-2OG1B 1C4X 2OG1 A B ---TVEIIEKRFPSGT---LASHALVAGDPQSPAVVLLH...EEEEEEE HHHHHHHHHHHHH 0 1C4X... A 1C4XA FPSGT---LASHA ...645107269287 4.700198173522949 1 1C4X... A 1C4XA

  17. Antithrombotic and anticoagulant effects of direct factor Xa inhibitor darexaban in rat and rabbit models of venous thrombosis.

    Science.gov (United States)

    Kaku, Seiji; Uemura, Toshio; Saitoh, Minori; Suzuki, Ken-ichi; Iwatsuki, Yoshiyuki; Funatsu, Toshiyuki; Kawasaki, Tomihisa

    2013-01-15

    The oral direct factor Xa inhibitor darexaban administered intraduodenally prevented venous thrombus formation in both rats and rabbits with no effect on bleeding. The indirect parenteral Factor Xa inhibitor fondaparinux exerted similar properties, only prolonging bleeding time at extremely high doses. In contrast, the thrombin inhibitor ximelagatran and low-molecular-weight heparin enoxaparin prolonged bleeding time at antithrombotic doses. Studies using human platelets showed darexaban glucuronide, a darexaban metabolite that predominantly determines darexaban antithrombotic effects in vivo, had no effect on platelet activation and aggregation, while heparin and enoxaparin activated platelets. Melagatran, heparin, and enoxaparin all inhibited thrombin-induced platelet aggregation at clinically relevant concentrations. Taken together, these results suggest that thrombin-inhibiting drugs may increase the risk of bleeding, while darexaban may have potential as an orally available antithrombotic agent with a wide therapeutic window. PMID:23200896

  18. Bioengineering factor Xa to treat bleeding.

    Science.gov (United States)

    Camire, Rodney M

    2016-05-01

    There is a clinical need to develop safe and rapid therapeutic strategies to control bleeding arising from a host of emergent situations. Over the past several years our laboratory has developed novel zymogen-like FXa variants and tested their safety and efficacy using hemophilia as a model system. The variants have a spectrum of properties resulting from an amino acid change at the N-terminus of the heavy chain that alters a critical conformational change. These properties, which include resistance to plasma protease inhibitors, low activity in the absence of FVa, and rescue of low activity upon incorporation in prothrombinase, yield remarkably effective pro-hemostatic agents. The FVa-dependent restoration of activity is a key aspect to their efficacy and also contributes to localizing the variants to the site of vascular injury. While pre-clinical data support their use in the setting of hemophilia, they have the potential to act as rapid pro-hemostatic agents for the treatment of a range of bleeding conditions. This review will discuss the biochemical properties of these FXa zymogen-like variants and their in vivo characterization. PMID:27207419

  19. AvrXa3:A novel member of avrBs3 gene family from Xanthomonas oryzae pv.oryzae has a dual function

    Institute of Scientific and Technical Information of China (English)

    LI Ping; LONG Juying; HUANG Yingchun; ZHANG Yan; WANG Jinsheng

    2004-01-01

    Two positive clones pUAV45 and pUAV47 were identified from the cDNA library of JxoⅢ, a race 3 strain of Xanthomonas oryzae pv. Oryzae Dye (Xoo) in Japanese system, using Tn5 based technology. pUAV45 clone contained a 25.4 kb Xoo genomic DNA insert. Southern blot analysis with avrXa10 as the probe showed that DNA insert in pUAV45 shares homology with avrX10. Furthermore within the Xoo insert, a smaller 5.7 kb KpnI fragment (pUAVSk) was identified through hybridization with avrXa10. The transformation of pUAV45 and pUAV5k into the strain Pxo99 (race 6 in Philippine system) led to the decrease of Pxo99pathogenicity on rice cultivar Wase Aikoku 3 (Xa3) and the increase of the pathogen pathogenicity on Cas209 (Xa10). The result of sequence analysis showed that there is a 2598 bp open reading frame (ORF) within the 5.7 kb Kpn 1 fragment (pUAVSk). The ORF shared high identity (97 % ) with avrXa10. The deduced sequence of the ORF contained 8.5 tandem repeat units of 34-amino-acids, one leucine zipper (LZ), three nuclear localization signal (NLS) motifs, and an acidic activation transcriptional domain (AAD) at C-terminus.We named this ORF avrXa3 and it is classified as a new member of avrBs3 (avr/pth) family with the dual-function determined by alternations of avirulence and aggressiveness on rice cultivars carrying different ‘ R' genes.

  20. Liver gene therapy by lentiviral vectors reverses anti-factor IX pre-existing immunity in haemophilic mice

    OpenAIRE

    Annoni, Andrea; Cantore, Alessio; Della Valle, Patrizia; Goudy, Kevin; Akbarpour, Mahzad; Russo, Fabio; Bartolaccini, Sara; D'Angelo, Armando; Roncarolo, Maria Grazia; Naldini, Luigi

    2013-01-01

    A major complication of factor replacement therapy for haemophilia is the development of anti-factor neutralizing antibodies (inhibitors). Here we show that liver gene therapy by lentiviral vectors (LVs) expressing factor IX (FIX) strongly reduces pre-existing anti-FIX antibodies and eradicates FIX inhibitors in haemophilia B mice. Concomitantly, plasma FIX levels and clotting activity rose to 50–100% of normal. The treatment was effective in 75% of treated mice. FIX-specific plasma cells (PC...

  1. A comparative approach expands the protein-protein interaction node of the immune receptor XA21 in wheat and rice

    OpenAIRE

    Yang, Baoju; Ruan, Randy; Cantu, Dario; Wang, Xiaodong; Ji, Wanquan; Ronald, Pamela C; Dubcovsky, Jorge

    2013-01-01

    The rice (Oryza sativa) OsXA21 receptor kinase is a well-studied immune receptor that initiates a signal transduction pathway leading to resistance to Xanthomonas oryzae pv. oryzae. Two homologs of OsXA21 were identified in wheat (Triticum aestivum): TaXA21-like1 located in a syntenic region with OsXA21, and TaXA21-like2 located in a non-syntenic region. Proteins encoded by these two wheat genes interact with four wheat orthologs of known OsXA21 interactors. In this study, we screened a wheat...

  2. Mutation of the rice XA21 predicted nuclear localization sequence does not affect resistance to Xanthomonas oryzae pv. oryzae

    Science.gov (United States)

    Ho, Yuen Ting

    2016-01-01

    Background The rice receptor kinase XA21 confers robust resistance to the bacterial pathogen Xanthomonas oryzaepv. oryzae(Xoo). We previously reported that XA21 is cleaved in transgenic plants overexpressing XA21 with a GFP tag (Ubi-XA21-GFP) and that the released C-terminal domain is localized to the nucleus. XA21 carries a predicted nuclear localization sequence (NLS) that directs the C-terminal domain to the nucleus in transient assays, whereas alanine substitutions in the NLS disrupt the nuclear localization. Methods To determine if the predicted NLS is required for XA21-mediated immunity in planta, we generated transgenic plants overexpressing an XA21 variant carrying the NLS with the same alanine substitutions (Ubi-XA21nls-GFP). Results Ubi-XA21nls-GFP plants displayed slightly longer lesion lengths, higher Xoobacterial populations after inoculation and lower levels of reactive oxygen species production compared with the Ubi-XA21-GFP control plants. However, the Ubi-XA21nls-GFP plants express lower levels of protein than that observed in Ubi-XA21-GFP. Discussion These results demonstrate that the predicted NLS is not required for XA21-mediated immunity.

  3. Purification of a Ni sup 2+ -binding protein, pNiXa, from Xenopus ovary

    Energy Technology Data Exchange (ETDEWEB)

    Beck, B.L.; Makowski, G.S.; Nomoto, S.; Sunderman, F.W. (Univ. of Connecticut, Farmington (United States))

    1991-03-11

    Previous research on nickel-induced teratogenesis in Xenopus laevis identified several Ni{sup 2+}-binding proteins, including pNiXa in Xenopus ovaries, unfertilized eggs, and embryos. A major goal of this research project is elucidating the role of pNiXa in the uptake, embryotoxicity, and teratogenicity of Ni{sup 2+} in Xenopus. To purify and identify pNiXa, ovarian tissue from mature Xenopus females was homogenized in 3 vol of Tris buffer and centrifuged. The supernatant was centrifuged; the ultracentrifugal supernatant was batch-adsorbed onto DEAE-cellulose. The pNiSa remained unbound and was subsequently adsorbed on phosphocellulose and eluted by a step-wise NaCl gradient. The pNiXa was eluted in 0.25 M NaCl; this fraction was concentrated, and further purified by reverse phase chromatography on a 5 {mu}m C-8 column, with a linear trifluoroacetic acid/acetonitrile gradient. The pNiXa was eluted at {approximately}56% acetonitrile, yielding a single protein band with mol wt {approximately}47 kD,based on SDS-PAGE analysis. Comparison of the amino acid composition of pNiXa versus the results obtained by automated Edman degradation indicated that the N-terminus of pNiXa was blocked. Sequencing of peptide fragments of pNiXa is underway.

  4. Transgenic expression of the rice Xa21 pattern-recognition receptor in banana (Musa sp.) confers resistance to Xanthomonas campestris pv. musacearum.

    Science.gov (United States)

    Tripathi, Jaindra N; Lorenzen, Jim; Bahar, Ofir; Ronald, Pamela; Tripathi, Leena

    2014-08-01

    Banana Xanthomonas wilt (BXW), caused by the bacterium Xanthomonas campestris pv. musacearum (Xcm), is the most devastating disease of banana in east and central Africa. The spread of BXW threatens the livelihood of millions of African farmers who depend on banana for food security and income. There are no commercial chemicals, biocontrol agents or resistant cultivars available to control BXW. Here, we take advantage of the robust resistance conferred by the rice pattern-recognition receptor (PRR), XA21, to the rice pathogen Xanthomonas oryzae pv. oryzae (Xoo). We identified a set of genes required for activation of Xa21-mediated immunity (rax) that were conserved in both Xoo and Xcm. Based on the conservation, we hypothesized that intergeneric transfer of Xa21 would confer resistance to Xcm. We evaluated 25 transgenic lines of the banana cultivar 'Gonja manjaya' (AAB) using a rapid bioassay and 12 transgenic lines in the glasshouse for resistance against Xcm. About 50% of the transgenic lines showed complete resistance to Xcm in both assays. In contrast, all of the nontransgenic control plants showed severe symptoms that progressed to complete wilting. These results indicate that the constitutive expression of the rice Xa21 gene in banana results in enhanced resistance against Xcm. Furthermore, this work demonstrates the feasibility of PRR gene transfer between monocotyledonous species and provides a valuable new tool for controlling the BXW pandemic of banana, a staple food for 100 million people in east Africa.

  5. RIVAROXABAN: AN ORAL DIRECT INHIBITOR OF FACTOR X-A

    Directory of Open Access Journals (Sweden)

    Mehta Hiren R

    2011-08-01

    Full Text Available Venous thrombo embolism (VTE, which includes deep vein thrombosis and pulmonary embolism, is a major cause of morbidity and mortality in patients undergoing major orthopaedic surgery, and routine thrombo prophylaxis has been the standard of care over the last 20 years. Currently available options for the prevention of venous thrombo embolism in major orthopedic surgery include low-molecular-weight heparins, vitamin K antagonists and, more recently, the synthetic pentasaccharide fondaparinux. Although effective, these drugs have several limitations, and new oral antithrombotics offering predictable, effective and safe anticoagulation are strongly needed. This overview focuses on the most advanced oral direct inhibitors of factor Xa, rivaroxaban.Rivaroxaban, an oral oxazolidinone-based anticoagulant, is a potent, selective direct inhibitor of factor Xa that is used in the prevention of venous thrombo embolism in adult patients after total hip replacement (THR or total knee replacement (TKR surgery. In four large, clinical trials, oral rivaroxaban was more effective than subcutaneous enoxaparin in preventing postoperative VTE in patients undergoing total hip replacement or total knee replacement surgery. Notably, the superior efficacy of rivaroxaban was achieved with a low but not significant increase in the incidence of major bleeding episodes. In addition, preliminary pharma co-economic analyses in several countries indicate that rivaroxaban is a cost-effective treatment strategy versus enoxaparin. Although the position of rivaroxaban relative to other therapies remains to be fully determined, it is an effective emerging option for the prevention of venous thrombo embolism following total hip replacement and total knee replacement.

  6. Sequences promoting the transcription of the human XA gene overlapping P450c21A correctly predict the presence of a novel, adrenal-specific, truncated form of tenascin-X

    Energy Technology Data Exchange (ETDEWEB)

    Tee, Meng Kian; Thomson, A.A.; Bristow, J.; Miller, W.L. [Univ. of California, San Francisco, CA (United States)

    1995-07-20

    A compact region in the human class III major histocompatibility locus contains the human genes for the fourth component of human complement (C4) and steroid 21-hydroxylase (P450c21) in one transcriptional orientation, while the gene for the extracellular matrix protein tenascin-X (TN-X) overlaps the last exon of P450c21 on the opposite strand of DNA in the opposite transcriptional orientation. This complex locus is duplicated into A and B loci, so that the organization is 5{prime}-C4A-21A-XA-C4B-21B-XB-3{prime}. Although this duplication event truncated the 65-kb X(B) gene to a 4.5-kb XA gene, the XA gene is transcriptionally active in the adrenal cortex. To examine the basis of the tissue-specific expression of XA and C4B, we cloned the 1763-bp region that lies between the cap sites for XA and C4B and analyzed its promoter activity in both the XA and the C4 orientations. Powerful, liver-specific sequences lie within the first 75 to 138 bp from the C4B cap site, and weaker elements lie within 128 bp of the XA cap site that function in both liver and adrenal cells. Because these 128 bp upstream from the XA cap site are perfectly preserved in the XB gene encoding TN-X, we sought to determine whether a transcript similar to XA arises within the SB gene. RNase protection assays, cDNA cloning, and RT/PCR show that adrenal cells contain a novel transcript, termed short XB (XB-S), which has the same open reading frame as TN-X. Cell-free translation and immunoblotting show that this transcript encodes a novel 74-kDa XB-S protein that is identical to the carboxy-terminal 673 residues of TN-X. Because this protein consists solely of fibronectin type III repeats and a fibrinogen-like domain, it appears to correspond to an evolutionary precursor of the tenascin family of extracellular matrix proteins. 40 refs., 6 figs.

  7. Clinical Use of Anti-Xa Monitoring in Malignancy-Associated Thrombosis

    Directory of Open Access Journals (Sweden)

    Sarah Yentz

    2015-01-01

    Full Text Available Introduction. Low molecular weight heparin (LMWH is preferred for malignancy-associated venous thromboembolism (VTE. Many providers monitor LMWH with anti-Xa levels, despite little validation on correspondence with patient outcome. Methods. This is a retrospective, single institution study of anti-Xa measurement in malignancy-associated thrombosis. Cases were identified using the Electronic Data Warehouse, and inclusion was confirmed by two independent reviewers. Malignancy type, thrombotic history, measurement rationale and accuracy, clinical context, and management changes were evaluated. Results. 167 cases met inclusion criteria. There was no clear rationale for anti-Xa testing in 56%. Impaired renal function (10%, documented or suspected recurrent thrombosis despite anticoagulation (9%, and bleeding (6% were the most common reasons for testing. Incorrect measurement occurred in 44%. Renal impairment was not a significant impetus for testing, as 70% had a GFR > 60. BMI > 30 was present in 40%, and 28% had a BMI < 25. Clinical impact was low, as only 11% of patients had management changes. Conclusions. Provider education in accuracy and rationale for anti-Xa testing is needed. Our study illustrates uncertainty of interpretation and clinical impact of routine anti-Xa testing, as management was affected in few patients. It is not yet clear in which clinical context providers should send anti-Xa levels.

  8. Fast rotation of a subkilometer-sized near-Earth object 2011 XA{sub 3}

    Energy Technology Data Exchange (ETDEWEB)

    Urakawa, Seitaro [Bisei Spaceguard Center, Japan Spaceguard Association, 1716-3 Okura, Bisei, Ibara, Okayama 714-1411 (Japan); Ohtsuka, Katsuhito [Tokyo Meteor Network, 1-27-5 Daisawa, Setagaya-ku, Tokyo 155-0032 (Japan); Abe, Shinsuke [Department of Aerospace Engineering, College of Science and Technology, Nihon University, 7-24-1 Narashinodai, Funabashi, Chiba 274-8501 (Japan); Ito, Takashi [National Astronomical Observatory of Japan, 2-21-1 Osawa, Mitaka, Tokyo 181-8588 (Japan); Nakamura, Tomoki, E-mail: urakawa@spaceguard.or.jp [Department of Earth and Planetary Material Sciences, Graduate School of Science, Tohoku University, Aoba, Sendai, Miyagi 980-8578 (Japan)

    2014-05-01

    We present light curve observations and their multiband photometry for near-Earth object (NEO) 2011 XA{sub 3}. The light curve has shown a periodicity of 0.0304 ± 0.0003 days (= 43.8 ± 0.4 minutes). The fast rotation shows that 2011 XA{sub 3} is in a state of tension (i.e., a monolithic asteroid) and cannot be held together by self-gravitation. Moreover, the multiband photometric analysis indicates that the taxonomic class of 2011 XA{sub 3} is S-complex, or V-type. Its estimated effective diameter is 225 ± 97 m (S-complex) and 166 ± 63 m (V-type), respectively. Therefore, 2011 XA{sub 3} is a candidate for the second-largest, fast-rotating, monolithic asteroid. Moreover, the orbital parameters of 2011 XA{sub 3} are apparently similar to those of NEO (3200) Phaethon, but F/B-type. We computed the orbital evolutions of 2011 XA{sub 3} and Phaethon. However, the results of the computation and distinct taxonomy indicate that neither of the asteroids is of common origin.

  9. Engineering Factor Xa Inhibitor with Multiple Platelet-Binding Sites Facilitates its Platelet Targeting

    Science.gov (United States)

    Zhu, Yuanjun; Li, Ruyi; Lin, Yuan; Shui, Mengyang; Liu, Xiaoyan; Chen, Huan; Wang, Yinye

    2016-01-01

    Targeted delivery of antithrombotic drugs centralizes the effects in the thrombosis site and reduces the hemorrhage side effects in uninjured vessels. We have recently reported that the platelet-targeting factor Xa (FXa) inhibitors, constructed by engineering one Arg-Gly-Asp (RGD) motif into Ancylostoma caninum anticoagulant peptide 5 (AcAP5), can reduce the risk of systemic bleeding than non-targeted AcAP5 in mouse arterial injury model. Increasing the number of platelet-binding sites of FXa inhibitors may facilitate their adhesion to activated platelets, and further lower the bleeding risks. For this purpose, we introduced three RGD motifs into AcAP5 to generate a variant NR4 containing three platelet-binding sites. NR4 reserved its inherent anti-FXa activity. Protein-protein docking showed that all three RGD motifs were capable of binding to platelet receptor αIIbβ3. Molecular dynamics simulation demonstrated that NR4 has more opportunities to interact with αIIbβ3 than single-RGD-containing NR3. Flow cytometry analysis and rat arterial thrombosis model further confirmed that NR4 possesses enhanced platelet targeting activity. Moreover, NR4-treated mice showed a trend toward less tail bleeding time than NR3-treated mice in carotid artery endothelium injury model. Therefore, our data suggest that engineering multiple binding sites in one recombinant protein is a useful tool to improve its platelet-targeting efficiency. PMID:27432161

  10. Engineering Factor Xa Inhibitor with Multiple Platelet-Binding Sites Facilitates its Platelet Targeting.

    Science.gov (United States)

    Zhu, Yuanjun; Li, Ruyi; Lin, Yuan; Shui, Mengyang; Liu, Xiaoyan; Chen, Huan; Wang, Yinye

    2016-01-01

    Targeted delivery of antithrombotic drugs centralizes the effects in the thrombosis site and reduces the hemorrhage side effects in uninjured vessels. We have recently reported that the platelet-targeting factor Xa (FXa) inhibitors, constructed by engineering one Arg-Gly-Asp (RGD) motif into Ancylostoma caninum anticoagulant peptide 5 (AcAP5), can reduce the risk of systemic bleeding than non-targeted AcAP5 in mouse arterial injury model. Increasing the number of platelet-binding sites of FXa inhibitors may facilitate their adhesion to activated platelets, and further lower the bleeding risks. For this purpose, we introduced three RGD motifs into AcAP5 to generate a variant NR4 containing three platelet-binding sites. NR4 reserved its inherent anti-FXa activity. Protein-protein docking showed that all three RGD motifs were capable of binding to platelet receptor αIIbβ3. Molecular dynamics simulation demonstrated that NR4 has more opportunities to interact with αIIbβ3 than single-RGD-containing NR3. Flow cytometry analysis and rat arterial thrombosis model further confirmed that NR4 possesses enhanced platelet targeting activity. Moreover, NR4-treated mice showed a trend toward less tail bleeding time than NR3-treated mice in carotid artery endothelium injury model. Therefore, our data suggest that engineering multiple binding sites in one recombinant protein is a useful tool to improve its platelet-targeting efficiency. PMID:27432161

  11. 3D/3D registration of coronary CTA and biplane XA reconstructions for improved image guidance

    Energy Technology Data Exchange (ETDEWEB)

    Dibildox, Gerardo, E-mail: g.dibildox@erasmusmc.nl; Baka, Nora; Walsum, Theo van [Biomedical Imaging Group Rotterdam, Departments of Radiology and Medical Informatics, Erasmus Medical Center, 3015 GE Rotterdam (Netherlands); Punt, Mark; Aben, Jean-Paul [Pie Medical Imaging, 6227 AJ Maastricht (Netherlands); Schultz, Carl [Department of Cardiology, Erasmus Medical Center, 3015 GE Rotterdam (Netherlands); Niessen, Wiro [Quantitative Imaging Group, Faculty of Applied Sciences, Delft University of Technology, 2628 CJ Delft, The Netherlands and Biomedical Imaging Group Rotterdam, Departments of Radiology and Medical Informatics, Erasmus Medical Center, 3015 GE Rotterdam (Netherlands)

    2014-09-15

    Purpose: The authors aim to improve image guidance during percutaneous coronary interventions of chronic total occlusions (CTO) by providing information obtained from computed tomography angiography (CTA) to the cardiac interventionist. To this end, the authors investigate a method to register a 3D CTA model to biplane reconstructions. Methods: The authors developed a method for registering preoperative coronary CTA with intraoperative biplane x-ray angiography (XA) images via 3D models of the coronary arteries. The models are extracted from the CTA and biplane XA images, and are temporally aligned based on CTA reconstruction phase and XA ECG signals. Rigid spatial alignment is achieved with a robust probabilistic point set registration approach using Gaussian mixture models (GMMs). This approach is extended by including orientation in the Gaussian mixtures and by weighting bifurcation points. The method is evaluated on retrospectively acquired coronary CTA datasets of 23 CTO patients for which biplane XA images are available. Results: The Gaussian mixture model approach achieved a median registration accuracy of 1.7 mm. The extended GMM approach including orientation was not significantly different (P > 0.1) but did improve robustness with regards to the initialization of the 3D models. Conclusions: The authors demonstrated that the GMM approach can effectively be applied to register CTA to biplane XA images for the purpose of improving image guidance in percutaneous coronary interventions.

  12. Contemporary developments in the discovery of selective factor Xa inhibitors: A review.

    Science.gov (United States)

    Patel, Nirav R; Patel, Dushyant V; Murumkar, Prashant R; Yadav, Mange Ram

    2016-10-01

    Thrombosis is a leading cause of death in cardiovascular diseases such as myocardial infarction (MI), unstable angina and acute coronary syndrome (ACS) in the industrialized world. Venous thromboembolism is observed in about 1 million people every year in United States causing significant morbidity and mortality. Conventional antithrombotic therapy has been reported to have several disadvantages and limitations like inconvenience in oral administration, bleeding risks (heparin analogs), narrow therapeutic window and undesirable interactions with food and drugs (vitamin K antagonist-warfarin). The unmet medical demand for orally active safe anticoagulants has generated widespread interest among the medicinal chemists engaged in this field. To modulate blood coagulation, various enzymes involved in the coagulation process have received great attention as potential targets by various research groups for the development of oral anticoagulants. Among these enzymes, factor Xa (FXa) has remained the centre of attention in the last decade. Intensive research efforts have been made by various research groups for the development of small, safe and orally bioavailable FXa inhibitors. This review is an attempt to compile the research work of various researchers in the direction of development of FXa inhibitors reported since 2010 onward. PMID:27322757

  13. Role of Factor Xa Inhibitors in Cancer-Associated Thrombosis: Any New Data?

    Directory of Open Access Journals (Sweden)

    Ali Zalpour

    2011-01-01

    Full Text Available The association between cancer and venous thromboembolism (VTE has been well documented in the literature. Prevention and treatment of VTE in cancer patients is imperative. Typically, the mainstay regimen for VTE prevention and treatment has been anticoagulation therapy, unless contraindicated. This therapy consists of unfractionated heparin (UFH, low-molecular-weight heparin (LMWH, factor Xa inhibitor, or vitamin K antagonist (VKA. Current guidelines recommend LMWH over VKA for the treatment of VTE in cancer patients. Factor-specific anticoagulants have been proven safe and effective, and recently factor Xa inhibitors have emerged as a treatment alternative to heparins and VKA. Currently, three factor Xa inhibitors have been identified: fondaparinux (the only one approved so far by the US Food and Drug Administration, idraparinux (in clinical trials, and idrabiotaparinux (in clinical trials. This paper will examine the role of these agents, focusing on fondaparinux, for the prevention and treatment of VTE in cancer patients.

  14. The Matrix Equation XA- AX=Xαg(X over Fields or Rings

    Directory of Open Access Journals (Sweden)

    Gerald Bourgeois

    2014-01-01

    Full Text Available Let n,α∈N≥2 and let K be an algebraically closed field with characteristic 0 or greater than n. We show that if f∈K[X] and A,B∈Mn(K satisfy [A,B]=f(A, then A,B are simultaneously triangularizable. Let R be a reduced ring such that n! is not a zero divisor and let A be a generic matrix over R; we show that X=0 is the sole solution of AX-XA=Xα. Let R be a commutative ring with unity; let A be similar to diag(λ1In1,…,λrInr such that, for every i≠j,λi-λj is not a zero divisor. If X is a nilpotent solution of XA-AX=Xαg(X where g∈R[X], then AX=XA.

  15. On Diophantine Equations of the Form $(x-a_1)(x-a_2)\\ldots(x-a_k)+r=y^n$

    Indian Academy of Sciences (India)

    Manisha Kulkarni; B Sury

    2011-08-01

    Erdős and Selfridge [3] proved that a product of consecutive integers can never be a perfect power. That is, the equation $x(x+1)(x+2)\\ldots(x+(m-1))=y^n$ has no solutions in positive integers $x,m,n$ where $m,n>1$ and $y\\in Q$. We consider the equation $$(x-a_1)(x-a_2)\\ldots(x-a_k)+r=y^n$$ where $0≤ a_1 < a_2 <\\cdots < a_k$ are integers and, with $r\\in Q,n≥ 3$ and we prove a finiteness theorem for the number of solutions in $Z,y$ in . Following that, we show that, more interestingly, for every nonzero integer >2 and for any nonzero integer which is not a perfect -th power for which the equation admits solutions, is bounded by an effective bound.

  16. Molecular analysis of two cDNAs encoding Xa1 and oxysterol binding proteins in sorghum (Sorghum bicolor)

    Science.gov (United States)

    Using suppression subtractive hybridization (SSH) and subsequent microarray analysis, expression profiles of sorghum genes responsive to greenbug phloem-feeding were obtained and identified. Among the profiles, two cDNAs designated to MM73 and MM95 were identified to encode Xa1 (Xa1) and oxysterol ...

  17. Introduction of a rice blight resistance gene, Xa21, into five Chinese rice varieties through an Agrobacterium-mediated system

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    A cloned gene, Xa21 was transferred into five widely-used Chinese rice varieties through an Agrobacterium-mediated system, and over 110 independent transgenic lines were obtained. PCR and Southern analysis of transgenic plants revealed the integration of the whole Xa21 gene into the host genomes. The integrated Xa21 gene was stably inherited, and segregated in a 3∶1 ratio in the selfed T1 generation when one copy of the gene was integrated in the transformants. Inoculation tests displayed that transgenic T0 plants and Xa21 PCR-positive T1 plants were highly resistant to bacterial blight disease. The selected Xa21 homozygous resistant transgenic lines with desirable qualities may be propagated as new varieties or utilized in hybrid rice breeding.

  18. Introduction of a rice blight resistance gene, Xa21, into five Chinese rice varieties through an Agrobacterium -mediated system

    Institute of Scientific and Technical Information of China (English)

    翟文学; 李晓兵; 田文忠; 周永力; 潘学彪; 曹守云; 赵显峰; 赵彬; 章琦; 朱立煌

    2000-01-01

    A cloned gene, Xa21 was transferred into five widely-used Chinese rice varieties through an Agrobacterium-mediated system, and over 110 independent transgenic lines were obtained. PCR and Southern analysis of transgenic plants revealed the integration of the whole Xa21 gene into the host genomes. The integrated Xa21 gene was stably inherited, and segregated in a 3 : 1 ratio in the selfed T1 generation when one copy of the gene was integrated in the transfor-mants. Inoculation tests displayed that transgenic T0 plants and Xa21 PCR-positive T1 plants were highly resistant to bacterial blight disease. The selected Xa21 homozygous resistant transgenic lines with desirable qualities may be propagated as new varieties or utilized in hybrid rice breeding.

  19. Factor Xa inhibitors: new anti-thrombotic agents and their characteristics.

    Science.gov (United States)

    Ieko, Masahiro; Tarumi, Takashi; Nakabayashi, Toru; Yoshida, Mika; Naito, Sumiyoshi; Koike, Takao

    2006-01-01

    Factor Xa (FXa) is a key enzyme that is positioned at the convergence of the intrinsic and extrinsic pathways in the blood coagulation cascade, and inactivation by a specific FXa inhibitor effectively prevents the generation of thrombin. Various types of low molecular weight (LMW) heparin, which function as semi-selective and indirect FXa inhibitors, are replacing unfractionated heparin (UFH) as agents for the prevention and treatment of venous thromboembolism (VTE), as well as in initial treatment for coronary events. Of those, heparinoid has been shown to be safer and more effective for the prevention of postoperative VTE than UFH, especially for treatment of heparin-induced thrombocytopenia (HIT). Further, synthetic pentasaccharide has been found to offer advantages over current thromboprophylactic regimens in a number of patients undergoing major orthopedic surgery. Other studies have shown that pentasaccharide is more effective for overall VTE in comparison with LMW heparin, though it was also associated with an increased rate of major bleeding. Synthetic, selective, and direct inhibitors to FXa, such as DX-9065a, are highly potent and orally bioavailable antithrombotic agents that have demonstrated an improved side effect profile, probably by allowing sufficient thrombin to remain for platelet activation and normal hemostasis, while preventing pathological thrombus formation. For thrombosis therapy, the most desirable type of antithrombotic agent is an orally active drug that has a broad range of effective doses and no hemorrhagic side effects. Presently, many types of direct inhibitors are in various stages of clinical trials and expected to provide significant benefits as compared to currently utilized therapy strategies. PMID:16146728

  20. Pleiotropic effects of factor Xa and thrombin : what to expect from novel anticoagulants

    NARCIS (Netherlands)

    Spronk, Henri M. H.; de Jong, Anne Margreet; Crijns, Harry J.; Schotten, Ulrich; Van Gelder, Isabelle C.; ten Cate, Hugo

    2014-01-01

    Factor Xa and thrombin are well-known components of the coagulation cascade and have been proven to be viable targets for effective anticoagulation treatment. However, accumulating evidence suggests that these serine proteases are also crucial modulators of other cellular mechanisms through the acti

  1. Data of evolutionary structure change: 1B5XA-2G4NF [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1B5XA-2G4NF 1B5X 2G4N A F KVFERCELARTLKRLGMDGYRGISLANWMCLAKWESGYN...G HHHH -GGGG -- EVID>EVID> 0 2G4N F 2G4NF ELKDL...242798 2.054610013961792 4.014041900634766 ...EVID> 1 2G4N F 2G4NF

  2. A Single-Tube, Functional Marker-Based Multiplex PCR Assay for Simultaneous Detection of Major Bacterial Blight Resistance GenesXa21, xa13 andxa5 in Rice

    Institute of Scientific and Technical Information of China (English)

    S. K. HAJIRA; M. ANILA; S. BHASKAR; V. ABHILASH; H. K. MAHADEVASWAMY; M. KOUSIK; T. DILIPKUMAR; G. HARIKA; G. REKHA; R. M. SUNDARAM; G. S. LAHA; A. YUGANDER; S. M. BALACHANDRAN; B. C. VIRAKTAMATH; K. SUJATHA; C. H. BALACHIRANJEEVI; K. PRANATHI

    2016-01-01

    In marker-assisted breeding for bacterial blight (BB) resistance in rice, three major resistance genes, viz.,Xa21, xa13andxa5,are routinely deployed either singly or in combinations. As efficient and functional markers are yet to be developed forxa13 andxa5,we have developed simple PCR-based functional markers for both the genes.Forxa13,we designed a functional PCR-based marker, xa13-prom targeting the InDel polymorphism in the promoter of candidate geneOs8N3 located on chromosome 8 of rice. With respect toxa5, a multiplex-PCR based functional marker system, named xa5FM, consisting of two sets of primer pairs targeting the 2-bp functional nucleotide polymorphism in the exon II of the geneTFIIAɤ5 (candidate forxa5), has been developed. Both xa13-prom and xa5FM can differentiate the resistant and susceptible alleles forxa13 andxa5, respectively, in a co-dominant fashion. Using these two functional markers along with the already reported functional PCR-based marker forXa21 (pTA248),we designed a single-tube multiplex PCR based assay for simultaneous detection of all the three major resistance genes and demonstrated the utility of the multiplex marker system in a segregating population.

  3. Coagulation-induced shedding of platelet glycoprotein VI mediated by factor Xa.

    Science.gov (United States)

    Al-Tamimi, Mohammad; Grigoriadis, George; Tran, Huy; Paul, Eldho; Servadei, Patricia; Berndt, Michael C; Gardiner, Elizabeth E; Andrews, Robert K

    2011-04-01

    This study evaluated shedding of the platelet collagen receptor, glycoprotein VI (GPVI) in human plasma. Collagen or other ligands induce metalloproteinase-mediated GPVI ectodomain shedding, generating approximately 55-kDa soluble GPVI (sGPVI) and approximately 10-kDa platelet-associated fragments. In the absence of GPVI ligands, coagulation of platelet-rich plasma from healthy persons induced GPVI shedding, independent of added tissue factor, but inhibitable by metalloproteinase inhibitor, GM6001. Factor Xa (FXa) common to intrinsic and tissue factor-mediated coagulation pathways was critical for sGPVI release because (1) shedding was strongly blocked by the FXa-selective inhibitor rivaroxaban but not FIIa (thrombin) inhibitors dabigatran or hirudin; (2) Russell viper venom that directly activates FX generated sGPVI, with complete inhibition by enoxaparin (inhibits FXa and FIIa) but not hirudin; (3) impaired GPVI shedding during coagulation of washed platelets resuspended in FX-depleted plasma was restored by adding purified FX; and (4) purified FXa induced GM6001-inhibitable GPVI shedding from washed platelets. In 29 patients with disseminated intravascular coagulation, mean plasma sGPVI was 53.9 ng/mL (95% confidence interval, 39.9-72.8 ng/mL) compared with 12.5 ng/mL (95% confidence interval, 9.0-17.3 ng/mL) in thrombocytopenic controls (n = 36, P coagulation-induced GPVI shedding via FXa down-regulates GPVI under procoagulant conditions. FXa inhibitors have an unexpected role in preventing GPVI down-regulation.

  4. Activated factor X signaling via protease-activated receptor 2 suppresses pro-inflammatory cytokine production from LPS-stimulated myeloid cells.

    LENUS (Irish Health Repository)

    Gleeson, Eimear M

    2013-07-19

    Vitamin K-dependent proteases generated in response to vascular injury and infection enable fibrin clot formation, but also trigger distinct immuno-regulatory signaling pathways on myeloid cells. Factor Xa, a protease crucial for blood coagulation, also induces protease-activated receptor-dependent cell signaling. Factor Xa can bind both monocytes and macrophages, but whether factor Xa-dependent signaling stimulates or suppresses myeloid cell cytokine production in response to Toll-like receptor activation is not known. In this study, exposure to factor Xa significantly impaired pro-inflammatory cytokine production from lipopolysaccharide-treated peripheral blood mononuclear cells, THP-1 monocytic cells and murine macrophages. Furthermore, factor Xa inhibited nuclear factor-kappa B activation in THP-1 reporter cells, requiring phosphatidylinositide 3-kinase activity for its anti-inflammatory effect. Active-site blockade, γ-carboxyglutamic acid domain truncation and a peptide mimic of the factor Xa inter-epidermal growth factor-like region prevented factor Xa inhibition of lipopolysaccharide-induced tumour necrosis factor-α release. In addition, factor Xa anti-inflammatory activity was markedly attenuated by the presence of an antagonist of protease-activated receptor 2, but not protease-activated receptor 1. The key role of protease-activated receptor 2 in eliciting factor Xa-dependent anti-inflammatory signaling on macrophages was further underscored by the inability of factor Xa to mediate inhibition of tumour necrosis factor-α and interleukin-6 release from murine bone marrow-derived protease-activated receptor 2-deficient macrophages. We also show for the first time that, in addition to protease-activated receptor 2, factor Xa requires a receptor-associated protein-sensitive low-density lipoprotein receptor to inhibit lipopolysaccharide-induced cytokine production. Collectively, this study supports a novel function for factor Xa as an endogenous, receptor

  5. Liver gene therapy by lentiviral vectors reverses anti-factor IX pre-existing immunity in haemophilic mice.

    Science.gov (United States)

    Annoni, Andrea; Cantore, Alessio; Della Valle, Patrizia; Goudy, Kevin; Akbarpour, Mahzad; Russo, Fabio; Bartolaccini, Sara; D'Angelo, Armando; Roncarolo, Maria Grazia; Naldini, Luigi

    2013-11-01

    A major complication of factor replacement therapy for haemophilia is the development of anti-factor neutralizing antibodies (inhibitors). Here we show that liver gene therapy by lentiviral vectors (LVs) expressing factor IX (FIX) strongly reduces pre-existing anti-FIX antibodies and eradicates FIX inhibitors in haemophilia B mice. Concomitantly, plasma FIX levels and clotting activity rose to 50-100% of normal. The treatment was effective in 75% of treated mice. FIX-specific plasma cells (PCs) and memory B cells were reduced, likely because of memory B-cell depletion in response to constant exposure to high doses of FIX. Regulatory T cells displaying FIX-specific suppressive capacity were induced in gene therapy treated mice and controlled FIX-specific T helper cells. Gene therapy proved safer than a regimen mimicking immune tolerance induction (ITI) by repeated high-dose FIX protein administration, which induced severe anaphylactoid reactions in inhibitors-positive haemophilia B mice. Liver gene therapy can thus reverse pre-existing immunity, induce active tolerance to FIX and establish sustained FIX activity at therapeutic levels. These data position gene therapy as an attractive treatment option for inhibitors-positive haemophilic patients. PMID:24106222

  6. The phylogenetically-related pattern recognition receptors EFR and XA21 recruit similar immune signaling components in monocots and dicots.

    Directory of Open Access Journals (Sweden)

    Nicholas Holton

    2015-01-01

    Full Text Available During plant immunity, surface-localized pattern recognition receptors (PRRs recognize pathogen-associated molecular patterns (PAMPs. The transfer of PRRs between plant species is a promising strategy for engineering broad-spectrum disease resistance. Thus, there is a great interest in understanding the mechanisms of PRR-mediated resistance across different plant species. Two well-characterized plant PRRs are the leucine-rich repeat receptor kinases (LRR-RKs EFR and XA21 from Arabidopsis thaliana (Arabidopsis and rice, respectively. Interestingly, despite being evolutionary distant, EFR and XA21 are phylogenetically closely related and are both members of the sub-family XII of LRR-RKs that contains numerous potential PRRs. Here, we compared the ability of these related PRRs to engage immune signaling across the monocots-dicots taxonomic divide. Using chimera between Arabidopsis EFR and rice XA21, we show that the kinase domain of the rice XA21 is functional in triggering elf18-induced signaling and quantitative immunity to the bacteria Pseudomonas syringae pv. tomato (Pto DC3000 and Agrobacterium tumefaciens in Arabidopsis. Furthermore, the EFR:XA21 chimera associates dynamically in a ligand-dependent manner with known components of the EFR complex. Conversely, EFR associates with Arabidopsis orthologues of rice XA21-interacting proteins, which appear to be involved in EFR-mediated signaling and immunity in Arabidopsis. Our work indicates the overall functional conservation of immune components acting downstream of distinct LRR-RK-type PRRs between monocots and dicots.

  7. Recent advances in the development of factor Xa%Xa因子抑制剂的研究进展

    Institute of Scientific and Technical Information of China (English)

    江凯; 张惠斌; 周金培; 邢俊豪

    2012-01-01

    Xa因子是一个维生素K依赖的丝氨酸蛋白酶,它占据了凝血瀑布反应中的中心位置,可以由内源性和外源性凝血途径激活,其位置特殊性决定了其作用的重要性.利伐沙班等Xa因子抑制剂作为未来重要的口服抗血栓药物已上市,相关的其他方面的药理作用也成为研究热点.文中对Xa因子的结构、作用模式及不同结构抑制剂的最新研究进展做一综述.%Factor Xa (fXa) is a Vk dependent serine protease playing a crucial role in the blood coagulation cascade. It occupies the central position in the coagulation cascade as the convergence point between intrinsic and extrinsic pathways, which decides its significance in role. Rivaroxaban and several other fXa inhibitors have been approved for antithrombus treatment. Related pharmacological studies also become hotspots. In this review, we will illustrate the structure of factor Xa, the action mode between the inhibitors and fXa, and the recent research advances of fXa inhibitors with different structures.

  8. Fine mapping of the rice bacterial blight resistance gene Xa-4 and its co-segregation marker

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    An F2 population developed from the Xa-4 near isogenic lines,IR24 and IRBB4,was used for fine mapping of the rice bacterial blight resistance gene,Xa-4.Some restriction fragment length polymorphism (RFLP) markers on the high-density map constructed by Harushima et al.and the amplified DNA fragments homologous to the conserved domains of plant disease resistance (R) genes were used to construct the genetic linkage map around the gene Xa-4 by scoring susceptible individuals in the population.Xa-4 was mapped between the RFLP marker G181 and the polymerase chain reaction (PCR) marker M55.The R gene homologous fragment marker RS13 was found co-segregating with Xa-4 by analyzing all the plants in the population.This result opened an approach to map-based cloning of this gene,and marker RS13 can be applied to molecular marker-assisted selection of Xa-4 in rice breeding programs.

  9. Characterization of the lymphocyte membrane receptor for factor H (β1H- globulin) with an antibody to anti-factor H idiotype

    OpenAIRE

    Lambris, JD; Ross, GD

    1982-01-01

    Antibody to the binding site (idiotype) of anti-factor H was shown to have specificity for both B lymphocyte membrane H receptors and C3b. Goat F(ab’)(2) anti-human H was purified by absorption and elution from H agarose and used for rabbit immunization to produce anti-anti-H (aaH). After absorption with nonimmune goat IgG, (125)I-labeled aaH bound to B lymphocytes and to sheep erythrocytes coated with C3b (EC3b) but did not bind to T lymphocytes or to EC3d. All B cell- and C3b-specific activ...

  10. AutoGPA-Based 3D-QSAR Modeling and Molecular Docking Study on Factor Xa Inhibitors as Anticoagulant Agents

    Directory of Open Access Journals (Sweden)

    Guo Fang Yuan

    2016-01-01

    Full Text Available The three-dimensional-quantitative structure activity relationship (3D-QSAR studies were performed on a series of direct factor Xa (FXa inhibitors using AutoGPA-based modeling method in this paper. A training set of 38 molecules and a test set containing 10 molecules were used to build the 3D-QSAR model and validate the derived model, respectively. The developed model with correlation coefficients (r2 of 0.8564 and cross-validated correlation coefficients (q2 of 0.6721 were validated by an external test set of 10 molecules with predicted correlation coefficient (rpred2 of 0.6077. Docking study of FXa inhibitors and FXa active site was performed to check the induced pharmacophore query and comparative molecular field analysis (CoMFA contour maps using MOE2012.10. It was proved to be coincidence with the interaction information between ligand and FXa active site and was rendered to provide a useful tool to improve FXa inhibitors.

  11. Sequence analysis of Xa21 gene promoter in rice (Oryza sativa ‘Nipponbare')and its expression characteristics under different conditions%水稻Xa21基因启动子序列分析及其在不同条件下的表达特征

    Institute of Scientific and Technical Information of China (English)

    牟少亮; 刘志钦; 赖燕; 蔡汉阳; 何水林

    2012-01-01

    developmental stages of T1 strain of transgenic rice and its expression characteristics under different conditions with stress and hormone treatments were researched.The results indicate that GUS activity in leaf, stem and root of transgenic rice can be detected but that is the highest in root, especially in stele of root tip.With increasing of seedling age (3-, 5- and 8- to 9-leaf stages) , GUS activity in leaf increases gradually and reaches the highest at 8- to 9-leaf stage.Treatments with mechanical damage or 100 μmol · L-1 methyl jasmonate (MeJA) can lead GUS activity to increase significantly or extremely significantly, respectively, but treatments with drought, 500 μmol · L-1 salicylic acid (SA) or 100 μmol · L-1 abscisic acid (ABA) have no obvious effect on GUS activity. It is suggested that external stress has an induction to expression of Xa21 gene promoter in rice, and the expression of promoter is controlled by developmental stages and possesses the specificity in organ or tissue with the highest expression in root.Disease resistance response mediated by Xa21 gene promoter depends on the jasmonate acid (JA) signal pathway.

  12. Assessment of apixaban plasma levels by laboratory tests: suitability of three anti-Xa assays. A multicentre French GEHT study.

    Science.gov (United States)

    Gouin-Thibault, Isabelle; Flaujac, Claire; Delavenne, Xavier; Quenet, Sara; Horellou, Marie-Hélenè; Laporte, Silvy; Siguret, V; Lecompte, T

    2014-02-01

    While laboratory monitoring is not required in patients treated with apixaban, a direct factor-Xa inhibitor, assessment of its concentration is useful in some critical situations. However, few data are available on its effect on coagulation tests and on the suitability of anti-Xa assays for its quantification. It was the objective of this study to identify laboratory tests suitable for apixaban concentration assessment. Coagulation tests - PT and aPTT- and anti-Xa assays were performed in apixaban-spiked plasma samples. To evaluate the sensitivity of PT and aPTT to apixaban, we conducted a first monocenter part, with a wide range of concentrations (50-1,000 ng/ml), a large panel of reagents (20 reagents), and two coagulometers (STAR®, Stago and ACL TOP®, IL), and a second multicenter part involving 13 laboratories using either a common PT reagent (RecombiPlastin2G®) or the local PT and aPTT reagents. In the multicentre part, five blinded apixaban-spiked plasma samples (0/100/200/400/800 ng/ml - checked by HPLC-MS/MS) were used; apixaban concentrations were measured with three anti-Xa assays, apixaban calibrators and controls (Stago). PT and aPTT tests using a large panel of reagents displayed a low sensitivity to a wide range of apixaban concentrations. The concentrations to double PT ranged from 400 to >1,000 ng/ml with the 10 reagents. With the three anti-Xa assays, inter-laboratory precision and accuracy were below 11% and 12%, respectively. In conclusion, whereas PT and aPTT tests were not sensitive enough to detect apixaban, the three anti-Xa assays tested using lyophilised apixaban calibrators and controls allowed to reliably quantify a wide range of apixaban concentrations.

  13. Identification and gene prediction of a 24 kb region containing xa5, a recessive bacterial blight resistance gene in rice (Oryza sativa L.)

    Institute of Scientific and Technical Information of China (English)

    ZHONG Yiming; JIANG Guanghuai; CHEN Xuewei; XIA Zhihui; LI Xiaobing; ZHU Lihuang; ZHAI Wenxue

    2003-01-01

    Rice xa5 gene provides recessive, race-specific resistance to bacterial blight disease caused by the pathogen Xanthomonas oryzae pv. oryzae and has great value for research and breeding. In an effort to clone xa5, an F2 population of 4892 individuals was developed from the xa5 near isogenic lines, IR24 and IRBB5. A fine mapping procedure was conducted and tightly linked RFLP markers were used to screen a BAC library of IRBB56, a resistant rice line containing the xa5 gene. A 213 kb contig covering the xa5 locus was constructed. According to the sequences from the International Rice Genome Sequening Project (IRGSP), the Chinese Superhybrid Rice Genome Project (SRGP) and some sub-clones of the contig, twelve SSLP and CAPS markers were developed for fine mapping. The xa5 gene was mapped to a 0.3 cM interval between markers K5 and T4, which spanned an interval of approximately 24 kb, co-segregating with marker T2. Sequence analysis of the 24 kb region revealed that an ABC transporter and a basal transcription factor (TFIIa) were potential candidates for the xa5 resistance gene product. The molecular mechanism by which the xa5 gene provides recessive, race-specific resistance to bacterial blight will be elucidated by the functional tests of the 24 kb DNA and the candidate genes.

  14. Advances in coagulation factor Xa inhibitor%凝血因子Xa抑制药研究进展

    Institute of Scientific and Technical Information of China (English)

    黄震华

    2012-01-01

    Factor Xa is located at the intersection of the intrinsic and extrinsic pathways in the coagulation cascade. The newer anticoagulant drugs targeting factor Xa have the advantage of good efficacy, more convenience, no laboratory monitoring, and less bleeding side effect. Indirect factor Xa inhibitor fondaparinux, idraparinux, idrabiotaparinux, SR123781 and direct factor Xa inhibitor rivaroxaban, apixaban, betrixaban, edoxaban, eribaxaban, LY517717, YM150, letaxaban, otamixaban are the more studied drugs nowadays.%凝血因子Xa是内源性凝血系统和外源性凝血系统的交汇点.针对凝血因子Xa的新型抗凝药物具有疗效显著、使用方便、不需实验室监测、出血不良反应少等优点.间接凝血因子Xa抑制药璜达肝素、艾屈肝素、idrabiotaparinux、SR123781和直接凝血因子Xa抑制药利伐沙班、apixaban、betrixaban、edoxaban、eribaxaban、LY517717、YM150、letaxaban、奥米沙班是目前研究较多的药物.

  15. Magnetization of mixed ferri-ferrimagnets composed of Prussian blue analogs A1xA21-xB

    Institute of Scientific and Technical Information of China (English)

    Jiang Wei; Guan Hong-Yu; Lo Weng-Cheng

    2011-01-01

    The magnetization of ternary metal Prussian blue analogues A1xA21-xB, formed by three different sublattices A1, A2 and B, is studied by using the effective-field theory with self-spin correlations. Effects of the mole fraction x,the anisotropy and the transverse magnetic field on the magnetization are discussed.

  16. [Surgery and invasive procedures in patients on long-term treatment with oral direct thrombin or factor Xa inhibitors].

    Science.gov (United States)

    Sié, P; Samama, C-M; Godier, A; Rosencher, N; Steib, A; Llau, J-V; van der Linden, P; Pernod, G; Lecompte, T; Gouin-Thibault, I; Albaladejo, P

    2011-09-01

    Direct oral anticoagulants (DOAs), inhibitors of factor IIa or Xa, are expected to replace vitamin K antagonists in most of their indications. It is likely that patients on long-term treatment with DOAs will be exposed to elective or emergency surgery or invasive procedures. Due to the present lack of experience in such conditions, we cannot make recommendations, but only propose perioperative management for optimal safety as regards the risk of bleeding and thrombosis. DOAs may increase surgical bleeding, they have no validated antagonists, they cannot be monitored by simple, standardised laboratory assays, and their pharmacokinetics vary significantly from patient to patient. Although DOAs differ in many respects, the proposals in the perioperative setting need not be specific to each. For procedures with low risk of haemorrhage, a therapeutic window of 48 h (last administration 24h before surgery, restart 24h after) is proposed. For procedures with medium or high haemorrhagic risk, we suggest stopping DOAs 5 days before surgery to ensure complete elimination of the drug in all patients. The treatment should be resumed only when the risk of bleeding has been controlled. In patients with a high risk of thrombosis (e.g. those in atrial fibrillation with an antecedent of stroke), bridging with heparin (low molecular weight, or unfractionated if the former is contraindicated) is proposed. In emergency, the procedure should be postponed for as long as possible (minimum 1-2 half-lives) and non-specific anti-haemorrhagic agents, such as recombinant human activated factor VIIa, or prothrombin concentrates, should not be given for prophylactic reversal, due to their uncertain benefit-risk. PMID:21820844

  17. Depolymerization of Fucosylated Chondroitin Sulfate with a Modified Fenton-System and Anticoagulant Activity of the Resulting Fragments

    Science.gov (United States)

    Li, Jun-hui; Li, Shan; Zhi, Zi-jian; Yan, Lu-feng; Ye, Xing-qian; Ding, Tian; Yan, Lei; Linhardt, Robert John; Chen, Shi-guo

    2016-01-01

    Fucosylated chondroitin sulfate (fCS) from sea cucumber Isostichopus badionotus (fCS-Ib) with a chondroitin sulfate type E (CSE) backbone and 2,4-O-sulfo fucose branches has shown excellent anticoagulant activity although has also show severe adverse effects. Depolymerization represents an effective method to diminish this polysaccharide’s side effects. The present study reports a modified controlled Fenton system for degradation of fCS-Ib and the anticoagulant activity of the resulting fragments. Monosaccharides and nuclear magnetic resonance (NMR) analysis of the resulting fragments indicate that no significant chemical changes in the backbone of fCS-Ib and no loss of sulfate groups take place during depolymerization. A reduction in the molecular weight of fCS-Ib should result in a dramatic decrease in prolonging activated partial thromboplastin time and thrombin time. A decrease in the inhibition of thrombin (FIIa) by antithromin III (AT III) and heparin cofactor II (HCII), and the slight decrease of the inhibition of factor X activity, results in a significant increase of anti-factor Xa (FXa)/anti-FIIa activity ratio. The modified free-radical depolymerization method enables preparation of glycosaminoglycan (GAG) oligosaccharides suitable for investigation of clinical anticoagulant application. PMID:27657094

  18. Xanthurenic acid binds to neuronal G-protein-coupled receptors that secondarily activate cationic channels in the cell line NCB-20.

    Science.gov (United States)

    Taleb, Omar; Maammar, Mohammed; Brumaru, Daniel; Bourguignon, Jean-Jacques; Schmitt, Martine; Klein, Christian; Kemmel, Véronique; Maitre, Michel; Mensah-Nyagan, Ayikoe Guy

    2012-01-01

    Xanthurenic acid (XA) is a metabolite of the tryptophan oxidation pathway through kynurenine and 3-hydroxykynurenine. XA was until now considered as a detoxification compound and dead-end product reducing accumulation of reactive radical species. Apart from a specific role for XA in the signaling cascade resulting in gamete maturation in mosquitoes, nothing was known about its functions in other species including mammals. Based upon XA distribution, transport, accumulation and release in the rat brain, we have recently suggested that XA may potentially be involved in neurotransmission/neuromodulation, assuming that neurons presumably express specific XA receptors. Recently, it has been shown that XA could act as a positive allosteric ligand for class II metabotropic glutamate receptors. This finding reinforces the proposed signaling role of XA in brain. Our present results provide several lines of evidence in favor of the existence of specific receptors for XA in the brain. First, binding experiments combined with autoradiography and time-course analysis led to the characterization of XA binding sites in the rat brain. Second, specific kinetic and pharmacological properties exhibited by these binding sites are in favor of G-protein-coupled receptors (GPCR). Finally, in patch-clamp and calcium imaging experiments using NCB-20 cells that do not express glutamate-induced calcium signals, XA elicited specific responses involving activation of cationic channels and increases in intracellular Ca(2+) concentration. Altogether, these results suggest that XA, acting through a GPCR-induced cationic channel modulatory mechanism, may exert excitatory functions in various brain neuronal pathways. PMID:23139790

  19. Xanthurenic acid binds to neuronal G-protein-coupled receptors that secondarily activate cationic channels in the cell line NCB-20.

    Directory of Open Access Journals (Sweden)

    Omar Taleb

    Full Text Available Xanthurenic acid (XA is a metabolite of the tryptophan oxidation pathway through kynurenine and 3-hydroxykynurenine. XA was until now considered as a detoxification compound and dead-end product reducing accumulation of reactive radical species. Apart from a specific role for XA in the signaling cascade resulting in gamete maturation in mosquitoes, nothing was known about its functions in other species including mammals. Based upon XA distribution, transport, accumulation and release in the rat brain, we have recently suggested that XA may potentially be involved in neurotransmission/neuromodulation, assuming that neurons presumably express specific XA receptors. Recently, it has been shown that XA could act as a positive allosteric ligand for class II metabotropic glutamate receptors. This finding reinforces the proposed signaling role of XA in brain. Our present results provide several lines of evidence in favor of the existence of specific receptors for XA in the brain. First, binding experiments combined with autoradiography and time-course analysis led to the characterization of XA binding sites in the rat brain. Second, specific kinetic and pharmacological properties exhibited by these binding sites are in favor of G-protein-coupled receptors (GPCR. Finally, in patch-clamp and calcium imaging experiments using NCB-20 cells that do not express glutamate-induced calcium signals, XA elicited specific responses involving activation of cationic channels and increases in intracellular Ca(2+ concentration. Altogether, these results suggest that XA, acting through a GPCR-induced cationic channel modulatory mechanism, may exert excitatory functions in various brain neuronal pathways.

  20. 800 XA Application in Prco es Automation of High Titanium Slag Furnace%800 XA 在高钛渣炉过程自动化中的应用

    Institute of Scientific and Technical Information of China (English)

    杨春旺

    2013-01-01

    Combined with special requirements of manufacturing technology for the high titanium slag DC electric arc furnace and distinct characteristics of ABB -800XA system, the operation practices of the optimization design and configuration for the production process automation with ABB -800 XA system were expounded so as to a-chieve the optimization control for technological process of high titanium slag DC electric arc furnace .%结合高钛渣直流电弧炉生产工艺的特殊需求与ABB-800 XA系统的鲜明特点,阐述了采用后者对生产过程自动化进行优化设计与配置的运用实践,从而实现了对高钛渣直流电弧炉工艺过程的优化控制。

  1. Effect of famotidine on the pharmacokinetics of apixaban, an oral direct factor Xa inhibitor

    Directory of Open Access Journals (Sweden)

    Upreti VV

    2013-04-01

    Full Text Available Vijay V Upreti,1 Yan Song,1 Jessie Wang,2 Wonkyung Byon,3 Rebecca A Boyd,3 Janice M Pursley,4 Frank LaCreta,1 Charles E Frost1 1Clinical Pharmacology and Pharmacometrics, Discovery Medicine and Clinical Pharmacology, 2Exploratory Development Global Biometric Sciences, Bristol-Myers Squibb, Princeton, NJ, 3Primary Care Clinical Pharmacology, Pfizer, Groton, CT, 4Analytical and Bioanalytical Department, Bristol-Myers Squibb, Princeton, NJ, USA Background: Apixaban is an oral, selective, direct factor Xa inhibitor approved for thromboprophylaxis after orthopedic surgery and stroke prevention in patients with atrial fibrillation, and under development for treatment of venous thromboembolism. This study investigated the effect of a gastric acid suppressant, famotidine (a histamine H2-receptor antagonist, on the pharmacokinetics of apixaban in healthy subjects. Methods: This two-period, two-treatment crossover study randomized 18 healthy subjects to receive a single oral dose of apixaban 10 mg with and without a single oral dose of famotidine 40 mg administered 3 hours before dosing with apixaban. Plasma apixaban concentrations were measured up to 60 hours post-dose and pharmacokinetic parameters were calculated. Results: Famotidine did not affect maximum apixaban plasma concentration (Cmax or area under the plasma concentration-time curve from zero to infinite time (AUC∞. Point estimates for ratios of geometric means with and without famotidine were close to unity for Cmax (0.978 and AUC∞ (1.007, and 90% confidence intervals were entirely contained within the 80%–125% no-effect interval. Administration of apixaban alone and with famotidine was well tolerated. Conclusion: Famotidine does not affect the pharmacokinetics of apixaban, consistent with the physicochemical properties of apixaban (lack of an ionizable group and pH-independent solubility. Apixaban pharmacokinetics would not be affected by an increase in gastrointestinal pH due to

  2. 争奇斗艳——丰田改装车Scion xA speedster

    Institute of Scientific and Technical Information of China (English)

    志华

    2006-01-01

    世界上的车展纷繁众多,有个叫SEMA的车展每年固定在赌城拉斯维加斯举行,车展的主题就是一个字:“怪”!丰田的这款Scion xA speedster就是其中之一小怪车。

  3. Chandra Imaging and Spectroscopy of the Eastern XA Region of the Cygnus Loop Supernova Remnant

    CERN Document Server

    McEntaffer, Randall L

    2011-01-01

    The XA region of the Cygnus Loop is a bright knot of X-ray emission on the eastern edge of the supernova remnant resulting from the interaction of the supernova blast wave with density enhancements at the edge of a precursor formed cavity. To study the nature and origin of the X-ray emission we use high spatial resolution images from Chandra. Our goal is to probe the density of various spectral extraction regions to form a picture of the cavity wall and characterize the interaction between this supernova and the local interstellar medium. We find that a series of regions along the edge of the X-ray emission appears to trace out the location of the cavity wall. The best fit plasma models result in two temperature component equilibrium models for each region. The low temperature components have densities that are an order of magnitude higher than the high temperature components. The high density plasma may exist in the cavity wall where it equilibrates rapidly and cools efficiently. The low density plasma is in...

  4. Pharmacokinetics of the direct factor Xa inhibitor edoxaban and digoxin administered alone and in combination.

    Science.gov (United States)

    Mendell, Jeanne; Noveck, Robert J; Shi, Minggao

    2012-10-01

    The oral anticoagulant edoxaban, a factor Xa inhibitor, will likely be coadministered with digoxin in some patients with atrial fibrillation. Both drugs are substrates for P-glycoprotein. The objective of this phase 1, parallel study was to assess the effects of coadministration of both drugs on their respective pharmacokinetics (PK) and pharmacodynamics (PD). Forty-eight subjects, aged 18 to 45 years, received either edoxaban 60 mg once daily × 7 days (n = 24) or digoxin 0.25 mg twice daily × 2 days and once daily × 5 days (n = 24) and then concomitantly for 7 days. Serial blood and urine samples were collected for digoxin and edoxaban concentrations on days 7 and 14. Serial coagulation assays were measured for edoxaban on days 7 and 14. Edoxaban PK parameters demonstrated mild increases in area under the curve and peak concentrations of 9.5% and 15.6%, respectively, when coadministered with digoxin. Although digoxin PK parameters demonstrated increased area under the curve and peak concentrations of 8.3% and 28%, respectively, plasma concentrations were within the established therapeutic range. Edoxaban PD were consistent with PK. Both drugs were well tolerated alone or in combination. No clinically significant changes in PK, PD, or renal elimination were observed with concomitant administration of edoxaban and digoxin. PMID:23064240

  5. Spitzer IRS Observations of the XA Region in the Cygnus Loop Supernova Remnant

    CERN Document Server

    Sankrit, R; Bautista, M; Gaetz, T J; Williams, B J; Blair, W P; Borkowski, K J; Long, K S

    2014-01-01

    We report on spectra of two positions in the XA region of the Cygnus Loop supernova remnant obtained with the InfraRed Spectrograph on the Spitzer Space Telescope. The spectra span the 10-35 micron wavelength range, which contains a number of collisionally excited forbidden lines. These data are supplemented by optical spectra obtained at the Whipple Observatory and an archival UV spectrum from the International Ultraviolet Explorer. Coverage from the UV through the IR provides tests of shock wave models and tight constraints on model parameters. Only lines from high ionization species are detected in the spectrum of a filament on the edge of the remnant. The filament traces a 180 km/s shock that has just begun to cool, and the oxygen to neon abundance ratio lies in the normal range found for Galactic H II regions. Lines from both high and low ionization species are detected in the spectrum of the cusp of a shock-cloud interaction, which lies within the remnant boundary. The spectrum of the cusp region is mat...

  6. Production of Transgenic Anliucheng Sweet Orange (Citrus sinensis Osbeck) with Xa21 Gene for Potential Canker Resistance

    Institute of Scientific and Technical Information of China (English)

    LI Ding-li; XIAO Xuan; and GUO Wen-wu

    2014-01-01

    Citrus canker, an epidemic quarantine disease caused by Xanthomonas axonopodis pv. citri, has brought a great damage in citrus production worldwide. Herein, a rice PRR (pattern recognition receptor) gene Xa21 together with GUS reporter gene and hygromycin phosphotransferase gene (HPT) was introduced into Anliucheng sweet orange (Citrus sinensis Osbeck) via Agrobacterium-mediated transformation of embryogenic callus. The transgenic calluses were screened on MT basal medium containing hygromycin (HYG) and detected by histochemical GUS staining. The transgenic plantlets were recovered through somatic embryogenesis pathway. The regenerated plantlets were accustomed to and maintained in the greenhouse. The transgene integration of recovered plantlets was identiifed by PCR and Southern blot hybridization. It showed that all the transgenic plantlets tested had undergone single copy integration, the expression of Xa21 in eight different transgenic lines detected by qRT-PCR can be divided into three grades, high for T5 and T6, middle for T4 and low for the rest. The tolerance to citrus canker disease of the three recovered transgenic lines T2, T4 and T6 was assessed by in vitro pin-puncture inoculation. The results showed that all the three transgenic lines conferred improved resistance to citrus canker bacterium infection and the T4 transgenic line displayed the highest resistance. The mechanism and feasibility of rice Xa21 in triggering innate immunity in citrus was brielfy discussed.

  7. Spitzer IRS observations of the XA region in the cygnus loop supernova remnant

    Energy Technology Data Exchange (ETDEWEB)

    Sankrit, Ravi [SOFIA Science Center, NASA Ames Research Center, M/S N211-3, Moffett Field, CA 94035 (United States); Raymond, John C.; Gaetz, Terrance J. [Smithsonian Astrophysical Observatory, 60 Garden Street, MS 15, Cambridge, MA 02138 (United States); Bautista, Manuel [Department of Physics, Western Michigan University, Kalamazoo MI 49008-5252 (United States); Williams, Brian J. [Goddard Space Flight Center, Mail Code 662, Greenbelt, MD 20771 (United States); Blair, William P. [Department of Physics and Astronomy, Johns Hopkins University, Baltimore, MD 21218 (United States); Borkowski, Kazimierz J. [North Carolina State University, Raleigh, NC 27607 (United States); Long, Knox S. [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States)

    2014-05-20

    We report on spectra of two positions in the XA region of the Cygnus Loop supernova remnant obtained with the InfraRed Spectrograph on the Spitzer Space Telescope. The spectra span the 10-35 μm wavelength range, which contains a number of collisionally excited forbidden lines. These data are supplemented by optical spectra obtained at the Whipple Observatory and an archival UV spectrum from the International Ultraviolet Explorer. Coverage from the UV through the IR provides tests of shock wave models and tight constraints on model parameters. Only lines from high ionization species are detected in the spectrum of a filament on the edge of the remnant. The filament traces a 180 km s{sup –1} shock that has just begun to cool, and the oxygen to neon abundance ratio lies in the normal range found for Galactic H II regions. Lines from both high and low ionization species are detected in the spectrum of the cusp of a shock-cloud interaction, which lies within the remnant boundary. The spectrum of the cusp region is matched by a shock of about 150 km s{sup –1} that has cooled and begun to recombine. The post-shock region has a swept-up column density of about 1.3 × 10{sup 18} cm{sup –2}, and the gas has reached a temperature of 7000-8000 K. The spectrum of the Cusp indicates that roughly half of the refractory silicon and iron atoms have been liberated from the grains. Dust emission is not detected at either position.

  8. HD-DVD曙光初现——东芝HD-XA1 HD DVD播放机

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    全球首部HD DVD播放机已经推出,它就是TOSHIBA HD—XA1,这也意味蕾HD高;膏视频时代即将来到我们身边。虽然在早期,HD视频相关产品的价格不可避免地的会高高在上,但并不影响我们第一时间对这款划时代的播放机进行评测。

  9. 直接Xa因子抑制剂贝曲沙班%Direct factor Xa inhibitor betrixaban

    Institute of Scientific and Technical Information of China (English)

    王兵; 刘颖; 刘登科; 王平保

    2015-01-01

    心脑血管疾病已成为全球致病和致死率最高的疾病之一,血栓形成是心脑血管疾病的主要诱因。传统的抗凝药物以肝素和华法林为主,但存在出血、血小板减少的明显不良反应。Xa 因子处于内源性凝血和外源性凝血通路的中心位置,并且每分子的Xa因子可活化产生约1000分子的凝血酶,Xa因子抑制剂的出现为抗凝药物的发展提供了新的方向。贝曲沙班是一种口服的直接Xa因子抑制剂,也是目前唯一经肾脏排泄最少的药物,在一系列研究中显示出良好的治疗前景。主要从贝曲沙班的药物概况、相关背景、合成路线、作用机制、临床研究等方面进行介绍。%Cardiovascular and cerebrovascular diseases have become one of the leading causes of morbidity and mortality in the world. Thrombosis is a major cause. Conventional antithrombotic therapy comprises heparin, warfarin, and so on. All these agents have a potential bleeding risk and a significant adverse reaction of thrombocytopenia. Factor Xa, presented at the juncture of the intrinsic and the extrinsic pathways, plays a pivotal role in the blood coagulation cascade, and per molecule produces thrombin approximately 1000 molecules. Factor Xa inhibitors provide a new direction for the development of anticoagnlant drugs. Betrixaban is an oral direct factor Xa inhibitor, and has the lowest renal excretion. In a series of researches, betrixaban shows a good prospect. The drug situation, background, route of synthesis, pharmacological action and clinical trials researches of betrixaban are reviewed in this paper.

  10. Pharmacokinetics and Pharmacodynamics of Edoxaban, a Non-Vitamin K Antagonist Oral Anticoagulant that Inhibits Clotting Factor Xa.

    Science.gov (United States)

    Parasrampuria, Dolly A; Truitt, Kenneth E

    2016-06-01

    Edoxaban, a once daily non-vitamin K antagonist oral anticoagulant, is a direct, selective, reversible inhibitor of factor Xa (FXa). In healthy subjects, single oral doses of edoxaban result in peak plasma concentrations within 1.0-2.0 h of administration, followed by a biphasic decline. Exposure is approximately dose proportional for once daily doses of 15-150 mg. Edoxaban is predominantly absorbed from the upper gastrointestinal tract, and oral bioavailability is approximately 62 %. Food does not affect total exposure to edoxaban. The terminal elimination half-life in healthy subjects ranges from 10 to 14 h, with minimal accumulation upon repeat once daily dosing up to doses of 120 mg. The steady-state volume of distribution is approximately 107 L, and total clearance is approximately 22 L/h; renal clearance accounts for approximately 50 % of total clearance, while metabolism and biliary secretion account for the remaining 50 %. Intrinsic factors, such as age, sex and race, do not affect edoxaban pharmacokinetics after renal function is taken into account. Oral administration of edoxaban results in rapid changes in anticoagulatory biomarkers, with peak effects on anticoagulation markers (such as anti-FXa), the prothrombin time and the activated partial thromboplastin time occurring within 1-2 h of dosing. PMID:26620048

  11. Holothurian glycosaminoglycan inhibits metastasis and thrombosis via targeting of nuclear factor-κB/tissue factor/Factor Xa pathway in melanoma B16F10 cells.

    Directory of Open Access Journals (Sweden)

    Yang Zhao

    Full Text Available Holothurian glycosaminoglycan (hGAG is a high-molecular-weight form of fucosylated chondroitin sulfate and has an antithrombotic effect. Our previous studies demonstrated that hGAG efficiently inhibited tumor cell metastasis. The interplays between thrombosis and tumor progression may have a major impact on hematogenous metastasis. In this study, we demonstrated that the mouse melanoma B16F10 cells treated with hGAG displayed a significant reduction of metastasis and coagulation capacity in vitro and in vivo. Mechanistic studies revealed that hGAG treatment in B16F10 cells remarkably inhibited the formation of fibrin through attenuating the generation of activated Factor Xa (FXa, without affecting the expression of urokinase (uPA and plasminogen activator inhibitor 1 (PAI-1 that involved in fibrinolysis. Moreover, hGAG treatment downregulated the transcription and protein expression of tissue factor (TF. Promoter deletions, site mutations and functional studies identified that the nuclear transcription factor NF-κB binding region is responsible for hGAG-induced inhibition of TF expression. While the hGAG treatment of B16F10 cells was unable to inhibit NF-κB expression and phosphorylation, hGAG significantly prevented nuclear translocation of NF-κB from the cytosol, a potential mechanism underlying the transcriptional suppression of TF. Moreover, hGAG markedly suppressed the activation of p38MAPK and ERK1/2 signaling pathways, the central regulators for the expression of metastasis-related matrix metalloproteinases (MMPs. Consequently, hGAG exerts a dual function in the inhibition of metastasis and coagulation activity in mouse melanoma B16F10 cells. Our studies suggest hGAG to be a promising therapeutic agent for metastatic cancer treatment.

  12. 基于P51XA-S3微机的剑杆织机控制系统%Utilize P51XA-S3 to Design Control System of Microcomputer Rapier Loom

    Institute of Scientific and Technical Information of China (English)

    俞建军

    2011-01-01

    采用飞利浦的16位微机P51XA-S3和大容量在系统存储芯片PSD934设计一种高档的剑杆织机控制器,同时采用实时时钟芯片RS5C372A、看门狗电路IMP706、通信芯片MAX232、75176以及先藕隔离器等器件,保证系统的稳定性与先进性,系统采用C语言编程,采用光电编码器对织机主轴转过的角度进行监控,所设计的系统可支持织机的最高转速可达600r/min.%Using 16-bit microprocessor P51 XA-S3 of Philips and high-capacity in-system memory chips PSD934 to design one kind of high-end controller of rapier loom, the paper adopted devices like real time clock chip RS5C372A, watch-dog circuit IMP706, communication chip MAX232, 75176 and optical coupling isolator, etc. To ensure stability and advancement of system. The system adopts C programming language and photoelectric encoder, etc. To monitor the turning angle of the main shaft of loom. The system designed can support the highest rotational speed of 600 r/min of the loom.

  13. Anti-CD20 as the B cells targeting agent in the combined therapy to modulate anti-factor VIII immune responses in hemophilia A inhibitor mice

    Directory of Open Access Journals (Sweden)

    Chao Lien eLiu

    2014-01-01

    Full Text Available Neutralizing antibody formation against transgene products can represent a major complication following gene therapy with treatment of genetic diseases, such as hemophilia A. Although successful approaches have been developed to prevent the formation of anti-factor VIII (FVIII antibodies, innovative strategies to overcome pre-existing anti-FVIII immune responses in FVIII-primed subjects are still lacking. Anti-FVIII neutralizing antibodies circulate for long periods in part due to persistence of memory B cells. Anti-CD20 targets a variety of B cells (pre-B cells to mature/memory cells; therefore, we investigated the impact of B cell depletion on anti-FVIII immune responses in hemophilia A mice using anti-CD20 combined with regulatory T (Treg cell expansion using IL-2/IL-2mAb complexes plus rapamycin. We found that anti-CD20 alone can partially modulate anti-FVIII immune responses in both unprimed and FVIII-primed hemophilia A mice. Moreover, in mice treated with anti-CD20 + IL-2/IL-2mAb complexes + rapamycin + FVIII, anti-FVIII antibody titers were significantly reduced in comparison to mice treated with regimens targeting only B or T cells. In addition, titers remained low after a second challenge with FVIII plasmid . Treg cells and activation markers were transiently and significantly increased in the groups treated with IL-2/IL-2mAb complexes ; however,significant B cell depletion was obtained in anti-CD20-treated groups. Importantly, both FVIII-specific antibody-secreting cells and memory B cells were significantly reduced in mice treated with combination therapy. This study demonstrates that a combination regimen is highly promising as a treatment option for modulating anti-FVIII antibodies and facilitating induction of long-term tolerance to FVIII in hemophilia A mice.

  14. Efficient selection of homozy-gous lines of hybrid rice restorer with the transgene Xa21 using test cross and PCR

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The homozygous restorer lines with a single copy of the transgene Xa21 have been obtained from the progenies of transgenic Minghui63 and Yanhui559 plants through PCR marker-assisted selection and test cross. These homozygous transgenic restorer lines can be used to breed hybrid rice with high resistance to bacterial leaf blight.

  15. Transgenic expression of the dicotyledonous pattern recognition receptor EFR in rice leads to ligand-dependent activation of defense responses.

    Directory of Open Access Journals (Sweden)

    Benjamin Schwessinger

    2015-03-01

    Full Text Available Plant plasma membrane localized pattern recognition receptors (PRRs detect extracellular pathogen-associated molecules. PRRs such as Arabidopsis EFR and rice XA21 are taxonomically restricted and are absent from most plant genomes. Here we show that rice plants expressing EFR or the chimeric receptor EFR::XA21, containing the EFR ectodomain and the XA21 intracellular domain, sense both Escherichia coli- and Xanthomonas oryzae pv. oryzae (Xoo-derived elf18 peptides at sub-nanomolar concentrations. Treatment of EFR and EFR::XA21 rice leaf tissue with elf18 leads to MAP kinase activation, reactive oxygen production and defense gene expression. Although expression of EFR does not lead to robust enhanced resistance to fully virulent Xoo isolates, it does lead to quantitatively enhanced resistance to weakly virulent Xoo isolates. EFR interacts with OsSERK2 and the XA21 binding protein 24 (XB24, two key components of the rice XA21-mediated immune response. Rice-EFR plants silenced for OsSERK2, or overexpressing rice XB24 are compromised in elf18-induced reactive oxygen production and defense gene expression indicating that these proteins are also important for EFR-mediated signaling in transgenic rice. Taken together, our results demonstrate the potential feasibility of enhancing disease resistance in rice and possibly other monocotyledonous crop species by expression of dicotyledonous PRRs. Our results also suggest that Arabidopsis EFR utilizes at least a subset of the known endogenous rice XA21 signaling components.

  16. Xanthurenic Acid Activates mGlu2/3 Metabotropic Glutamate Receptors and is a Potential Trait Marker for Schizophrenia.

    Science.gov (United States)

    Fazio, Francesco; Lionetto, Luana; Curto, Martina; Iacovelli, Luisa; Cavallari, Michele; Zappulla, Cristina; Ulivieri, Martina; Napoletano, Flavia; Capi, Matilde; Corigliano, Valentina; Scaccianoce, Sergio; Caruso, Alessandra; Miele, Jessica; De Fusco, Antonio; Di Menna, Luisa; Comparelli, Anna; De Carolis, Antonella; Gradini, Roberto; Nisticò, Robert; De Blasi, Antonio; Girardi, Paolo; Bruno, Valeria; Battaglia, Giuseppe; Nicoletti, Ferdinando; Simmaco, Maurizio

    2015-12-08

    The kynurenine pathway of tryptophan metabolism has been implicated in the pathophysiology of psychiatric disorders, including schizophrenia. We report here that the kynurenine metabolite, xanturenic acid (XA), interacts with, and activates mGlu2 and mGlu3 metabotropic glutamate receptors in heterologous expression systems. However, the molecular nature of this interaction is unknown, and our data cannot exclude that XA acts primarily on other targets, such as the vesicular glutamate transporter, in the CNS. Systemic administration of XA in mice produced antipsychotic-like effects in the MK-801-induced model of hyperactivity. This effect required the presence of mGlu2 receptors and was abrogated by the preferential mGlu2/3 receptor antagonist, LY341495. Because the mGlu2 receptor is a potential drug target in the treatment of schizophrenia, we decided to measure serum levels of XA and other kynurenine metabolites in patients affected by schizophrenia. Serum XA levels were largely reduced in a large cohort of patients affected by schizophrenia, and, in patients with first-episode schizophrenia, levels remained low after 12 months of antipsychotic medication. As opposed to other kynurenine metabolites, XA levels were also significantly reduced in first-degree relatives of patients affected by schizophrenia. We suggest that lowered serum XA levels might represent a novel trait marker for schizophrenia.

  17. Determination of factor Xa inhibition doses of low-molecular heparin, nadroparin and reviparin in urological patients

    Directory of Open Access Journals (Sweden)

    Pavlović Svetlana

    2007-01-01

    Full Text Available Background/Aim. The inhibition of factor Xa (FX by the use of low-molecular heparin (LMH is important clinical procedure in patients with moderate and high risk for the developament of venous thromboembolism (VTE and pulmonary embolism (PE. The aim of this study was to determine the level of inhibition of FXa by the use of prophylactic doses of LMH nadroparin-calcium and reviparine-sodium which were applied in urological patients with moderate risk for VTE and PE. Methods. The examination included 80 urological patients divided into 4 groups after urological, uroradiological and anesthesiological preoperative preparation and categorization of anesthesiological risk according to the ASA III classification. The first two groups, of 20 patients each, received the recommended doses of LMH in accordance with the preoperative risk, and an inhibition of FXa 48 hours after the surgical operation and four hours after the administration of LMH was determined. Heptest and homogenous anti-Xa test were used for monitoring of FXa inhibition. Since the obtained anti-Xa values were not satisfactory, two more groups were formed and given double the recommended doses. In these new groups, inhibition of FXa was in recommended range. Standard descriptive statistical parameters were used for describing the charateristics of the people from the formed groups. Results. All the patients examined were clinically estimated as patients of moderate risk, for VTE and PE. There were no statistically singificant difference in body weight of the patients who received nadroparin-calcium 0.3 ml and reviparine-sodium 0.25 ml and those who received their double doses, respectively. The level of FXa inhibition in the group in which the dose of nadroparin-calcium of 0.6 ml was applied was statistically significantly higher than in the group which received the dose of 0.3 ml (Mann-Whitney U test: Z = 5.416; p < 0.0001. The level of FXa in the group given reviparine-sodium 0.5 ml was

  18. Coagulation Factor Xa inhibits cancer cell migration via LIMK1-mediated cofilin inactivation

    NARCIS (Netherlands)

    Borensztajn, Keren; Peppelenbosch, Maikel P.; Spek, C. Arnold

    2010-01-01

    Previously, we showed that activated coagulation factor X (FXa) inhibits migration of breast, lung and colon cancer cells. We showed that the effect of FXa on migration was protease-activated receptor (PAR)-1-dependent, but the subsequent cellular signaling routes remained elusive. In the current ma

  19. RUBY-1: a randomized, double-blind, placebo-controlled trial of the safety and tolerability of the novel oral factor Xa inhibitor darexaban (YM150) following acute coronary syndrome

    DEFF Research Database (Denmark)

    Steg, Ph Gabriel; Mehta, Shamir R; Jukema, J Wouter;

    2011-01-01

    To establish the safety, tolerability and most promising regimen of darexaban (YM150), a novel, oral, direct factor Xa inhibitor, for prevention of ischaemic events in acute coronary syndrome (ACS)....

  20. MODEL GROUP INVESTIGATION (GI) DIPADU PROBLEM BASED LEARNING (PBL) UNTUK MENINGKATKAN KETERAMPILAN BEKERJA ILMIAH DAN KEMAMPUAN KOGNITIF SISWA KELAS X-A1 SMAN 2 MALANG

    OpenAIRE

    Prasmala, Erfitra Rezqi

    2016-01-01

    ABSTRACTThe purpose of this study to improve (1) the skills of scientific work, (2) the cognitive abilities of students of class X-A1 at SMAN 2 Malang through the application of models Group Investigation (GI) combined with the Problem Based Learning (PBL). Type of research is Action Research Action (PTK) with research subjects-A1 class X SMAN 2 Malang. Data collected by the research instrument consisting of a sheet of observation skills of scientific work, scientific work reports, students' ...

  1. Drug-Drug Interaction Studies of Cardiovascular Drugs Involving P-Glycoprotein, an Efflux Transporter, on the Pharmacokinetics of Edoxaban, an Oral Factor Xa Inhibitor

    OpenAIRE

    Mendell, Jeanne; Zahir, Hamim; Matsushima, Nobuko; Noveck, Robert; Lee, Frank; Chen, Shuquan; Zhang, George; Shi, Minggao

    2013-01-01

    Background Edoxaban, an oral direct factor Xa inhibitor, is in development for thromboprophylaxis, including prevention of stroke and systemic embolism in patients with atrial fibrillation (AF). P-glycoprotein (P-gp), an efflux transporter, modulates absorption and excretion of xenobiotics. Edoxaban is a P-gp substrate, and several cardiovascular (CV) drugs have the potential to inhibit P-gp and increase drug exposure. Objective To assess the potential pharmacokinetic interactions of edoxaban...

  2. Edoxaban: A Novel Factor Xa Inhibitor for the Management of Non-valvular Atrial Fibrillation and Venous Thromboembolism.

    Science.gov (United States)

    Kubli, Kara A; Snead, Jessica A; Cheng-Lai, Angela

    2016-01-01

    Warfarin has been a highly prevalent agent for over 70 years; however, its use has been limited by drug-drug interactions, adverse events, and the need for frequent monitoring. To minimize these complications, several non-vitamin K oral anticoagulants have been approved, including the latest agent, edoxaban. Edoxaban is a factor Xa inhibitor approved for the prevention of stroke/systemic embolism in patients with non-valvular atrial fibrillation and for the treatment of venous thromboembolism. Edoxaban was largely studied in the Edoxaban versus Warfarin in Patients with Atrial Fibrillation (ENGAGE AF-TIMI 48) and Edoxaban versus Warfarin for the Treatment of Symptomatic Venous Thromboembolism (Hokusai-VTE) trials, both showing noninferiority when compared with warfarin. Similar to other oral anticoagulants, the most serious adverse effects of edoxaban are related to bleeding. However, there are currently no approved reversal agents. Andexanet alfa and ciraparantag are the latest agents being studied for reversal. This article provides an overview of the safety and efficacy along with the advantages and disadvantages of edoxaban. PMID:26991962

  3. Microfluidic Chip-Based Online Screening Coupled to Mass Spectrometry: Identification of Inhibitors of Thrombin and Factor Xa.

    Science.gov (United States)

    Iyer, Janaki Krishnamoorthy; Otvos, Reka A; Kool, Jeroen; Kini, R Manjunatha

    2016-02-01

    Thrombin and factor Xa (FXa) are critical enzymes of the blood coagulation cascade and are excellent targets of anticoagulant agents. Natural sources present an array of anticoagulants that can be developed as antithrombotic drugs. High-resolution, online screening techniques have been developed for the identification of drug leads from complex mixtures. In this study, we have developed and optimized a microfluidic online screening technique coupled to nano-liquid chromatography (LC) and in parallel with a mass spectrometer for the identification of thrombin and FXa inhibitors in mixtures. Inhibitors eluting from the nano-LC were split postcolumn in a 1:1 ratio; half was fed into a mass spectrometer (where its mass is detected), and the other half was fed into a microfluidic chip (which acts as a microreactor for the online assays). With our platform, thrombin and FXa inhibitors were detected in the assay in parallel with their mass identification. These methods are suitable for the identification of inhibitors from sample amounts as low as sub-microliter volumes. PMID:26323281

  4. CP1H-XA40CDR-A可编程器内置模拟量功能在制冷试验装置中应用%The Built-in Analog Functions of CP1H-XA40CDR-A Programmable Used in the Refrigeration Test Device

    Institute of Scientific and Technical Information of China (English)

    杨厚太; 郝颖磊

    2011-01-01

    主要介绍CP1H-XA40CDR-A可编程控制器的内置模拟量输入功能在制冷试验装置中的应用,着重介绍模拟量输入在恒温水箱上的应用,模拟输出在控制无级冷水机组上的应用以及编程时候需要注意的事项。%This article mainly introduces the CP1H-XA40CDR-A built-in analog input capability of programmable logic controller application in refrigeration test equipment,focuses on analog input application in thermostat water tank,analog output in controlled stepless chiller applications,and programming time on matters requiring attention.

  5. Prevention of venous thromboembolism with an oral factor Xa inhibitor, YM150, after total hip arthroplasty. A dose finding study (ONYX-2)

    DEFF Research Database (Denmark)

    Eriksson, B I; Turpie, A G G; Lassen, M R;

    2010-01-01

    , 60 or 120 mg) (double-blind) or preoperative subcutaneous (open label) enoxaparin (40 mg) for 5 weeks. The primary efficacy endpoint comprised VTE diagnosed by mandatory bilateral venography or verified symptomatic deep vein thrombosis (DVT) plus all deaths up to 9 days after surgery. The primary......BACKGROUND: Anticoagulant prophylaxis substantially reduces the risk of venous thromboembolism (VTE) after major orthopedic surgery. The direct factor Xa inhibitor YM150 is currently under investigation for the prevention of VTE, stroke and ischemic vascular events in patients after orthopedic...

  6. Studies of antimicrobial activities of some 4-thiazolidinone fused pyrimidines, [1,5]-benzodiazepines and their oxygen substituted hydroxylamine derivatives

    Directory of Open Access Journals (Sweden)

    Singh Bhawani

    2010-01-01

    Full Text Available Thiazolidin-4-one fused pyrimidines, [1,5]-benzodiazepines and their oxygen substituted hydroxylamine derivatives have been screened for antibacterial, antifungal and antimalarial activity. Bacillus subtilis, Escherichia coli, Proteus mirabilis and Salmonella typhi were used for antibacterial screening. Aspergillus fumigatus and Candida albicans were used for antifungal screening and Plasmodium species were used for antimalarial screening. The antibacterial and antifungal activities are expressed in terms of zone of inhibition and antimalarial activity is expressed in IC 50 value. Fifteen compounds 2Xa, 2Xb, 2Xc, 2Xs, 3IV, 3Va, 3Vc, 3VIIIa, 3VIIIh, 3IXa, 3IXb, 3IXc, 3Xa, 4IXa and 4Xa were tested for antibacterial as well as antifungal activity and seven compounds 2IXb, 2Xb, 3VIIIc, 3Xc, 4IXa, 4Xa and 4IXw were tested for antimalarial activity. Streptomycin, griseofulvin and chloroquine were taken as standard drugs in antibacterial, antifungal and antimalarial activity, respectively. The compound 2Xs was found significant antimicrobial against Bacillus subtilis, E. coli, Aspergillus fumigatus and Candida albicans as well as compound 3Xa was significant antimicrobial against Bacillus subtilis, E. coli, Salmonella typhi, Aspergillus fumigatus and Candida albicans. The compound 2Xb showed significant antimalarial activity.

  7. Development of clinical research on apixaban, an oral direct inhibitor of factor Xa%口服Xa因子直接抑制剂阿哌沙班的临床研究进展

    Institute of Scientific and Technical Information of China (English)

    王磊; 钟静芬; 时惠麟

    2012-01-01

      As an oral direct inhibitor of factor Xa, Apixaban is approved after dabigatran etexilate and rivaroxaban, which has been used for prevention of venous thromboembolic events in adult patients who have undergone elective hip or knee replacement surgery. This article discusses the discovery, mechanism, pharmacokinetics, and clinical trials of this emerging drug.%  阿哌沙班是口服 Xa 因子直接抑制剂,继达比加群酯和利伐沙班后上市,用于择期髋关节或膝关节置换手术的成年患者,以预防静脉血栓形成。本文主要介绍这个新药的研发背景、作用机制、药动学和临床试验。

  8. Sur quelques oxydes de cuivre La 1-xA xCuO 3-δ (A = Sr, Y) lacunaires en oxygène et dérivés de la perovskite LaCuO 3

    Science.gov (United States)

    Darracq, S.; Demazeau, G.; Largeteau, A.

    1995-05-01

    LaCuO 3 was the first Cu(III) oxide with the perovskite structure. In 1990, J.F. Bringley et al. described the structures of new non-stoichiometric oxides LaCuO 3-δ. This paper deals with new materials La 1-xA xCuO 3-δ (A = Sr, Y) isostructural with the previous oxides. Their preparation conditions, their stability domain and their physical properties are correlated to the nature of the A cation.

  9. Efficacy and safety of rivaroxaban compared with warfarin among elderly patients with nonvalvular atrial fibrillation in the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF)

    DEFF Research Database (Denmark)

    Halperin, Jonathan L; Hankey, Graeme J; Wojdyla, Daniel M;

    2014-01-01

    BACKGROUND: Nonvalvular atrial fibrillation is common in elderly patients, who face an elevated risk of stroke but difficulty sustaining warfarin treatment. The oral factor Xa inhibitor rivaroxaban was noninferior to warfarin in the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compar...... younger patients, but the efficacy and safety of rivaroxaban relative to warfarin did not differ with age, supporting rivaroxaban as an alternative for the elderly....

  10. Computational investigation of potential dosing schedules for a switch of medication from warfarin to rivaroxaban – an oral, direct Factor Xa inhibitor

    Directory of Open Access Journals (Sweden)

    Rolf eBurghaus

    2014-11-01

    Full Text Available The long-lasting anticoagulant effect of vitamin K antagonists can be problematic in cases of adverse drug reactions or when patients are switched to another anticoagulant therapy. The objective of this study was to examine in silico the anticoagulant effect of rivaroxaban, an oral, direct Factor Xa inhibitor, combined with the residual effect of discontinued warfarin. Our simulations were based on the recommended anticoagulant dosing regimen for stroke prevention in patients with atrial fibrillation. The effects of the combination of discontinued warfarin plus rivaroxaban were simulated using an extended version of a previously validated blood coagulation computer model. A strong synergistic effect of the two distinct mechanisms of action was observed in the first 2–3 days after warfarin discontinuation; thereafter, the effect was close to additive. Nomograms for the introduction of rivaroxaban therapy after warfarin discontinuation were derived for Caucasian and Japanese patients using safety and efficacy criteria described previously, together with the coagulation model. The findings of our study provide a mechanistic pharmacologic rationale for dosing schedules during the therapy switch from warfarin to rivaroxaban and support the switching strategies as outlined in the Summary of Product Characteristics and Prescribing Information for rivaroxaban.

  11. Comparative evaluation of direct thrombin and factor Xa inhibitors with antiplatelet agents under flow and static conditions: an in vitro flow chamber model.

    Directory of Open Access Journals (Sweden)

    Kazuya Hosokawa

    Full Text Available Dabigatran and rivaroxaban are novel oral anticoagulants that specifically inhibit thrombin and factor Xa, respectively. The aim of this study is to elucidate antithrombotic properties of these anticoagulant agents under arterial and venous shear conditions. Whole blood samples treated with dabigatran or rivaroxaban at 250, 500, and 1000 nM, with/without aspirin and AR-C66096, a P2Y12 antagonist, were perfused over a microchip coated with collagen and tissue thromboplastin at shear rates of 240 and 600 s(-1. Fibrin-rich platelet thrombus formation was quantified by monitoring flow pressure changes. Dabigatran at higher concentrations (500 and 1000 nM potently inhibited thrombus formation at both shear rates, whereas 1000 nM of rivaroxaban delayed, but did not completely inhibit, thrombus formation. Dual antiplatelet agents weakly suppressed thrombus formation at both shear rates, but intensified the anticoagulant effects of dabigatran and rivaroxaban. The anticoagulant effects of dabigatran and rivaroxaban were also evaluated under static conditions using thrombin generation (TG assay. In platelet-poor plasma, dabigatran at 250 and 500 nM efficiently prolonged the lag time (LT and moderately reduce peak height (PH of TG, whereas rivaroxaban at 250 nM efficiently prolonged LT and reduced PH of TG. In platelet-rich plasma, however, both anticoagulants efficiently delayed LT and reduced PH of TG. Our results suggest that dabigatran and rivaroxaban may exert distinct antithrombotic effects under flow conditions, particularly in combination with dual antiplatelet therapy.

  12. The direct thrombin inhibitors (argatroban, bivalirudin and lepirudin) and the indirect Xa-inhibitor (danaparoid) increase fibrin network porosity and thus facilitate fibrinolysis.

    Science.gov (United States)

    He, Shu; Blombäck, Margareta; Bark, Niklas; Johnsson, Hans; Wallén, N Hakan

    2010-05-01

    The present study aimed to assess whether the fibrin network structure is modified by the direct thrombin-inhibitors lepirudin, argatroban or bivalirudin and by the indirect Xa-inhibitor danaparoid. Using an in vitro assay that imitates the physiological process of coagulation from thrombin generation to fibrin formation, we examined a normal plasma pool spiked with one of the inhibitors. At concentrations considered to be the plasma levels observed during therapy, almost no influence was detected for lepirudin despite clear-cut effects on "clotting time". However, argatroban, bivalirudin and danaparoid increased the fibrin gel permeability (Ks) to a similar extent. At concentrations higher than the "therapeutic" levels, the dose-response curve in the Ks assay became very steep for lepirudin while those were shallow for the others. In parallel with the drug-induced increases of Ks, larger network pores in 3D-microscopic images and significant shortenings in "clot lysis time" induced by addition of rtPA were observed. Recombinant factor VIII (rFVIII) added to danaparoid-treated samples profoundly counteracted the increase of Ks but had only a slight or no effect on the other drugs. Thus, in vitro, argatroban, bivalirudin and danaparoid have comparable anticoagulating effects, rendering the fibrin network more permeable and less resistant to fibrinolysis. For lepirudin, the steep dose-response curve supports previous clinical findings, i.e. this thrombin inhibitor has a narrow therapeutic window. Furthermore, our data suggest that the haemostatic agent, rFVIII, might be effective in treatment of bleeding complications induced by danaparoid. PMID:20216982

  13. Home treatment of patients with low-risk pulmonary embolism with the oral factor Xa inhibitor rivaroxaban. Rationale and design of the HoT-PE Trial.

    Science.gov (United States)

    Barco, Stefano; Lankeit, Mareike; Binder, Harald; Schellong, Sebastian; Christ, Michael; Beyer-Westendorf, Jan; Duerschmied, Daniel; Bauersachs, Rupert; Empen, Klaus; Held, Matthias; Schwaiblmair, Martin; Fonseca, Cândida; Jiménez, David; Becattini, Cecilia; Quitzau, Kurt; Konstantinides, Stavros

    2016-07-01

    Pulmonary embolism (PE) is a potentially life-threatening acute cardiovascular syndrome. However, more than 95 % of patients are haemodynamically stable at presentation, and among them are patients at truly low risk who may qualify for immediate or early discharge. The Home Treatment of Pulmonary Embolism (HoT-PE) study is a prospective international multicentre single-arm phase 4 management (cohort) trial aiming to determine whether home treatment of acute low-risk PE with the oral factor Xa inhibitor rivaroxaban is feasible, effective, and safe. Patients with confirmed PE, who have no right ventricular dysfunction or free floating thrombi in the right atrium or ventricle, are eligible if they meet none of the exclusion criteria indicating haemodynamic instability, serious comorbidity or any condition mandating hospitalisation, or a familial/social environment unable to support home treatment. The first dose of rivaroxaban is given in hospital, and patients are discharged within 48 hours of presentation. Rivaroxaban is taken for at least three months. The primary outcome is symptomatic recurrent venous thromboembolism or PE-related death within three months of enrolment. Secondary outcomes include quality of life and patient satisfaction, and health care resource utilisation compared to existing data on standard-duration hospital treatment. HoT-PE is planned to analyse 1,050 enrolled patients, providing 80 % power to reject the null hypothesis that the recurrence rate of venous thromboembolism is >3 % with α≤0.05. If the hypothesis of HoT-PE is confirmed, early discharge and out-of-hospital treatment may become an attractive, potentially cost-saving option for a significant proportion of patients with acute PE.

  14. Home treatment of patients with low-risk pulmonary embolism with the oral factor Xa inhibitor rivaroxaban. Rationale and design of the HoT-PE Trial.

    Science.gov (United States)

    Barco, Stefano; Lankeit, Mareike; Binder, Harald; Schellong, Sebastian; Christ, Michael; Beyer-Westendorf, Jan; Duerschmied, Daniel; Bauersachs, Rupert; Empen, Klaus; Held, Matthias; Schwaiblmair, Martin; Fonseca, Cândida; Jiménez, David; Becattini, Cecilia; Quitzau, Kurt; Konstantinides, Stavros

    2016-07-01

    Pulmonary embolism (PE) is a potentially life-threatening acute cardiovascular syndrome. However, more than 95 % of patients are haemodynamically stable at presentation, and among them are patients at truly low risk who may qualify for immediate or early discharge. The Home Treatment of Pulmonary Embolism (HoT-PE) study is a prospective international multicentre single-arm phase 4 management (cohort) trial aiming to determine whether home treatment of acute low-risk PE with the oral factor Xa inhibitor rivaroxaban is feasible, effective, and safe. Patients with confirmed PE, who have no right ventricular dysfunction or free floating thrombi in the right atrium or ventricle, are eligible if they meet none of the exclusion criteria indicating haemodynamic instability, serious comorbidity or any condition mandating hospitalisation, or a familial/social environment unable to support home treatment. The first dose of rivaroxaban is given in hospital, and patients are discharged within 48 hours of presentation. Rivaroxaban is taken for at least three months. The primary outcome is symptomatic recurrent venous thromboembolism or PE-related death within three months of enrolment. Secondary outcomes include quality of life and patient satisfaction, and health care resource utilisation compared to existing data on standard-duration hospital treatment. HoT-PE is planned to analyse 1,050 enrolled patients, providing 80 % power to reject the null hypothesis that the recurrence rate of venous thromboembolism is >3 % with α≤0.05. If the hypothesis of HoT-PE is confirmed, early discharge and out-of-hospital treatment may become an attractive, potentially cost-saving option for a significant proportion of patients with acute PE. PMID:27010343

  15. Determination of factor X activator in the venom of the saw-scaled viper (Echis carinatus).

    Science.gov (United States)

    Stocker, K; Fischer, H; Brogli, M

    1986-01-01

    Factor X activator in Echis carinatus venom was determined by incubating the zymogen 'factor X' with venom, interrupting the activation process by ethylenediaminetetraacetic acid and measuring the generated proteinase 'factor Xa' by means of a synthetic chromogenic substrate. A comparison of factor X- and prothrombin-activating potencies in E. carinatus venoms of five different geographic origins revealed no correlation between these two procoagulant activities. PMID:3715901

  16. Anticoagulant therapy with the oral direct factor Xa inhibitors rivaroxaban, apixaban and edoxaban and the thrombin inhibitor dabigatran etexilate in patients with hepatic impairment.

    Science.gov (United States)

    Graff, Jochen; Harder, Sebastian

    2013-04-01

    The direct factor Xa (FXa) inhibitors rivaroxaban, apixaban and edoxaban, and the thrombin inhibitor dabigatran etexilate (dabigatran) have gained approval for use in several indications, most notably for the prevention and treatment of venous thromboembolism (VTE) and for the prevention of stroke in patients with atrial fibrillation. Hepatic impairment can affect the disposition of these anticoagulants considerably not only because of the hepatic metabolism of the direct FXa inhibitors but also because moderate to severely impaired hepatic function will affect coagulation. This review describes the key pharmacological properties of novel oral anticoagulants with special attention to patients with impaired hepatic function. In subjects with moderately impaired liver function (i.e. Child-Pugh classification B), the area under the plasma concentration-time curve (AUC) of rivaroxaban (10 mg single dose) is increased by 2.27-fold, which is paralleled by an increase in FXa inhibition. The AUC of apixaban (5 mg single dose) is increased by 1.09-fold, whereas the AUC of edoxaban (15 mg single dose) is decreased by 4.8 % and the AUC of dabigatran (150 mg single dose) is decreased by 5.6 %. Specific labelling restrictions for rivaroxaban, apixaban and dabigatran regarding impaired hepatic function are based on both the Child-Pugh classification and liver-related exclusion criteria applied in pivotal clinical trials. Rivaroxaban is contraindicated in patients with hepatic disease associated with coagulopathy and clinically relevant bleeding risk, including cirrhotic patients classified as Child-Pugh B and C. Apixaban can be used with caution in patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment or in patients with alanine aminotransferase and aspartate aminotransferase levels >2× upper limit of normal (ULN). Apixaban is not recommended in patients with severe hepatic impairment and is contraindicated in those with hepatic disease associated with

  17. Close linkage of a blast resistance gene, Pias(t), with a bacterial leaf blight resistance gene, Xa1-as(t), in a rice cultivar ‘Asominori’

    Science.gov (United States)

    Endo, Takashi; Yamaguchi, Masayuki; Kaji, Ryota; Nakagomi, Koji; Kataoka, Tomomori; Yokogami, Narifumi; Nakamura, Toshiki; Ishikawa, Goro; Yonemaru, Jun-ichi; Nishio, Takeshi

    2012-01-01

    It has long been known that a bacterial leaf blight-resistant line in rice obtained from a crossing using ‘Asominori’ as a resistant parent also has resistance to blast, but a blast resistance gene in ‘Asominori’ has not been investigated in detail. In the present study, a blast resistance gene in ‘Asominori’, tentatively named Pias(t), was revealed to be located within 162-kb region between DNA markers YX4-3 and NX4-1 on chromosome 4 and to be linked with an ‘Asominori’ allele of the bacterial leaf blight resistance gene Xa1, tentatively named Xa1-as(t). An ‘Asominori’ allele of Pias(t) was found to be dominant and difference of disease severity between lines having the ‘Asominori’ allele of Pias(t) and those without it was 1.2 in disease index from 0 to 10. Pias(t) was also closely linked with the Ph gene controlling phenol reaction, suggesting the possibility of successful selection of blast resistance using the phenol reaction. Since blast-resistant commercial cultivars have been developed using ‘Asominori’ as a parent, Pias(t) is considered to be a useful gene in rice breeding for blast resistance. PMID:23341747

  18. Industrial 800xA系统在无缝钢管生产中的应用%Application of Industrial 800xA System in Seamless Tube Mill

    Institute of Scientific and Technical Information of China (English)

    李建军; 余志伟; 王歌; 刘占国

    2009-01-01

    Application of ABB Industrial 800xA System in Seamless Tube Mill is described,including technological process,system configuration,software function and performance analysis etc.The automation level,productivity and control accuracy in seamless tube are extremely improved by using Industrial 800xA system,stability and reliability of production are ensured as well.%介绍ABB Industrial 800xA系统在无缝钢管生产领域中的应用,主要包括工艺流程、系统配置、软件控制功能、性能分析等内容.该系统的使用显著地提高了缝钢管生产的自动化控制水平,有效地提升了生产节奏和控制精度,生产的稳定性和可靠性得到了有效保障.

  19. Anticoagulant synergism of heparin and activated protein C in vitro. Role of a novel anticoagulant mechanism of heparin, enhancement of inactivation of factor V by activated protein C.

    OpenAIRE

    Petäjä, J; Fernández, J. A.; Gruber, A.; Griffin, J H

    1997-01-01

    Interactions between standard heparin and the physiological anticoagulant plasma protein, activated protein C (APC) were studied. The ability of heparin to prolong the activated partial thromboplastin time and the factor Xa- one-stage clotting time of normal plasma was markedly enhanced by addition of purified APC to the assays. Experiments using purified clotting factors showed that heparin enhanced by fourfold the phospholipid-dependent inactivation of factor V by APC. In contrast to factor...

  20. Efficacy and safety of new oral anticoagulants in prophylaxis and treatment of venous thromboembolism

    OpenAIRE

    Luca Masotti; Cecilia Becattini; Roberto Cappelli; Giancarlo Landini; Alessandro Pampana; Domenico Prisco; Giancarlo Agnelli

    2011-01-01

    One of the main innovation emerged in recent years in the field of venous thromboembolism (VTE) has been represented by the clinical development and marketing of new oral anticoagulant agents used for prophylaxis and acute treatment. These drugs are represented by direct thrombin inhibitors (anti-factor IIa) and the direct inhibitors of activated factor X (anti-Xa). The main achievement of these new agents is represented by their ease of use without laboratory monitoring or dose adjustment. D...

  1. Isolation, identification and predation activity of Arthrobotrys oligospora Xinjiang isolates%少孢节丛孢菌的分离鉴定及捕食线虫活性研究

    Institute of Scientific and Technical Information of China (English)

    孟庆玲; 王为升; 王俊伟; 才学鹏; 罗建勋; 陈创夫; 乔军

    2011-01-01

    为研究新疆地区捕食线虫性真菌的生物活性,本实验采用玉米粉琼脂培养基(cMA)培养分离自新疆不同地区的捕食线虫性真菌,通过对分离株纯培养物的形态学观察和18S rDNA基因序列分析,鉴定4株少孢节丛孢菌,分别命名为XA3、XA6、XD1和XD4.18S rDNA基因遗传进化分析表明,XA3、XA6、XD1和XD4新疆分离株之间同源性较高,与GenBank登录的少孢节丛孢菌CBS 289.82株同源性最高,分别为99.6%、99.5%、99.1%和98.9%.与形态学鉴定结果一致.捕食线虫活性测定试验表明,4个分离株在CMA中的捕食率为92.8%~97.6%;体外对绵羊粪便中线虫幼虫的捕食率为90.7%~95.4%,均具有很强的捕食活性.本研究为研究绵羊消化道线虫生物防控制剂奠定基础.%Nematode-trapping fungi were isolated from soils in different regions of Xinjiang province with com meal agar (CMA). Four isolates were identified as Atthrobotrys oligospora through observation of colony characteristics, mycelium, spores and sequence analysis of 18S rDNA gene, which were designated as XA3, XA6, XD1 and XD4 isolates. Phylogenetic analysis of 18S rDNA gene showed that XA3, XA6, XD1, XD4 had high homologies and the homologies were 99.6%, 99.5%, 99.1% and 98.9%, respectively, compared with A. oligosporus strain CBS 289.82, which was consistent with the results of morphological identification. The results of nematode activity of XA3, XA6, XD1, XD4 showed that the predation rates in CMA medium and in sheep feces were between 92.8% to 97.6% and 90.7% to 95.4%, respectively, showing stronger predation activity. This study laid a good foundation to develop biological agents with independent intellectual property rights in the control of gastrointestinal nematodes of sheep.

  2. Comparative physical mapping of rice BAC clones linked to resistance genes Glh,Bph-3 and xa-5 in Oryza sativa L.and O.granulata Nees et Am.ex Watt.

    Institute of Scientific and Technical Information of China (English)

    XIONG Zhiyong; TAN Guangxuan; YOU Aiqing; HE Guangyuan; SHE Chaowen; LI Lijia; SONG Yunchun

    2004-01-01

    Oryza granulata Nees et Arn. ex Watt. is one of the three wild relatives of rice, which are the most valuable for study and utilization in China. In this study, the homology and physical locations of three rice resistance genes, Glh,Bph-3 and xa-5 are comparatively analyzed between O. sativa and O. granulata by Southern blotting and fluorescence in situ hybridization (FISH). The results of Southern blotting indicate that there exist homologous sequences of the tested RFLP markers in O. granulata. By using three bacterial artificial chromosome (BAC) clones scanned by the tested RFLP as probes, FISH signals are detected on both mitotic and pachytene chromosomes in O. sativa and O. granulata.Dual-color FISH demonstrates that two of the three BAC clones (14E16 and 38J9) are located on the short arm of the same chromosome pair in O. granulata. Additionally, colinearity is shown for the two clones between O. sativa and O.granulata. Another BAC clone 44B4 is located on the end of the short arm of other chromosome pair in these two species.Although the phylogenetic relationship between O. sativa and O. granulata is the most distinct in Oryza and these two species have evidently different biological features and ecological habits, the relative lengths and arm ratios of the detected chromosomes and the relative positions of the tested clone signals on chromosomes in O. granulata are quite similar to those in O. sativa.

  3. Histones Differentially Modulate the Anticoagulant and Profibrinolytic Activities of Heparin, Heparin Derivatives, and Dabigatran.

    Science.gov (United States)

    Ammollo, Concetta Tiziana; Semeraro, Nicola; Carratù, Maria Rosaria; Colucci, Mario; Semeraro, Fabrizio

    2016-02-01

    The antithrombin activity of unfractionated heparin (UFH) is offset by extracellular histones, which, along with DNA, represent a novel mediator of thrombosis and a structural component of thrombi. Here, we systematically evaluated the effect of histones, DNA, and histone-DNA complexes on the anticoagulant and profibrinolytic activities of UFH, its derivatives enoxaparin and fondaparinux, and the direct thrombin inhibitor dabigatran. Thrombin generation was assessed by calibrated automated thrombinography, inhibition of factor Xa and thrombin by synthetic substrates, tissue plasminogen activator-mediated clot lysis by turbidimetry, and thrombin-activatable fibrinolysis inhibitor (TAFI) activation by a functional assay. Histones alone delayed coagulation and slightly stimulated fibrinolysis. The anticoagulant activity of UFH and enoxaparin was markedly inhibited by histones, whereas that of fondaparinux was enhanced. Histones neutralized both the anti-Xa and anti-IIa activities of UFH and preferentially blocked the anti-IIa activity of enoxaparin. The anti-Xa activity of fondaparinux was not influenced by histones when analyzed by chromogenic substrates, but was potentiated in a plasma prothrombinase assay. Histones inhibited the profibrinolytic activity of UFH and enoxaparin and enhanced that of fondaparinux by acting on the modulation of TAFI activation by anticoagulants. Histone H1 was mainly responsible for these effects. Histone-DNA complexes, as well as intact neutrophil extracellular traps, impaired the activities of UFH, enoxaparin, and fondaparinux. Dabigatran was not noticeably affected by histones and/or DNA, whatever the assay performed. In conclusion, histones and DNA present in the forming clot may variably influence the antithrombotic activities of anticoagulants, suggesting a potential therapeutic advantage of dabigatran and fondaparinux over heparins.

  4. Intracranial bleedings in patients on long-term anticoagulant treatment: Benefits from oral thrombin and factor Xa inhibitors in clinical practice.

    Science.gov (United States)

    Łukasik, Maria; Zawilska, Krystyna; Undas, Anetta

    2015-01-01

    Dabigatran, a direct thrombin inhibitor and activated factor X inhibitors, rivaroxaban and apixaban, used in the prevention of stroke or systemic embolism in patients with nonvalvular atrial fibrillation (AF), have several advantages over vitamin K antagonists (VKAs). The non-vitamin K oral anticoagulants (NOACs) have been shown to reduce the risk of intracranial bleedings by 50%. The current review summarizes the available data on the epidemiology, mechanisms and treatment of intracranial bleedings observed on oral anticoagulation with the focus on the specificity of NOACs in this context. PMID:26048605

  5. Amino acid region 1000-1008 of factor V is a dynamic regulator for the emergence of procoagulant activity.

    Science.gov (United States)

    Wiencek, Joesph R; Na, Mahesheema; Hirbawi, Jamila; Kalafatis, Michael

    2013-12-27

    Single chain factor V (fV) circulates as an Mr 330,000 quiescent pro-cofactor. Removal of the B domain and generation of factor Va (fVa) are vital for procoagulant activity. We investigated the role of the basic amino acid region 1000-1008 within the B domain of fV by constructing a recombinant mutant fV molecule with all activation cleavage sites (Arg(709)/Arg(1018)/Arg(1545)) mutated to glutamine (fV(Q3)), a mutant fV molecule with region 1000-1008 deleted (fV(ΔB9)), and a mutant fV molecule containing the same deletion with activation cleavage sites changed to glutamine (fV(ΔB9/Q3)). The recombinant molecules along with wild type fV (fV(WT)) were transiently expressed in COS-7L cells, purified, and assessed for their ability to bind factor Xa (fXa) prior to and following incubation with thrombin. The data showed that fV(Q3) was severely impaired in its interaction with fXa before and after incubation with thrombin. In contrast, KD(app) values for fV(ΔB9) (0.9 nM), fVa(ΔB9) (0.4 nM), and fV(ΔB9/Q3) (0.7 nM) were similar to the affinity of fVa(WT) for fXa (0.3 nM). Two-stage clotting assays revealed that although fV(Q3) was deficient in its clotting activity, fV(ΔB9/Q3) had clotting activity comparable with fVa(WT). The kcat value of prothrombinase assembled with fV(ΔB9/Q3) was minimally affected, whereas the Km value of the reaction was increased 57-fold compared with the Km value obtained with prothrombinase assembled with fVa(WT). These findings strongly suggest that amino acid region 1000-1008 of fV is a regulatory sequence protecting the organisms from spontaneous binding to fXa and unnecessary prothrombinase complex formation, which in turn results in catastrophic physiological consequences. PMID:24178294

  6. The effect of a new direct Factor Xa inhibitor on human osteoblasts: an in-vitro study comparing the effect of rivaroxaban with enoxaparin

    LENUS (Irish Health Repository)

    Solayar, Gandhi N

    2011-10-28

    Abstract Background Current treatments for the prevention of thromboembolism include heparin and low-molecular weight heparins (LMWHs). A number of studies have suggested that long term administration of these drugs may adversely affect osteoblasts and therefore, bone metabolism. Xarelto™ (Rivaroxaban) is a new anti-thrombotic drug for the prevention of venous thromboembolism in adult patients undergoing elective hip and knee replacement surgery. The aim of this in vitro study was to investigate the possible effects of rivaroxaban on osteoblast viability, function and gene expression compared to enoxaparin, a commonly used LMWH. Methods Primary human osteoblast cultures were treated with varying concentrations of rivaroxaban (0.013, 0.13, 1.3 and 13 μg\\/ml) or enoxaparin (1, 10 and 100 μg\\/ml). The effect of each drug on osteoblast function was evaluated by measuring alkaline phosphatase activity. The MTS assay was used to assess the effect of drug treatments on cell proliferation. Changes in osteocalcin, Runx2 and BMP-2 messenger RNA (mRNA) expression following drug treatments were measured by real-time polymerase chain reaction (PCR). Results Rivaroxaban and enoxaparin treatment did not adversely affect osteoblast viability. However, both drugs caused a significant reduction in osteoblast function, as measured by alkaline phosphatase activity. This reduction in osteoblast function was associated with a reduction in the mRNA expression of the bone marker, osteocalcin, the transcription factor, Runx2, and the osteogenic factor, BMP-2. Conclusions These data show that rivaroxaban treatment may negatively affect bone through a reduction in osteoblast function.

  7. Effects of C-reactive protein and pentosan polysulphate on human complement activation.

    Science.gov (United States)

    Klegeris, Andis; Singh, Edith A; McGeer, Patrick L

    2002-07-01

    Complement (C) activation is believed to play an adverse role in several chronic degenerative disease processes, including atherosclerosis, myocardial infarction and Alzheimer's disease. We developed several in vitro quantitative assays to evaluate processes which activate C in human serum, and to assess candidates which might block that activation. Binding of C-reactive protein (CRP) to immobilized cell surfaces was used as a tissue-based method of activation, while immunoglobulin G in solution was used as a surrogate antibody method. Activation was assessed by deposition of C fragments on fixed cell surfaces, or by capture of C5b-9 from solution. We observed that several cell lines, including SH-SY5Y, U-937, THP-1 and ECV304, bound CRP and activated C following attachment of cells to a plastic surface by means of air drying. Treatment of human neuroblastoma SH-SY5Y cells with the reactive oxygen intermediates generated by xanthine (Xa) - xanthine oxidase (XaOx) prior to air drying or by hydrogen peroxide solutions after air drying, enhanced C activation, possibly through oxidation of the cell lipid membrane. Several C inhibitors were tested for their effectiveness in blocking these systems. Pentosan polysulphate (PPS), an orally active agent, blocked C activation in the same concentration range of 1-1000 microg/ml as heparin, dextran sulphate, compstatin and fucoidan. PPS may have practical application as a C inhibitor. PMID:12100726

  8. AVE5026, a new hemisynthetic ultra-low-molecular-weight heparin for the prevention of venous thromboembolism in patients after total knee replacement surgery

    DEFF Research Database (Denmark)

    Lassen, Michael Rud; Dahl, O E; Mismetti, P;

    2009-01-01

    -daily doses of AVE5026 (5, 10, 20, 40, or 60 mg) or enoxaparin 40 mg in the calibrator arm. The primary efficacy end point was VTE until post-operative day 11, defined as deep vein thrombosis (DVT) detected by bilateral venography, symptomatic DVT, non-fatal pulmonary embolism (PE) and VTE-related death......BACKGROUND: AVE5026 is a new hemisynthetic ultra-low-molecular-weight heparin, with a novel anti-thrombotic profile resulting from high anti-factor (F)Xa activity and residual anti-FIIa activity. AVE5026 is in clinical development for venous thromboembolism (VTE) prevention, a frequent complication...

  9. AVE5026, a new hemisynthetic ultra-low-molecular-weight heparin for the prevention of venous thromboembolism in patients after total knee replacement surgery--TREK: a dose-ranging study

    DEFF Research Database (Denmark)

    Lassen, M R; Dahl, O E; Mismetti, P;

    2009-01-01

    -daily doses of AVE5026 (5, 10, 20, 40, or 60 mg) or enoxaparin 40 mg in the calibrator arm. The primary efficacy end point was VTE until post-operative day 11, defined as deep vein thrombosis (DVT) detected by bilateral venography, symptomatic DVT, non-fatal pulmonary embolism (PE) and VTE-related death......BACKGROUND: AVE5026 is a new hemisynthetic ultra-low-molecular-weight heparin, with a novel anti-thrombotic profile resulting from high anti-factor (F)Xa activity and residual anti-FIIa activity. AVE5026 is in clinical development for venous thromboembolism (VTE) prevention, a frequent complication...

  10. CD-ROM和CD-ROM XA

    Institute of Scientific and Technical Information of China (English)

    申江

    1995-01-01

    @@ 供计算机作大容量存储器用的激光唱片称激光唱片只读存储器(Compact Disc Read Only Memory),简称CD-ROM,其机械和光学性能大多与普通CD相同,不同之处仅在于数据格式.

  11. Bivalirudin in combination with heparin to control mesenchymal cell procoagulant activity.

    Directory of Open Access Journals (Sweden)

    Xavier Stephenne

    Full Text Available Islet and hepatocyte transplantation are associated with tissue factor-dependent activation of coagulation which elicits instant blood mediated inflammatory reaction, thereby contributing to a low rate of engraftment. The aim of this study was i to evaluate the procoagulant activity of human adult liver-derived mesenchymal progenitor cells (hALPCs, ii to compare it to other mesenchymal cells of extra-hepatic (bone marrow mesenchymal stem cells and skin fibroblasts or liver origin (liver myofibroblasts, and iii to determine the ways this activity could be modulated. Using a whole blood coagulation test (thromboelastometry, we demonstrated that all analyzed cell types exhibit procoagulant activity. The hALPCs pronounced procoagulant activity was associated with an increased tissue factor and a decreased tissue factor pathway inhibitor expression as compared with hepatocytes. At therapeutic doses, the procoagulant effect of hALPCs was inhibited by neither antithrombin activators nor direct factor Xa inhibitor or direct thrombin inhibitors individually. However, concomitant administration of an antithrombin activator or direct factor Xa inhibitor and direct thrombin inhibitor proved to be a particularly effective combination for controlling the procoagulant effects of hALPCs both in vitro and in vivo. The results suggest that this dual antithrombotic therapy should also improve the efficacy of cell transplantation in humans.

  12. Anticoagulation activity of salivary gland extract of oriental blackfly Simulium indicum

    Institute of Scientific and Technical Information of China (English)

    Subhalaxmi Borah; Ashok Naglot; Sewali Goswami; Imtiaz Rahman; Manab Deka

    2014-01-01

    Objective: To study the morphology of the salivary gland of the female blackfly of the speciesSimulium indicum gland extract.Methods:(S. indicum) along with protein profile and anticoagulant activity of the salivary protein profile of the salivary gland extract (SGE) and anticoagulant activities against thrombin, and the extrinsic and intrinsic coagulation pathways were found in S. indicum SGE in the TT, PT and APTT assays, respectively.Results:Sodium dodecyl sulphate polyacrylamide gel electrophoresis was used to analyze the and a more or less spherical reservoir. The protein contents of whole salivary glands were also quantified and the amount of salivary gland proteins in the adult female S. indicum was found out to be approximately 1.12±0.13 µg/female. At least 16 major and several minor protein bands Results revealed that each gland consisted of a cylindrical U-shaped secretory lobe were detected in the female salivary glands. The molecular masses of these major protein bands were estimated at 69, 65, 61, 58, 44, 42, 39, 33, 30, 28, 27, 26, 23, 21, 18 and 16 kDa, consecutively. Anticoagulant activities were found in S. indicum SGE in all the assays. It was found that SGE prolonged human plasma clotting time in a dose-dependent manner. Factor Xa inhibition was shown by the SGE of S. indicum. Percent inhibition value was 93.8. A positive correlation (r=0.89) was observed between total protein and percent inhibition of factor Xa. Conclusions: The present study demonstrated that the mode of action of the anticoagulant(s) is mainly on the inhibition of thrombin and factor Xa along with other target factors of the coagulation cascade.

  13. [Anticoagulation in patients with chronic renal failure].

    Science.gov (United States)

    Niksic, L; Saudan, P; Boehlen, F

    2006-03-01

    Anticoagulation may be difficult to implement in patients suffering from chronic renal failure on account of platelet disorders and impaired clearance of some anticoagulant drugs. Although no adjustment of heparin and coumarin dosage is necessary, more frequent testing of coagulation pathways may be required when these drugs are used in patients with renal failure. Long-term use of LMWH should be implemented cautiously with regular testing of anti-factor Xa activity and a half-dose may be advocated in patients with a creatinine clearance heparin-induced thrombocytopenia with regular monitoring of coagulation tests. PMID:16562602

  14. Activities.

    Science.gov (United States)

    Moody, Mally

    1992-01-01

    A series of four activities are presented to enhance students' abilities to appreciate and use trigonometry as a tool in problem solving. Activities cover problems applying the law of sines, the law of cosines, and matching equivalent trigonometric expressions. A teacher's guide, worksheets, and answers are provided. (MDH)

  15. EPCR-dependent PAR2 activation by the blood coagulation initiation complex regulates LPS-triggered interferon responses in mice.

    Science.gov (United States)

    Liang, Hai Po H; Kerschen, Edward J; Hernandez, Irene; Basu, Sreemanti; Zogg, Mark; Botros, Fady; Jia, Shuang; Hessner, Martin J; Griffin, John H; Ruf, Wolfram; Weiler, Hartmut

    2015-04-30

    Infection and inflammation are invariably associated with activation of the blood coagulation mechanism, secondary to the inflammation-induced expression of the coagulation initiator tissue factor (TF) on innate immune cells. By investigating the role of cell-surface receptors for coagulation factors in mouse endotoxemia, we found that the protein C receptor (ProcR; EPCR) was required for the normal in vivo and in vitro induction of lipopolysaccharide (LPS)-regulated gene expression. In cultured bone marrow-derived myeloid cells and in monocytic RAW264.7 cells, the LPS-induced expression of functionally active TF, assembly of the ternary TF-VIIa-Xa initiation complex of blood coagulation, and the EPCR-dependent activation of protease-activated receptor 2 (PAR2) by the ternary TF-VIIa-Xa complex were required for the normal LPS induction of messenger RNAs encoding the TLR3/4 signaling adaptor protein Pellino-1 and the transcription factor interferon regulatory factor 8. In response to in vivo challenge with LPS, mice lacking EPCR or PAR2 failed to fully initiate an interferon-regulated gene expression program that included the Irf8 target genes Lif, Iigp1, Gbp2, Gbp3, and Gbp6. The inflammation-induced expression of TF and crosstalk with EPCR, PAR2, and TLR4 therefore appear necessary for the normal evolution of interferon-regulated host responses.

  16. Comparative Assessment of the Anticoagulant Activity of Rivaroxaban and Dabigatran in Patients With Nonvalvular Atrial Fibrillation: A Noninterventional Study.

    Science.gov (United States)

    Tsantes, Argirios E; Kyriakou, Elias; Ikonomidis, Ignatios; Katogiannis, Konstantinos; Papadakis, Ioannis; Douramani, Panagiota; Kopterides, Petros; Kapsimali, Violetta; Lekakis, John; Tsangaris, Iraklis; Bonovas, Stefanos

    2016-04-01

    There is a shortage of data in everyday clinical practice about the anticoagulant effects caused by the new oral anticoagulants (NOAs). Our aim was to estimate the intensity of anticoagulant activity induced by rivaroxaban 20 mg qd and dabigatran 110 mg bid among patients with nonvalvular atrial fibrillation (NV-AF).We studied 20 patients with NV-AF treated with dabigatran, and 20 patients treated with rivaroxaban. We performed conventional coagulation tests, thrombin generation (TG) test, thromboelastometry (ROTEM), and epinephrine-induced light transmission aggregometry (LTA) in all 40 patients and 20 controls. Hemoclot Thrombin Inhibitors (HTI) and Factor Xa Direct Inhibitor (DiXaI) assay were used to measure dabigatran and rivaroxaban plasma levels, respectively.Measurements of all assays estimating anticoagulant activity across the 2 patient groups were similar, except for aPTT. Patients on dabigatran exhibited statistically significantly prolonged aPTT values (P dabigatran also showed decreased aggregation compared to those on rivaroxaban (P = 0.045). Regarding the TG test, there was no association between endogenous thrombin potential (ETP) and rivaroxaban plasma levels (P = 0.33) as opposed to dabigatran levels (P dabigatran as compared to rivaroxaban.

  17. Two acidic, anticoagulant PLA2 isoenzymes purified from the venom of monocled cobra Naja kaouthia exhibit different potency to inhibit thrombin and factor Xa via phospholipids independent, non-enzymatic mechanism.

    Directory of Open Access Journals (Sweden)

    Ashis K Mukherjee

    Full Text Available BACKGROUND: The monocled cobra (Naja kaouthia is responsible for snakebite fatality in Indian subcontinent and in south-western China. Phospholipase A2 (PLA2; EC 3.1.1.4 is one of the toxic components of snake venom. The present study explores the mechanism and rationale(s for the differences in anticoagulant potency of two acidic PLA2 isoenzymes, Nk-PLA2α (13463.91 Da and Nk-PLA2β (13282.38 Da purified from the venom of N. kaouthia. PRINCIPAL FINDINGS: By LC-MS/MS analysis, these PLA2s showed highest similarity (23.5% sequence coverage with PLA2 III isolated from monocled cobra venom. The catalytic activity of Nk-PLA2β exceeds that of Nk-PLA2α. Heparin differentially regulated the catalytic and anticoagulant activities of these Nk-PLA2 isoenzymes. The anticoagulant potency of Nk-PLA2α was comparable to commercial anticoagulants warfarin, and heparin/antithrombin-III albeit Nk-PLA2β demonstrated highest anticoagulant activity. The anticoagulant action of these PLA2s was partially contributed by a small but specific hydrolysis of plasma phospholipids. The strong anticoagulant effect of Nk-PLA2α and Nk-PLA2β was achieved via preferential, non-enzymatic inhibition of FXa (Ki = 43 nM and thrombin (Ki = 8.3 nM, respectively. Kinetics study suggests that the Nk-PLA2 isoenzymes inhibit their "pharmacological target(s" by uncompetitive mechanism without the requirement of phospholipids/Ca(2+. The anticoagulant potency of Nk-PLA2β which is higher than that of Nk-PLA2α is corroborated by its superior catalytic activity, its higher capacity for binding to phosphatidylcholine, and its greater strength of thrombin inhibition. These PLA2 isoenzymes thus have evolved to affect haemostasis by different mechanisms. The Nk-PLA2β partially inhibited the thrombin-induced aggregation of mammalian platelets suggesting its therapeutic application in the prevention of unwanted clot formation. CONCLUSION/SIGNIFICANCE: In order to develop peptide

  18. Factor V activation and inactivation by venom proteases.

    Science.gov (United States)

    Rosing, J; Govers-Riemslag, J W; Yukelson, L; Tans, G

    2001-01-01

    Blood coagulation factor V is a single-chain glycoprotein with M(r) = 330,000 which plays an important role in the procoagulant and anticoagulant pathways. Thrombin activates factor V into factor Va, a two-chain molecule which is composed of a heavy (M(r) = 105,000) and a light chain (M(r) = 71,000/74,000). Factor Va accelerates factor Xa-catalysed prothrombin activation more than 1,000-fold and under physiological conditions the cofactor activity of factor Va in prothrombin activation is down-regulated by activated protein C. Factor V can also be activated by a wide variety of snake venoms (e.g. from Vipera species, Naja naja oxiana, Bothrops atrox) and by proteases present in the bristles of a South American caterpillar (Lonomia achelous). Some venoms, notably of Vipera lebetina turanica and Lonomia achelous, contain proteases that are able to inactivate factor V or factor Va. Venom factor V activators are excellent tools in studying the structure-function relationship of factor V(a) and they are also used in diagnostic tests for quantification of plasma factor V levels and for the screening of defects in the protein C pathway. In this review, the structural and functional properties of animal venom factor V activators and inactivators is described. PMID:11910191

  19. Asymmetric nitrogen. Communications 38. Optically active 1-hydroxyl-, 1-alkoxycarbonyloxy-, and 1-tosyloxy-2, 2-bis(trifluoromethyl)-aziridines

    Energy Technology Data Exchange (ETDEWEB)

    Kostyanovskii, R.G.; Chervin, I.I.; Kadorkina, G.K.; Maldonado, I.K.A.; Nasibov, S.S.

    1985-08-20

    The authors accomplish the separation of diastereomers Xa,b and KIa,b obtained from chiral alkoxycarbonyl derivatives of hexafluoracetone oxime by reaction with CH/sub 2/N/sub 2/ through the corresponding triazolines, which were decomposed to the aziridines by photolysis or by the action of Et/sub 2/O.BF/sub 3/ at 20 C. Diasteromeric 1-alkoxycarbonyloxy-2,2-bis(trifluormethyl)ariridines, which were speated by crystallization and chromatography, under the influence of phenylhydrazine acylates give optically active 1-hydroxy-2,2-bis(trifluoromethyl)aziridine, on the basis of which optically active 1-tosyloxy-2,2-bis(trifluoromethyl)aziridine was obtained. The activation parameters of the epimerization of diasteromeric 1-alkoxycarbonyloxy-2,2-bis(trifluoromethyl)aziridine were found.

  20. Xa因子抑制剂与华法林对房颤患者抗凝疗效的比较--Meta分析与系统性评价%Meta Analysis and System Review on Comparison of Factor Xa Inhibitors and Warfarin on the Anticoagulation Effect in Patient with Artrial Fibrillation

    Institute of Scientific and Technical Information of China (English)

    刘入源; 郭凤; 阿尔达克

    2015-01-01

    目的:系统性评价口服Xa抑制剂和华法林用于房颤患者抗凝治疗的有效性和安全性。方法按照Cochrane系统评价制作方法,计算机检索Pub Med数据库、Ovid数据库、EMBASE数据库、Medline光盘数据库、同方数据库检索相关文献,查找网络上有关的所有文章及未发表的病例对照实验,并用手工检索等方法收集相关文献,并对所有文献的参考文献进行进一步的检索。收集所有相关的病例对照试验,采用Cochrane协作网提供的RevMan5.0软件进行Meta分析,以获得口服Xa抑制剂和华法林相比对房颤患者抗凝效果的有效性和安全性的相关证据。结果 Xa抑制剂与华法林相比,能明显降低总死亡率【P=0.01,优势比(OR)0.89,95%可信区间(CI)(0.82,0.98)】、出血性脑卒中发生率【P<0.00001,优势(OR)0.49,95%可信区间(CI)(0.39,0.60)】、主要部位出血发生率【P=0.07,优势比(OR)0.76,95%可信区间(CI)(0.57,1.02)】;然而缺血性脑卒中发生率【P=0.18,优势比(OR)1.08,95%可信区间(CI)(0.97,1.20)】、心肌梗死发生率【P=0.19,优势比(OR)0.94,95%可信区间(CI)(0.82,1.08)】、消化道出血发生率【P=0.65,优势比(OR)1.07,95%可信区间(CI)(0.78,1.47)】无差别。结论新型口服抗凝剂利伐沙班、阿哌沙班、依度沙班的最大优势在于出血风险减少和用药方便,但目前此类药物临床使用时间过短和上市后可能昂贵的价格,同时缺乏明确的解救药物,尚不足以将这些药物作为一线用药考虑。%Objective To evaluation system of oral factor Xa inhibitor and warfarin for the effectiveness and safety of anticoagulation in patients with atrial fibrillation treatment. Methods the method of making Cochrane system in accordance with the evaluation, Pub Med database, Ovid database, EMBASE data base, Medline CD

  1. Meta Analysis and System Review on Comparison of Factor Xa Inhibitors and Warfarin on the Anticoagulation Effect in Patient with Artrial Fibrillation%Xa因子抑制剂与华法林对房颤患者抗凝疗效的比较--Meta分析与系统性评价

    Institute of Scientific and Technical Information of China (English)

    刘入源; 郭凤; 阿尔达克

    2015-01-01

    Objective To evaluation system of oral factor Xa inhibitor and warfarin for the effectiveness and safety of anticoagulation in patients with atrial fibrillation treatment. Methods the method of making Cochrane system in accordance with the evaluation, Pub Med database, Ovid database, EMBASE data base, Medline CD ROM database, Tong fang database retrieval of relevant literature of computer retrieval, control experiments all articles related to search on the network and the case unpublished and manual search methods to collect relevant literature, and all references for further retrieval. Collect all relevant case-control trials were Meta analyzed using the Cochrane collaboration provided by RevMan 5.0 software;to obtain the oral factor Xa inhibitor and warfarin compared the relevant evidence on the efficacy and safety in patients with atrial fibrillation anticoagulation effect. Results factor Xa inhibitors compared with wafarlin can significantly reduce overall mortality [p=0.01, v odds ratio (OR)0.89, 95%confidence intercal (CI)(0.89,0.98),) hemor hemorrhagic stroke incidence [P<0.00001, OR 0.49, 95%CI(0.39,0.60) and the main parts of bleeding rate [P=0.07, OR 0.76,95%CI(0.57,1.02)];howener, ischemic stroke incidence [p=0.18, (OR) 1.08, 95%CI(0.97,1.20), and the incidence of myocardial infarction [P=0.19, (OR)0.94, 95%CI (0.82,1.08)], the incidence of gastrointestinal bleeding were [P=0.65, odds ratio (OR) 1.07, 95%confidence interval (CI) (0.78,1.47)]no difference. Conclusions The new oral anticoagulants Apixaban、Rivaroxaban、Edoxaban can reduce the bleeding risk and convenient medication, but at present the clinical drug use for too short a time and after the listing may be eapensive, and the lack of clear rescue drugs are insufficient to these drugs as first-line grugs considered.%目的:系统性评价口服Xa抑制剂和华法林用于房颤患者抗凝治疗的有效性和安全性。方法按照Cochrane系统评价制作方法,计算机检索Pub Med

  2. Laboratory determination of old and new targeted anticoagulant agents for prevention of bleeding and thrombotic events in cancer patients.

    Science.gov (United States)

    Harenberg, Job

    2016-04-01

    A two-fold prolongation of activated partial thromboplastin time (APTT) is established as therapeutic range for therapy with unfractionated heparin, hirudin and argatroban. The international normalized ratio (INR) of 2 to 3 is required to maintain anticoagulation in the therapeutic range of vitamin K antagonists. The therapeutic range of anti-factor Xa activity during therapy with low-molecular weight heparins and danaparoid are less well and of direct oral anticoagulants (DOAC) poorly defined. The relation of aPTT and INR values to thrombotic and bleeding events are well established despite a large variation of values in affected patients. The relation of coagulation values of the other anticoagulants to clinical events is open. The value of determination in cancer patients is higher because of the increased risk for thrombotic and bleeding events of this patient group. Several activities are currently undertaken to certify methods for in vitro diagnostic testing for DAOCs. PMID:27067972

  3. Obtenção e caracterização de anticorpo monoclonal murino anti-fator VIII da coagulação sangüínea Attainment and characterization of murine monoclonal anti-factor VIII antibodies

    Directory of Open Access Journals (Sweden)

    Rosana Rossi-Ferreira

    2006-06-01

    Full Text Available Entre os avanços da engenharia celular e biotecnologia nas últimas décadas, destaca-se a produção de anticorpos monoclonais murinos (AcMm utilizados no aprimoramento diagnóstico nas rotinas laboratoriais. A produção de fator VIII de alta pureza sempre foi o desejo e a preocupação das indústrias de hemoderivados para tratamento de pacientes portadores de hemofilia A, porém este produto inexiste no Brasil, sendo necessária sua obtenção no mercado internacional a custos elevados. O trabalho tem por objetivo a produção de AcMm anti-fator VIII humano (FVIII H através da expansão dos clones e caracterização imunoquímica do anticorpo. Camundongos Balb/c foram imunizados com FVIII H purificado como também proveniente de crioprecipitado e as células esplênicas dos animais foram fusionadas com células mielomatosas murinas segundo o método descrito por Kohler e Milstein para produção de híbridos em cultura. Foram testados 1.983 híbridos dos quais 105 foram submetidos à clonagem. Destes, 39 obtiveram monoclonalidade e 7 destes clones foram caracterizados através de técnicas de immunoblotting. Foram submetidas à purificação por cromatografia três imunoglobulinas de diferentes classes pertencentes aos clones LAMB1-10A1A4, LAMB1-17A1A1 e LAMB1-24A2A1. A imunoglobulina purificada pertencente ao clone LAMB1-10A1A4 foi adsorvida em coluna de imunoafinidade para purificação de concentrado de FVIII proveniente de crioprecipitado plasmático.Among the advances in cellular engineering and biotechnology over the last decades, the production of murine monoclonal antibodies (AcMm, used to improve laboratory diagnoses, stands out. The production of very pure factor VIII has always been a concern of suppliers of blood products to treat patients with hemophilia A and this product is still not produced in Brazil. Hence, it can only be attained on the international market at a high cost. The aim of this work was to produce AcMm anti-factor

  4. RIVAROXABAN: AN ORAL DIRECT INHIBITOR OF FACTOR X-A

    OpenAIRE

    Mehta Hiren R; Patel Paresh B; Galani Varsha J

    2011-01-01

    Venous thrombo embolism (VTE), which includes deep vein thrombosis and pulmonary embolism, is a major cause of morbidity and mortality in patients undergoing major orthopaedic surgery, and routine thrombo prophylaxis has been the standard of care over the last 20 years. Currently available options for the prevention of venous thrombo embolism in major orthopedic surgery include low-molecular-weight heparins, vitamin K antagonists and, more recently, the synthetic pentasaccharide fondaparinux....

  5. Características de los bovinos faenados en la Xa Región (Chile según las pautas indicadas en las normas oficiales de clasificación y tipificación Characteristics of cattle slaughtered within the Xth Region (Chile According to the terms stated by the official chilean standards for classification and carcass grading

    Directory of Open Access Journals (Sweden)

    C. GALLO

    1999-01-01

    Full Text Available Se describió el sexo y la edad de 114.666 bovinos faenados en los 22 mataderos habilitados en la Xa Región durante 1994 y las características de sus canales, utilizando las pautas impuestas por las normas chilenas oficiales de clasificación del ganado bovino y tipificación de sus canales. En cuanto a la clasificación de los bovinos, basada en la edad por cronometría dentaria (presencia de dientes de leche sin nivelar=DL , pinzas de leche niveladas=DL*, número de incisivos permanentes=2-8D, segundos medianos nivelados 8D* y el sexo, se encontró que la distribución regional de clases fue: 40.3% Novillito (DL* ó 2D; 16.1% Vaquilla (DL* ó 2D; 1.5% Torito (DL*; 10.6% Novillo (4-6D; 7.6% Vaca joven (4-6D; 9.0% Vaca adulta (8D; 6.1% Vaca vieja (8D*; 0.0% Toruno (2-8D*; 2.4% Toro (2-8D*; 4.2% Buey (8D ó 8D* y 2.2% Ternero/a (DL. Para las categorías de tipificación de las canales la distribución fue la siguiente: V=55.9%; A= 12.7%; C= 4,6%; U= 15.2%; N= 10.4% y O= 1.2%. Los diferentes grados de cobertura grasa se presentaron en un 10.1% el grado 0 (prácticamente no existe, un 78.3% el grado 1 (escasa, un 10.2% el grado 2 (abundante y un 1.4% el grado 3 (excesiva. Se registró un 7.7% de contusiones en el total de canales, de las cuales un 4.8% correspondió a contusiones de primer grado (afectan sólo tejido subcutáneo, un 2.1% de segundo grado (afectan también músculo y un 0.8% de tercer grado (afectan incluso hueso . Se concluye que en la Xa Región predomina la faena de bovinos jóvenes, de hasta 2 dientes incisivos permanentes, especialmente novillitos y vaquillas, cuyas canales presentan una cobertura grasa escasa, siendo categorizadas en V. Además, las contusiones que afectan la categorización (grado 2 y 3 se presentan en un bajo porcentajeThe present study describes the characteristics of 114.666 cattle slaughtered during 1994 in the 22 slaughterhouses functioning within the Xth Region and the corresponding carcasses produced

  6. The role of autolysis loop in determining the specificity of coagulation proteases

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    L. Yang

    2007-08-01

    Full Text Available We recently demonstrated that the substitution of the autolysis loop (residues 143 to 154 in the chymotrypsin numbering system of activated protein C (APC with the corresponding loop of factor Xa (fXa renders the APC mutant (APC/fX143-154 susceptible to inhibition by antithrombin (AT in the presence of pentasaccharide. Our recent results further indicated, that in addition to an improvement in the reactivity of APC/fX143-154 with AT, both the amidolytic and anti-factor Va activities of the mutant APC have also been significantly increased. Since the autolysis loop of APC is five residues longer than the autolysis loop of fXa, it could not be ascertained whether this loop in the mutant APC specifically interacts with the activated conformation of AT or if a shorter autolysis loop is responsible for a global improvement in the catalytic activity of the mutant protease. To answer this question, we prepared another APC mutant in which the autolysis loop of the protease was replaced with the corresponding loop of trypsin (APC/Tryp143-154. Unlike an ~500-fold improvement in the reactivity of APC/fX143-154 with AT in the presence of pentasaccharide, the reactivity of APC/Tryp143-154 with the serpin was improved ~10-fold. These results suggest that both the length and structure of residues of the autolysis loop are critical for the specificity of the coagulation protease interaction with AT. Further factor Va inactivation studies with the APC mutants revealed a similar role for the autolysis loop of APC in the interaction with its natural substrate.

  7. Semisynthesis and analysis of lipophilically modified unfractionated and low molecular mass heparins.

    Science.gov (United States)

    Malsch, R; Harenberg, J; Guerrini, M; Torri, G; Casu, B; Heene, D L

    1994-01-01

    Unfractionated heparin and LMMH were substituted with different lipophilic organic compounds. Specifically endpoint attached (LMMH-tyramine and LMMH-tyramine-FITC) and nonspecifically substituted heparins (acylated heparins, and LMMH-biotin and LMMH-cholesterol hemisuccinate) were obtained. The lipophilically substituted heparins were analysed by HPSEC and showed different retention times, high peak purity, different UV/VIS absorbances, and areas under the absorbance time curve. The determination of the average molecular mass Mn, Mm, and Mz and the polydispersity P was performed by PAGE. The substituted heparins showed an increase in their molecular mass Mm, ranging from 2.9 to 129.7% unfractionated heparin and 3.9 to 224.0% (LMMH) compared with the parent compounds (unfractionated heparin and LMMH). The anticoagulant activity was measured by anti-Factor Xa. Lipophilically modified heparin had an aXa activity ranging from 52 to 168 U/mg (unfractionated) and 60 to 108 U/mg (LMMH) and antithrombin activity ranging from 31 to 270 U/mg (unfractionated) and 5 to 15 U/mg (LMMH). The thrombin generation inhibition assay demonstrated an effective anticoagulant potency of the modified compounds. They were neutralized by different amounts (1.1 to 4.1, w/w) of protamin. 1H NMR spectroscopy revealed the specific endpoint attachment of tyramine to LMMH and FITC to LMMH-tyramine. The lipophilically modified heparins showed intact anticoagulant properties and are now used for pharmacokinetic investigations. PMID:7997890

  8. The Levels of Tissue Factor Pathway Inhibitor in Sepsis Patients Receiving Prophylactic Enoxaparin

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    Hadil A. Al Otair

    2016-05-01

    Full Text Available Objective: Sepsis syndrome is usually accompanied by activation of blood coagulation mechanisms. Earlier studies found deficiencies of the 3 main natural anticoagulants, antithrombin, protein C, and protein S. However, none of these inhibitors block tissue factor, the prime trigger of coagulation during sepsis that is controlled specifically by the tissue factor pathway inhibitor (TFPI. The aim of this study was to characterize the fluctuations in the levels of natural anticoagulants, particularly TFPI, in the course of sepsis and to find out their association with the anticoagulant action of the lowmolecular-weight heparin enoxaparin. Materials and Methods: We studied 51 consecutive patients with sepsis. Blood samples were collected from patients at baseline (0 h and at 4, 12, and 24 h after enoxaparin administration. The following assays were undertaken using commercial kits: activated partial thromboplastin time, prothrombin time, thrombin time, total and free TFPI, protein C and protein S, antithrombin, fibrinogen, and anti-factor Xa. Results: Before enoxaparin administration, there was significant prolongation of the prothrombin time and activated partial thromboplastin time, and this remained the case in the 3 subsequent samples. There was marked reduction in the levels of antithrombin, protein C, and total and free protein S to below control values throughout the study. In contrast, plasma levels of both total and free TFPI were markedly elevated and increased after enoxaparin therapy. Anti-factor Xa levels were within the therapeutic range throughout. There was no difference in TFPI levels between those patients who died and those who survived. Conclusion: Sepsis triggered marked release of TFPI from endothelial cells. This persisted and was increased further following the administration of enoxaparin. In contrast, there was marked consumption of the natural coagulation inhibitors antithrombin, protein C, and protein S. These results go

  9. Efficacy and safety of new oral anticoagulants in prophylaxis and treatment of venous thromboembolism

    Directory of Open Access Journals (Sweden)

    Luca Masotti

    2011-04-01

    Full Text Available One of the main innovation emerged in recent years in the field of venous thromboembolism (VTE has been represented by the clinical development and marketing of new oral anticoagulant agents used for prophylaxis and acute treatment. These drugs are represented by direct thrombin inhibitors (anti-factor IIa and the direct inhibitors of activated factor X (anti-Xa. The main achievement of these new agents is represented by their ease of use without laboratory monitoring or dose adjustment. Dabigatran (anti-factor IIa, rivaroxaban, and apixaban (anti-Xa are in advanced phase of clinical development with concluded phase III trials. Up to now the results of efficacy and safety of phase III clinical trials are available, while phase IV studies are currently ongoing. Overall, the phase III clinical trials showed the non inferiority of new oral anticoagulants in VTE prophylaxis of patients undergone to major orthopedic surgery, such as hip and knee arthroplasty, compared to conventional prophylaxis represented by subcutaneous low molecular weight heparin with similar safety. Moreover dabigatran has shown to be not inferior when compared to warfarin for the prevention of six months VTE recurrences, with a significative lower incidence of bleedings. Awaiting the results of many other ongoing phase III trials, since now it is possible to think that, in the next future, new oral anticoagulants will be widely diffused in clinical practice for their ease of use and feasibility. In this review the Authors analyse the available results of phase III clinical trials for dabigatran, rivaroxaban and apixaban, focusing on the antithrombotic endpoints for prevention and treatment of VTE and the bleeding risk. Moreover synthesis of ongoing trials will be displayed.

  10. Protamine sulfate down-regulates thrombin generation by inhibiting factor V activation.

    LENUS (Irish Health Repository)

    Ni Ainle, Fionnuala

    2009-08-20

    Protamine sulfate is a positively charged polypeptide widely used to reverse heparin-induced anticoagulation. Paradoxically, prospective randomized trials have shown that protamine administration for heparin neutralization is associated with increased bleeding, particularly after cardiothoracic surgery with cardiopulmonary bypass. The molecular mechanism(s) through which protamine mediates this anticoagulant effect has not been defined. In vivo administration of pharmacologic doses of protamine to BALB\\/c mice significantly reduced plasma thrombin generation and prolonged tail-bleeding time (from 120 to 199 seconds). Similarly, in pooled normal human plasma, protamine caused significant dose-dependent prolongations of both prothrombin time and activated partial thromboplastin time. Protamine also markedly attenuated tissue factor-initiated thrombin generation in human plasma, causing a significant decrease in endogenous thrombin potential (41% +\\/- 7%). As expected, low-dose protamine effectively reversed the anticoagulant activity of unfractionated heparin in plasma. However, elevated protamine concentrations were associated with progressive dose-dependent reduction in thrombin generation. To assess the mechanism by which protamine mediates down-regulation of thrombin generation, the effect of protamine on factor V activation was assessed. Protamine was found to significantly reduce the rate of factor V activation by both thrombin and factor Xa. Protamine mediates its anticoagulant activity in plasma by down-regulation of thrombin generation via a novel mechanism, specifically inhibition of factor V activation.

  11. Purification and characterization of a prothrombin-activating protease from Nephila clavata.

    Science.gov (United States)

    Joo, Han-Seung; Park, Gun-Chun; Cho, Woo Ri; Tak, Eunsik; Paik, Seung R; Chang, Chung-Soon

    2002-03-01

    We report upon the purification and characterization of a novel prothrombin-activating enzyme from the body fluid (total homogenates of isolated digestive tract without eggs, spinnerets and silk glands) of the spider, Nephila clavata by a combination of acetone fractionation, ion exchange, and Soybean trypsin inhibitor-Sepharose chromatography. Analysis of the purified enzyme with SDS-PAGE and gel filtration revealed a single polypeptide chain with an apparent molecular weight of 24kDa. The proteolytic activity of the enzyme was stable up to 50 degrees C, however, it became unstable over 55 degrees C. The enzyme had an optimum pH of 8, and Ca(2+) was not required for the enzyme activity. According to inhibition profiles obtained with several serine protease inhibitors such as PMSF and benzamidine, the purified protease is a member of the serine proteases. Bz-Ile-Glu(gamma-OR)- Gly-Arg-pNA and Z-Arg-Gly-Arg-pNA which are known as substrates for factor Xa, were hydrolyzed favorably by the enzyme. And the Nephila protease could produce thrombin from prothrombin at nM range, and form the turbid ring using fibrinogen-agarose plate. The results obtained confirmed that the purified protease is a potent prothrombin-activating activity belonging to the family of serine protease. PMID:11711126

  12. Complement Activation in Arterial and Venous Thrombosis is Mediated by Plasmin

    Science.gov (United States)

    Foley, Jonathan H.; Walton, Bethany L.; Aleman, Maria M.; O'Byrne, Alice M.; Lei, Victor; Harrasser, Micaela; Foley, Kimberley A.; Wolberg, Alisa S.; Conway, Edward M.

    2016-01-01

    Thrombus formation leading to vaso-occlusive events is a major cause of death, and involves complex interactions between coagulation, fibrinolytic and innate immune systems. Leukocyte recruitment is a key step, mediated partly by chemotactic complement activation factors C3a and C5a. However, mechanisms mediating C3a/C5a generation during thrombosis have not been studied. In a murine venous thrombosis model, levels of thrombin–antithrombin complexes poorly correlated with C3a and C5a, excluding a central role for thrombin in C3a/C5a production. However, clot weight strongly correlated with C5a, suggesting processes triggered during thrombosis promote C5a generation. Since thrombosis elicits fibrinolysis, we hypothesized that plasmin activates C5 during thrombosis. In vitro, the catalytic efficiency of plasmin-mediated C5a generation greatly exceeded that of thrombin or factor Xa, but was similar to the recognized complement C5 convertases. Plasmin-activated C5 yielded a functional membrane attack complex (MAC). In an arterial thrombosis model, plasminogen activator administration increased C5a levels. Overall, these findings suggest plasmin bridges thrombosis and the immune response by liberating C5a and inducing MAC assembly. These new insights may lead to the development of strategies to limit thrombus formation and/or enhance resolution. PMID:27077125

  13. Increased procoagulant activity of red blood cells in the presence of cisplatin

    Institute of Scientific and Technical Information of China (English)

    L(U) Cheng-fang; YU Hong-juan; HOU Jin-xiao; ZHOU Jin

    2008-01-01

    Background Cisplatin based chemotherapy is a well recognized risk factor for coagulation disordrs and thrombosis.The pathophysiological mechanisms by which cisplatin promote thrombosis are not well understood.Methods Red blood cells (RBCs) were separated from peripheral blood of patients with breast cancer (n=10) and healthy adults (n=6) and treated with cisplatin. Coagulation time of RBCs was assessed by one step recalcification time and the productions of thrombin, intrinsic and extrinsic factor Xa were measured in the presence or absence of various concentrations of lactadherin. Exposed phosphatidylserine was stained with lactadherin and observed by confocal microscopy and flow cytometry.Results Neither fresh RBCs nor RBCs treated without cisplatin had potent procoagulant activity. Cisplatin treatment increased procoagulant activity of RBCs in a cell number- and concentration-dependent manner. Exposed phosphatidylserine was stained with lactadherin and after cisplatin treatment, strong fluorescence was revealed by confocal microscopy. Lactadherin bound RBCs from patients with breast cancer increased from (1.9±0.5)% on control RBCs to (68.0±3.5)% on RBCs treated with 10 pmol/L cisplatin for 24 hours.Conclusions Cisplatin treatment increases procoagulant activity of RBCs, which have a strong association with exposure of phosphatidylserine. The increased procoagulant activity may contribute to the pathogenesis of thrombophilia during cisplatin based chemotherapy in breast cancer patients.

  14. The down-stream effects of mannan-induced lectin complement pathway activation depend quantitatively on alternative pathway amplification

    DEFF Research Database (Denmark)

    Harboe, Morten; Garred, Peter; Karlstrøm, Ellen;

    2009-01-01

    was not observed even at high mannan concentrations since addition of the inhibiting anti-MBL mAb 3F8 completely abolished generation of the terminal C5b-9 complex (TCC). However, selective blockade of AP by anti-factor D inhibited more than 80% of TCC release into the fluid phase after LP activation showing...... that AP amplification is quantitatively responsible for the final effect of initial specific LP activation. TCC generation on the solid phase was distinctly but less inhibited by anti-fD. C2 bypass of the LP pathway could be demonstrated, and AP amplification was also essential during C2 bypass in LP...... as shown by complete inhibition of TCC generation in C2-deficient serum by anti-fD and anti-properdin antibodies. In conclusion, the down-stream effect of LP activation depends strongly on AP amplification in normal human serum and in the C2 bypass pathway....

  15. Studies on prekallikrein of bovine plasma. II. Activation of prekallikrein with proteinases and properties of kallikrein activated by bovine Hageman factor.

    Science.gov (United States)

    Takahashi, H; Nagasawa, S; Suzuki, T

    1980-01-01

    Activation of bovine plasma prekallikrein was investigated with several proteinases. Highly purified bovine plasma prekallikrein was rapidly activated to kallikrein [EC 3.4.21.8] by bovine activated Hageman factor, trypsin [EC 3.4.21.4] and Pronase P (proteinases from Streptomyces griseus) and more gradually by papain [EC 3.4.22.2] and ficin [EC 3.4.22.3]. Activation of prekallikrein was also observed with bovine plasmin [EC 3.4.21.7], but not with bovine clotting factors Xa (Stuart factor) [EC 3.4.21.6] and IXa (Christmas factor) or thrombin [EC 3.4.21.5]. Urokinase [EC 3.4.99.26], Reptilase, collagenase [EC 3.4.24.3], elastase [EC 3.4.21.11], alpha-chymotrypsin [EC 3.4.21.1], Nagarse [EC 3.4.21.14], and stem bromelain [EC 3.4.22 4] did not convert prekallikrein to kallikrein. Plasma kallikrein activated to Hageman factor released kinin rapidly from bovine high molecular weight (HMW) kininogen. However, from bovine low molecular weight (LMW) kininogen, liberation of kinin was extremely slow. The kallikrein activity was inhibited by soybean trypsin inhibitor (SBTI), Trasylol, diisopropylfluorophosphate (DFP), and N-alpha-tosyl-L-lysine chloromethylketone (TLCK), but not by egg-white trypsin inhibitor (EWTI), lima bean trypsin inhibitor (LBTI), heparin or hexadimethrine bromide (Polybrene). The kallikrein formed an enzyme-inhibitor complex with SBTI and Trasylol, but not with LBTI. Prekallikrein did not react with SBTI. Prekallikrein consists of a single polypeptide chain of molecular weight about 90,000, as estimated by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. Activation of prekallikrein by Hageman factor was found to involve cleavage of the single peptide bond on the disulfide-bridged polypeptide chain, and no change of molecular weight was observed during the activation. The peptide bond cleaved in prekallikrein by the activation was an Arg-X peptide bond on a disulfide-bridged polypeptide chain.

  16. Exactin: A specific inhibitor of Factor X activation by extrinsic tenase complex from the venom of Hemachatus haemachatus.

    Science.gov (United States)

    Girish, Vallerinteavide Mavelli; Kini, R Manjunatha

    2016-01-01

    Unwanted clots lead to heart attack and stroke that result in a large number of deaths. Currently available anticoagulants have some drawbacks including their non-specific actions. Therefore novel anticoagulants that target specific steps in the coagulation pathway are being sought. Here we describe the identification and characterization of a novel anticoagulant protein from the venom of Hemachatus haemachatus (African Ringhals cobra) that specifically inhibits factor X (FX) activation by the extrinsic tenase complex (ETC) and thus named as exactin. Exactin belongs to the three-finger toxin (3FTx) family, with high sequence identity to neurotoxins and low identity to the well-characterized 3FTx anticoagulants-hemextin and naniproin. It is a mixed-type inhibitor of ETC with the kinetic constants, Ki' and Ki determined as 30.62 ± 7.73 nM and 153.75 ± 17.96 nM, respectively. Exactin does not bind to the active site of factor VIIa and factor Xa based on its weak inhibition (IC50 ≫ 300 μM) to the amidolytic activities of these proteases. Exactin shows exquisite macromolecular specificity to FX activation as compared to factor IX activation by ETC. Exactin thus displays a distinct mechanism when compared to other anticoagulants targeting ETC, with its selective preference to ETC-FX [ES] complex. PMID:27558950

  17. Exactin: A specific inhibitor of Factor X activation by extrinsic tenase complex from the venom of Hemachatus haemachatus

    Science.gov (United States)

    Girish, Vallerinteavide Mavelli; Kini, R. Manjunatha

    2016-01-01

    Unwanted clots lead to heart attack and stroke that result in a large number of deaths. Currently available anticoagulants have some drawbacks including their non-specific actions. Therefore novel anticoagulants that target specific steps in the coagulation pathway are being sought. Here we describe the identification and characterization of a novel anticoagulant protein from the venom of Hemachatus haemachatus (African Ringhals cobra) that specifically inhibits factor X (FX) activation by the extrinsic tenase complex (ETC) and thus named as exactin. Exactin belongs to the three-finger toxin (3FTx) family, with high sequence identity to neurotoxins and low identity to the well-characterized 3FTx anticoagulants-hemextin and naniproin. It is a mixed-type inhibitor of ETC with the kinetic constants, Ki’ and Ki determined as 30.62 ± 7.73 nM and 153.75 ± 17.96 nM, respectively. Exactin does not bind to the active site of factor VIIa and factor Xa based on its weak inhibition (IC50 ≫ 300 μM) to the amidolytic activities of these proteases. Exactin shows exquisite macromolecular specificity to FX activation as compared to factor IX activation by ETC. Exactin thus displays a distinct mechanism when compared to other anticoagulants targeting ETC, with its selective preference to ETC-FX [ES] complex. PMID:27558950

  18. The missense Thr211Pro mutation in the factor X activation peptide of a bleeding patient causes molecular defect in the clotting cascade.

    Science.gov (United States)

    Ding, Qiulan; Shen, Yiping; Yang, Likui; Wang, Xuefeng; Rezaie, Alireza R

    2013-07-01

    Factor X (FX) is a vitamin K-dependent coagulation zymogen, which upon activation to factor Xa assembles into the prothrombinase complex to activate prothrombin to thrombin. FX can be activated by either factor VIIa-tissue factor or factor IXa-factor VIIIa in extrinsic and intrinsic pathways, respectively. In this study, we identified a bleeding patient with moderate FX deficiency who exhibits a clotting defect only in the intrinsic pathway. Exome sequencing revealed that the patient carries a novel homozygous missense mutation that results in substitution of Thr211 with Pro in the activation peptide of FX. Thr211 is the site of an O-linked glycosylation in the activation peptide of FX. We postulated that the lack of this post-translational modification specifically impacts the activation of FX by intrinsic Xase, thereby impairing thrombin generation in the subject. To test this hypothesis, we expressed both wild-type FX and FX containing this mutation in mammalian cells and following the purification of the zymogens to homogeneity characterized their properties in both purified and plasma-based assay systems. Analysis of the results suggests that Thr211 to Pro substitution renders the FX mutant a poor substrate for both physiological activators, however, at physiological concentration of the substrate, the clotting defect manifest itself only in the intrinsic pathway, thus explaining the bleeding phenotype for the patient carrying this mutation. PMID:23677006

  19. Structure and biological activity of a fucosylated chondroitin sulfate from the sea cucumber Cucumaria japonica.

    Science.gov (United States)

    Ustyuzhanina, Nadezhda E; Bilan, Maria I; Dmitrenok, Andrey S; Shashkov, Alexander S; Kusaykin, Mikhail I; Stonik, Valentin A; Nifantiev, Nikolay E; Usov, Anatolii I

    2016-05-01

    A fucosylated chondroitin sulfate (FCS) was isolated from the body wall of Pacific sea cucumber Cucumaria japonicaby extraction in the presence of papain followed by Cetavlon precipitation and anion-exchange chromatography. FCS was shown to contain D-GalNAc, D-GlcA, L-Fuc and sulfate in molar proportions of about 1:1:1:4.5. Structure of FCS was elucidated using NMR spectroscopy and methylation analysis of the native polysaccharide and products of its desulfation and carboxyl reduction. The polysaccharide was shown to contain a typical chondroitin core → 3)-β-D-GalNAc-(1 → 4)-β-D-GlcA-(1 →. Sulfate groups in this core occupy O-4 and the majority of O-6 of GalNAc. Fucosyl branches are represented by 3,4- and 2,4-disulfated units in a ratio of 4:1 and are linked to O-3 of GlcA. In addition, ∼ 33% of GlcA are 3-O-sulfated, and hence, the presence of short fucooligosaccharide chains side by side with monofucosyl branches cannot be excluded. FCS was shown to inhibit platelets aggregation in vitro mediated by collagen and ristocetin, but not adenosine diphosphate, and demonstrated significant anticoagulant activity, which is connected with its ability to enhance inhibition of thrombin and factor Xa by antithrombin III, as well as to influence von Willebrand factor activity. The latest property significantly distinguished FCS from low-molecular-weight heparin. PMID:26681734

  20. The conformational activation of antithrombin. A 2.85-A structure of a fluorescein derivative reveals an electrostatic link between the hinge and heparin binding regions.

    Science.gov (United States)

    Huntington, J A; McCoy, A; Belzar, K J; Pei, X Y; Gettins, P G; Carrell, R W

    2000-05-19

    Antithrombin is unique among the serpins in that it circulates in a native conformation that is kinetically inactive toward its target proteinase, factor Xa. Activation occurs upon binding of a specific pentasaccharide sequence found in heparin that results in a rearrangement of the reactive center loop removing constraints on the active center P1 residue. We determined the crystal structure of an activated antithrombin variant, N135Q S380C-fluorescein (P14-fluorescein), in order to see how full activation is achieved in the absence of heparin and how the structural effects of the substitution in the hinge region are translated to the heparin binding region. The crystal structure resembles native antithrombin except in the hinge and heparin binding regions. The absence of global conformational change allows for identification of specific interactions, centered on Glu(381) (P13), that are responsible for maintenance of the solution equilibrium between the native and activated forms and establishes the existence of an electrostatic link between the hinge region and the heparin binding region. A revised model for the mechanism of the allosteric activation of antithrombin is proposed.

  1. Prothrombin kringle-2 domain has a growth inhibitory activity against basic fibroblast growth factor-stimulated capillary endothelial cells.

    Science.gov (United States)

    Lee, T H; Rhim, T; Kim, S S

    1998-10-30

    Recently, O'Reilly et al. (O'Reilly, M. S., Holmgren, L., Shing, Y., Chen, C., Rosenthal, R. A., Moses, M., Lane, W. S., Cao, Y., Sage, E. H., and Folkman, J. (1994) Cell 79, 315-328; O'Reilly, M. S., Boehm, T., Shing, Y., Fukai, N., Vasios, G., Lane, W. S., Flynn, E., Birkhead, J. R., Olsen, B. R., and Folkman, J. (1997) Cell 88, 277-285) developed a simple in vitro angiogenesis assay system using bovine capillary endothelial cell proliferation and purified potent angiogenic inhibitors, including angiostatin and endostatin. Using a simple in vitro assay for angiogenesis, we purified a protein molecule that showed anti-endothelial cell proliferative activity from the serum of New Zealand White rabbits, which was stimulated by lipopolysaccharide. The purified protein showed only bovine capillary endothelial cell growth inhibition and not any cytotoxicity. This molecule was identified as a prothrombin kringle-2 domain (fragment-2) using Edman degradation and the amino acid sequence deduced from the cloned cDNA. Both the prothrombin kringle-2 domain released from prothrombin by factor Xa cleavage and the angiogenic inhibitor purified from rabbit sera exhibited anti-endothelial cell proliferative activity. The recombinant rabbit prothrombin kringle-2 domain showed potent inhibitory activity with half-maximal concentrations (ED50) of 2 microg/ml media. As in angiostatin, the recombinant rabbit prothrombin kringle-2 domain also inhibited angiogenesis in the chorioallantoic membrane of chick embryos. PMID:9786880

  2. Systems biology of coagulation initiation: kinetics of thrombin generation in resting and activated human blood.

    Directory of Open Access Journals (Sweden)

    Manash S Chatterjee

    Full Text Available Blood function defines bleeding and clotting risks and dictates approaches for clinical intervention. Independent of adding exogenous tissue factor (TF, human blood treated in vitro with corn trypsin inhibitor (CTI, to block Factor XIIa will generate thrombin after an initiation time (T(i of 1 to 2 hours (depending on donor, while activation of platelets with the GPVI-activator convulxin reduces T(i to ∼20 minutes. Since current kinetic models fail to generate thrombin in the absence of added TF, we implemented a Platelet-Plasma ODE model accounting for: the Hockin-Mann protease reaction network, thrombin-dependent display of platelet phosphatidylserine, VIIa function on activated platelets, XIIa and XIa generation and function, competitive thrombin substrates (fluorogenic detector and fibrinogen, and thrombin consumption during fibrin polymerization. The kinetic model consisting of 76 ordinary differential equations (76 species, 57 reactions, 105 kinetic parameters predicted the clotting of resting and convulxin-activated human blood as well as predicted T(i of human blood under 50 different initial conditions that titrated increasing levels of TF, Xa, Va, XIa, IXa, and VIIa. Experiments with combined anti-XI and anti-XII antibodies prevented thrombin production, demonstrating that a leak of XIIa past saturating amounts of CTI (and not "blood-borne TF" alone was responsible for in vitro initiation without added TF. Clotting was not blocked by antibodies used individually against TF, VII/VIIa, P-selectin, GPIb, protein disulfide isomerase, cathepsin G, nor blocked by the ribosome inhibitor puromycin, the Clk1 kinase inhibitor Tg003, or inhibited VIIa (VIIai. This is the first model to predict the observed behavior of CTI-treated human blood, either resting or stimulated with platelet activators. CTI-treated human blood will clot in vitro due to the combined activity of XIIa and XIa, a process enhanced by platelet activators and which proceeds

  3. Matriptase activation connects tissue factor-dependent coagulation initiation to epithelial proteolysis and signaling.

    Science.gov (United States)

    Le Gall, Sylvain M; Szabo, Roman; Lee, Melody; Kirchhofer, Daniel; Craik, Charles S; Bugge, Thomas H; Camerer, Eric

    2016-06-23

    The coagulation cascade is designed to sense tissue injury by physical separation of the membrane-anchored cofactor tissue factor (TF) from inactive precursors of coagulation proteases circulating in plasma. Once TF on epithelial and other extravascular cells is exposed to plasma, sequential activation of coagulation proteases coordinates hemostasis and contributes to host defense and tissue repair. Membrane-anchored serine proteases (MASPs) play critical roles in the development and homeostasis of epithelial barrier tissues; how MASPs are activated in mature epithelia is unknown. We here report that proteases of the extrinsic pathway of blood coagulation transactivate the MASP matriptase, thus connecting coagulation initiation to epithelial proteolysis and signaling. Exposure of TF-expressing cells to factors (F) VIIa and Xa triggered the conversion of latent pro-matriptase to an active protease, which in turn cleaved the pericellular substrates protease-activated receptor-2 (PAR2) and pro-urokinase. An activation pathway-selective PAR2 mutant resistant to direct cleavage by TF:FVIIa and FXa was activated by these proteases when cells co-expressed pro-matriptase, and matriptase transactivation was necessary for efficient cleavage and activation of wild-type PAR2 by physiological concentrations of TF:FVIIa and FXa. The coagulation initiation complex induced rapid and prolonged enhancement of the barrier function of epithelial monolayers that was dependent on matriptase transactivation and PAR2 signaling. These observations suggest that the coagulation cascade engages matriptase to help coordinate epithelial defense and repair programs after injury or infection, and that matriptase may contribute to TF-driven pathogenesis in cancer and inflammation. PMID:27114461

  4. Crystal Structure of the Fab Fragment of an Anti-factor IX Antibody 10C12

    Institute of Scientific and Technical Information of China (English)

    SHI Xiao-Li; ZENG Tu; HUANG Ming-Dong

    2008-01-01

    10C12 is an anticoagulant antibody identified from a phage display single-chain Fv human antibody library. It can be directed at the calcium-stabilized Gla domain of Factor-IX, an important coagulation factor in intrinsic pathway of blood coagulation cascade, and interfere with membrane anchoring of Factor IX, thus inhibiting blood coagulation function. 10C12 has been demonstrated as an effective anti-coagulant in attenuating thrombosis in several different animal models. Here, we report the crystal structure of the Fab fragment of 10C12. The crystal contains two Fab molecules in the asymmetric unit with identical conformation, forming a lattice with large cavities. In addition, comparison of this free Fab with the antigen-bound structure of 10C12 shows no change in CDR conformations and the relative disposition of the variable subunits of H and L chains, suggesting the rigid conformation of this 10C12 Fab and a lock-and-key mechanism of antibody-antigen recognition for 10C 12.

  5. How I diagnose and manage HIT.

    Science.gov (United States)

    Warkentin, Theodore E

    2011-01-01

    Heparin-induced thrombocytopenia (HIT) is a prothrombotic drug reaction caused by platelet-activating IgG antibodies that recognize platelet factor 4 (PF4)/polyanion complexes. Platelet activation assays, such as the serotonin-release assay, are superior to PF4-dependent immunoassays in discerning which heparin-induced antibodies are clinically relevant. When HIT is strongly suspected, standard practice includes substituting heparin with an alternative anticoagulant; the 2 US-approved agents are the direct thrombin inhibitors (DTIs) lepirudin and argatroban, which are "niche" agents used only to manage HIT. However, only ~ 10% of patients who undergo serological investigation for HIT actually have this diagnosis. Indeed, depending on the clinical setting, only 10%-50% of patients with positive PF4-dependent immunoassays have platelet-activating antibodies. Therefore, overdiagnosis of HIT can be minimized by insisting that a positive platelet activation assay be required for definitive diagnosis of HIT. For these reasons, a management strategy that considers the real possibility of non-HIT thrombocytopenia is warranted. One approach that I suggest is to administer an indirect, antithrombin (AT)-dependent factor Xa inhibitor (danaparoid or fondaparinux) based upon the following rationale: (1) effectiveness in treating and preventing HIT-associated thrombosis; (2) effectiveness in treating and preventing thrombosis in diverse non-HIT situations; (3) both prophylactic- and therapeutic-dose protocols exist, permitting dosing appropriate for the clinical situation; (4) body weight-adjusted dosing protocols and availability of specific anti-factor Xa monitoring reduce risk of under- or overdosing (as can occur with partial thromboplastin time [PTT]-adjusted DTI therapy); (5) their long half-lives reduce risk of rebound hypercoagulability; (6) easy coumarin overlap; and (7) relatively low cost. PMID:22160026

  6. Representation of molecular structure using quantum topology with inductive logic programming in structure-activity relationships.

    Science.gov (United States)

    Buttingsrud, Bård; Ryeng, Einar; King, Ross D; Alsberg, Bjørn K

    2006-06-01

    The requirement of aligning each individual molecule in a data set severely limits the type of molecules which can be analysed with traditional structure activity relationship (SAR) methods. A method which solves this problem by using relations between objects is inductive logic programming (ILP). Another advantage of this methodology is its ability to include background knowledge as 1st-order logic. However, previous molecular ILP representations have not been effective in describing the electronic structure of molecules. We present a more unified and comprehensive representation based on Richard Bader's quantum topological atoms in molecules (AIM) theory where critical points in the electron density are connected through a network. AIM theory provides a wealth of chemical information about individual atoms and their bond connections enabling a more flexible and chemically relevant representation. To obtain even more relevant rules with higher coverage, we apply manual postprocessing and interpretation of ILP rules. We have tested the usefulness of the new representation in SAR modelling on classifying compounds of low/high mutagenicity and on a set of factor Xa inhibitors of high and low affinity. PMID:17054018

  7. Procoagulant Phospholipids and Tissue Factor Activity in Cerebrospinal Fluid from Patients with Intracerebral Haemorrhage

    Directory of Open Access Journals (Sweden)

    Patrick Van Dreden

    2014-01-01

    Full Text Available Brain contains large amounts of tissue factor, the major initiator of the coagulation cascade. Neuronal apoptosis after intracerebral haemorrhage (ICH leads to the shedding of procoagulant phospholipids (PPLs. The aim of this study was to investigate the generation of PPL, tissue factor activity (TFa, and D-Dimer (D-Di in the cerebrospinal fluid (CSF at the acute phase of ICH in comparison with other brain diseases and to examine the relationship between these factors and the outcome of ICH. CSF was collected from 112 patients within 48 hours of hospital admission. Thirty-one patients with no neurological or biochemical abnormalities were used to establish reference range in the CSF (“controls”. Thirty had suffered an ICH, and 51 other neurological diagnoses [12: ventricular drainage following brain surgery, 13: viral meningitis, 15: bacterial meningitis, and 11 a neurodegenerative disease (NDD]. PPL was measured using a factor Xa-based coagulation assay and TFa by one home test. PPL, D-Di, and TFa were significantly higher (P<0.001 in the CSF of patients with ICH than in controls. TFa levels were significantly (P<0.05 higher in ICH than in patients with meningitides or NDD. Higher levels (P<0.05 of TFa were observed in patients with ICH who died than in survivors. TFa measurement in the CSF of patients with ICH could constitute a new prognostic marker.

  8. Serine proteinase inhibition by the active site titrant N alpha-(N, N-dimethylcarbamoyl)-alpha-azaornithine p-nitrophenyl ester. A comparative study.

    Science.gov (United States)

    Ascenzi, P; Balliano, G; Gallina, C; Polticelli, F; Bolognesi, M

    2000-02-01

    Kinetics for the hydrolysis of the chromogenic active-site titrant N alpha-(N,N-dimethylcarbamoyl)-alpha-azaornithine p-nitrophenyl ester (Dmc-azaOrn-ONp) catalysed by bovine beta-trypsin, bovine alpha-thrombin, bovine Factor Xa, human alpha-thrombin, human Factor Xa, human Lys77-plasmin, human urinary kallikrein, Mr 33 000 and Mr 54 000 species of human urokinase, porcine pancreatic beta-kallikrein-A and -B and Ancrod (the coagulating serine proteinase from the Malayan pit viper Agkistrodon rhodostoma venom) have been obtained between pH 6.0 and 8.0, at 21.0 degrees C, and analysed in parallel with those for the enzymatic cleavage of N alpha-(N,N-dimethylcarbamoyl)-alpha-azalysine p-nitrophenyl ester (Dmc-azaLys-ONp). The enzyme kinetics are consistent with the minimum three-step catalytic mechanism of serine proteinases, the rate-limiting step being represented by the deacylation process. Bovine beta-trypsin kinetics are modulated by the acid-base equilibrium of the His57 catalytic residue (pKa approximately 6.9). Dmc-azaOrn-ONp and Dmc-azaLys-ONp bind stoichiometrically to the serine proteinase active site, and allow the reliable determination of the active enzyme concentration between 1.0 x 10-6 M and 3.0 x 10-4 M. The affinity and the reactivity for Dmc-azaOrn-ONp (expressed by Ks and k+2/Ks, respectively) of the serine proteinases considered are much lower than those for Dmc-azaLys-ONp. The very different affinity and reactivity properties for Dmc-azaOrn-ONp and Dmc-azaLys-ONp have been related to the different size of the ornithine/lysine side chains, and to the ensuing different positioning of the active-site titrants upon binding to the enzyme catalytic centre (i.e. to P1-S1 recognition). These data represent the first detailed comparative investigation on the catalytic properties of serine proteinases towards an ornithine derivative (i. e. Dmc-azaOrn-ONp).

  9. Hemorrhagic, coagulant and fibrino(geno)lytic activities of crude venom and fractions from mapanare (Bothrops colombiensis) snakes.

    Science.gov (United States)

    Girón, María E; Salazar, Ana M; Aguilar, Irma; Pérez, John C; Sánchez, Elda E; Arocha-Piñango, Carmen L; Rodríguez-Acosta, Alexis; Guerrero, Belsy

    2008-01-01

    Bothrops colombiensis venom from two similar geographical locations were tested for their hemostatic functions and characterized by gel-filtration chromatography and SDS-PAGE electrophoresis. The snakes were from Caucagua and El Guapo towns of the Venezuelan state of Miranda. Fibrino(geno)lytic, procoagulant, hemorrhagic, lethal activities, gel-filtration chromatography and SDS-PAGE profiles were analyzed and compared for both venoms. The highest hemorrhagic activity of 5.3 mug was seen in El Guapo venom while Caucagua venom had the lowest LD(50) of 5.8 mg/kg. Both venoms presented similar thrombin-like activity. El Guapo showed a factor Xa-like activity two times higher than Caucagua. Differences were observed in kallikrein-like and t-PA activities, being highest in El Guapo. Caucagua venom showed the maximum fibrin lysis. Both crude venom runs on Sephadex G-100 chromatography gave fraction SII with the high fibrinolytic activity. Proteases presented in SII fractions and eluted from Benzamidine-Sepharose (not bound to the column) provoked a fast degradation of fibrinogen alpha chains and a slower degradation of beta chains, which could possibly be due to a higher content of alpha fibrinogenases in these venoms. The fibrinogenolytic activity was decreased by metalloprotease inhibitors. The results suggested that metalloproteases in SII fractions were responsible for the fibrinolytic activity. The analysis of samples for fibrin-zymography of SII fractions showed an active band with a molecular mass of approximately 30 kDa. These results reiterate the importance of using pools of venoms for antivenom immunization, to facilitate the neutralization of the maximum potential number of toxins.

  10. Evidence for a compensatory mechanism regulating Ag-NOR activity in families with de novo 21;21 translocation Down syndrome.

    Science.gov (United States)

    Nikolis, J; Kekic, V

    1988-01-01

    Nucleolus organizing region (NOR) activity in seven probands with Down syndrome due to a de novo (21;21) translocation and their parents was analyzed on the basis of total Ag-NOR size per cell, mean Ag-NOR size per cell (Xc), mean Ag-NOR size per acrocentic (Xa), and the characteristic Ag-NOR number of each subject. The results showed intercellular variations in total Ag-NOR size per cell in all subjects, as well as interindividual variations in mean Ag-NOR size per cell. When the subjects were grouped according to their characteristic Ag-NOR number and the mean Ag-NOR size per cell for each group (GXc) and the mean Ag-NOR size per acrocentric for each group (GXa) were calculated, a number of interesting and significant correlations were found: (1) GXc correlated perfectly with the group's characteristic Ag-NOR number, (2) GXa varied inversely with the group's characteristic Ag-NOR number, and (3) GXc and GXa varied inversely with each other. These results suggest that if the Ag-NOR number of a cell decreases, the total NOR activity of the cell also decreases, but the NOR activity of its chromosomes increases. This finding supports the existence of a compensatory mechanism that regulates NOR activity on the cellular level. PMID:2458214

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

    International Nuclear Information System (INIS)

    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 Arg152-Ile153. 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 Arg152 → 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 Mr∼40 000. The results are consistent with the proposal that zymogen factor VII possesses no intrinsic proteolytic activity toward factor X or factor IX

  12. A model ternary heparin conjugate by direct covalent bond strategy applied to drug delivery system.

    Science.gov (United States)

    Wang, Ying; Xin, Dingcheng; Hu, Jiawen; Liu, Kaijian; Pan, Jiangao; Xiang, Jiannan

    2009-01-01

    A model ternary heparin conjugate by direct covalent bond strategy has been developed, in which modified heparin using active mix anhydride as intermediate conjugates with model drug molecule and model specific ligand, respectively. Designed ester bonds between model drug and heparin facilitate hydrolysis kinetics research. The strategy can be extended to design and synthesize a targeted drug delivery system. The key point is to use mixed anhydride groups as activating intermediates to mediate the synthesis of the ternary heparin conjugate. Formation of mixed anhydride is detected by the conductimetry experiment. The ternary heparin conjugate is characterized by (13)C NMR, FT-IR and GPC, respectively. The decreased trend on degree of substitution (DS) is consistent with that of introduced anticancer drug and specific ligand in drug delivery system. Moreover, their anticoagulant activity is evaluated by measuring activated partial thromboplastin time (APTT) and anti-factor Xa activity. The results show that model ternary heparin conjugate with reduced anticoagulant activity may avoid the risk of severe hemorrhagic complication during the administration and is potential to develop a safe and effective drug delivery system on anticancer research.

  13. Impact of nonsynonymous mutations of factor X on the functions of factor X and anticoagulant activity of edoxaban.

    Science.gov (United States)

    Noguchi, Kengo; Morishima, Yoshiyuki; Takahashi, Shinichi; Ishihara, Hiroaki; Shibano, Toshiro; Murata, Mitsuru

    2015-03-01

    Edoxaban is an oral direct factor Xa (FXa) inhibitor and its efficacy as an oral anticoagulant is less subject to drug-food and drug-drug interaction than existing vitamin K antagonists. Although this profile of edoxaban suggests it is well suited for clinical use, it is not clear whether genetic variations of factor X influence the activity of edoxaban. Our aim was to investigate a possible impact of single-nucleotide polymorphisms (SNPs) in the factor X gene on the functions of factor X and the activity of edoxaban. Two nonsynonymous SNPs within mature factor X, Ala152Thr and Gly192Arg, were selected as possible candidates that might affect the functions of FXa and the activity of edoxaban. We measured catalytic activities of wild type and mutant FXas in a chromogenic assay using S-2222 and coagulation times including prothrombin time (PT) and activated partial thrombin time (aPTT) of plasma-containing recombinant FXs in the presence and absence of edoxaban. Michaelis-Menten kinetic parameters of FXas, Km and Vmax values, PT and aPTT were not influenced by either mutation indicating these mutations do not affect the FXa catalytic and coagulation activities. The Ki values of edoxaban for the FXas and the concentrations of edoxaban required to double PT and aPTT were not different between wild type and mutated FXas indicating that both mutations have little impact on the activity of edoxaban. In conclusion, these data suggest that edoxaban has little interpatient variability stemming from SNPs in the factor X gene. PMID:24911450

  14. The in-vitro anticoagulant effect of rivaroxaban in neonates.

    Science.gov (United States)

    Attard, Chantal; Monagle, Paul; Kubitza, Dagmar; Ignjatovic, Vera

    2014-04-01

    The use of anticoagulants in neonates is increasing because of the medical advances improving the long-term survival of very sick infants who are at risk of venous thromboembolism (VTE). Current anticoagulation therapy in neonates is less than ideal, because of the physiological differences compared to children and adults regarding the pathophysiology of thrombosis and pharmacology of the drug. Limitations associated with conventional anticoagulants have prompted the development of novel drugs that specifically target the key proteins in the coagulation system. Rivaroxaban is the first oral, direct Factor Xa inhibitor available for the prevention of VTE in adults. Its predictable pharmacokinetic profile, high oral bioavailability and once-daily dosing make rivaroxaban an optimal anticoagulant that warrants investigation in neonates. This study was designed to determine whether there are age-related differences in the pharmacodynamic effects of rivaroxaban in vitro amongst neonates. Neonatal and adult plasma pools were created and spiked with increasing concentrations of rivaroxaban (0-500 ng/ml). Commercially available prothrombin time (PT), activated partial thromboplastin time (aPTT) and anti-Factor Xa assays as well as a sub-sampling thrombin generation assay were used to measure the rivaroxaban effect. A dose-dependent response was observed for PT, aPTT and lag time in both the age groups. Rivaroxaban caused a significant increase in the clotting time for PT and aPTT as well as an increase in lag time (as measured by thrombin generation) in neonates when compared with adults. In-vivo studies are required to confirm the consistency of dose-response in neonates. PMID:24418940

  15. Apixaban versus enoxaparin for thromboprophylaxis after hip replacement

    DEFF Research Database (Denmark)

    Lassen, Michael Rud; Gallus, Alexander; Raskob, Gary E;

    2010-01-01

    There are various regimens for thromboprophylaxis after hip replacement. Low-molecular-weight heparins such as enoxaparin predominantly inhibit factor Xa but also inhibit thrombin to some degree. Orally active, specific factor Xa inhibitors such as apixaban may provide effective thromboprophylaxi...

  16. The Direct Factor Xa Inhibitor Rivaroxaban Passes Into Human Breast Milk.

    Science.gov (United States)

    Wiesen, Martin H J; Blaich, Cornelia; Müller, Carsten; Streichert, Thomas; Pfister, Roman; Michels, Guido

    2016-07-01

    Thromboembolic disorders frequently require antithrombotic treatment during pregnancy and lactation. Vitamin K antagonists and heparins are the treatment options of choice in breastfeeding women. Factors including the route of administration, discomfort during treatment, and fetal and neonatal safety affect women's choices about anticoagulant therapy. Direct-acting oral anticoagulants (DOACs) have emerged as alternatives to these agents and may offer advantages compared with vitamin K antagonists. As breastfeeding women were excluded from clinical trials evaluating DOACs, no safety and efficacy data are available for these special patients and, crucially, estimates for infant exposure are lacking. Therefore, the manufacturer recommends against using DOACs during the lactation period. We present the case of a patient who stopped breastfeeding owing to a diagnosis of postpartum cardiomyopathy. Anticoagulation with enoxaparin that commenced after the diagnosis of postpartum pulmonary embolism was switched to rivaroxaban. At that time, breast milk samples were collected and rivaroxaban concentrations were determined by liquid chromatography tandem-mass spectrometry. Rivaroxaban appears in human breast milk in comparatively small amounts; its safety has not been determined. PMID:27396794

  17. Ancylostoma caninum anticoagulant peptide: a hookworm-derived inhibitor of human coagulation factor Xa.

    OpenAIRE

    Cappello, M; Vlasuk, G P; Bergum, P W; Huang, S.; Hotez, P. J.

    1995-01-01

    Human hookworm infection is a major cause of gastrointestinal blood loss and iron deficiency anemia, affecting up to one billion people in the developing world. These soil-transmitted helminths cause blood loss during attachment to the intestinal mucosa by lacerating capillaries and ingesting extravasated blood. We have isolated the major anticoagulant used by adult worms to facilitate feeding and exacerbate intestinal blood loss. This 8.7-kDa peptide, named the Ancylostoma caninum anticoagul...

  18. AquaPathogen X--A template database for tracking field isolates of aquatic pathogens

    Science.gov (United States)

    Emmenegger, Evi; Kurath, Gael

    2012-01-01

    AquaPathogen X is a template database for recording information on individual isolates of aquatic pathogens and is available for download from the U.S. Geological Survey (USGS) Western Fisheries Research Center (WFRC) website (http://wfrc.usgs.gov). This template database can accommodate the nucleotide sequence data generated in molecular epidemiological studies along with the myriad of abiotic and biotic traits associated with isolates of various pathogens (for example, viruses, parasites, or bacteria) from multiple aquatic animal host species (for example, fish, shellfish, or shrimp). The simultaneous cataloging of isolates from different aquatic pathogens is a unique feature to the AquaPathogen X database, which can be used in surveillance of emerging aquatic animal diseases and clarification of main risk factors associated with pathogen incursions into new water systems. As a template database, the data fields are empty upon download and can be modified to user specifications. For example, an application of the template database that stores the epidemiological profiles of fish virus isolates, called Fish ViroTrak (fig. 1), was also developed (Emmenegger and others, 2011).

  19. Physical activity

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/001941.htm Physical activity To use the sharing features on this page, please enable JavaScript. Physical activity -- which includes an active lifestyle and routine exercise -- ...

  20. Activation detector

    Energy Technology Data Exchange (ETDEWEB)

    Bell, Zane William [Oak Ridge, TN; Boatner, Lynn Allen [Oak Ridge, TN

    2009-12-08

    A method of detecting an activator, the method including impinging with an activator a receptor material lacking a photoluminescent material and generating a by-product of a radioactive decay due to the activator impinging the reeptor material. The method further including, generating light from the by-product via the Cherenkov effect and identifying a characteristic of the activator based on the light.

  1. Oral fondaparinux: use of lipid nanocapsules as nanocarriers and in vivo pharmacokinetic study.

    Science.gov (United States)

    Ramadan, Alyaa; Lagarce, Frederic; Tessier-Marteau, Anne; Thomas, Olivier; Legras, Pierre; Macchi, Laurent; Saulnier, Patrick; Benoit, Jean Pierre

    2011-01-01

    Oral anticoagulant therapy could be advanced using lipid-based nanoparticulate systems. This study examined lipid nanocapsules for their oral absorption potential as the first step in developing oral fondaparinux (Fp) novel carriers. Using phase inversion method and cationic surfactants such as hexadecyltrimethyl ammonium bromide (CTAB) or stearylamine (SA), cationic lipid nanocapsules (cLNCs), loaded with Fp on their surface, were prepared and characterized (zeta potential, size and Fp association efficiency and content). In vivo studies were conducted after single oral increasing doses of Fp-loaded cLNCs (0.5 to 5 mg/kg of Fp) in rats and the concentration of Fp in the plasma was measured by anti-factor Xa activity assay. The monodisperse, (~50 nm), positively charged Fp-cLNCs with high drug loadings demonstrated linear pharmacokinetic profiles of the drug with an increased oral absolute bioavailability (up to ~21%) compatible with therapeutic anticoagulant effect (>0.2 μg/mL). PMID:22162653

  2. Active turbulence in active nematics

    Science.gov (United States)

    Thampi, S. P.; Yeomans, J. M.

    2016-07-01

    Dense, active systems show active turbulence, a state characterised by flow fields that are chaotic, with continually changing velocity jets and swirls. Here we review our current understanding of active turbulence. The development is primarily based on the theory and simulations of active liquid crystals, but with accompanying summaries of related literature.

  3. Get Active

    Science.gov (United States)

    ... feeling the benefits of getting active, such as sleeping better or getting toned. Here are 2 ways to add more activity to your life. Be active for longer each time. If you are walking 3 days a week for 30 minutes, try ...

  4. Activation analysis

    International Nuclear Information System (INIS)

    The neutron activation analysis, which appears to be in limits for further advance, is the most suitable for providing information on the principal as well as the microcomponents in any sample of solid form. Then, instrumental activation analysis is capable of determination of far many elements in various samples. Principally on the neutron activation analysis, the following are described in literature survey from 1982 to middle 1984: bibliography, review, data collection, etc.; problems in spectral analysis and measurement; activation analysis with neutrons; charged particle and photo-nucleus reactions; chemical separation, isotopic dilution activation analysis; molecular activation analysis; standard materials; life and its relation samples; environmental, food, court trial and archaeological samples; space and earth sciences. (Mori, K.)

  5. Conformation analysis of a surface loop that controls active site access in the GH11 xylanase A from Bacillus subtilis.

    Science.gov (United States)

    Vieira, Davi Serradella; Ward, Richard John

    2012-04-01

    Xylanases (EC 3.2.1.8 endo-1,4-glycosyl hydrolase) catalyze the hydrolysis of xylan, an abundant hemicellulose of plant cell walls. Access to the catalytic site of GH11 xylanases is regulated by movement of a short β-hairpin, the so-called thumb region, which can adopt open or closed conformations. A crystallographic study has shown that the D11F/R122D mutant of the GH11 xylanase A from Bacillus subtilis (BsXA) displays a stable "open" conformation, and here we report a molecular dynamics simulation study comparing this mutant with the native enzyme over a range of temperatures. The mutant open conformation was stable at 300 and 328 K, however it showed a transition to the closed state at 338 K. Analysis of dihedral angles identified thumb region residues Y113 and T123 as key hinge points which determine the open-closed transition at 338 K. Although the D11F/R122D mutations result in a reduction in local inter-intramolecular hydrogen bonding, the global energies of the open and closed conformations in the native enzyme are equivalent, suggesting that the two conformations are equally accessible. These results indicate that the thumb region shows a broader degree of energetically permissible conformations which regulate the access to the active site region. The R122D mutation contributes to the stability of the open conformation, but is not essential for thumb dynamics, i.e., the wild type enzyme can also adapt to the open conformation.

  6. Active ratchets

    Science.gov (United States)

    Angelani, L.; Costanzo, A.; Di Leonardo, R.

    2011-12-01

    We analyze self-propelling organisms, or active particles, in a periodic asymmetric potential. Unlike standard ratchet effect for Brownian particles requiring external forcing, in the case of active particles asymmetric potential alone produces a net drift speed (active ratchet effect). By using theoretical models and numerical simulations we demonstrate the emergence of the rectification process in the presence of an asymmetric piecewise periodic potential. The broken spatial symmetry (external potential) and time symmetry (active particles) are sufficient ingredients to sustain unidirectional transport. Our findings open the way to new mechanisms to move in directional manner motile organisms by using external periodic static fields.

  7. Physical Activity

    DEFF Research Database (Denmark)

    Andersen, Lars Bo; Anderssen, Sigmund Alfred; Wisløff, Ulrik;

    2014-01-01

    Andersen LB, Anderssen SA, Wisløff U, Hellénius M-L, Fogelholm M, Ekelund U. (Expert Group) Nordic Nutrition Recommendations 2012. Integrating nutrition and physical activity. Chapter: Physical Activity p. 195-217.Nordic Counsil of Ministers.......Andersen LB, Anderssen SA, Wisløff U, Hellénius M-L, Fogelholm M, Ekelund U. (Expert Group) Nordic Nutrition Recommendations 2012. Integrating nutrition and physical activity. Chapter: Physical Activity p. 195-217.Nordic Counsil of Ministers....

  8. 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. PMID:25820758

  9. Activity report

    International Nuclear Information System (INIS)

    The Department of Physics and Measurement Technology, Biology and Chemistry (IFM) presents every year a progress report containing a brief description of activities in research and education within the department. The report is intended as an information for colleagues and institutions. The present report contains activities for the academic year July 1989 to June 1990

  10. Abnormal X : autosome ratio, but normal X chromosome inactivation in human triploid cultures

    Directory of Open Access Journals (Sweden)

    Norwood Thomas H

    2006-07-01

    Full Text Available Abstract Background X chromosome inactivation (XCI is that aspect of mammalian dosage compensation that brings about equivalence of X-linked gene expression between females and males by inactivating one of the two X chromosomes (Xi in normal female cells, leaving them with a single active X (Xa as in male cells. In cells with more than two X's, but a diploid autosomal complement, all X's but one, Xa, are inactivated. This phenomenon is commonly thought to suggest 1 that normal development requires a ratio of one Xa per diploid autosomal set, and 2 that an early event in XCI is the marking of one X to be active, with remaining X's becoming inactivated by default. Results Triploids provide a test of these ideas because the ratio of one Xa per diploid autosomal set cannot be achieved, yet this abnormal ratio should not necessarily affect the one-Xa choice mechanism for XCI. Previous studies of XCI patterns in murine triploids support the single-Xa model, but human triploids mostly have two-Xa cells, whether they are XXX or XXY. The XCI patterns we observe in fibroblast cultures from different XXX human triploids suggest that the two-Xa pattern of XCI is selected for, and may have resulted from rare segregation errors or Xi reactivation. Conclusion The initial X inactivation pattern in human triploids, therefore, is likely to resemble the pattern that predominates in murine triploids, i.e., a single Xa, with the remaining X's inactive. Furthermore, our studies of XIST RNA accumulation and promoter methylation suggest that the basic features of XCI are normal in triploids despite the abnormal X:autosome ratio.

  11. Activated Charcoal

    Science.gov (United States)

    ... reduce intestinal gas (flatulence), lower cholesterol levels, prevent hangover, and treat bile flow problems (cholestasis) during pregnancy. ... pregnancy, according to some early research reports. Preventing hangover. Activated charcoal is included in some hangover remedies, ...

  12. Origin of serpin-mediated regulation of coagulation and blood pressure.

    Directory of Open Access Journals (Sweden)

    Yunjie Wang

    Full Text Available Vertebrates evolved an endothelium-lined hemostatic system and a pump-driven pressurized circulation with a finely-balanced coagulation cascade and elaborate blood pressure control over the past 500 million years. Genome analyses have identified principal components of the ancestral coagulation system, however, how this complex trait was originally regulated is largely unknown. Likewise, little is known about the roots of blood pressure control in vertebrates. Here we studied three members of the serpin superfamily that interfere with procoagulant activity and blood pressure of lampreys, a group of basal vertebrates. Angiotensinogen from these jawless fish was found to fulfill a dual role by operating as a highly selective thrombin inhibitor that is activated by heparin-related glycosaminoglycans, and concurrently by serving as source of effector peptides that activate type 1 angiotensin receptors. Lampreys, uniquely among vertebrates, thus use angiotensinogen for interference with both coagulation and osmo- and pressure regulation. Heparin cofactor II from lampreys, in contrast to its paralogue angiotensinogen, is preferentially activated by dermatan sulfate, suggesting that these two serpins affect different facets of thrombin's multiple roles. Lampreys also express a lineage-specific serpin with anti-factor Xa activity, which demonstrates that another important procoagulant enzyme is under inhibitory control. Comparative genomics suggests that orthologues of these three serpins were key components of the ancestral hemostatic system. It appears that, early in vertebrate evolution, coagulation and osmo- and pressure regulation crosstalked through antiproteolytically active angiotensinogen, a feature that was lost during vertebrate radiation, though in gnathostomes interplay between these traits is effective.

  13. Changing trends in anti-coagulant therapies. Are heparins and oral anti-coagulants challenged?

    Science.gov (United States)

    Fareed, J; Iqbal, O; Cunanan, J; Demir, M; Wahi, R; Clarke, M; Adiguzel, C; Bick, R

    2008-06-01

    The conventional management of thrombotic and cardiovascular disorders is based on the use of heparin, oral anticoagulants and aspirin. Despite progress in the sciences, these drugs still remain a challenge and mystery. The development of low molecular weight heparins (LMWHS) and the synthesis of heparinomimetics represent a refined use of heparin. Additional drugs will continue to develop. However, none of these drugs will ever match the polypharmacology of heparin. Aspirin still remains the leading drug in the management of thrombotic and cardiovascular disorders. The newer antiplatelet drugs such as adenosine diphosphate receptor inhibitors, GPIIb/IIIa inhibitors and other specific inhibitors have limited effects and have been tested in patients who have already been treated with aspirin. Warfarin provides a convenient and affordable approach in the long-term outpatient management of thrombotic disorders. The optimized use of these drugs still remains the approach of choice to manage thrombotic disorders. The new anticoagulant targets, such as tissue factor, individual clotting factors, recombinant forms of serpins (antithrombin, heparin co-factor II and tissue factor pathway inhibitors), recombinant activated protein C, thrombomodulin and site specific serine proteases inhibitors complexes have also been developed. There is a major thrust on the development of orally bioavailable anti-Xa and IIa agents, which are slated to replace oral anticoagulants. Both the anti-factor Xa and anti-IIa agents have been developed for oral use and have provided impressive clinical results. However, safety concerns related to liver enzyme elevations and thrombosis rebound have been reported with their use. For these reasons, the US Food and Drug Administration did not approve the orally active antithrombin agent Ximelagatran for several indications. The synthetic pentasaccharide (Fondaparinux) has undergone clinical development. Unexpectedly, Fondaparinux also produced major

  14. Regulatory activities

    International Nuclear Information System (INIS)

    This publication, compiled in 8 chapters, presents the regulatory system developed by the Nuclear Regulatory Authority (NRA) of the Argentine Republic. The following activities and developed topics in this document describe: the evolution of the nuclear regulatory activity in Argentina; the Argentine regulatory system; the nuclear regulatory laws and standards; the inspection and safeguards of nuclear facilities; the emergency systems; the environmental systems; the environmental monitoring; the analysis laboratories on physical and biological dosimetry, prenatal irradiation, internal irradiation, radiation measurements, detection techniques on nuclear testing, medical program on radiation protection; the institutional relations with national and international organization; the training courses and meeting; the technical information

  15. Active Power

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    ActivePower,Inc.(NASDAQ股票代号:ACPW)成立于1992年,是一家久负盛誉的不间断电源解决方案供应商。Active Power凭借其卓越的飞轮储能技术,Cleansouce UPS系统和全系列的电源解决方案,为客户提供高效,可靠且环保的电源系统,以确保在发生电源波动时实现业务连续。

  16. Synthesis and detection of N-sulfonated oversulfated chondroitin sulfate in marketplace heparin.

    Science.gov (United States)

    Mans, Daniel J; Ye, Hongping; Dunn, Jamie D; Kolinski, Richard E; Long, Dianna S; Phatak, Nisarga L; Ghasriani, Houman; Buhse, Lucinda F; Kauffman, John F; Keire, David A

    2015-12-01

    N-sulfonated oversulfated chondroitin sulfate (NS-OSCS), recently reported as a potential threat to the heparin supply, was prepared along with its intermediate derivatives. All compounds were spiked into marketplace heparin and subjected to United States Pharmacopeia (USP) identification assays for heparin (proton nuclear magnetic resonance [(1)H NMR], chromatographic identity, % galactosamine [%GalN], anti-factor IIa potency, and anti-factor Xa/IIa ratio). The U.S. Food and Drug Administration (FDA) strong-anionic exchange high-performance liquid chromatography (SAX-HPLC) method resolved NS-OSCS from heparin and OSCS and had a limit of detection of 0.26% (w/w) NS-OSCS. The %GalN test was sensitive to the presence of NS-OSCS in heparin. Therefore, current USP heparin monograph tests (i.e., SAX-HPLC and %GalN) detect the presence of NS-OSCS in heparin.

  17. Synthesis and detection of N-sulfonated oversulfated chondroitin sulfate in marketplace heparin.

    Science.gov (United States)

    Mans, Daniel J; Ye, Hongping; Dunn, Jamie D; Kolinski, Richard E; Long, Dianna S; Phatak, Nisarga L; Ghasriani, Houman; Buhse, Lucinda F; Kauffman, John F; Keire, David A

    2015-12-01

    N-sulfonated oversulfated chondroitin sulfate (NS-OSCS), recently reported as a potential threat to the heparin supply, was prepared along with its intermediate derivatives. All compounds were spiked into marketplace heparin and subjected to United States Pharmacopeia (USP) identification assays for heparin (proton nuclear magnetic resonance [(1)H NMR], chromatographic identity, % galactosamine [%GalN], anti-factor IIa potency, and anti-factor Xa/IIa ratio). The U.S. Food and Drug Administration (FDA) strong-anionic exchange high-performance liquid chromatography (SAX-HPLC) method resolved NS-OSCS from heparin and OSCS and had a limit of detection of 0.26% (w/w) NS-OSCS. The %GalN test was sensitive to the presence of NS-OSCS in heparin. Therefore, current USP heparin monograph tests (i.e., SAX-HPLC and %GalN) detect the presence of NS-OSCS in heparin. PMID:26278168

  18. Active house

    DEFF Research Database (Denmark)

    Eriksen, Kurt Emil; Olesen, Gitte Gylling Hammershøj

    2010-01-01

    Formålet med dette abstrakt er at illustrere, at huse kan være konstrueret til at basere sig udelukkende på vedvarende energikilder og samtidig være CO2-neutrale og producere mere energi end de forbruger. Active House Visionen undersøger disse muligheder i otte demonstration huse i fem forskellige...

  19. Activated Sludge.

    Science.gov (United States)

    Saunders, F. Michael

    1978-01-01

    Presents the 1978 literature review of wastewater treatment. This review covers: (1) activated sludge process; (2) process control; (3) oxygen uptake and transfer; (4) phosphorus removal; (5) nitrification; (6) industrial wastewater; and (7) aerobic digestion. A list of 136 references is also presented. (HM)

  20. Activity report

    Energy Technology Data Exchange (ETDEWEB)

    Yu, S W

    2008-08-11

    This report is aimed to show the author's activities to support the LDRD. The title is 'Investigation of the Double-C Behavior in the Pu-Ga Time-Temperature-Transformation Diagram' The sections are: (1) Sample Holder Test; (2) Calculation of x-ray diffraction patterns; (3) Literature search and preparing publications; (4) Tasks Required for APS Experiments; and (5) Communications.

  1. Hepatoprotective Activity.

    Science.gov (United States)

    2016-01-01

    The liver performs a vital role in metabolism, secretion, storage, and detoxification of endogenous and exogenous substances. Oxidative stress and free radicals enhance the severity of hepatic damage, which can be overcome by the antioxidant mechanism. Plant extracts can be the best source of such antioxidants and mediate hepatoprotective activity. In this chapter, high-dose paracetamol-induced hepatotoxicity in rat model is discussed with explanations of biochemical and histopathological studies. PMID:26939279

  2. Glucokinase activators.

    Science.gov (United States)

    Filipski, Kevin J; Futatsugi, Kentaro; Pfefferkorn, Jeffrey A; Stevens, Benjamin D

    2012-07-01

    In this review we highlight recently disclosed progress in the field of small-molecule activators of the human glucokinase enzyme. Several of the reported chemotypes possess structural features that diverge from known leads; some of these modifications appear to be specifically designed to modulate tissue selectivity or discrete parameters of enzyme function (e.g., S0.5 v Vmax). This review will inform the reader of the extent of continued effort being directed toward discovery of a first-in-class drug for Type II diabetes mellitus that functions through this target. Patents were selected from those published in December 2009 up to November 2011; foreign filings were translated where possible to understand the claims and biological techniques utilized to characterize the reported glucokinase activators. Overall, there appears to be a recent trend leading to reduced patent filings for small-molecule glucokinase activators. There are many possible explanations for this trend; however, it is likely that the field has reached maturity and that the downturn of new disclosures represents the transition of many of these programs to the clinic.

  3. Synthetic heparin pentasaccharide depolymerization by heparinase I: molecular and biological implications.

    Science.gov (United States)

    Daud, A N; Ahsan, A; Iqbal, O; Walenga, J M; Silver, P J; Ahmad, S; Fareed, J

    2001-01-01

    A synthetic pentasaccharide (SR90107/ ORG31540) representing the antithrombin III (ATIII) binding sequence in heparin is under clinical development for the prophylaxis and management of venous thromboembolism. This pentasaccharide exhibits potent anti-factor Xa (AXa) effects (>750 IU/mg) and does not exhibit any anti-factor IIa (AIIa) activity. Previous reports have suggested that synthetic heparin pentasaccharides are resistant to the digestive effects of heparinase I. To investigate the effect of heparinase I on the AXa activity of pentasaccharide SR90107/ORG31540, graded concentrations (1.25-100 microg/ml) were incubated with a fixed amount of heparinase I (0.1 U/ml). Heparinase I produced a strong neutralizing effect on this pentasaccharide, as measured by AXa activity. This observation led to further studies where high performance liquid chromatography (HPLC) analysis was employed to determine the potential breakdown products of the pentasaccharide. The experiment with the pentasaccharide included incubation (37 degrees C) at 1 mg/ml and exposure to graded concentrations of heparinase I (0.125-1 U/ml). After 30 min of incubation, the enzymatic activity was stopped by heat treatment and the mixture was analyzed using high performance size exclusion chromatography (HPSEC). Heparinase I concentration-dependent cleavage of the pentasaccharide was evident. The breakdown products exhibited a mass of 1,034 d and 743 d, respectively, suggesting the generation of a trisaccharide and a disaccharide moiety. The extinction of a disaccharide moiety in the UV region was high, indicating the presence of a double bond in this molecule. These data clearly suggest that pentasaccharide SR90107/ORG31540 is digestible by heparinase I into its two components. Furthermore, these data support the hypothesis that heparinase I can be used as a neutralizing agent for pentasaccharide overdose. Additionally, a highly methylated analog of the previously mentioned synthetic pentasaccharide

  4. Activating schoolyards

    DEFF Research Database (Denmark)

    Andersen, Henriette Bondo; Pawlowski, Charlotte Skau; Scheller, Hanne Bebendorf;

    2015-01-01

    objectively determine where and how active the students are in the schoolyard, before and after the intervention. This provides a type of data that, to our knowledge, has not been used before in schoolyard interventions. Exploring the change in behavior in relation to specific intervention elements in the...... accelerometer, GPS and GIS; 3) a process evaluation facilitating the intervention development process and identifying barriers and facilitators in the implementation process; 4) a post-intervention end-user evaluation aimed at exploring who uses the schoolyards and how the schoolyards are used. The seven...

  5. Active packaging with antifungal activities.

    Science.gov (United States)

    Nguyen Van Long, N; Joly, Catherine; Dantigny, Philippe

    2016-03-01

    There have been many reviews concerned with antimicrobial food packaging, and with the use of antifungal compounds, but none provided an exhaustive picture of the applications of active packaging to control fungal spoilage. Very recently, many studies have been done in these fields, therefore it is timely to review this topic. This article examines the effects of essential oils, preservatives, natural products, chemical fungicides, nanoparticles coated to different films, and chitosan in vitro on the growth of moulds, but also in vivo on the mould free shelf-life of bread, cheese, and fresh fruits and vegetables. A short section is also dedicated to yeasts. All the applications are described from a microbiological point of view, and these were sorted depending on the name of the species. Methods and results obtained are discussed. Essential oils and preservatives were ranked by increased efficacy on mould growth. For all the tested molecules, Penicillium species were shown more sensitive than Aspergillus species. However, comparison between the results was difficult because it appeared that the efficiency of active packaging depended greatly on the environmental factors of food such as water activity, pH, temperature, NaCl concentration, the nature, the size, and the mode of application of the films, in addition to the fact that the amount of released antifungal compounds was not constant with time.

  6. Active packaging with antifungal activities.

    Science.gov (United States)

    Nguyen Van Long, N; Joly, Catherine; Dantigny, Philippe

    2016-03-01

    There have been many reviews concerned with antimicrobial food packaging, and with the use of antifungal compounds, but none provided an exhaustive picture of the applications of active packaging to control fungal spoilage. Very recently, many studies have been done in these fields, therefore it is timely to review this topic. This article examines the effects of essential oils, preservatives, natural products, chemical fungicides, nanoparticles coated to different films, and chitosan in vitro on the growth of moulds, but also in vivo on the mould free shelf-life of bread, cheese, and fresh fruits and vegetables. A short section is also dedicated to yeasts. All the applications are described from a microbiological point of view, and these were sorted depending on the name of the species. Methods and results obtained are discussed. Essential oils and preservatives were ranked by increased efficacy on mould growth. For all the tested molecules, Penicillium species were shown more sensitive than Aspergillus species. However, comparison between the results was difficult because it appeared that the efficiency of active packaging depended greatly on the environmental factors of food such as water activity, pH, temperature, NaCl concentration, the nature, the size, and the mode of application of the films, in addition to the fact that the amount of released antifungal compounds was not constant with time. PMID:26803804

  7. A randomized direct comparison of the pharmacokinetics and pharmacodynamics of apixaban and rivaroxaban

    Directory of Open Access Journals (Sweden)

    Frost C

    2014-11-01

    Full Text Available Charles Frost,1 Yan Song,1 Yu Chen Barrett,1 Jessie Wang,2 Janice Pursley,3 Rebecca A Boyd,4 Frank LaCreta1 1Exploratory Clinical and Translational Research, 2Exploratory Development Global Biometric Sciences, 3Analytical and Bioanalytical Development, Bristol-Myers Squibb Company, Princeton, NJ, USA; 4Global Innovative Pharma Business Clinical Pharmacology, Pfizer Inc., Groton, CT, USA Background: Currently, there are no direct comparisons of apixaban and rivaroxaban, two new oral direct factor Xa inhibitors approved for management of thromboembolic disorders. Objective: Compare the pharmacokinetics and anti-factor Xa activity (AXA of apixaban and rivaroxaban. Methods: In this randomized, open-label, two-period, two-treatment crossover study, healthy subjects (N=14 received apixaban 2.5 mg twice daily (BID and rivaroxaban 10 mg once daily (QD for 4 days with a ≥4.5-day washout. Plasma samples were obtained for pharmacokinetic and AXA assessments; parameters were calculated using noncompartmental methods. Results: Median time-to-maximum concentration was 2 hours for both compounds, and the mean half-life was 8.7 and 7.9 hours for apixaban and rivaroxaban, respectively. Daily exposure, the area under the curve (AUC(0–24, appeared similar for rivaroxaban (1,094 ng · h/mL and apixaban (935 ng · h/mL, whereas mean peak-to-trough plasma concentration ratio was 3.6-fold greater for rivaroxaban (16.9 than apixaban (4.7. Coefficient of variation for exposure parameters (AUC0–24, Cmax, Cmin was 20%–24% for apixaban versus 29%–46% for rivaroxaban. Peak AXA, AXA AUC(0–24, and AXA fluctuation were ~2.5-, 1.3-, and 3.5-fold higher for rivaroxaban than apixaban, respectively. Trough concentrations and AXA were lower for rivaroxaban (10 ng/mL and 0.17 IU/mL vs 17 ng/mL and 0.24 IU/mL for apixaban, respectively. Rivaroxaban exhibited a steeper concentration–AXA response (slope: 0.0172 IU/ng vs 0.0134 IU/ng for apixaban, P<0.0001. Conclusion

  8. Halal Activism

    DEFF Research Database (Denmark)

    Fischer, Johan

    2016-01-01

    The purpose of this article is to further our understanding of contemporary Muslim consumer activism in Malaysia with a particular focus on halal (in Arabic, literally “permissible” or “lawful”) products and services. Muslim activists and organisations promote halal on a big scale in the interface...... zones between new forms of Islamic revivalism, the ethnicised state and Muslim consumer culture. Organisations such as the Muslim Consumers Association of Malaysia play an important role in pushing and protecting halal in Malaysia, that is, halal activists constantly call on the state to tighten halal...... in particular historical/national settings and that these issues should be explored in the interfaces between Islam, the state and market. More specifically, this article examines the above issues building on ethnography from fieldwork with three Muslim organisations in Malaysia....

  9. The antioxidant role of xanthurenic acid in the Aedes aegypti midgut during digestion of a blood meal.

    Directory of Open Access Journals (Sweden)

    Vitor L A Lima

    Full Text Available In the midgut of the mosquito Aedes aegypti, a vector of dengue and yellow fever, an intense release of heme and iron takes place during the digestion of a blood meal. Here, we demonstrated via chromatography, light absorption and mass spectrometry that xanthurenic acid (XA, a product of the oxidative metabolism of tryptophan, is produced in the digestive apparatus after the ingestion of a blood meal and reaches milimolar levels after 24 h, the period of maximal digestive activity. XA formation does not occur in the White Eye (WE strain, which lacks kynurenine hydroxylase and accumulates kynurenic acid. The formation of XA can be diminished by feeding the insect with 3,4-dimethoxy-N-[4-(3-nitrophenylthiazol-2-yl] benzenesulfonamide (Ro-61-8048, an inhibitor of XA biosynthesis. Moreover, XA inhibits the phospholipid oxidation induced by heme or iron. A major fraction of this antioxidant activity is due to the capacity of XA to bind both heme and iron, which occurs at a slightly alkaline pH (7.5-8.0, a condition found in the insect midgut. The midgut epithelial cells of the WE mosquito has a marked increase in occurrence of cell death, which is reversed to levels similar to the wild type mosquitoes by feeding the insects with blood supplemented with XA, confirming the protective role of this molecule. Collectively, these results suggest a new role for XA as a heme and iron chelator that provides protection as an antioxidant and may help these animals adapt to a blood feeding habit.

  10. Active sharing

    CERN Multimedia

    2012-01-01

    The big news this week is, of course, the conclusions from the LHC performance workshop held in Chamonix from 6 to 10 February . The main recommendation, endorsed by CERN’s Machine Advisory Committee and adopted by the Management, is that the LHC will run at 4 TeV per beam this year. You can find all the details from Chamonix in the slides presented on Wednesday at the summary session, which leaves me free to talk about another important development coming up soon.   In ten days time, a new kind of gathering will be taking place in Geneva, bringing together two previously separate conferences, one driven by physics, the other by the medical community, but both looking to apply physics to the advancement of health. The merger of the International Conference for Translational Research in Radio-Oncology and CERN’s workshop on Physics for Health in Europe (ICTR-PHE) makes for a very eclectic mix. Presentations range from active shielding for interplanetary flight to the rather...

  11. DAVIC activities

    Science.gov (United States)

    Fujiwara, Hiroshi

    1995-12-01

    DAVIC (Digital Audio Visual Council) is the defacto standardization organization established in Mar. 1994, based on international consensus for digital audio visual services. After completion of MPEG2 standardization, the broadcasting industry, the communication industry, the computer industry, and consumer electronics industry have started development of concrete services and products. Especially the interactive digital audio visual services, such as Video On Demand (VOD) or Near Video On Demand (NVOD), have become hot topics all over the world. Such interactive digital audio visual services are combined technologies of multi-media coding, digital transmission and computer networking. Therefore more than 150 organizations from all industry sectors have participated in DAVIC and are contributing from their own industrial contexts. DAVIC's basic policy is to use the available technologies specified by the other standards bodies as much as possible. So DAVIC's standardization activities have close relationship with ISO IEC/JTC1/SC29, ITU-T SG 9, ATM-Forum, IETF, IMA, DVB, etc. DAVIC is trying to specify Applications, Reference Models, Security, Usage Information Control, and the interfaces and protocols among the Content Provider, the Server, the core network, the access network, and the Set Top Unit. DAVIC's first goal is to specify DAVIC1.0 based on CFP1 (Call for Proposal) and CFP2 by Dec. 1995, and the next direction is under preparation for further progress based on CFP3 and CFP4.

  12. Molecular Diversity between Salivary Proteins from New World and Old World Sand Flies with Emphasis on Bichromomyia olmeca, the Sand Fly Vector of Leishmania mexicana in Mesoamerica

    Science.gov (United States)

    Townsend, Shannon; Pasos-Pinto, Silvia; Sanchez, Laura; Rasouli, Manoochehr; B. Guimaraes-Costa, Anderson; Aslan, Hamide; Francischetti, Ivo M. B.; Oliveira, Fabiano; Becker, Ingeborg; Kamhawi, Shaden; Ribeiro, Jose M. C.; Jochim, Ryan C.; Valenzuela, Jesus G.

    2016-01-01

    Background Sand fly saliva has been shown to have proteins with potent biological activities, salivary proteins that can be used as biomarkers of vector exposure, and salivary proteins that are candidate vaccines against different forms of leishmaniasis. Sand fly salivary gland transcriptomic approach has contributed significantly to the identification and characterization of many of these salivary proteins from important Leishmania vectors; however, sand fly vectors in some regions of the world are still neglected, as Bichromomyia olmeca (formerly known as Lutzomyia olmeca olmeca), a proven vector of Leishmania mexicana in Mexico and Central America. Despite the importance of this vector in transmitting Leishmania parasite in Mesoamerica there is no information on the repertoire of B. olmeca salivary proteins and their relationship to salivary proteins from other sand fly species. Methods and Findings A cDNA library of the salivary glands of wild-caught B. olmeca was constructed, sequenced, and analyzed. We identified transcripts encoding for novel salivary proteins from this sand fly species and performed a comparative analysis between B. olmeca salivary proteins and those from other sand fly species. With this new information we present an updated catalog of the salivary proteins specific to New World sand flies and salivary proteins common to all sand fly species. We also report in this work the anti-Factor Xa activity of Lofaxin, a salivary anticoagulant protein present in this sand fly species. Conclusions This study provides information on the first transcriptome of a sand fly from Mesoamerica and adds information to the limited repertoire of salivary transcriptomes from the Americas. This comparative analysis also shows a fast degree of evolution in salivary proteins from New World sand flies as compared with Old World sand flies. PMID:27409591

  13. Development of subcutaneous sustained release nanoparticles encapsulating low molecular weight heparin

    Directory of Open Access Journals (Sweden)

    Satheesh Jogala

    2015-01-01

    Full Text Available The objective of the present research work was to prepare and evaluate sustained release subcutaneous (s.c. nanoparticles of low molecular weight heparin (LMWH. The nanoparticles were prepared by water-in-oil in-water (w/o/w emulsion and evaporation method using different grades of polylactide co-glycolide (50:50, 85:15, and different concentrations of polyvinyl alcohol (0.1%, 0.5%, 1% aqueous solution as surfactant. The fabricated nanoparticles were evaluated for size, shape, zeta potential, encapsulation efficiency, in vitro drug release, and in vivo biological activity (anti-factor Xa activity using the standard kit. The drug and excipient compatibility was analyzed by Fourier transform infrared spectroscopy (FTIR, differential scanning calorimetry (DSC and X-ray diffraction (XRD studies. The formation of nanoparticles was confirmed by scanning electron microscopy; nanoparticles were spherical in shape. The size of prepared nanoparticles was found between 195 nm and 251 nm. The encapsulation efficiency of the nanoparticles was found between 46% and 70%. In vitro drug, release was about 16-38% for 10 days. In vivo drug, release shows the sustained release of drug for 10 days in rats. FTIR studies indicated that there was no loss in chemical integrity of the drug upon fabrication into nanoparticles. DSC and XRD results demonstrated that the drug was changed from the crystalline form to the amorphous form in the formulation during the fabrication process. The results of this study revealed that the s.c. nanoparticles were suitable candidates for sustained delivery of LMWH.

  14. Metabolic engineering of Chinese hamster ovary cells: towards a bioengineered heparin.

    Science.gov (United States)

    Baik, Jong Youn; Gasimli, Leyla; Yang, Bo; Datta, Payel; Zhang, Fuming; Glass, Charles A; Esko, Jeffrey D; Linhardt, Robert J; Sharfstein, Susan T

    2012-03-01

    Heparin is the most widely used pharmaceutical to control blood coagulation in modern medicine. A health crisis that took place in 2008 led to a demand for production of heparin from non-animal sources. Chinese hamster ovary (CHO) cells, commonly used mammalian host cells for production of foreign pharmaceutical proteins in the biopharmaceutical industry, are capable of producing heparan sulfate (HS), a related polysaccharide naturally. Since heparin and HS share the same biosynthetic pathway, we hypothesized that heparin could be produced in CHO cells by metabolic engineering. Based on the expression of endogenous enzymes in the HS/heparin pathways of CHO-S cells, human N-deacetylase/N-sulfotransferase (NDST2) and mouse heparan sulfate 3-O-sulfotransferase 1 (Hs3st1) genes were transfected sequentially into CHO host cells growing in suspension culture. Transfectants were screened using quantitative RT-PCR and Western blotting. Out of 120 clones expressing NDST2 and Hs3st1, 2 clones, Dual-3 and Dual-29, were selected for further analysis. An antithrombin III (ATIII) binding assay using flow cytometry, designed to recognize a key sugar structure characteristic of heparin, indicated that Hs3st1 transfection was capable of increasing ATIII binding. An anti-factor Xa assay, which affords a measure of anticoagulant activity, showed a significant increase in activity in the dual-expressing cell lines. Disaccharide analysis of the engineered HS showed a substantial increase in N-sulfo groups, but did not show a pattern consistent with pharmacological heparin, suggesting that further balancing the expression of transgenes with the expression levels of endogenous enzymes involved in HS/heparin biosynthesis might be necessary. PMID:22326251

  15. IASS Activity

    Science.gov (United States)

    Hojaev, Alisher S.; Ibragimova, Elvira M.

    2015-08-01

    It’s well known, astronomy in Uzbekistan has ancient roots and traditions (e.g., Mirzo Ulugh Beg, Abū al-Rayhān al-Bīrūnī, Abū ‘Abdallāh al-Khwārizmī) and astronomical heritage carefully preserved. Nowadays uzbek astronomers play a key role in scientific research but also in OAD and Decadal Plan activity in the Central Asia region. International Aerospace School (IASS) is an amazing and wonderful event held annually about 30 years. IASS is unique project in the region, and at the beginning we spent the Summer and Winter Schools. At present in the summer camp we gather about 50 teenage and undergraduate students over the country and abroad (France, Malaysia, Turkey, Azerbaijan, Pakistan, Russia, etc.). They are selected on the basis of tests of astronomy and space issues. During two weeks of IASS camp the invited scientists, cosmonauts and astronauts as well as other specialists give lectures and engage in practical exercises with IASS students in astronomy, including daily observations of the Sun and night sky observations with meniscus telescope, space research and exploration, aerospace modelling, preparation and presentation of original projects. This is important that IASS gives not theoretical grounds only but also practically train the students and the hands-on training is the major aims of IASS. Lectures and practice in the field of astronomy carried out with the direct involvement and generous assistance of Uranoscope Association (Paris, France). The current 26-th IASS is planned to held in July 2015.

  16. Fusion of CTA and XA data using 3D centerline registration for plaque visualization during coronary intervention

    Science.gov (United States)

    Kaila, Gaurav; Kitslaar, Pieter; Tu, Shengxian; Penicka, Martin; Dijkstra, Jouke; Lelieveldt, Boudewijn

    2016-03-01

    Coronary Artery Disease (CAD) results in the buildup of plaque below the intima layer inside the vessel wall of the coronary arteries causing narrowing of the vessel and obstructing blood flow. Percutaneous coronary intervention (PCI) is usually done to enlarge the vessel lumen and regain back normal flow of blood to the heart. During PCI, X-ray imaging is done to assist guide wire movement through the vessels to the area of stenosis. While X-ray imaging allows for good lumen visualization, information on plaque type is unavailable. Also due to the projection nature of the X-ray imaging, additional drawbacks such as foreshortening and overlap of vessels limit the efficacy of the cardiac intervention. Reconstruction of 3D vessel geometry from biplane X-ray acquisitions helps to overcome some of these projection drawbacks. However, the plaque type information remains an issue. In contrast, imaging using computed tomography angiography (CTA) can provide us with information on both lumen and plaque type and allows us to generate a complete 3D coronary vessel tree unaffected by the foreshortening and overlap problems of the X-ray imaging. In this paper, we combine x-ray biplane images with CT angiography to visualize three plaque types (dense calcium, fibrous fatty and necrotic core) on x-ray images. 3D registration using three different registration methods is done between coronary centerlines available from x-ray images and from the CTA volume along with 3D plaque information available from CTA. We compare the different registration methods and evaluate their performance based on 3D root mean squared errors. Two methods are used to project this 3D information onto 2D plane of the x-ray biplane images. Validation of our approach is performed using artificial biplane x-ray datasets.

  17. Physical Activity (Exercise)

    Science.gov (United States)

    ... Our ePublications > Physical activity (exercise) fact sheet ePublications Physical activity (exercise) fact sheet How can physical activity improve ... Have had recent hip surgery More information on physical activity (exercise) For more information about physical activity (exercise), ...

  18. Survival of heparins, oral anticoagulants, and aspirin after the year 2010.

    Science.gov (United States)

    Fareed, Jawed; Hoppensteadt, Debra A; Fareed, Daniel; Demir, Muzaffer; Wahi, Rakesh; Clarke, Melaine; Adiguzel, Cafer; Bick, Rodger

    2008-02-01

    The conventional management of thrombotic and cardiovascular disorders is based on the use of heparin, oral anticoagulants, and aspirin. Despite remarkable progress in life sciences, these drugs still remain a challenge and a mystery to us, and their use is far from optimized. The development of low-molecular-weight heparins and the synthesis of heparinomimetics, such as the chemically synthesized pentasaccharide, represent a refined use of heparin. Additional drugs from this knowledge will continue to develop; however, none of these drugs will ever match the polypharmacology of heparin. Aspirin still remains the leading drug in the management of thrombotic and cardiovascular disorders. The newer antiplatelet drugs such as adenosine diphosphate receptor inhibitors, glycoprotein IIb/IIIa inhibitors, and other specific inhibitors have limited effects and have been tested in patients who have already been treated with aspirin. Warfarin provides a convenient and affordable approach in the long-term outpatient management of thrombotic disorders. The optimized use of these drugs still remains as the approach of choice to manage thrombotic disorders. The new anticoagulant targets, including specific sites in the hemostatic network such as tissue factor, individual clotting factors (IIa, VIIa, IXa, Xa, XIIa, and XIIIa), recombinant forms of serpins (antithrombin, heparin cofactor II, and tissue factor pathway inhibitors), recombinant activated protein C, thrombomodulin, and site-specific serine protease inhibitor complexes have also been developed. There is a major thrust on the development of orally bioavailable anticoagulant drugs (anti-Xa and anti-IIa agents), which are slated to replace oral anticoagulants. Both the anti-factor Xa and antithrombin agents have been developed for oral use and have provided impressive clinical outcomes in sponsor trials for the postsurgical prophylaxis of venous thrombosis; however, safety concerns related to liver enzyme elevations and

  19. How to use unfractionated heparin to treat neonatal thrombosis in clinical practice.

    Science.gov (United States)

    Bhatt, Mihir D; Paes, Bosco A; Chan, Anthony K

    2016-09-01

    Among children, neonates have the highest incidence of thrombosis due to risk factors such as catheter instrumentation, an evolving coagulation system and congenital heart disease. Unfractionated heparin (UFH) is one of the most commonly used anticoagulants in neonates. Published guidelines delineate dosing and monitoring protocols for UFH therapy in newborns. However, challenging clinical situations frequently present that warrants healthcare providers to think critically beyond the range of guidelines, and judiciously resolve specific problems. This review focuses briefly on the epidemiology of neonatal thrombosis and the use of UFH in this population. It is followed by a discussion on dosing of UFH in neonates, limited evidence that forms the basis of published guidelines with justification for a treatment regimen that precludes the use of a heparin loading dose in newborns and monitoring of UFH therapy with currently available tests such as antifactor Xa (anti-Xa) level and activated partial thromboplastin time (APTT). Multiple studies have demonstrated a lack of correlation between anti-Xa levels and APTT as well as between different anti-Xa assays. Many centers world-wide rely only on APTT for monitoring purposes and do not have access to anti-Xa assays. To address these difficulties, we propose two practical algorithms, with and without the use of anti-Xa levels that clinicians can follow when monitoring UFH therapy in neonates. The article concludes with an overview of the side-effects of UFH. PMID:26656898

  20. Oral fondaparinux: use of lipid nanocapsules as nanocarriers and in vivo pharmacokinetic study

    Directory of Open Access Journals (Sweden)

    Ramadan A

    2011-11-01

    Full Text Available Alyaa Ramadan1,4, Frederic Lagarce1,3, Anne Tessier-Marteau2, Olivier Thomas1, Pierre Legras5, Laurent Macchi2, Patrick Saulnier1, Jean Pierre Benoit1,31LUNAM Université, Ingénierie de la Vectorisation Particulaire, Inserm U-646, Angers, France; 2Hematology Department, Angers University Hospital, Angers, France; 3Department of Pharmacy, Angers University Hospital, Angers, France; 4Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; 5SCAHU, Animal House, Angers, FranceAbstract: Oral anticoagulant therapy could be advanced using lipid-based nanoparticulate systems. This study examined lipid nanocapsules for their oral absorption potential as the first step in developing oral fondaparinux (Fp novel carriers. Using phase inversion method and cationic surfactants such as hexadecyltrimethyl ammonium bromide (CTAB or stearylamine (SA, cationic lipid nanocapsules (cLNCs, loaded with Fp on their surface, were prepared and characterized (zeta potential, size and Fp association efficiency and content. In vivo studies were conducted after single oral increasing doses of Fp-loaded cLNCs (0.5 to 5 mg/kg of Fp in rats and the concentration of Fp in the plasma was measured by anti-factor Xa activity assay. The monodisperse, (~50 nm, positively charged Fp-cLNCs with high drug loadings demonstrated linear pharmacokinetic profiles of the drug with an increased oral absolute bioavailability (up to ~21% compatible with therapeutic anticoagulant effect (>0.2 µg/mL.Keywords: oral anticoagulant, fondaparinux, lipid nanocapsules, bioavailability, pharmacokinetics, rats

  1. Anticoagulation intensity of rivaroxaban for stroke patients at a special low dosage in Japan.

    Directory of Open Access Journals (Sweden)

    Takuya Okata

    Full Text Available In Japan, low-dose rivaroxaban [15 mg QD/10 mg QD for creatinine clearance of 30-49 mL/min] was approved for clinical use in NVAF patients partly because of its unique pharmacokinetics in Japanese subjects. The aim of the study was to determine the anticoagulation intensity of rivaroxaban and its determinant factors in Japanese stroke patients.Consecutive stroke patients with NVAF admitted between July 2012 and December 2013 were studied. Prothrombin time (PT, activated partial thromboplastin time (aPTT, and estimated plasma concentration of rivaroxaban (Criv based on an anti-factor Xa chromogenic assay were measured just before and 4 and 9 h after administration at the steady state level of rivaroxaban. Determinant factors for Criv were explored using a linear mixed-model approach.Of 110 patients (37 women, 75±9 years old, 59 took 15 mg QD of rivaroxaban and 51 took 10 mg QD. Criv at 4 h was 186 ng/mL for patients taking 15 mg QD and 147 ng/mL for those taking 10 mg QD. Both PT and aPTT were positively correlated with Criv. Criv was 72% lower at 4 h in 15 patients receiving crushed tablets than in the other patients, and tablet crushing was significantly associated with lower Criv (adjusted estimate -0.43, 95% CI -0.60 to -0.26 after multivariate-adjustment.The anticoagulation effects of rivaroxaban in the acute stroke setting for Japanese NVAF patients were relatively low as compared with those in the ROCKET-AF and J-ROCKET AF trials. Tablet crushing, common in dysphagic patients, decreased Criv.

  2. Charitable activities in Azerbaijan

    OpenAIRE

    Ismailova Sevil Aydin

    2015-01-01

    In this article, found its proper reflection questions related to the issue of charitable activities in Azerbaijan. Briefly described the history of charitable activities in Azerbaijan. Also shown is the legal framework of charitable activities in Azerbaijan.

  3. Guide to Physical Activity

    Science.gov (United States)

    ... Families ( We Can! ) Health Professional Resources Guide to Physical Activity Physical activity is an important part of your ... to injury. Examples of moderate-intensity amounts of physical activity Common Chores Washing and waxing a car for ...

  4. Physical Activity Assessment

    Science.gov (United States)

    Current evidence convincingly indicates that physical activity reduces the risk of colon and breast cancer. Physical activity may also reduce risk of prostate cancer. Scientists are also evaluating potential relationships between physical activity and other cancers.

  5. Bacterial Blight Resistance Genes Anchored to Physics Map of Rice Genome%水稻抗白叶枯病基因在物理图谱上的锚定

    Institute of Scientific and Technical Information of China (English)

    鲍思元

    2013-01-01

    到目前为止,经国际注册确认和期刊报道的水稻白叶枯病抗性基因共35个.已被定位的抗性基因有26个,即第1染色体上有2个,Xa29(t)和xa34(t);第3染色体上有Xa11;第4染色体上有6个,Xa1、Xa2、Xa12、Xa14、Xa25(t)、Xa31(t);第5染色体上有xa5;第6染色体上有3个,Xa7、Xa27(t)、xa33(t);第7染色体上有xa8;第8染色体上有xa13;第11染色体上有9个,Xa3/Xa26、Xa4、Xa1O、Xa21、Xa22(t)、Xa23、Xa30(t)、Xa32(t)、Xa36(t);第12染色体上有2个,xa25、xa32(t).Xa1、xa5、xa13、Xa21、Xa23、xa25、Xa26、Xa27已成功克隆.文中利用GRAMENE网站公布的抗白叶枯病基因的分子标记,在日本晴的测序图谱Gramene Annotated NipponbareSequence2009上进行物理图谱锚定,将已定位的26个抗白叶枯病基因锚定在其物理图谱的26个位点上,为抗白叶枯病基因的基因克隆、分子标记辅助选择奠定了基础.%Up to the present day, there are a total of 35 bacterial blight resistance genes registered internationally or reported in international journals. Among them, 26 genes were mapped, including Xa29(t) , xa34(t) on chromosome 1; Xall on chromosome 3; Xal, Xal, XaYl, Xal4, Xa25(t) , Xa31(t) on chromosome 4; xa5 on chromosome 5; Xal, Xall(t) , xa33(t) on chromosome 6; xd& on chromosome 7; xal3 on chromosome 8; Xa3/Xa26, XaA, XaW, Xa21 , Xa22(t) , Xa23, Xa30(t) , Xa32(t) , Xa36(t) on chromosome 11; xa25, xa32(t) on chromosome 12. 8 bacterial blight resistance genes were cloned, including Xal, xa5, xal3 , Xa21 , Xa23, xa25 , Xa26 and Xa21. Molecular markers of bacterial blight resistance genes from GRAMENE website were anchored to the physics map of Gramene Annotated Nipponbare Sequence 2009. 26 bacterial blight resistance genes were anchored to the physics map 26 units place through this research. The work laid the foundation for cloning bacterial blight resistance genes and the marker-assisted selection in breeding programs.

  6. Political activity for physical activity: health advocacy for active transport

    Directory of Open Access Journals (Sweden)

    Amun Qa-t-a

    2011-05-01

    Full Text Available Abstract Effective health advocacy is a priority for efforts to increase population participation in physical activity. Local councils are an important audience for this advocacy. The aim of the current study was to describe features of advocacy for active transport via submissions to city council annual plans in New Zealand, and the impact of an information sheet to encourage the health sector to be involved in this process. Written submissions to city council's annual consultation process were requested for 16 city councils over the period of three years (2007/08, 2008/09, and 2009/10. Submissions were reviewed and categories of responses were created. An advocacy information sheet encouraging health sector participation and summarising some of the evidence-base related to physical activity, active transport and health was released just prior to the 2009/10 submission time. Over the period of the study, city councils received 47,392 submissions, 17% of which were related to active transport. Most submissions came from city residents, with a small proportion (2% from the health sector. The largest category of submissions was in support of pedestrian and cycling infrastructure, design and maintenance of facilities and additional features to support use of these transport modes. Health arguments featured prominently in justifications for active transport initiatives, including concerns about injury risk, obesity, physical inactivity, personal safety and facilities for people with disabilities. There was evidence that the information sheet was utilised by some health sector submitters (12.5%, providing tentative support for initiatives of this nature. In conclusion, the study provides novel information about the current nature of health advocacy for active transport and informs future advocacy efforts about areas for emphasis, such as health benefits of active transport, and potential alliances with other sectors such as environmental

  7. Los niveles de anticuerpos anti factor plaquetario 4-heparina y el índice 4T para trombocitopenia inducida por heparina

    Directory of Open Access Journals (Sweden)

    Marta E. Martinuzzo

    2012-02-01

    Full Text Available La trombocitopenia inducida por heparina (HIT es un efecto adverso del tratamiento con heparina, mediada por anticuerpos anti complejo factor plaquetario 4 (PF4-heparina (HPIA. La HIT es frecuentemente moderada pero pueden desarrollarse complicaciones trombóticas. El diagnóstico precoz es importante. La detección de HPIA por ELISA tiene alta sensibilidad pero baja especificidad (títulos bajos sin significación clínica. El índice de las 4T (índice 4T puede detectar pacientes con alto riesgo de HIT. El propósito del estudio fue correlacionar los niveles de HPIA y el índice 4T de un grupo de pacientes derivados a nuestro centro. Evaluamos 84 pacientes, 34 de ellos desarrollaron trombosis. Cada médico completó un cuestionario clínico que fue remitido con la muestra a nuestro centro. Los cuestionarios fueron analizados por un investigador externo y el índice 4T se calculó previamente al ensayo. Los HPIA se determinaron por un ELISA (Asserachrom HPIA que detecta los 3 isotipos, IgG, IgM e IgA, único reactivo disponible en Argentina. Los resultados se expresaron como porcentaje de absorbancia (%ABS. La correlación del índice 4T con los HPIA fue 0.472 (rho spearman, p < 0.001. Los pacientes con índice 4T ≥ 6 presentaban %ABS mayores que los ≤ 5 (67 vs. 39, p < 0.001. Aquéllos con trombosis presentaron títulos mayores que los que no la desarrollaron (%ABS 59 vs. 39, p = 0.017. En conclusión: Los títulos altos de HPIA medidos por ELISA, que detecta los 3 isotipos, correlacionaron claramente con el índice 4T ≥ 6 y fueron más frecuentes en los pacientes con trombosis, coincidiendo con lo ya descripto para ensayos de ELISA específicos para isotipo IgG.

  8. Active commuting to school

    Science.gov (United States)

    Declines in physical activity levels have coincided with increasing rates of obesity in children. This is problematic because physical activity has been shown to attenuate weight gain in children. Active commuting to school is one way of increasing children's physical activity. However, given the hi...

  9. Increasing Youth Physical Activity with Activity Calendars

    Science.gov (United States)

    Eckler, Seth

    2016-01-01

    Physical educators often struggle with ways to get their students to be active beyond the school day. One strategy to accomplish this is the use of physical activity calendars (PACs). The purpose of this article is to support the use of PACs and give practical advice for creating effective PACs.

  10. Persistent active longitudes in sunspot activity

    Science.gov (United States)

    Berdyugina, S.; Usoskin, I.

    It has been recently shown that spot activity of cool stars including solar analogues, is grouped in two clearly distinguished active longitudes which are persistent within at least one starspot cycle. Solar data including positional information of individual sunspots / groups extends back for about 130 years covering 12 solar cycles. Here we present the results of our research of longitudinal distribution of sunspot activity using an analysis similar to that applied to the stars. First, we synthesized, from the actual sunspot data, the sun's light curve as if it was defined only by spots. Then solar images were calculated from this light curve, giving a natural smoothing of the spot pattern. For each Carrington rotation, longitudinal position of these smoothed spot regions was calculated. The analysis reveals the following main features: - Sunspot activity is grouped in two active longitudes (with the differential rotation taken into account) 180o apart from each other which are persistent through the entire studied period of 12 cycles, similarly to stars. - The longitude migration is determined by changing the mean latitude of sunspot activity (the Maunder butterfly) and differential rotation. - The two longitudes periodically alternate the dominant activity with about 3.7 year period implying for the existence of the Sflip-flopT phenomenon known in - starspot activity.

  11. Virulence of Xanthomonas oryzae pv.oryzae on Rice Near-lsogenic Lines with Single Resistance Gene and Pyramiding Lines in China

    Institute of Scientific and Technical Information of China (English)

    LIU Hong-xia; LIU Feng-quan; HU Bai-shi; YANG Wan-feng; CHEN Zhi-yi; XU Zhi-gang

    2004-01-01

    Ninety one isolates of Xanthomonas oryzae pv. Oryzae were collected from different rice growing regions in China and determined for their virulence on 24 rice near-isogenic lines containing single resistance gene and 2-4 genes:IRBB1 (Xa1),IRBB2 (Xa2),IRBB3 (Xa3), IRBB4 (Xa4), IRBB5 (xa5), IRBB7 (Xa7), IRBB8 (xa8), IRBB10 (Xa10), IRBB11 (Xa11),IRBB13 (xa13),IRBB14 (Xa14), IRBB21 (Xa21), IR24 (Xa18), IRBB50 (Xa4 + xa5), IRBB51 (Xa4 + xa13), IRBB52 (Xa4 + Xa21), IRBB53 (xa5 + xa13), IRBB54 (xa5 + Xa21), IRBB55 (xa13 + Xa21),IRBB56 (Xa4 + xa5 + xa13), IRBB57 (Xa4 + xa5 + Xa21), IRBB58 (Xa4 + xa13 + Xa21),IRBB59 (xa5 + xa13 + Xa21) and IRBB60 (Xa4 + xa5 + xa13 + Xa21). The results showed that most isolates were less virulent on lines with more than one genes pyramided than those with single resistance gene. The isolates tested were more virulent on IR24 and IRBB10,less virulent on IRBB5, IRBB7 and IRBB21. Based on interactions between isolates and rice near-isogenic lines, 7 cultivars with single gene (IRBB5, IRBB4, IRBB3, IRBB14, IRBB2, IRBB1 and IR24) were chosen as the differentials, and the tested isolates were classified into 7 virulence groups. The reaction patterns of the 7 groups in order were: RRRRRRR,RRRRRRS, RRRRRSS, RR/SRRSSS, RRRSSSS, RRSSSSS, RSSSSSS. The virulence frequencies were 7.69, 6.59, 14.29, 12.09, 14.29, 28.57 and 16.48% respectively. The elementary system for races identification has been established in China based on the results. It will be possible to compare with races in other countries, and the results will facilitate the evelopment of rice resistance breeding to bacterial blight in China.

  12. Neutron Activation Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Corliss, William R.

    1968-01-01

    In activation analysis, a sample of an unknown material is first irradiated (activated) with nuclear particles. In practice these nuclear particles are almost always neutrons. The success of activation analysis depends upon nuclear reactions which are completely independent of an atom's chemical associations. The value of activation analysis as a research tool was recognized almost immediately upon the discovery of artificial radioactivity. This book discusses activation analysis experiments, applications and technical considerations.

  13. On the activation of bovine plasma factor XIII. Amino acid sequence of the peptide released by thrombin and the terminal residues of the subunit polypeptides.

    Science.gov (United States)

    Nakamura, S; Iwanaga, S; Suzuki, T

    1975-12-01

    by thrombin must be accompanied by a limited proteolysis of the arginyl-glycyl bond located in the N-terminal region of the a chain, liberating the "Activation peptide." The possibility of activating Factor XII with other porteinases was examined using Factor Xa [EC 3.4.21.6], Factor XIIa, kallikreins [EC 3.4.21.8], urokinase [EC 3.4.99.26], trypsin [EC 3.4.21.4], ficin [EC 3.4.22.3], papain [EC 3.4.22.2], and bromelain [EC 3.4.22.4]. Among these enzymes, only bromelain and trypsin showed clear activating effects.

  14. Lectures Abandoned: Active Learning by Active Seminars

    DEFF Research Database (Denmark)

    Christensen, Henrik Bærbak; Corry, Aino Vonge

    2012-01-01

    Traditional lecture-based courses are widely criticised for be- ing less eective in teaching. The question is of course what should replace the lectures and various active learning tech- niques have been suggested and studied. In this paper, we report on our experiences of redesigning a software ......- tive seminars as a replacement of traditional lectures, an activity template for the contents of active seminars, an ac- count on how storytelling supported the seminars, as well as reports on our and the students' experiences....

  15. Accessibility, activity participation and location of activities

    DEFF Research Database (Denmark)

    Næss, Petter

    2006-01-01

    By investigating relationships between residential location and the availability of facilities, location of activities, trip distances, activity participation and trip frequencies, this paper seeks to contribute to a more detailed and nuanced understanding of the relationships between residential...... location and the amount of daily-life travel in an urban region. The empirical data are from a comprehensive study of residential location and travel in Copenhagen Metropolitan Area. Differences between inner- and outer-area residents in activity frequencies and trip frequencies are modest and partly...

  16. Antifeedant activity of quassinoids.

    Science.gov (United States)

    Leskinen, V; Polonsky, J; Bhatnagar, S

    1984-10-01

    The antifeedant activity of 13 quassinoids of different structural types has been studied against the Mexican bean beetle (Epilachna varivestis Mulsant) 4th instar larvae and the southern armyworm (Spodoptera eridania Crawer) 5th instar larvae. All quassinoids tested displayed significant activity against the Mexican bean beetle and, thus, do not reveal a simple structure-activity relationship. Five quassinoids were active against the southern armyworm. Interestingly, four of these-bruceantin (I), glaucarubinone (VI), isobruceine A (VIII), and simalikalactone D (XI)-possess the required structural features for antineoplastic activity. The noncytotoxic quassin (X) is an exception; it is active against both pests. PMID:24318349

  17. Major operations and activities

    Energy Technology Data Exchange (ETDEWEB)

    Black, D.G.

    1995-06-01

    This section of the 1994 Hanford Site Environmental Report summarizes the major operations and activities on the site. These operations and activities include site management, waste management, environmental restoration and corrective actions, and research and technology development.

  18. Forensic activation analysis

    International Nuclear Information System (INIS)

    Basic principles of neutron activation analysis are outlined. Examples of its use in police science include analysis for gunshot residues, toxic element determinations and multielement comparisons. Advantages of neutron activation analysis over other techniques are described. (R.L.)

  19. USAID Activity Locatons

    Data.gov (United States)

    US Agency for International Development — The USAID Activities dataset is a snapshot of activities supported by USAID including their geographical locations within countries at the time of the snapshot. The...

  20. Active ageing technologies

    DEFF Research Database (Denmark)

    Lassen, Aske Juul

    of physical and productive activity; e.g. that a game of billiards is a technology of active aging. Thus, active aging is enacted in the socio-material practices of the technologies in this paper. The paper contributes with a strengthening of the concept of active aging, by focusing on entangled practices......In the recent decade the concept of active aging has become important in the Western hemisphere. The World Health Organization and The European Union have staged active aging as a core policy area and initiated programs of physical activity, independence and prolonged working lives among...... the elderly. As part of this rearticulation of old age, many new technologies take form. This paper uses a wide concept of technologies (devices, regimes, strategies and ways of doing) and argues that technologies form active aging subjectivities, and on the other hand, that these subjectivities...

  1. Active Marine Station Metadata

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Active Marine Station Metadata is a daily metadata report for active marine bouy and C-MAN (Coastal Marine Automated Network) platforms from the National Data...

  2. Active magnetic regenerator

    Science.gov (United States)

    Barclay, John A.; Steyert, William A.

    1982-01-01

    The disclosure is directed to an active magnetic regenerator apparatus and method. Brayton, Stirling, Ericsson, and Carnot cycles and the like may be utilized in an active magnetic regenerator to provide efficient refrigeration over relatively large temperature ranges.

  3. Physical Activity and Children

    Science.gov (United States)

    ... Food and Beverage Toolkit The AHA's Recommendations for Physical Activity in Children Updated:Jul 21,2016 Click image ... Inactive children are likely to become inactive adults. Physical activity helps with: controlling weight reducing blood pressure raising ...

  4. Preschoolers’ Physical Activity Behaviours

    Science.gov (United States)

    Irwin, Jennifer D.; He, Meizi; Bouck, L. Michelle Sangster; Tucker, Patricia; Pollett, Graham L.

    2016-01-01

    Objectives To understand parents’ perspectives of their preschoolers’ physical activity behaviours. Methods A maximum variation sample of 71 parents explored their preschoolers’ physical activity behaviours through 10 semi-structured focus group discussions. Results Parents perceived Canada’s Physical Activity Guidelines for Children as inadequate; that their preschoolers get and need more than 30–90 minutes of activity daily; and that physical activity habits must be established during the preschool years. Nine barriers against and facilitators toward adequate physical activity were proposed: child’s age, weather, daycare, siblings, finances, time, society and safety, parents’ impact, and child’s activity preferences. Discussion The need for education and interventions that address current barriers are essential for establishing physical activity as a lifestyle behaviour during early childhood and, consequently, helping to prevent both childhood and adulthood obesity. PMID:16625802

  5. Italian active volcanoes

    Institute of Scientific and Technical Information of China (English)

    RobertoSantacroce; RenawCristofolini; LuigiLaVolpe; GiovanniOrsi; MauroRosi

    2003-01-01

    The eruptive histories, styles of activity and general modes of operation of the main active Italian volcanoes,Etna, Vulcano, Stromboli, Vesuvio, Campi Flegrei and Ischia, are described in a short summary.

  6. Family Activities for Fitness

    Science.gov (United States)

    Grosse, Susan J.

    2009-01-01

    This article discusses how families can increase family togetherness and improve physical fitness. The author provides easy ways to implement family friendly activities for improving and maintaining physical health. These activities include: walking, backyard games, and fitness challenges.

  7. Canonical active Brownian motion

    OpenAIRE

    Gluck, Alexander; Huffel, Helmuth; Ilijic, Sasa

    2008-01-01

    Active Brownian motion is the complex motion of active Brownian particles. They are active in the sense that they can transform their internal energy into energy of motion and thus create complex motion patterns. Theories of active Brownian motion so far imposed couplings between the internal energy and the kinetic energy of the system. We investigate how this idea can be naturally taken further to include also couplings to the potential energy, which finally leads to a general theory of cano...

  8. Pathotype and genetic diversity amongst Indian isolates of Xanthomonas oryzae pv. oryzae.

    Directory of Open Access Journals (Sweden)

    Deo Mishra

    Full Text Available A number of rice resistance genes, called Xa genes, have been identified that confer resistance against various strains of Xanthomonas oryzae pv. oryzae (Xoo, the causal agent of bacterial blight. An understanding of pathotype diversity within the target pathogen population is required for identifying the Xa genes that are to be deployed for development of resistant rice cultivars. Among 1024 isolates of Xoo collected from 20 different states of India, 11 major pathotypes were distinguished based on their reaction towards ten Xa genes (Xa1, Xa3, Xa4, xa5, Xa7, xa8, Xa10, Xa11, xa13, Xa21. Isolates belonging to pathotype III showing incompatible interaction towards xa8, xa13 and Xa21 and compatible interaction towards the rest of Xa genes formed the most frequent (41% and widely distributed pathotype. The vast majority of the assayed Xoo isolates were incompatible with one or more Xa genes. Exceptionally, the isolates of pathotype XI were virulent on all Xa genes, but have restricted distribution. Considering the individual R-genes, Xa21 appeared as the most broadly effective, conferring resistance against 88 % of the isolates, followed in decreasing order by xa13 (84 %, xa8 (64 %, xa5 (30 %, Xa7 (17 % and Xa4 (14 %. Fifty isolates representing all the eleven pathotypes were analyzed by southern hybridization to determine their genetic relatedness using the IS1112 repeat element of Xoo. Isolates belonging to pathotype XI were the most divergent. The results suggest that one RFLP haplotype that is widely distributed all over India and is represented in strains from five different pathotypes might be an ancestral haplotype. A rice line with xa5, xa13 and Xa21 resistance genes is resistant to all strains, including those belonging to pathotype XI. This three gene combination appears to be the most suitable Xa gene combination to be deployed in Indian rice cultivars.

  9. Woodsy Owl Activity Guide.

    Science.gov (United States)

    Forest Service (USDA), Washington, DC.

    This guide offers teachers and after-school group leaders 12 fun and engaging activities. Activities feature lessons on trees, water, wind, the earth, food, and waste. The activities are designed to help children aged 5-8 become more aware of the natural environment and fundamental conservation principles. Titles of children's books are embedded…

  10. Activity Theory and Ontology

    Science.gov (United States)

    Peim, Nick

    2009-01-01

    This paper seeks to re-examine Yrio Engestrom's activity theory as a technology of knowledge designed to enable positive transformations of specific practices. The paper focuses on a key paper where Engestrom defines the nature and present state of activity theory. Beginning with a brief account of the relations between activity theory and…

  11. Ras activation by SOS

    DEFF Research Database (Denmark)

    Iversen, Lars; Tu, Hsiung-Lin; Lin, Wan-Chen;

    2014-01-01

    Activation of the small guanosine triphosphatase H-Ras by the exchange factor Son of Sevenless (SOS) is an important hub for signal transduction. Multiple layers of regulation, through protein and membrane interactions, govern activity of SOS. We characterized the specific activity of individual ...

  12. Recurrent radio activity in active galactic nuclei

    Directory of Open Access Journals (Sweden)

    Jamrozy M.

    2012-12-01

    Full Text Available There has been a growing body of persuasive evidence to indicate that AGN activity, powered by mass accretion onto a supermassive black hole, can involve multiple episodes. Thus thinking of jet activity as occurring within a unique brief period in the life of a galaxy is no longer valid. The most striking examples of AGNs with recurrent jet activity are the double-double radio sources, which contain two or more pairs of distinct lobes on the opposite sides of a parent optical object. On the other hand, we have now conclusive arguments that galaxy mergers and interactions are principal triggers for AGNs. Quite a number of examples of powerful radio sources hosted by galaxies with peculiar optical morphologies (tails, shells, dust-lanes, etc. can be cited to support such a scenario. The structure and spectra of extended radio emission from radio galaxies, with sizes ranging up to a few Mpc, can provide a lot of information on the history of the central AGN activity, while the spectral and dynamical ages of these extended radio lobes could be used to constrain the time scales of recurrent AGN activity.

  13. Xanthurenic acid distribution, transport, accumulation and release in the rat brain.

    Science.gov (United States)

    Gobaille, Serge; Kemmel, Véronique; Brumaru, Daniel; Dugave, Christophe; Aunis, Dominique; Maitre, Michel

    2008-05-01

    Tryptophan metabolism through the kynurenine pathway leads to several neuroactive compounds, including kynurenic and picolinic acids. Xanthurenic acid (Xa) has been generally considered as a substance with no physiological role but possessing toxic and apoptotic properties. In the present work, we present several findings which support a physiological role for endogenous Xa in synaptic signalling in brain. This substance is present in micromolar amounts in most regions of the rat brain with a heterogeneous distribution. An active vesicular synaptic process inhibited by bafilomycin and nigericin accumulates xanthurenate into pre-synaptic terminals. A neuronal transport, partially dependant on adenosine 5'-triphosphate (ATP), sodium and chloride ions exists in NCB-20 neurons which could participate in the clearance of extracellular xanthurenate. Both transports (neuronal and vesicular) are greatly enhanced by the presence of micromolar amounts of zinc ions. Finally, electrical in vivo stimulation of A10-induced Xa release in the extracellular spaces of the rat prefrontal cortex. This phenomenon is reproduced by veratrine, K+ ions and blocked by EGTA and tetrodotoxin. These results strongly argue for a role for Xa in neurotransmission/neuromodulation in the rat brain, thus providing the existence of specific Xa receptors. PMID:18182052

  14. Physiologic activities of the contact activation system.

    Science.gov (United States)

    Schmaier, Alvin H

    2014-05-01

    The plasma contact activation (CAS) and kallikrein/kinin (KKS) systems consist of 4 proteins: factor XII, prekallikrein, high molecular weight kininogen, and the bradykinin B2 receptor. Murine genetic deletion of factor XII (F12(-/-)), prekallikrein (Klkb1(-/-)), high molecular weight kininogen (Kgn1(-/-)) and the bradykinin B2 receptor (Bdkrb2(-/-)) yield animals protected from thrombosis. With possible exception of F12(-/-) and Kgn1(-/-) mice, the mechanism(s) for thrombosis protection is not reduced contact activation. Bdkrb2(-/-) mice are best characterized and they are protected from thrombosis through over expression of components of the renin angiotensin system (RAS) leading to elevated prostacyclin with vascular and platelet inhibition. Alternatively, prolylcarboxypeptidase, a PK activator and degrader of angiotensin II, when deficient in the mouse leads to a prothrombotic state. Its mechanism for increased thrombosis also is mediated in part by components of the RAS. These observations suggest that thrombosis in mice of the CAS and KKS are mediated in part through the RAS and independent of reduced contact activation. PMID:24759141

  15. NEA activities in 1980. 9. Activity Report

    International Nuclear Information System (INIS)

    This report describes the main features of the Agency's work during 1980 and discusses the state and prospects of the nuclear industry in OECD countries. Trends in nuclear power, radiological and environmental impacts of nuclear fuel cycle activities, nuclear safety research and licensing, nuclear law, nuclear development and fuel cycle studies technical co-operation, nuclear science organisation and administration are reviewed

  16. Active knee joint flexibility and sports activity

    DEFF Research Database (Denmark)

    Hahn, Thomas; Foldspang, Anders; Vestergaard, E;

    1999-01-01

    was significantly higher in women than in men and significantly positively associated with weekly hours of swimming and weekly hours of competitive gymnastics. Active knee flexion was significantly positively associated with participation in basketball, and significantly negatively associated with age and weekly...

  17. Activity-based design

    DEFF Research Database (Denmark)

    Andersen, Peter Bøgh

    2006-01-01

    and instrumental actions, between human and non-human participants, and between an activity and its spatio-temporal context. The advent of pervasive technologies, where active or passive systems become embedded in our working and living spaces, from where they offer their services to us, puts the need...... and automatic machinery can replace one another in an activity. It also gives an example of how to use the framework for design....

  18. Active Travel - Healthy Lives

    OpenAIRE

    Institute of Public Health in Ireland

    2011-01-01

    Across Ireland, there is considerable scope to replace many short car journeys with walking and cycling which would bring about a range of benefits to health as well as saving money for individuals and society.'Active travel, healthy lives' presents a summary of international evidence on the health and economic benefits of active travel and makes recommendations on how active travel can become a viable, safe and attractive alternative to car use.

  19. Active unilateral condylar hyperplasia.

    Science.gov (United States)

    Luz, J G; de Rezende, J R; de Araújo, V C; Chilvarquer, I

    1994-01-01

    Two cases of active unilateral condylar hyperplasia which were treated with condylectomy alone are presented. The first case was an adult form and the other a juvenile form. Both were classified as active by using 99Tc bone scintigraphy. Clinical and radiographic features of both cases conformed to the hemimandibular hypertrophy type. Satisfactory facial symmetry and dental occlusion were achieved. Histopathological data confirmed the activity of the articular cartilage layers. PMID:8181091

  20. Poverty And Civic Activism

    OpenAIRE

    William R. DiPietro

    2013-01-01

    This paper hypothesizes that country poverty is negatively associated with the civic activism of its citizens. It employs cross country regression analysis to test the proposition. In general, the findings of the paper lend support to the contention that greater civic activism leads to reduced poverty.Poverty is a worldwide problem. One of the possible ways that pressure can be brought to bear to change a countrys policies, institutions, attitudes, and beliefs is through civic activism and pr...

  1. Lupus Activity in Pregnancy

    OpenAIRE

    Clowse, Megan E. B.

    2007-01-01

    Pregnancy in a woman with Systemic Lupus Erythematosus (SLE) can be complicated by both lupus activity and pregnancy mishaps. The majority of recent studies demonstrate an increase in lupus activity during pregnancy, perhaps exacerbated by hormonal shifts required to maintain pregnancy. Increased lupus activity, in turn, prompts an elevated risk for poor pregnancy outcomes, including stillbirth, preterm birth, low birth weight, and preeclamspsia. Fortunately, the majority of pregnancies in wo...

  2. CDBG Economic Development Activity

    Data.gov (United States)

    Department of Housing and Urban Development — CDBG activity related to economic development, including commercial or industrial rehab, commercial or industrial land acquisition, commercial or industrial...

  3. CDBG Public Improvements Activity

    Data.gov (United States)

    Department of Housing and Urban Development — CDBG activity related to public improvements, including senior centers, youth centers, parks, street improvements, water/sewer improvements, child care centers,...

  4. CDBG Public Services Activity

    Data.gov (United States)

    Department of Housing and Urban Development — CDBG activity related to public services, including senior services, legal services, youth services, employment training, health services, homebuyer counseling,...

  5. CDBG Housing Activity

    Data.gov (United States)

    Department of Housing and Urban Development — CDBG activity related to housing, including multifamily rehab, housing services, code enforcement, operation and repair of foreclosed property and public housing...

  6. NEA activities in 1983. 12. Activity report

    International Nuclear Information System (INIS)

    This report describes the main features of the Agency's work during 1983 and discusses the state and prospects of the nuclear industry in OECD countries. Trends in nuclear power, nuclear development and the fuel cycles nuclear safety technology and licensing, radiological and environmental impacts of nuclear fuel cycle activities, legal affairs, nuclear science, joint undertakings and other NEA joint projects, organisation and administration are reviewed

  7. SwissProt search result: AK061101 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK061101 006-207-A12 (P81428) Coagulation factor X (EC 3.4.21.6) (Trocarin prothrom...bin activator) [Contains: Factor X light chain; Activated factor Xa heavy chain; Factor X heavy chain] (Fragments) FA10_TROCA 2e-20 ...

  8. SwissProt search result: AK109059 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK109059 002-154-F02 (P81428) Coagulation factor X (EC 3.4.21.6) (Trocarin prothrom...bin activator) [Contains: Factor X light chain; Activated factor Xa heavy chain; Factor X heavy chain] (Fragments) FA10_TROCA 7e-18 ...

  9. SwissProt search result: AK112005 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK112005 006-202-F10 (P81428) Coagulation factor X (EC 3.4.21.6) (Trocarin prothrom...bin activator) [Contains: Factor X light chain; Activated factor Xa heavy chain; Factor X heavy chain] (Fragments) FA10_TROCA 3e-16 ...

  10. SwissProt search result: AK112119 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK112119 006-303-H09 (P81428) Coagulation factor X (EC 3.4.21.6) (Trocarin prothrom...bin activator) [Contains: Factor X light chain; Activated factor Xa heavy chain; Factor X heavy chain] (Fragments) FA10_TROCA 9e-17 ...

  11. NEA activities in 1982

    International Nuclear Information System (INIS)

    This report presents an account of the activities of the Nuclear Energy Agency. It deals with current nuclear trends, nuclear development and the fuel cycle, nuclear safety research and licensing, radiological and environmental impacts of nuclear fuel cycle activities, legal affairs, nuclear science, joint undertakings, and, organization and administration

  12. Activities of the ILO.

    Science.gov (United States)

    Labour Education, 1984

    1984-01-01

    Seven articles on International Labour Organization (ILO) activities cover study groups at ILO headquarters, a Philippine rural workers seminar, women's participation in Central American union activities, worksite courses in India, and seminars and symposia in Cape Verde, Mauritius, and Sierra Leone. (SK)

  13. Obesity, Physical Activity - Children.

    Science.gov (United States)

    Gilliam, Thomas B.

    Childhood obesity starts at a very early age, and preventive measures taken early enough may retard the development of fat cells. It appears that physical activity plays an important role in reducing obesity. The activity program must start early, in preschool days. It is felt that screening children for obesity when they first enter school and…

  14. Plasminogen activation in cancer

    NARCIS (Netherlands)

    Reijerkerk, Arie

    2004-01-01

    The subject of this thesis focusses on the role of the plasminogen activation system in angiogenesis and cancer. The plasminogen activation system regulates fibrinolysis and controls cell migration and invasion by plasmin-mediated matrix proteolysis. Plasmin is formed upon cleavage of the zymogen pl

  15. Encapsulation of active ingredients

    NARCIS (Netherlands)

    Gotlieb, K.F.; Schijndel, van R.J.G.; Soest, van J.J.G.

    1999-01-01

    Microspheres having a particle size of 50 nm to 1 nm and a polydispersity of less than 40%, consisting of a chemically cross-linked starch shell containing an active ingredient, are obtained by preparing an oil-in-water emulsion of the active ingredient in a hydrophobic phase and starch or a dispers

  16. Encapsulation of active ingredients

    NARCIS (Netherlands)

    Soest, van J.J.G.; Schijndel, van R.J.G.; Gotlieb, K.F.

    2000-01-01

    Microspheres having a particle size of 50 nm to 1 nm and a polydispersity of less than 40%, consisting of a chemically cross-linked starch shell containing an active ingredient, are obtained by preparing an oil-in-water emulsion of the active ingredient in a hydrophobic phase and starch or a dispers

  17. Encapsulation of active ingredients

    NARCIS (Netherlands)

    Soest, van J.J.G.; Schijndel, van R.J.G.; Gotlieb, K.F.

    2002-01-01

    Microspheres having a particle size of 50 nm to 1 nm and a polydispersity of less than 40%, consisting of a chemically cross-linked starch shell containing an active ingredient, are obtained by preparing an oil-in-water emulsion of the active ingredient in a hydrophobic phase and starch or a dispers

  18. HYDRATION AND ENZYME ACTIVITY

    OpenAIRE

    Poole, P.

    1984-01-01

    Hydration induced conformation and dynamic changes are followed using a variety of experimental techniques applied to hen egg white lysozyme. These changes are completed just before the onset of enzyme activity, which occurs before all polar groups are hydrated, and before monolayer coverage is attained. We suggest that these hydration induced changes are necessary for the return of enzyme activity.

  19. RTE activity report 2005

    International Nuclear Information System (INIS)

    The RTE (electric power transport network) is the french manger of the electric power transport. This activity report provides information on the company results for the year 2005: panorama of the year, management and organization, the place of RTE in the european market, the customers, the industrial tool, the environment the human resources, the international activity and the management report. (A.L.B.)

  20. Active and Healthy Schools

    Science.gov (United States)

    Ball, Stephen; Kovarik, Jessica; Leidy, Heather

    2015-01-01

    The Active and Healthy School Program (AHS) can be used to alter the culture and environment of a school to help children make healthier choices. The purpose of this study was to determine the effectiveness of AHS to increase physical activity while decreasing total screen time, increase healthy food choices, and improve knowledge about physical…

  1. Active Students in Webinars

    Science.gov (United States)

    Kolås, Line; Nordseth, Hugo; Yri, Jørgen Sørlie

    2015-01-01

    To ensure student activity in webinars we have defined 10 learning tasks focusing on production and communication e.g. collaborative writing, discussion and polling, and investigated how the technology supports the learning activities. The three project partners in the VisPed-project use different video-conferencing systems, and we analyzed how it…

  2. Activity report 2002

    International Nuclear Information System (INIS)

    This annual report deals with the activities, the program management and the financial aspects of the ANDRA (National Agency for the radioactive wastes management) during 2002. After a presentation of the activities during the year 2002, it provides the financial accounting, data on company cash, the ANDRA missions and publications. (A.L.B.)

  3. Laboratory Activities in Israel

    Science.gov (United States)

    Mamlok-Naaman, Rachel; Barnea, Nitza

    2012-01-01

    Laboratory activities have long had a distinctive and central role in the science curriculum, and science educators have suggested that many benefits accrue from engaging students in science laboratory activities. Many research studies have been conducted to investigate the educational effectiveness of laboratory work in science education in…

  4. Peak Longevity Physical Activity

    Science.gov (United States)

    People who engage in three to five times the recommended minimum level of leisure-time physical activity derive the greatest benefit in terms of mortality reduction when compared with people who do not engage in leisure-time physical activity.

  5. Reflections on Activity Theory

    Science.gov (United States)

    Bakhurst, David

    2009-01-01

    It is sometimes suggested that activity theory represents the most important legacy of Soviet philosophy and psychology. But what exactly "is" activity theory? The canonical account in the West is given by Engestrom, who identifies three stages in the theory's development: from Vygotsky's insights, through Leontiev's articulation of the…

  6. [Field Learning Activities].

    Science.gov (United States)

    Nolde Forest Environmental Education Center, Reading, PA.

    Seventy field activities, pertinent to outdoor, environmental studies, are described in this compilation. Designed for elementary and junior high school students, the activities cover many discipline areas--science, social studies, language arts, health, history, mathematics, and art--and many are multidisciplinary in use. Topics range from soil…

  7. Activation Force Splines

    DEFF Research Database (Denmark)

    Engell-Nørregård, Morten Pol; Erleben, Kenny

    We present a method for simulating the active contraction of deformable models, usable for interactive animation of soft deformable objects. We present a novel physical principle as the governing equation for the coupling between the low dimensional 1D activation force model and the higher...

  8. Rainy Day Activities.

    Science.gov (United States)

    Texas Child Care, 1997

    1997-01-01

    Experienced caregivers plan ahead for rainy days. This article describes specific rainy day activities for young children, such as books and crafts to learn about rain (rain in a jar, making a rainbow), simple cooking activities (taffy pull, cinnamon candy tea), and games (mummy wrap, hunt the thimble, rain lotto). (EV)

  9. A designated centre for people with disabilities, operated by Sunbeam House Services Ltd, Wicklow

    LENUS (Irish Health Repository)

    Quinlan, Catherine

    2012-08-27

    Children on hemodialysis are at increased risk of thrombosis, especially when dialyzed via a central venous catheter (CVC); there are limited published data regarding the safety and efficacy of tinzaparin in this group. We conducted a retrospective chart review of all children in the National Pediatric Hemodialysis Centre for Ireland diagnosed with a CVC thrombus and treated with subcutaneous tinzaparin over a 10 year period. Seven children were treated with subcutaneous tinzaparin for 10 CVC thrombi. Tinzaparin was commenced at 175 IU\\/kg\\/day and the dose was titrated by measuring anti-factor Xa levels, aiming for levels of 0.3-1.0 IU\\/ml. Treatment was continued until resolution of the CVC thrombus. Restoration of normal flows during dialysis occurred within 3 days in all patients. There were no episodes of bleeding and all children tolerated the treatment well.

  10. Tinzaparin is safe and effective in the management of hemodialysis catheter thrombosis.

    LENUS (Irish Health Repository)

    Quinlan, Catherine

    2012-08-27

    Children on hemodialysis are at increased risk of thrombosis, especially when dialyzed via a central venous catheter (CVC); there are limited published data regarding the safety and efficacy of tinzaparin in this group. We conducted a retrospective chart review of all children in the National Pediatric Hemodialysis Centre for Ireland diagnosed with a CVC thrombus and treated with subcutaneous tinzaparin over a 10 year period. Seven children were treated with subcutaneous tinzaparin for 10 CVC thrombi. Tinzaparin was commenced at 175 IU\\/kg\\/day and the dose was titrated by measuring anti-factor Xa levels, aiming for levels of 0.3-1.0 IU\\/ml. Treatment was continued until resolution of the CVC thrombus. Restoration of normal flows during dialysis occurred within 3 days in all patients. There were no episodes of bleeding and all children tolerated the treatment well.

  11. Analgesic effects of an ethanol extract of the fruits of Xylopia aethiopica (Dunal A. Rich (Annonaceae and the major constituent, xylopic acid in murine models

    Directory of Open Access Journals (Sweden)

    Eric Woode

    2012-01-01

    Full Text Available Background: Fruit extracts of Xylopia aethiopica are used traditionally in the management of pain disorders including rheumatism, headache, colic pain, and neuralgia. Little pharmacological data exists in scientific literature of the effect of the fruit extract and its major diterpene, xylopic acid, on pain. The present study evaluated the analgesic properties of the ethanol extract of X. aethiopica (XAE and xylopic acid (XA, in murine models. Materials and Methods: XAE and XA were assessed in chemical (acetic acid-induced abdominal writhing and formalin tests, thermal (Tail-flick and Hargreaves thermal hyperalgesia tests, and mechanical (Randall-Selitto paw pressure test pain models. Results: XAE and XA exhibited significant analgesic activity in all the pain models used. XAE (30-300 mg kg -1 , p.o. and XA (10-100 mg kg -1 , p.o. inhibited acetic acid-induced visceral nociception, formalin- induced paw pain (both neurogenic and inflammatory, thermal pain as well as carrageenan-induced mechanical and thermal hyperalgesia in animals. Morphine (1-10 mg kg -1 , i.p. and diclofenac (1-10 mg kg -1 , i.p., used as controls, exhibited similar anti-nociceptive activities. XAE and XA did not induce tolerance to their respective anti-nociceptive effects in the formalin test after chronic administration. Morphine tolerance did not also cross-generalize to the analgesic effects of XAE or XA. Conclusions: These findings establish the analgesic properties of the ethanol fruit extract of X. aethiopica and its major diterpene, xylopic acid.

  12. GOVERNOR ORGANIZATIONS ACTIVITY LICENSING

    Directory of Open Access Journals (Sweden)

    Maslennikova L. V.

    2015-03-01

    Full Text Available The author analyses the licensing of governor organizations activity in connection with amendments to the Housing Code of the Russian Federation by adoption of a Federal law of 21.07.2014 N 255-FZ «On amendments to the Housing Code of the Russian Federation, some legislative acts of the Russian Federation and on declare force Certain Provisions of Legislative Acts of the Russian Federation void » and the Government Resolution adoption of the of 28.10.2014г. N 1110 «On entrepreneur activity in apartment buildings’ government licensing». The urgency of the issue of the apartment buildings licensing activity is associated with the modernization of housing and communal services and legal regulation in this area. Introduction of the governor organizations activity licensing without securing in law the concept of "governor organizations" is a significant flaw of the legislator. As a result, the author gives the concept of governor organizations based on the analysis of scientific papers and current legislation. In addition, the article analyzes the introduction of licensing control, assesses the established order of the three registers on the governor organizations activity. The presented paper examines the experience of foreign countries associated with the activities on the apartment building common property management as well, and the state control over such activity. The authors examine violations of housing legislation that may cause the governor organizations and their officials’ administrative responsibility

  13. Emotionally Intense Science Activities

    Science.gov (United States)

    King, Donna; Ritchie, Stephen; Sandhu, Maryam; Henderson, Senka

    2015-08-01

    Science activities that evoke positive emotional responses make a difference to students' emotional experience of science. In this study, we explored 8th Grade students' discrete emotions expressed during science activities in a unit on Energy. Multiple data sources including classroom videos, interviews and emotion diaries completed at the end of each lesson were analysed to identify individual student's emotions. Results from two representative students are presented as case studies. Using a theoretical perspective drawn from theories of emotions founded in sociology, two assertions emerged. First, during the demonstration activity, students experienced the emotions of wonder and surprise; second, during a laboratory activity, students experienced the intense positive emotions of happiness/joy. Characteristics of these activities that contributed to students' positive experiences are highlighted. The study found that choosing activities that evoked strong positive emotional experiences, focused students' attention on the phenomenon they were learning, and the activities were recalled positively. Furthermore, such positive experiences may contribute to students' interest and engagement in science and longer term memorability. Finally, implications for science teachers and pre-service teacher education are suggested.

  14. IPSN's 2001 activity report

    International Nuclear Information System (INIS)

    This report summarizes the 2001 activities and operation of the French institute of nuclear protection and safety (IPSN) which has become the institute of radioprotection and nuclear safety (IRSN) after its merging with the office of protection against ionizing radiations (OPRI). IPSN's activities cover: the safety of nuclear facilities, the safety of nuclear wastes, the management of emergencies, the management of sensible materials, the protection of the environment and of the public health, some research activities with foreign partners (central and eastern Europe, Asia..), and a partnership with the GRS, the German homologue of IPSN. (J.S.)

  15. Encapsulation of active ingredients

    OpenAIRE

    Soest, van, A.J.; Schijndel, van, AWM Jos; Gotlieb, K.F.

    2002-01-01

    Microspheres having a particle size of 50 nm to 1 nm and a polydispersity of less than 40%, consisting of a chemically cross-linked starch shell containing an active ingredient, are obtained by preparing an oil-in-water emulsion of the active ingredient in a hydrophobic phase and starch or a dispersion of a solid active ingredient and starch in water, incorporating the oil-in-water emulsion or solid dispersion in an outer hydrophobic phase, particles of the oil-in-water emulsion or solid disp...

  16. Physics of solar activity

    Science.gov (United States)

    Sturrock, Peter A.

    1993-01-01

    The aim of the research activity was to increase our understanding of solar activity through data analysis, theoretical analysis, and computer modeling. Because the research subjects were diverse and many researchers were supported by this grant, a select few key areas of research are described in detail. Areas of research include: (1) energy storage and force-free magnetic field; (2) energy release and particle acceleration; (3) radiation by nonthermal electrons; (4) coronal loops; (5) flare classification; (6) longitude distributions of flares; (7) periodicities detected in the solar activity; (8) coronal heating and related problems; and (9) plasma processes.

  17. Creative activity and inclusion

    Directory of Open Access Journals (Sweden)

    Shemanov A.Yu.

    2013-09-01

    Full Text Available The aim of the article was to analyze the inclusion potential of art creative activity, namely of theatre performance, in people with disabilities. The article provides examples of disagreements in understanding the significance of these art activities for exercising the rights of people with disabilities to contribute to culture and art and some problems arising here. The conclusion is made that theatre art performed by people with disabilities is gradually changing its function: from being a means of self-affirmation to the determination of its specific place in overall theatre process. These changes confirm the inclusion potential of theatre art activity.

  18. Inspector measurement verification activities

    International Nuclear Information System (INIS)

    e most difficult and complex activity facing a safeguards inspector involves the verification of measurements and the performance of the measurement system. Remeasurement is the key to measurement verification activities. Remeasurerements using the facility's measurement system provide the bulk of the data needed for determining the performance of the measurement system. Remeasurements by reference laboratories are also important for evaluation of the measurement system and determination of systematic errors. The use of these measurement verification activities in conjunction with accepted inventory verification practices provides a better basis for accepting or rejecting an inventory. (U.S.)

  19. 1985. Activity progress report

    International Nuclear Information System (INIS)

    The research program of the Laboratory of nuclear and high energy physics (LPNHE) of the Institute of nuclear and particle physics (IN2P3) presents the research activities of its groups: principally, the Delphi group which constructs the outer detector of Delphi at LEP, the neutrino group which studies the neutrino mass, the Hera group whose work is collaboration to the construction of a detector for Hera collisioner; in parallel to these activities, other more little groups continue analysis of activities which are going to be finished: they are the CELLO group, the EHS group, the omega prime group and the nuclear emulsion group

  20. Activity report 1977

    International Nuclear Information System (INIS)

    The Research and Development (R and D) activities of the Reactor Research Centre, Kalpakkam, during the year 1977 are reported. The report is presented in the form of individual summaries of R and D activities most of which are connected with the FBTR project. These R and D activities deal with various aspects of the FBTR project such as reactor physics, reactor design, reactor engineering, fabrication, testing and quality assurance of reactor materials and components, reactor chemistry, reactor safety, reprocessing, systems analysis and instrumentation. (M.G.B.)

  1. Scientific activities 1979

    International Nuclear Information System (INIS)

    The scientific activities and achievements of the Nuclear Research Center Democritus for the year 1979 are presented in the form of a list of 78 projects giving title, objectives, commencement year, responsible of each project, developed activities and the pertaining lists of publications. The 15 chapters of this work cover the activities of the main Divisions of the Democritus NRC: Electronics, Biology, Physics, Chemistry, Health Physics, Reactor, Radioisotopes, Environmental Radioactivity, Soil Science, Computer Center, Uranium Exploration, Medical Service, Technological Applications and Training. (T.A.)

  2. Active Directory cookbook

    CERN Document Server

    Hunter, Laura

    2008-01-01

    When you need practical hands-on support for Active Directory, the updated edition of this extremely popular Cookbook provides quick solutions to more than 300 common (and uncommon) problems you might encounter when deploying, administering, and automating Microsoft's network directory service. For the third edition, Active Directory expert Laura E. Hunter offers troubleshooting recipes based on valuable input from Windows administrators, in addition to her own experience. You'll find solutions for the Lightweight Directory Access Protocol (LDAP), ADAM (Active Directory Application Mode), m

  3. Forecast of auroral activity

    International Nuclear Information System (INIS)

    A new technique is developed to predict auroral activity based on a sample of over 9000 auroral sites identified in global auroral images obtained by an ultraviolet imager on the NASA Polar satellite during a 6-month period. Four attributes of auroral activity sites are utilized in forecasting, namely, the area, the power, and the rates of change in area and power. This new technique is quite accurate, as indicated by the high true skill scores for forecasting three different levels of auroral dissipation during the activity lifetime. The corresponding advanced warning time ranges from 22 to 79 min from low to high dissipation levels

  4. Mnemonic activation by SPECT

    International Nuclear Information System (INIS)

    Data of literature show that SPECT is able to detect cerebral activations induced by sensory-motor stimuli. The facts are not clearly established in what concerns the cognitive activations the amplitude of which is lower. We have studied an activation paradigm such as the Grober and Bruschke test which implies the long term explicit memory. It comprises a visual presentation of words followed by their indexed recall. By using a two-day protocol, 2 SPECTs were achieved in 4 healthy right-handed voluntaries as follows: one of activation (A) and one of control (B). The fifth subject benefited by a SPECT B and of an MRI. The injection for the examination A has been done during the indexed recall stage and for the examination B at the moment when the patient repeated several times the same 3 words. The SPECT data were collected 1 hour after the injection of 370 MBq of ECD making use of a 3-head camera equipped with UHR fan collimators and ending by a LMH on the reconstructed images of 8 mm. The MRI has been achieved by means of a Signa 1.5 Tesla magnet. The SPECT A and B of the subjects 1 to 4 were matched elastically to that of the subject 5 and that of the subject 5 was rigidly matched on its MRI. In this way the individual activation cards of the 4 subjects could be averaged and superimposed on the MRI of the 5. subject. One observes an internal temporal activation (maximal activation of left tonsil, +25% and right uncus, +23%) and a right cingulum activation (maximal activation, +25%), in agreement with the neuro-physiological data. The elastic matching makes possible the inter-subject averaging, what increases the signal-to-noise ratio of activation. The inter-modality rigid matching facilitates the anatomical localisation of the activation site. With these adapted tools, the cognitive activation is thus possible by SPECT and opens perspectives for early diagnosis of neurological troubles, namely of Alzheimer's disease

  5. China's Space Activities

    Institute of Scientific and Technical Information of China (English)

    China National Space Administration

    2004-01-01

    @@ Currently, space activities are very active around the world. Space technologies continuously expand to various areas of human activities, and space technology and applications are becoming an indispensable part of modern information society,while the development of space science brings a brand-new view to the development of science and technology. The development of space law is not only an important approach to improving people' s quality of lives, expanding the living space of human being, and exploiting new resources, but also an important symbol of the comprehensive strength and civilization of a nation.

  6. Active Fire Mapping Program

    Science.gov (United States)

    Active Fire Mapping Program Current Large Incidents (Home) New Large Incidents Fire Detection Maps MODIS Satellite Imagery VIIRS Satellite Imagery Fire Detection GIS Data Fire Data in Google Earth ...

  7. Physical Activity and Cancer

    Science.gov (United States)

    ... of insulin and insulin-like growth factor I (IGF-I), improving the immune response ; and assisting with ... studies have started examining the factors related to long-term behavior change and increases in physical activity. ...

  8. Extravehicular activity technology discipline

    Science.gov (United States)

    Webbon, Bruce W.

    1990-01-01

    Viewgraphs on extravehicular activity technology discipline for Space Station Freedom are presented. Topics covered include: extravehicular mobility unit; airlock and EMU support equipment; tools, mobility aids, and workstations; and telerobotic work aids interfaces.

  9. OTI Activity Database

    Data.gov (United States)

    US Agency for International Development — OTI's worldwide activity database is a simple and effective information system that serves as a program management, tracking, and reporting tool. In each country,...

  10. Creating Art Appreciation Activities.

    Science.gov (United States)

    Heidt, Ann H.

    1986-01-01

    The experiences of college students enrolled as majors in elementary education in designing art appreciation activities for use in elementary classrooms are described. The college students had no art background. (RM)

  11. Facts about Physical Activity

    Science.gov (United States)

    ... stroke, type 2 diabetes, depression, and some cancers. Physical activity can also help with weight control, and may improve academic achievement in students. There's more . Inactive adults have a ...

  12. Home Activities Reports

    Data.gov (United States)

    Department of Housing and Urban Development — This monthly report is an Excel spreadsheet, broken up by state. PJs can use this report to view activities with the 2012 or 2013 program year in IDIS, including;...

  13. Physical activity: genes & health

    CERN Multimedia

    2002-01-01

    Carl Johan SUNDBERG is an Associate Professor in Physiology and Licenced Physician. His research focus is Molecular mechanisms involved in the adaptation of human skeletal muscle to physical activity.

  14. Vessel Activity Record

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Vessel Activity Record is a bi-weekly spreadsheet that shows the status of fishing vessels. It records whether fishing vessels are fishing without an observer...

  15. Homebuyer Activities Report

    Data.gov (United States)

    Department of Housing and Urban Development — This monthly report is an Excel spreadsheet. PJs can use this report to view homebuyer activities with the 2012 or 2013 program year in IDIS that are in final draw,...

  16. DPHPE activities during 1978

    International Nuclear Information System (INIS)

    This annual report gives a short summary of experiments in progress and of approved proposals of experiments to be performed by the Elementary Particle Physics Department of Saclay, and also publication lists and informations about the Department activities during 1978

  17. 13. seminar 'Activation analysis'

    International Nuclear Information System (INIS)

    Collection of the abstracts of contributions to the seminar covering broad ranges of application of activation analysis and improvements of systems and process steps. Most of them have been prepared separately for the energy data bases. (RB)

  18. Active at Any Size

    Science.gov (United States)

    ... Coordinating Committees NIDDK Advisory Council, Board of Scientific Advisors, and committees that coordinate research activities Research Areas ... the rest of the way. Even a shopping trip can be exercise because it provides a chance ...

  19. Active flows on trees

    CERN Document Server

    Forrow, Aden; Dunkel, Jörn

    2016-01-01

    Coherent, large scale dynamics in many nonequilibrium physical, biological, or information transport networks are driven by small-scale local energy input. We introduce and explore a generic model for compressible active flows on tree networks. In contrast to thermally-driven systems, active friction selects discrete states with only a small number of oscillation modes activated at distinct fixed amplitudes. This state selection interacts with graph topology to produce different localized dynamical time scales in separate regions of large networks. Using perturbation theory, we systematically predict the stationary states of noisy networks and find good agreement with a Bayesian state estimation based on a hidden Markov model applied to simulated time series data on binary trees. While the number of stable states per tree scales exponentially with the number of edges, the mean number of activated modes in each state averages $\\sim 1/4$ the number of edges. More broadly, these results suggest that the macrosco...

  20. The Active Asteroids

    CERN Document Server

    Jewitt, David; Agarwal, Jessica

    2015-01-01

    Some asteroids eject dust, producing transient, comet-like comae and tails; these are the active asteroids. The causes of activity in this newly-identified population are many and varied. They include impact ejection and disruption, rotational instabilities, electrostatic repulsion, radiation pressure sweeping, dehydration stresses and thermal fracture, in addition to the sublimation of asteroidal ice. These processes were either unsuspected or thought to lie beyond the realm of observation before the discovery of asteroid activity. Scientific interest in the active asteroids lies in their promise to open new avenues into the direct study of asteroid destruction, the production of interplanetary debris, the abundance of asteroid ice and the origin of terrestrial planet volatiles.

  1. Activities in Teaching Weather

    Science.gov (United States)

    Tonn, Martin

    1977-01-01

    Presented is a unit composed of activities for teaching weather. Topics include cloud types and formation, simple weather instruments, and the weather station. Illustrations include a weather chart and instruments. A bibliography is given. (MA)

  2. Designing for Design Activity

    OpenAIRE

    Kang, Sunghyun

    2009-01-01

    The area of graphic design has expanded since digital media was introduced, and it requires new creative thinking skills in the design process. This paper proposes a design process for a graphic design graduate class using activity theory as a theoretical background. This design process consists of three phases to solve the design problems within diverse design projects. Each phase was examined in terms of how the elements of activity theory could apply to the design process. As a research me...

  3. Creative activity and inclusion

    OpenAIRE

    Shemanov A.Yu.; Vostrov I.M.; Yegorova V.A.

    2013-01-01

    The aim of the article was to analyze the inclusion potential of art creative activity, namely of theatre performance, in people with disabilities. The article provides examples of disagreements in understanding the significance of these art activities for exercising the rights of people with disabilities to contribute to culture and art and some problems arising here. The conclusion is made that theatre art performed by people with disabilities is gradually changing its function: from being...

  4. ACTIVITY - BASED COSTING DESIGNING

    OpenAIRE

    Wioletta Skibiñska; Marta Kad³ubek

    2010-01-01

    The traditional costing system sometimes does not give accurate information about the consumption of different resources and the activities of the organisation. The activity-based costing system is an information-rich costing system which is more and more necessary for the success of many European companies. Base of designing and implementation of an ABC system in the enterprises are presented in the article.

  5. TPR And TPR Activities

    Institute of Scientific and Technical Information of China (English)

    宋丽萍

    2008-01-01

    This paper presents the definition of Total Physical Response(TPR),elaborates the process and the principles of it 80 that more and more TPR activities can be created according to them.The use of TPR shows us an interesting and effective way of teaching and learning English.TPR activities are interesting,challenging and motivating that almost all the students enjoy them.

  6. Asteroseismic stellar activity relations

    OpenAIRE

    Bonanno, A.; Corsaro, E.; Karoff, C.

    2014-01-01

    In asteroseismology an important diagnostic of the evolutionary status of a star is the small frequency separation which is sensitive to the gradient of the mean molecular weight in the stellar interior. It is thus interesting to discuss the classical age-activity relations in terms of this quantity. Moreover, as the photospheric magnetic field tends to suppress the amplitudes of acoustic oscillations, it is important to quantify the importance of this effect by considering various activity i...

  7. Activation Energy for Fission

    Energy Technology Data Exchange (ETDEWEB)

    Seaborg, Glenn T.

    1952-08-29

    The experimentally determined exponential dependence of spontaneous fission rate on Z{sup 2}/A has been used to derive an expression for the dependence of the fission activation energy on Z{sup 2}/A. This expression has been used to calculate the activation energy for slow neutron induced fission and photofission. The correlation with the experimental data on these types of fission seems to be quite good.

  8. Antibacterial Activity of Grepafloxacin

    OpenAIRE

    Wiedemann, B; Heisig, P

    1998-01-01

    Grepafloxin has an extremely broad spectrum of activity. Its activity against Gram-positive bacteria exceeds that of currently available quinolones. Grepafloxacin-resistant mutants seem to occur less frequently than ciprofloxacin - or ofloxacin-resistant mutants, and the increase in minimum inhibitory concentration (MIC) against the former mutants is less than that of the latter. This applies only to the relative differences (in dilution steps); the absolute values are similar. Grepafloxacin ...

  9. Enzyme with rhamnogalacturonase activity.

    OpenAIRE

    Kofod, L.V.; Andersen, L N; Dalboge, H; Kauppinen, M.S.; Christgau, S; Heldt-Hansen, H.P.; Christophersen, C.; Nielsen, P.M.; Voragen, A. G. J.; Schols, H.A.

    1998-01-01

    An enzyme exhibiting rhamnogalacturonase activity, capable of cleaving a rhamnogalacturonan backbone in such a manner that galacturonic acids are left as the non-reducing ends, and which exhibits activity on hairy regions from a soy bean material and/or on saponified hairy regions from a sugar beet material. The enzyme has the amino acid sequence of SEQ ID NO:2 and is encoded by the DNA sequence of SEQ ID NO:1

  10. Liquidity and Shareholder Activism

    OpenAIRE

    Norli, Øyvind; Østergaard, Charlotte; Schindele, Ibolya

    2009-01-01

    Blockholders' incentives to intervene in corporate governance are weakened by free-rider problems and high costs of activism. Theory suggests activists may recoup expenses through informed trading of target rms' stock when stocks are liquid. We show that stock liquidity increases the probability of activism but does less so for potentially overvalued rms for which privately informed blockholders may have greater incentives to sell their stake than to intervene. We also document ...

  11. Antitrypanosomal Activity of Fluoroquinolones

    OpenAIRE

    Nenortas, Elizabeth; Burri, Christian; Shapiro, Theresa A.

    1999-01-01

    Six fluoroquinolones presently in clinical use and four investigational tetracyclic fluoroquinolones were tested for in vitro activity against bloodstream-form Trypanosoma brucei brucei. All compounds had measurable activity, but the tetracyclic analogs were most potent, with 50% effective concentrations in the low micromolar range. In general, trypanosomes were more susceptible than L1210 leukemia cells. Consistent with the notion that they target type II topoisomerase in trypanosomes, the f...

  12. Intercreativity: Mapping Online Activism

    Science.gov (United States)

    Meikle, Graham

    How do activists use the Internet? This article maps a wide range of activist practice and research by applying and developing Tim Berners-Lee's concept of ‘intercreativity' (1999). It identifies four dimensions of Net activism: intercreative texts, tactics, strategies and networks. It develops these through examples of manifestations of Net activism around one cluster of issues: support campaigns for refugees and asylum seekers.

  13. Habitats, activities, and signs

    DEFF Research Database (Denmark)

    Andersen, Peter Bøgh; Brynskov, Martin

    2004-01-01

    Digital habitats is a framework for designing and modeling environments for activities that involve mobile and embedded computing systems. This paper 1) introduces the basic concepts of the framework, i.e. activity, thematic role, and the three ‘dimensions’ of a habitat: physical, informational......, and pragmatic, 2) proposes a notation, and 3) sketches a method and exemplifies areas of application using authentic cases from hospital work, primary school education, the maritime domain, and other areas...

  14. Active Noice Reduction headset

    OpenAIRE

    Fransson, Henrik

    2009-01-01

    Conventional (passive) headsets used in propeller aircrafts are reasonably good at attenuating mid to high frequency noise, but fail to achieve good attenuation in the low frequency region (below approximately 300 Hz). Active Noise Reduction (ANR) improves the low frequency attenuation by introducing an anti-noise signal creating destructive interference thus decreasing the residual noise level. The aim of this thesis is to develop and implement a digital narrowband active noise reduction hea...

  15. Active social insurance

    OpenAIRE

    Røed, Knut

    2012-01-01

    The paper argues that a comprehensive activation strategy is called for - in both unemployment and disability insurance - to minimize the conflict between income insurance and work incentives and to prevent the economic crisis from causing a long-lasting decline in labor force participation. A review of recent empirical evidence, particularly from the Scandinavian countries, indicates that 'mild' activation requirements effectively counteract moral hazard problems in social insurance. The pap...

  16. RAVEN Quality Assurance Activities

    Energy Technology Data Exchange (ETDEWEB)

    Cogliati, Joshua Joseph [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2015-09-01

    This report discusses the quality assurance activities needed to raise the Quality Level of Risk Analysis in a Virtual Environment (RAVEN) from Quality Level 3 to Quality Level 2. This report also describes the general RAVEN quality assurance activities. For improving the quality, reviews of code changes have been instituted, more parts of testing have been automated, and improved packaging has been created. For upgrading the quality level, requirements have been created and the workflow has been improved.

  17. Activity report 1976

    International Nuclear Information System (INIS)

    The research and development activities of the Reactor Research Centre, Kalpakkam, during 1976 are reported. The main thrust of the R and D activities is directed towards the FBTR Project and they deal with the various aspects of the project such as reactor physics, reactor design, fuel handling, reactor instrumentation, reactor operation, reactor construction, reactor safety, reactor materials, reactor chemistry and fuel reprocessing. (M.G.B.)

  18. Fraudulent activities in accounting

    OpenAIRE

    Fábriová, Kristína

    2014-01-01

    This thesis is focused on fraudulent activities in accounting. The aim of this thesis is to analyze current cases of accounting fraud and examine motives for committing accounting fraud, identify methods used by companies to commit accounting fraud and reasons why these fraud cases were not revealed sooner. The thesis is divided into two parts -- theoretical and practical. First part provides theoretical introduction to the topic of fraudulent activities in accounting and describes various me...

  19. RAVEN Quality Assurance Activities

    International Nuclear Information System (INIS)

    This report discusses the quality assurance activities needed to raise the Quality Level of Risk Analysis in a Virtual Environment (RAVEN) from Quality Level 3 to Quality Level 2. This report also describes the general RAVEN quality assurance activities. For improving the quality, reviews of code changes have been instituted, more parts of testing have been automated, and improved packaging has been created. For upgrading the quality level, requirements have been created and the workflow has been improved.

  20. Activity report 1979

    International Nuclear Information System (INIS)

    The activites of the Eurochemic (European Company for the Chemical Processing of Irradiated Fuels) at Mol is summarized under the following headings: the decontamination and intervention in the Fuel Reception and Storage Building, the active operation of the bituminization facility, the construction of two additional storage bunkers, the full active operation of the section for the handling of solid waste and the construction of various units for the conditioning of organic liquid waste and plutonium hearing solid wastes. (AF)

  1. Active Travel Behavior

    OpenAIRE

    Burbidge, Shaunna K; Goulias, Konstadinos G.

    2008-01-01

    Physical inactivity has become a dominant feature of most American’s lives over the past quarter century. This has spurred an entire research domain straddling several different disciplines. Although model development within the field of travel behavior as a whole continues today with more momentum than ever, the focus on active mode choice has largely been overlooked and left to a small fragment of transportation and public health researchers. Research regarding active mode choice has been...

  2. ABB: active bandwidth broker

    Science.gov (United States)

    Wong, Kason; Law, Eddie

    2001-07-01

    In this paper, we shall discuss a novel design on the policy-based management for the Internet. This design deploys the concept of active networking. As opposed to the traditional network design, active network empowers network node with the ability to manipulate data and program code in packets, and configure the network properties according to the needs of different applications. The policy-based management can control network routers in order to realize end-to-end Quality of Service (QoS), such as differentiated and integrated services, across the Internet. For the moment, the Internet Engineering Task Force (IETF) has defined the framework of the policy-based management. It employs a simple client/server model that uses Common Open Policy Service (COPS) protocol to facilitate policy management and control. Our design of Active Bandwidth Broker (ABB) belongs to an active application. Our goals are to distribute centralized workload of the policy-based management over multiple active nodes in the active networks, introduce mobility of the bandwidth brokers, and allows load sharing to the policy-based management. This results a network-wide intelligent, highly available, and consistent QoS control that allows performance protection for voice, video and Internet business application while reducing costs for growing networks.

  3. Identification of an avirulence gene,avrxa5,from the rice pathogen Xanthomonas oryzae pv.oryzae

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Xanthomonas oryzae pv.oryzae,the causal agent of bacterial blight in rice,interacts with rice plants in a gene-for-gene manner.The specificity of the interaction is dictated by avirulence(avr) genes in the pathogen and resistance(R) genes in the host.To date,no avr genes that correspond to recessive R genes have been isolated.We isolated an avrBs3/pthA family gene,avrxa5,from our previously isolated clone p58,which was originally from strain JXOIII.The avrxa5 gene converted the PXO99A strain from compatible to incompatible in rice cultivars containing the recessive xa5 gene,but not in those containing the dominant Xa5 gene.Sequencing indicated that avrxa5,which is highly similar to members of the avrBs3/pthA family,encodes a protein of 1238 amino acid residues with a conserved carboxy-terminal region containing three nuclear localization signals and a transcription activation domain.It has 19.5 34-amino-acid direct repeats,but the 13th amino acid is missing in the fifth and ninth repetitive units.Domain swapping of the repetitive regions between avrxa5 and avrXa7 changed the avirulence specificity of the genes in xa5 and Xa7 rice lines,respectively.This indicates that avrxa5 is distinct from previously characterized avrBs3/pthA members.The specificity of avrxa5 toward recessive xa5 in rice could help us better understand the molecular mechanisms of plant-pathogen specific interactions.

  4. Rivaroxaban and Hemostasis in Emergency Care

    Directory of Open Access Journals (Sweden)

    Jürgen Koscielny

    2014-01-01

    Full Text Available Rivaroxaban is an oral, direct Factor Xa inhibitor, approved for the prevention and treatment of several thromboembolic disorders. Rivaroxaban does not require routine coagulation monitoring and has a short half-life. However, confirmation of rivaroxaban levels may be required in circumstances such as life-threatening bleeding or perioperative management. Here, we explore the management strategies in patients receiving rivaroxaban who have a bleeding emergency or require emergency surgery. Rivaroxaban plasma concentrations can be assessed quantitatively using anti-Factor Xa chromogenic assays, or qualitatively using prothrombin time assays (using rivaroxaban-sensitive reagents. In patients receiving long-term rivaroxaban therapy who require elective surgery, discontinuation of rivaroxaban 20–30 hours beforehand is normally sufficient to minimize bleeding risk. For emergency surgery, we advise against prophylactic use of hemostatic blood products, even with high rivaroxaban concentrations. Temporary rivaroxaban discontinuation is recommended if minor bleeding occurs; for severe bleeding, rivaroxaban withdrawal may be necessary, along with compression or appropriate surgical treatment. Supportive measures such as blood product administration might be beneficial. Life-threatening bleeding demands comprehensive hemostasis management, including potential use of agents such as prothrombin complex concentrate. Patients taking rivaroxaban who require emergency care for bleeding or surgery can be managed using established protocols and individualized assessment.

  5. Psychomotor activities with seniors

    Directory of Open Access Journals (Sweden)

    Jitka Kopřivová

    2015-07-01

    Full Text Available BACKGROUND: Given that the population all over the world is aging, it is necessary to fi nd ways to help maintain or improve the quality of life of seniors. The main goal of this paper is to show how appropriate physical activity programs contribute to the improvement of the functionality and psychosocial wellbeing of seniors. We are particularly interested in the possibilities of preserving self-suffi ciency and self-service, independence and the ability to perform everyday activities. One of the most eff ective forms of physical activity is psychomotr activity.OBJECTIVE: The aim of our paper is to present basic information concerning the meaning and the application of the psychomotr activities in intervention movement programmes in order to improve seniors’ life quality.METHODS: We defi ne the term psychomotr activities according to Adamírová (1995 and Novotná (2010. In this paper we present some results of research that stress the positive eff ect of psychomotor exercises and games on the life satisfaction of the elderly (Stará 2011; Stará & Kopřivová, 2011.DESCRIPTION: According to the results of our research and practical experience gained from working with the elderly it is strongly recommended to include suitable psychomotor exercises and games focusing on the development of manual dexterity in training programs in order to improve the balance abilities and the psychosocial area. In terms of prevention, because of the growing number of neurological disorders at an old age it is appropriate to include psychomotor exercises that encourage the development of cognitive functions in the physical interventions.CONCLUSION: We were able to positively infl uence the emotional aspect from performing physical activities, to enhance self-esteem of the exercising subjects and to create new social relationships. Motion programs, which also included psychomotor exercises and games, had a positive eff ect on the physical assessment of the

  6. Antimutagenic activity of spearmint.

    Science.gov (United States)

    Yu, Tian-Wei; Xu, Meirong; Dashwood, Roderick H

    2004-01-01

    The antimutagenic activity of spearmint (Mentha spicata), a popular food flavoring agent, was studied in the Salmonella assay. Spearmint leaves were brewed in hot water for 5 min at concentrations up to 5% (w/v), and the water extracts were tested against the direct-acting mutagens 4-nitro-1,2-phenylenediamine (NPD) and 2-hydroxyamino-3-methyl-3H-imidazo[4,5-f]quinoline (N-OH-IQ) using Salmonella typhimurium strain TA98. Nontoxic concentrations of spearmint extract inhibited the mutagenic activity of N-OH-IQ in a concentration-dependent fashion, but had no effect against NPD. These experiments by design focused on the water extract consumed commonly as an herbal tea, but chloroform and methanol extracts of spearmint also possessed antimutagenic activity against N-OH-IQ. Water extract of spearmint inhibited the mutagenic activity of the parent compound, 2-amino-3-methyl-3H-imidazo[4,5-f]quinoline (IQ), in the presence of rat liver S9; however, the concentration for 50% inhibition (IC50) against IQ was approximately 10-fold higher than in assays with N-OH-IQ minus S9. At concentrations similar to those used in the Salmonella assays, spearmint extract inhibited two of the major enzymes that play a role in the metabolic activation of IQ, namely, cytochromes P4501A1 and 1A2, based on ethoxyresorufin O-deethylase and methoxyresorufin O-demethylase assays in vitro. In vivo, rats were given spearmint water extract (2%; w/v) as the sole source of drinking fluid before, during, and after 2-week treatment with IQ; colonic aberrant crypt foci were inhibited significantly at 8 weeks (P < 0.05, compared with rats given IQ alone). Collectively, these findings suggest that spearmint tea protects against IQ and possibly other heterocyclic amines through inhibition of carcinogen activation and via direct effects on the activated metabolite(s).

  7. ACTIVATION ENERGY OF DESORPTION OF DIBENZOFURAN ON ACTIVATED CARBONS

    Institute of Scientific and Technical Information of China (English)

    LI Xiang; LI Zhong; XI Hongxia; LUO Lingai

    2004-01-01

    Three kinds of commercial activated carbons, such as Norit RB1, Monolith and Chemviron activated carbons, were used as adsorbents for adsorption of dibenzofuran. The average pore size and specific surface area of these activated carbons were measured. Temperature Programmed Desorption (TPD) experiments were conducted to measure the TPD curves of dibenzofuran on the activated carbons, and then the activation energy for desorption of dibenzofuran on the activated carbons was estimated. The results showed that the Chemviron and the Norit RB1 activated carbon maintained higher specific surface area and larger micropore pore volume in comparison with the Monolith activated carbon, and the activation energy for the desorption of dibenzofuran on these two activated carbons was higher than that on the Monolith activated carbon. The smaller the pore of the activated carbon was, the higher the activated energy of dibenzofuran desorption was.

  8. Youth Physical Activity Resources Use and Activity Measured by Accelerometry

    Science.gov (United States)

    Maslow, Andréa L.; Colabianchi, Natalie

    2014-01-01

    Objectives To examine whether utilization of physical activity resources (eg, parks) was associated with daily physical activity measured by accelerometry. Methods 111 adolescents completed a travel diary with concurrent accelerometry. The main exposure was self-reported utilization of a physical activity resource (none/1+ resources). The main outcomes were total minutes spent in daily 1) moderate-vigorous physical activity and 2) vigorous physical activity. Results Utilizing a physical activity resource was significantly associated with total minutes in moderate-vigorous physical activity. African-Americans and males had significantly greater moderate-vigorous physical activity. Conclusions Results from this study support the development and use of physical activity resources. PMID:21204684

  9. Mechanochemically Active Soft Robots.

    Science.gov (United States)

    Gossweiler, Gregory R; Brown, Cameron L; Hewage, Gihan B; Sapiro-Gheiler, Eitan; Trautman, William J; Welshofer, Garrett W; Craig, Stephen L

    2015-10-14

    The functions of soft robotics are intimately tied to their form-channels and voids defined by an elastomeric superstructure that reversibly stores and releases mechanical energy to change shape, grip objects, and achieve complex motions. Here, we demonstrate that covalent polymer mechanochemistry provides a viable mechanism to convert the same mechanical potential energy used for actuation in soft robots into a mechanochromic, covalent chemical response. A bis-alkene functionalized spiropyran (SP) mechanophore is cured into a molded poly(dimethylsiloxane) (PDMS) soft robot walker and gripper. The stresses and strains necessary for SP activation are compatible with soft robot function. The color change associated with actuation suggests opportunities for not only new color changing or camouflaging strategies, but also the possibility for simultaneous activation of latent chemistry (e.g., release of small molecules, change in mechanical properties, activation of catalysts, etc.) in soft robots. In addition, mechanochromic stress mapping in a functional robotic device might provide a useful design and optimization tool, revealing spatial and temporal force evolution within the robot in a way that might be coupled to autonomous feedback loops that allow the robot to regulate its own activity. The demonstration motivates the simultaneous development of new combinations of mechanophores, materials, and soft, active devices for enhanced functionality. PMID:26390078

  10. Software Activation Using Multithreading

    Directory of Open Access Journals (Sweden)

    Jianrui Zhang

    2012-11-01

    Full Text Available Software activation is an anti-piracy technology designed to verify that software products have been legitimately licensed. Activation should be quick and simple while simultaneously being secure and protecting customer privacy. The most common form of software activation is for the user to enter a legitimate product serial number. However, software activation based on serial numbers appears to be weak, since cracks for many programs are readily available on the Internet. Users can employ such cracks to bypass software activation.Serial number verification logic usually executes sequentially in a single thread. Such an approach is relatively easy to break since attackers can trace the code to understand how the logic works. In this paper, we develop a practical multi-threaded verification design. Our results show that by proper use of multi-threading, the amount of traceable code in a debugger can be reduced to a low percentage of the total and the traceable code in each run can differ as well. This makes it significantly more difficult for an attacker to reverse engineer the code as a means of bypassing a security check. Finally, we attempt to quantify the increased effort needed to break our verification logic.

  11. Active noise control primer

    CERN Document Server

    Snyder, Scott D

    2000-01-01

    Active noise control - the reduction of noise by generating an acoustic signal that actively interferes with the noise - has become an active area of basic research and engineering applications. The aim of this book is to present all of the basic knowledge one needs for assessing how useful active noise control will be for a given problem and then to provide some guidance for designing, setting up, and tuning an active noise-control system. Written for students who have no prior knowledge of acoustics, signal processing, or noise control but who do have a reasonable grasp of basic physics and mathematics, the book is short and descriptive. It leaves for more advanced texts or research monographs all mathematical details and proofs concerning vibrations, signal processing and the like. The book can thus be used in independent study, in a classroom with laboratories, or in conjunction with a kit for experiment or demonstration. Topics covered include: basic acoustics; human perception and sound; sound intensity...

  12. Global physical activity levels

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  13. CEREM activity report

    International Nuclear Information System (INIS)

    This 1997 issue of the activity report of the CEREM (CEA) gives a general overview of the CEREM organization, activities and human resources with some budgetary information. The main activities described concern the materials fabrication for the nuclear and automotive industries, the powders metallurgy (molding by injection, cold pressing modelling), the simulation of the hot and cold working processes, the surface treatments, the joining (brazed joints, sintering, welding), the electrochemical storage of the energy (fuel cells, lithium accumulators), the corrosion and the physico-chemistry of fluids, the mechanical properties and the cracks, the robots for nuclear units dismantlement, the alteration mechanisms of properties under different solicitations (thermal, mechanical, chemical, irradiation) and the solidification-crystallogenesis. (O.M.)

  14. Lesion activity assessment

    DEFF Research Database (Denmark)

    Ekstrand, K R; Zero, D T; Martignon, S;

    2009-01-01

    This chapter focusses on the probability of a caries lesion detected during a clinical examination being active (progressing) or arrested. Visual and tactile methods to assess primary coronal lesions and primary root lesions are considered. The evidence level is rated as low (R(w)), as there are...... response to cariogenic plaque as well as lesion arrest. Based on this understanding, different clinical scoring systems have been developed to assess the severity/depth and activity of lesions. A recent system has been devised by the International Caries Detection and Assessment System Committee. The...... literature suggests that there is a fair agreement between visual/tactile external scripts of caries and the severity/depth of the lesion. The reproducibility of the different systems is, in general, substantial. No single clinical predictor is able to reliably assess activity. However, a combination of...

  15. Active Photonic Crystal Waveguides

    DEFF Research Database (Denmark)

    Ek, Sara

    This thesis deals with the fabrication and characterization of active photonic crystal waveguides, realized in III-V semiconductor material with embedded active layers. The platform offering active photonic crystal waveguides has many potential applications. One of these is a compact photonic...... crystal semiconductor optical amplier. As a step towards such a component, photonic crystal waveguides with a single quantum well, 10 quantum wells and three layers of quantum dots are fabricated and characterized. An experimental study of the amplied spontaneous emission and a implied transmission...... are presented in this thesis. A variation of photonic crystal design parameters are used leading to a spectral shift of the dispersion, it is veried that the observed effects shift accordingly. An enhancement of the amplified spontaneous emission was observed close to the band edge, where light is slowed down...

  16. Active Elbow Orthosis

    Directory of Open Access Journals (Sweden)

    Tomas Ripel

    2014-09-01

    Full Text Available This paper presents a novel approach to the design of a motorized rehabilitation device – active elbow orthosis (AEO – inspired by the principles of robotic exoskeletons. The device is currently designed for the elbow joint, but can be easily modified for other joints as well. AEO determines the motion activity of the patient using a strain gauge and utilizes this measurement to control the actuator that drives the forearm part of the orthosis. Patient activity level is related to a free arm measurement obtained via a calibration procedure prior to the exercise. A high-level control module offers several types of exercises mimicking the physiotherapist. The device was successfully verified by tests on a number of patients, resulting in extended range of elbow-joint motion.

  17. Physical activity & depression

    Directory of Open Access Journals (Sweden)

    Tsiantoula E.

    2012-07-01

    Full Text Available Depression is a major public health disorder. Clinical depression is the most frequent disability in North America among other countries and by 2020 it is estimated that it will represent the second most common disability worldwide. Physical activity can be used to prevent as well as treat depression. Its characteristics and structure should be individualized to the personality and special needs of the patient as well as to the severity of the disorder. Intensity, duration and the place of performance are of special importance. Research has identified neurobiological and psychological paths that can develop between physical activity and well being. More studies although are needed in order to standardize the use of physical activity as a treatment option, mainly in the groups of children and teenagers.

  18. Prenucleosomes and Active Chromatin

    Science.gov (United States)

    Khuong, Mai T.; Fei, Jia; Ishii, Haruhiko; Kadonaga, James T.

    2016-01-01

    Chromatin consists of nucleosomes as well as nonnucleosomal histone-containing particles. Here we describe the prenucleosome, which is a stable conformational isomer of the nucleosome that associates with ~80 bp DNA. Prenucleosomes are formed rapidly upon the deposition of histones onto DNA and can be converted into canonical nucleosomes by an ATP-driven chromatin assembly factor such as ACF. Different lines of evidence reveal that there are prenucleosome-sized DNA-containing particles with histones in the upstream region of active promoters. Moreover, p300 acetylates histone H3K56 in prenucleosomes but not in nucleosomes, and H3K56 acetylation is found at active promoters and enhancers. These findings therefore suggest that there may be prenucleosomes or prenucleosome-like particles in the upstream region of active promoters. More generally, we postulate that prenucleosomes or prenucleosome-like particles are present at dynamic chromatin, whereas canonical nucleosomes are at static chromatin. PMID:26767995

  19. Activity report 1977

    International Nuclear Information System (INIS)

    The principal activities of Eurochemic plant in the fields of reprocessing and the solidification and conditioning of liquid wastes are presented in this report that covers the period 1 January to 31 December 1977. Works in the plant are closely related to the handling of fuel element and the treatment of solid wastes as well as the management of liquid wastes. Industrial development activities have been primarily devoted to the solidification of HEWC (highly enriched waste concentrate) by means of the Lotes process; the treatment of spent solvent by means of the Eurowatt process; the treatment of the plutonium-bearing solid wastes by the Eurowetcomb process and the conditioning of highly activity non-combustible solid wastes by incorporation into polymer-concrete matrix . (AF)

  20. Activity report 1978

    International Nuclear Information System (INIS)

    The principal activities of Eurochemic plant in the fields of reprocessing and the solidification and conditioning of liquid and solid wastes are presented in this report that covers the period 1 January to 31 December 1978. Works in the plant are closely related to the decontamination in cooperation with specialized firms. Active operation of bituminization facility was started in June, and a total of 66 m3 of medium level waste was incorporated into bitumen by the end of 1978. The associated storage facility was in active operation since June and preliminary studies for its extension were completed. A facility was completed for the conditioning of solid wastes arising from the decontamination operation of solid wastes whch were stored under water during plant operation. (AF)

  1. Activity report CEREM 1998

    International Nuclear Information System (INIS)

    The CEREM (Centre d'Etudes et de Recherches sur les Materiaux) is one of the departments in CEA. The aim of this report is to outline the main developments in the department activities. It si divide din three main chapters. The first one presents the material design and processing, the researches on the energy electrochemical storage and a presentation of the robotic activities. The chapter 2 deals with the material characterization and testing. The last chapter presents the works of simulation on Material Science. The report is completed by some data on the budget and the staff. (A.L.B.)

  2. SCOR announces new activities

    Science.gov (United States)

    Urban, Edward R., Jr.

    Roger Revelle had many good ideas during his long and productive career. One of them came to fruition in 1957 in the form of the Scientific Committee on Oceanic Research (SCOR), which the International Council for Science created as its first interdisciplinary body, to promote international activities in oceanography. Revelle served as SCOR's first president from 1957 to 1960. SCOR offers opportunities for scientists from different countries to cooperate in planning and executing international programs in ocean sciences. Over its 44 years in existence, SCOR has sponsored 120 working groups and has actively participated in many of the major international oceanographic projects. Thirty-six nations presently participate as SCOR members.

  3. Activity report 1984

    International Nuclear Information System (INIS)

    For the fiscal year 1984, the technical activities of Eurochemic were: a) the cleaning of the vessels having contained medium level liquid wastes and the incorporation into bitumen of the resulting solution, b) the conditioning of plutonium contaminated solid waste, c) the civil engineering works of Building 29 were completed and the mounting of equipment was begun. The installation will assure the surface storage of the blocks resulting from vitrification, by means of Pamela installation of the high-level liquid wastes. The report includes administrative matters as well as health and safety activity. (AF)

  4. IPSN activity report 1999

    International Nuclear Information System (INIS)

    The IPSN (Institut de Protection et de Surete Nucleaire) carries out for the Government, studies and inspections on nuclear installations at many life steps (design, realisation, exploitation, shutdown and dismantling). To obtain quality researches, the Institut performs studies in all domains concerned by the safety and its improvement. The main projects of the year 1999, in the following topics are presented: the nuclear installations and the radioactive wastes safety, the crisis and nuclear materials management, the human and the environment protection, the international activities and cooperation, the quality insurance. It provides also information on the cooperation, the budget, the human resource policy and the communication activities. (A.L.B.)

  5. Andra 1997 activity report

    International Nuclear Information System (INIS)

    This activity report comprises two parts. The first part describes the missions and activities of the ANDRA (the French agency for the management of radioactive wastes): quality control of wastes produced by EdF, CEA, Cogema and the 1100 other small producers, design, construction and management of storage centres, anticipation and development of new management solutions, research and evaluation studies on deep storage facilities, inventory and control of all radioactive materials present in the French territory. The second part is a presentation of financial data. (J.S.)

  6. Reference neutron activation library

    International Nuclear Information System (INIS)

    Many scientific endeavors require accurate nuclear data. Examples include studies of environmental protection connected with the running of a nuclear installation, the conceptual designs of fusion energy producing devices, astrophysics and the production of medical isotopes. In response to this need, many national and international data libraries have evolved over the years. Initially nuclear data work concentrated on materials relevant to the commercial power industry which is based on the fission of actinides, but recently the topic of activation has become of increasing importance. Activation of materials occurs in fission devices, but is generally overshadowed by the primary fission process. In fusion devices, high energy (14 MeV) neutrons produced in the D-T fusion reaction cause activation of the structure, and (with the exception of the tritium fuel) is the dominant source of activity. Astrophysics requires cross-sections (generally describing neutron capture) or its studies of nucleosynthesis. Many analytical techniques require activation analysis. For example, borehole logging uses the detection of gamma rays from irradiated materials to determine the various components of rocks. To provide data for these applications, various specialized data libraries have been produced. The most comprehensive of these have been developed for fusion studies, since it has been appreciated that impurities are of the greatest importance in determining the overall activity, and thus data on all elements are required. These libraries contain information on a wide range of reactions: (n,γ), (n,2n), (n,α), (n,p), (n,d), (n,t), (n,3He)and (n,n')over the energy range from 10-5 eV to 15 or 20 MeV. It should be noted that the production of various isomeric states have to be treated in detail in these libraries,and that the range of targets must include long-lived radioactive nuclides in addition to stable nuclides. These comprehensive libraries thus contain almost all the

  7. Do transgenesis and marker-assisted backcross breeding produce substantially equivalent plants? - A comparative study of transgenic and backcross rice carrying bacterial blight resistant gene Xa21

    OpenAIRE

    Gao, Lifen; Cao, Yinghao; Xia, Zhihui; Jiang, Guanghuai; Liu, Guozhen; Zhang, Weixiong; Zhai, Wenxue

    2013-01-01

    Background The potential impact of genetically modified (GM) plants on human health has attracted much attention worldwide, and the issue remains controversial. This is in sharp contrast to the broad acceptance of plants produced by breeding through Marker Assisted Backcrossing (MAB). Results Focusing on transcriptome variation and perturbation to signaling pathways, we assessed the molecular and biological aspects of substantial equivalence, a general principle for food safety endorsed by th...

  8. Prevention of venous thromboembolism with an oral factor Xa inhibitor, YM150, after total hip arthroplasty. A dose finding study (ONYX-2)

    DEFF Research Database (Denmark)

    Eriksson, B I; Turpie, A G G; Lassen, M R;

    2010-01-01

    surgery, with atrial fibrillation and with acute coronary syndrome, respectively. OBJECTIVES: To investigate the efficacy and safety of YM150 for the prevention of VTE following elective total hip arthroplasty. PATIENTS/METHODS: Patients were randomized to postoperative, once-daily, oral YM150 (5, 10, 30......, 60 or 120 mg) (double-blind) or preoperative subcutaneous (open label) enoxaparin (40 mg) for 5 weeks. The primary efficacy endpoint comprised VTE diagnosed by mandatory bilateral venography or verified symptomatic deep vein thrombosis (DVT) plus all deaths up to 9 days after surgery. The primary...... safety outcome was major bleeding up to 9 days after surgery. RESULTS: Primary efficacy endpoint: of 1017 patients randomized, 960 patients were evaluable for safety and 729 patients for efficacy. A dose-related decrease in VTE incidence from YM150 5 to 60 mg (P = 0.0005) and from 5 to 120 mg (P = 0...

  9. Att växa upp i våldets närhet : ungdomars berättelser om våld i hemmet

    OpenAIRE

    Weinehall, Katarina

    1997-01-01

    In this dissertation, teenagers (13-19 years) are allowed to speak out. The purpose of the study was to gain knowledge regarding the conditions related to socialization in the proximity of violence through listening to, interpreting and attempting to understand the teenagers' narratives about life when violence is an everyday occurrence. Primarily, I wanted to obtain a picture of the conditions under which these girls and boys grew up as they themselves described them. My questions are primar...

  10. Ischaemic cardiac outcomes in patients with atrial fibrillation treated with vitamin K antagonism or factor Xa inhibition: results from the ROCKET AF trial

    Science.gov (United States)

    Mahaffey, Kenneth W.; Stevens, Susanna R.; White, Harvey D.; Nessel, Christopher C.; Goodman, Shaun G.; Piccini, Jonathan P.; Patel, Manesh R.; Becker, Richard C.; Halperin, Jonathan L.; Hacke, Werner; Singer, Daniel E.; Hankey, Graeme J.; Califf, Robert M.; Fox, Keith A.A.; Breithardt, Günter

    2014-01-01

    Aims We investigated the prevalence of prior myocardial infarction (MI) and incidence of ischaemic cardiovascular (CV) events among atrial fibrillation (AF) patients. Methods and results In ROCKET AF, 14 264 patients with nonvalvular AF were randomized to rivaroxaban or warfarin. The key efficacy outcome for these analyses was CV death, MI, and unstable angina (UA). This pre-specified analysis was performed on patients while on treatment. Rates are per 100 patient-years. Overall, 2468 (17%) patients had prior MI at enrollment. Compared with patients without prior MI, these patients were more likely to be male (75 vs. 57%), on aspirin at baseline (47 vs. 34%), have prior congestive heart failure (78 vs. 59%), diabetes (47 vs. 39%), hypertension (94 vs. 90%), higher mean CHADS2 score (3.64 vs. 3.43), and fewer prior strokes or transient ischaemic attacks (46 vs. 54%). CV death, MI, or UA rates tended to be lower in patients assigned rivaroxaban compared with warfarin [2.70 vs. 3.15; hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.73–1.00; P = 0.0509]. CV death, MI, or UA rates were higher in those with prior MI compared with no prior MI (6.68 vs. 2.19; HR 3.04, 95% CI 2.59–3.56) with consistent results for CV death, MI, or UA for rivaroxaban compared with warfarin in prior MI compared with no prior MI (P interaction = 0.10). Conclusion Prior MI was common and associated with substantial risk for subsequent cardiac events. Patients with prior MI assigned rivaroxaban compared with warfarin had a non-significant 14% reduction of ischaemic cardiac events. PMID:24132190

  11. 76 FR 67151 - Marine Mammals; File No. 13927

    Science.gov (United States)

    2011-10-31

    .... SUPPLEMENTARY INFORMATION: On December 10, 2008, notice was published in the Federal Register (73 FR 75084) that... National Oceanic and Atmospheric Administration RIN 0648-XA774 Marine Mammals; File No. 13927 AGENCY... the activities requested by the applicant has been issued under the authority of the Marine...

  12. A comparative study of varying doses of enoxaparin for thromboprophylaxis in critically ill patients

    DEFF Research Database (Denmark)

    Robinson, Sian; Zincuk, Aleksander; Larsen, Ulla Lei;

    2013-01-01

    critically ill patients weighing 50 - 90 kilograms were randomised in a double-blinded study to receive subcutaneous (sc) enoxaparin: 40 mg once daily (QD), 30 mg twice daily (BID), 40mg BID, or 1mg/kg QD, each administered for three days. Anti-Xa activity was measured at baseline, and daily at 4, 12, 16...

  13. SwissProt search result: AK112005 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK112005 006-202-F10 (P00742) Coagulation factor X precursor (EC 3.4.21.6) (Stuart facto...r) (Stuart-Prower factor) [Contains: Factor X light chain; Factor X heavy chain; Activated factor Xa heavy chain] FA10_HUMAN 8e-18 ...

  14. SwissProt search result: AK061101 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK061101 006-207-A12 (P00742) Coagulation factor X precursor (EC 3.4.21.6) (Stuart facto...r) (Stuart-Prower factor) [Contains: Factor X light chain; Factor X heavy chain; Activated factor Xa heavy chain] FA10_HUMAN 2e-27 ...

  15. SwissProt search result: AK109059 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK109059 002-154-F02 (P00742) Coagulation factor X precursor (EC 3.4.21.6) (Stuart facto...r) (Stuart-Prower factor) [Contains: Factor X light chain; Factor X heavy chain; Activated factor Xa heavy chain] FA10_HUMAN 3e-21 ...

  16. SwissProt search result: AK112119 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK112119 006-303-H09 (P00742) Coagulation factor X precursor (EC 3.4.21.6) (Stuart facto...r) (Stuart-Prower factor) [Contains: Factor X light chain; Factor X heavy chain; Activated factor Xa heavy chain] FA10_HUMAN 3e-18 ...

  17. Dose-effect relationships of intravenous enoxaparin in patients undergoing percutaneous coronary intervention:a population and bayesian approach based study

    Institute of Scientific and Technical Information of China (English)

    PaolaSANCHEZ-PENA; JeanSEBASTIENHULOT[; SalkURIEN; MD; AnnickANKRI; GillesMONTALESCOT; PhilippeLECHAT

    2004-01-01

    AIM: Recent studies have suggested that intravenous enoxaparin can be used as an alternative therapy in patients percutaneous coronary intervention (PCI); yet the optimal regimen is to be defined. METHODS: Anti-Xa activities were measured in 556 patients who received a single 0.5 mg/kg dose of enoxaparin intravenously immediately before PCI. A population pharmacoki-

  18. Dynamic Activity-Related Incentives for Physical Activity.

    OpenAIRE

    Schüler, Julia; Brunner, Sibylle

    2012-01-01

    The present studies adopted the theoretical framework of activity- and purpose-related incentives (Rheinberg, 2008) to explain the maintenance of physical activity. We hypothesized that activity-related incentives (e.g., “fun”) increase more than purpose-related incentives (e.g., “health”) between the initiation and maintenance phase of physical activity. Additionally, change in activity-related incentives was hypothesized to be a better predictor of maintenance of physical activity than chan...

  19. Low activity aluminum blanket

    Energy Technology Data Exchange (ETDEWEB)

    Benenati, R.; Tichler, P.; Powell, J.R.

    1976-03-01

    The basic design of the breeding blanket consists of cylindrical aluminium canisters filled with a ceramic bed of moderating, shielding, and breeding materials all suitably cooled. A technical analysis of the blanket for an EPR design is given. Activation studies are presented. The effect of pulsed magnetic fields on module structure is investigated. (MOW)

  20. Asteroseismic stellar activity relations

    CERN Document Server

    Bonanno, A; Karoff, C

    2014-01-01

    In asteroseismology an important diagnostic of the evolutionary status of a star is the small frequency separation which is sensitive to the gradient of the mean molecular weight in the stellar interior. It is thus interesting to discuss the classical age-activity relations in terms of this quantity. Moreover, as the photospheric magnetic field tends to suppress the amplitudes of acoustic oscillations, it is important to quantify the importance of this effect by considering various activity indicators. We propose a new class of age-activity relations that connects the Mt. Wilson $S$ index and the average scatter in the light curve with the small frequency separation and the amplitude of the p-mode oscillations. We used a Bayesian inference to compute the posterior probability of various empirical laws for a sample of 19 solar-like active stars observed by the Kepler telescope. We demonstrate the presence of a clear correlation between the Mt. Wilson $S$ index and the relative age of the stars as indicated by ...

  1. NEA activities in 1981

    International Nuclear Information System (INIS)

    This report describes the main features of the Agency's work during 1981 and discusses the state and prospects of the nuclear industry in OECD countries. Trends in nuclear power, radiological and environmental impacts of nuclear fuel cycle activities, nuclear safety research and licensing, nuclear law, nuclear development and fuel cycle studies technical co-operation, nuclear science organisation and administration are reviewed

  2. 'Active' Thin Sections

    NARCIS (Netherlands)

    De Rooij, M.R.; Bijen, J.M.J.M.

    1999-01-01

    Optical microscopy using thin sections has become more and more important over the last decade to study concrete. Unfortunately, this technique is not capable of studying actually hydrating cement paste. At Delft University of Technology a new technique has been developed using 'active' thin section

  3. Correlates of physical activity

    DEFF Research Database (Denmark)

    Bauman, Adrian E; Reis, Rodrigo S; Sallis, James F;

    2012-01-01

    , such as urban planning, transportation systems, and parks and trails. New areas of determinants research have identified genetic factors contributing to the propensity to be physically active, and evolutionary factors and obesity that might predispose to inactivity, and have explored the longitudinal tracking...

  4. Physical Education Activities

    Science.gov (United States)

    Russo, Letty P.

    1978-01-01

    Described are three physical activity games designed to help young children develop a sense of mastery over their bodies: (which will in turn improve their self concepts): a poem to be acted out, Simon Says, and a story play to be acted out. (DLS)

  5. Physical Activities for Preschool.

    Science.gov (United States)

    Adkins, Dorothy C.; And Others

    The underlying premise of the University of Hawaii Physical Activities for Preschool curriculum is that important contributions to a positive self-concept are made by motor independence and a realistic body image. Program objectives include: (1) the development of strength, endurance, and flexibility in skills that involve the muscles,…

  6. Diagramming Complex Activities

    DEFF Research Database (Denmark)

    Andersen, Peter Bøgh

    2005-01-01

    We increasingly live in heterogeneous ever-changing webs of activities where human actions are intertwined with events created by automatic machines.  In order to make such webs understandable to its human participants, their structure should be represented by displays emphasizing their action as...

  7. An electrochemical active valve

    NARCIS (Netherlands)

    Neagu, C.R.; Gardeniers, J.G.E.; Elwenspoek, M.; Kelly, J.J.

    1997-01-01

    A novel electrochemical microactuator was developed, which operates as an active valve. The microactuator consists of an electrochemical cell and a membrane that deflects because of the pressure of oxygen gas generated by electrolysis. Relatively large pressures (up to tens of bars) can be reached w

  8. Nursing activities score

    NARCIS (Netherlands)

    Miranda, DR; Nap, R; de Rijk, A; Schaufeli, W; Lapichino, G

    2003-01-01

    Objectives. The instruments used for measuring nursing workload in the intensive care unit (e.g., Therapeutic Intervention Scoring System-28) are based on therapeutic interventions related to severity of illness. Many nursing activities are not necessarily related to severity of illness, and cost-ef

  9. Elusive active galactic nuclei

    NARCIS (Netherlands)

    Maiolino, R; Comastri, A; Gilli, R; Nagar, NM; Bianchi, S; Boker, T; Colbert, E; Krabbe, A; Marconi, A; Matt, G; Salvati, M

    2003-01-01

    A fraction of active galactic nuclei do not show the classical Seyfert-type signatures in their optical spectra, i.e. they are optically 'elusive'. X-ray observations are an optimal tool to identify this class of objects. We combine new Chandra observations with archival X-ray data in order to obtai

  10. Active Math Learning

    DEFF Research Database (Denmark)

    The presentation is concerned with general course planning philosophy and a specific case study (boomerang flight geometro-dynamics) for active learning of mathematics via computer assisted and hands-on unfolding of first principles - in this case the understanding of rotations and Eulers equatio...

  11. Mechanism of charity activity

    Directory of Open Access Journals (Sweden)

    Roman B. Golovkin

    2015-12-01

    Full Text Available Objective to establish the essential properties of the mechanism of charitable activities and to formulate the concept of quotmechanism of charitable activityquot. Methods the objective of the study is achieved using the complex of methods which are based on the interaction of dialectical and metaphysical analysis the epistemological properties of which allowed to reveal various aspects of the charitable activities mechanism functioning taking into account the principles of comprehensiveness complexity specificity and objectivity of the research. Results the rules are stated of using the term quotmechanismquot to characterize actions of state and law the essence of the charity mechanism is defined the definition of quotthe mechanism of charitable activity quot is formulated. Scientific novelty for the first time at theoretical level in legal science the definition of quotthe mechanism of charitable activityquot is formulated and its essential properties are set. Practical significance the research will contribute to improving the legal regulation in the field of philanthropy as well as to improving the efficiency and quality of charitable activity in the Russian Federation. nbsp

  12. Activation analysis in Greece

    International Nuclear Information System (INIS)

    A review of research and development on NAA as well as examples of applications of this method are presented, taken from work carried out over the last 21 years at the Radioanalytical Laboratory of the Department of Chemistry in the Greek Nuclear Research Center ''Demokritos''. Improved and faster radiochemical NAA methods have been developed for the determination of Au, Ni, Cl, As, Cu, U, Cr, Eu, Hg and Mo in several materials, for the simultaneous determination of Br and I; Mg, Sr and Ni; As and Cu; As, Sb and Hg; Mn, Sr and Ba; Cd and Zn; Se and As; Mo and Cr in biological materials. Instrumental NAA methods have also been developed for the determination of Ag, Cl and Na in lake waters, Al, Ca, Mg and V in wines, 7 trace elements in biological materials, 17 trace elements in sediments and 20 minor and trace elements in ceramics. A comprehensive computer program for routine activation analysis using Ge(Li) detectors have been worked out. A rather extended charged-particle activation analysis program is carried out for the last 10 years, including particle induced X-ray emission (PIXE) analysis, particle induced prompt gamma-ray emission analysis (PIGE), other nuclear reactions and proton activation analysis. A special neutron activation method, the delayed fission neutron counting method is used for the analysis of fissionable elements, as U, Th, Pu, in samples of the whole nuclear fuel cycle including geological, enriched and nuclear safeguards samples

  13. Antifungal activity of diethyldithiocarbamate.

    Science.gov (United States)

    Allerberger, F; Reisinger, E C; Söldner, B; Dierich, M P

    1989-10-01

    Sodium diethyldithiocarbamate (DTC) was evaluated for its ability to combat four different species of fungi in vitro. Using a microtiter-broth-dilution method we were able to demonstrate an antifungal activity against Candida albicans, Cryptococcus neoformans, Aspergillus fumigatus and Mucor mucedo in doses achievable by intravenous administration in man.

  14. Shark Tagging Activities.

    Science.gov (United States)

    Current: The Journal of Marine Education, 1998

    1998-01-01

    In this group activity, children learn about the purpose of tagging and how scientists tag a shark. Using a cut-out of a shark, students identify, measure, record data, read coordinates, and tag a shark. Includes introductory information about the purpose of tagging and the procedure, a data sheet showing original tagging data from Tampa Bay, and…

  15. CMMs Development Activities

    Institute of Scientific and Technical Information of China (English)

    HU Jun; HU Yefa; HUANG Anyi

    2006-01-01

    The coordinate measuring machine (CMM) has been an important role in the digital manufacturing. This paper reviews CMM early stage development history and current activities. The authors provide some ideas about the areas that academic research can help to the CMMs development.

  16. Activity report 1992

    International Nuclear Information System (INIS)

    This activity report of the DSIN ( Direction of Nuclear Installations Safety) is divided into 4 parts bearing on: (1) Organisation, Safety principles, Regulations (2) Nuclear basis installations following (3) Surveillance by the regional directions of the Ministry of Industry, Research and Environment (4) Other missions of the DSIN

  17. Regional Activities Division. Papers.

    Science.gov (United States)

    International Federation of Library Associations, The Hague (Netherlands).

    Papers on library network activities in Canada, the Third World, Japan, Malaysia, Brazil, and Sweden which were presented at the 1982 International Federation of Library Associations (IFLA) conference include: (1) "Canada: A Voluntary and Flexible Network," a review by Guy Sylvestre of the political, social, and economic structures affecting…

  18. 85 Engaging Movement Activities.

    Science.gov (United States)

    Weikart, Phyllis S.; Carlton, Elizabeth B.

    This book presents activities to keep K-6 students moving in a variety of ways as they learn. The movement experiences are planned around key curriculum concepts in movement and music as well as in academic curriculum areas. The experiences develop students' basic timing, language abilities, vocabulary, concentration, planning skills, and…

  19. Active Optical Lattice Filters

    OpenAIRE

    Gary Evans; MacFarlane, Duncan L.; Govind Kannan; Jian Tong; Issa Panahi; Vishnupriya Govindan; L. Roberts Hunt

    2005-01-01

    Optical lattice filter structures including gains are introduced and analyzed. The photonic realization of the active, adaptive lattice filter is described. The algorithms which map between gains space and filter coefficients space are presented and studied. The sensitivities of filter parameters with respect to gains are derived and calculated. An example which is relevant to adaptive signal processing is also provided.

  20. Grooming. Learning Activity Package.

    Science.gov (United States)

    Stark, Pamela

    This learning activity package on grooming for health workers is one of a series of 12 titles developed for use in health occupations education programs. Materials in the package include objectives, a list of materials needed, information sheets, reviews (self evaluations) of portions of the content, and answers to reviews. These topics are…

  1. Antimalarial activity of cedronin.

    Science.gov (United States)

    Moretti, C; Deharo, E; Sauvain, M; Jardel, C; David, P T; Gasquet, M

    1994-06-01

    Cedronin was isolated from Simaba cedron Planchon (Simaroubaceae), a species popularly believed in South America to have antimalarial properties. It was examined for in vitro and in vivo antimalarial activities and for cytotoxicity against KB cells. Experimental results showed that cedronin was active against chloroquine-sensitive and resistant strain, with an IC50 of 0.25 micrograms/ml (0.65 mumol/ml). It was also found to be active in vivo against Plasmodium vinkei with an IC50 of 1.8 mg/kg (4.7 nM/kg) in the classic 4-day test. Cedronin belongs to the small group of quassinoids with a C19 basic skeleton and shows a rather low cytotoxicity against KB cells (IC50 = 4 micrograms/ml, 10.4 microM) as compared with C20 biologically active quassinoids; however its toxic/therapeutic ratio (10/1.8) remains lower than chloroquine (10/0.5).

  2. Interdisciplinary Astronomy Activities

    Science.gov (United States)

    Nerantzis, Nikolaos; Mitrouda, Aikaterini; Reizopoulou, Ioanna; Sidiropoulou, Eirini; Hatzidimitriou, Antonios

    2016-04-01

    On November 9th, 2015, three didactical hours were dedicated to Interdisciplinary Astronomy Activities (http://wp.me/p6Hte2-1I). Our students and their teachers formed three groups and in rotation, were engaged with the following activities: (a) viewing unique images of the Cosmos in the mobile planetarium STARLAB (http://www.planitario.gr/tholos-starlab-classic-standard.html), (b) watching the following videos: Journey to the end of the universe (https://youtu.be/Ufl_Nwbl8xs), Rosetta update (https://youtu.be/nQ9ivd7wv30), The Solar System (https://youtu.be/d66dsagrTa0), Ambition the film (https://youtu.be/H08tGjXNHO4) in the school's library. Students and teachers were informed about our solar system, the Rosetta mission, the universe, etc. and (c) tactile activities such as Meet our home and Meet our neighbors (http://astroedu.iau.org, http://nuclio.org/astroneighbours/resources) and the creation of planets' 3D models (Geology-Geography A' Class Student's book, pg.15). With the activities above we had the pleasure to join the Cosmic Light Edu Kit / International Year of Light 2015 program. After our Interdisciplinary Astronomy Activities, we did a "small" research: our students had to fill an evaluation about their educational gains and the results can be found here http://wp.me/p6Hte2-2q. Moreover, we discussed about Big Ideas of Science (http://wp.me/p3oRiZ-dm) and through the "big" impact of the Rosetta mission & the infinity of our universe, we print posters with relevant topics and place them to the classrooms. We thank Rosa Doran (Nuclio - President of the Executive Council) for her continuous assistance and support on innovative science teaching proposals. She is an inspiration.

  3. Integration of Active Video Games in Extracurricular Activity at Schools

    Science.gov (United States)

    Lee, Jung Eun; Huang, Charles; Pope, Zachary; Gao, Zan

    2015-01-01

    Active video games require players to be physically active. Dance Dance Revolution (DDR) is an interactive dancing game that requires fast-foot movement coordinated with energetic music and visuals. The Wii and Xbox Kinect games have also become good active video games for the promotion of physical activity participation. These games are much more…

  4. Is Enhanced Physical Activity Possible Using Active Videogames?

    OpenAIRE

    Baranowski, Tom; Baranowski, Janice; O'Connor, Teresia; Lu, Amy Shirong; Thompson, Debbe

    2012-01-01

    Our research indicated that 10–12-year-old children receiving two active Wii™ (Nintendo®; Nintendo of America, Inc., Redmond, WA) console videogames were no more physically active than children receiving two inactive videogames. Research is needed on how active videogames may increase physical activity.

  5. Is Enhanced Physical Activity Possible Using Active Videogames?

    Science.gov (United States)

    Baranowski, Tom; Baranowski, Janice; O'Connor, Teresia; Lu, Amy Shirong; Thompson, Debbe

    2012-06-01

    Our research indicated that 10-12-year-old children receiving two active Wii(™) (Nintendo(®); Nintendo of America, Inc., Redmond, WA) console videogames were no more physically active than children receiving two inactive videogames. Research is needed on how active videogames may increase physical activity.

  6. Planets around active stars

    CERN Document Server

    Setiawan, J; Henning, T; Hatzes, A P; Pasquini, L; da Silva, L; Girardi, L; Von der Lühe, O; Dollinger, M P; Weiss, A; Biazzo, K

    2007-01-01

    We present the results of radial velocity measurements of two samples of active stars. The first sample contains field G and K giants across the Red Giant Branch, whereas the second sample consists of nearby young stars (d < 150 pc) with ages between 10 - 300 Myrs. The radial velocity monitoring program has been carried out with FEROS at 1.52 m ESO telescope (1999 - 2002) and continued since 2003 at 2.2 m MPG/ESO telescope. We observed stellar radial velocity variations which originate either from the stellar activity or the presence of stellar/substellar companions. By means of a bisector technique we are able to distinguish the sources of the radial velocity variation. Among them we found few candidates of planetary companions, both of young stars and G-K giants sample.

  7. Study on activation analysis

    International Nuclear Information System (INIS)

    High purity aluminum has been analyzed by neutron activation analysis. The determination of copper contents is aluminum has been used to evaluate its purity level. A new sensitive method has been developed by using graphite thermal column to reduce or eliminate the interference of 24Na which is generated from 27Al (n,α) 24Na reaction by fast neutron. Influence for activity of 24Na due to above reaction is found to be between 2.3 - 2.8 %. Copper contents in the high purity aluminum come out 0.542±0.084 ppm. In addition, contents of 23 other impurity elements (<0.1 - 0.01 ppm) are measured using general method after detection limit and optimum conditions are established. (author)

  8. Industrial Activity at CERN

    CERN Document Server

    Kowalik, G

    2000-01-01

    The decrease in the number of CERN staff creates the need for optimization of the non-core, infrastructure-related activities. An industrial, service-orientated approach has long been considered as an appropriate way to cope with the problem of diminishing resources. This paper presents industrial and service activity issues at CERN based on the experience of the exploitation of the power network. The most important problems linked to the application of the industrial approach to the exploitation of equipment in the CERN research environment are covered. These include the interface between accelerators and electrical exploitation services, external and internal regulations, sharing of responsibility between CERN staff and external contractors, continuous modification of clients' requirements, the balance between the cost of accelerator downtime versus the cost of infrastructure upgrade. A benchmarking through a comparison with a big industrial manufacturer is followed by recommendations for possible improveme...

  9. IPSN activity report 1999

    International Nuclear Information System (INIS)

    The ''Institut de Protection et de Surete Nucleaire'' (IPSN), carries out researches and expert studies needed to manage nuclear risks and their consequences on people and environment. These activities cover the installation safety, the radioactive matter transport, the public health and environmental control, the nuclear matters safety and control and the crisis situation management. The IPSN have got also a mission of public information and participates to international actions in the domain of scientific researches or expert's report. This annual report presents the highlights of the year 1999, information on staff, budgets and geographical situation. Then technical and scientific papers gathers the activities of the year covered by the IPSN: the ''Free Tribune'', installations and radioactive wastes safety, crisis and nuclear matter management, public health and environment control, international cooperation. (A.L.B.)

  10. Stellar Chromospheric Activity

    Directory of Open Access Journals (Sweden)

    Hall Jeffrey C.

    2008-03-01

    Full Text Available The Sun, stars similar to it, and many rather dissimilar to it, have chromospheres, regions classically viewed as lying above the brilliant photosphere and characterized by a positive temperature gradient and a marked departure from radiative equilibrium. Stellar chromospheres exhibit a wide range of phenomena collectively called activity, stemming largely from the time evolution of their magnetic fields and the mass flux and transfer of radiation through the complex magnetic topology and the increasingly optically thin plasma of the outer stellar atmosphere. In this review, I will (1 outline the development of our understanding of chromospheric structure from 1960 to the present, (2 discuss the major observational programs and theoretical lines of inquiry, (3 review the origin and nature of both solar and stellar chromospheric activity and its relationship to, and effect on, stellar parameters including total energy output, and (4 summarize the outstanding problems today.

  11. Active optical clock

    Institute of Scientific and Technical Information of China (English)

    CHEN JingBiao

    2009-01-01

    This article presents the principles and techniques of active optical clock, a special laser combining the laser physics of one-atom laser, bad-cavity gas laser, super-cavity stabilized laser and optical atomic clock together. As a simple example, an active optical clock based on thermal strontium atomic beam shows a quantum-limited linewidth of 0.51 Hz, which is insensitive to laser cavity-length noise, and may surpass the recorded narrowest 6.7 Hz of Hg ion optical clock and 1.5 Hz of very recent optical lattice clock. The estimated 0.1 Hz one-second instability and 0.27 Hz uncertainty are limited only by the rela-tivistic Doppler effect, and can be improved by cold atoms.

  12. Apheresis activity in Venezuela.

    Science.gov (United States)

    Saltiel, Christiane

    2005-07-01

    Interest for apheresis activity has been growing in Venezuela. In 1976 there were only a few devices; in 2003, 80 apheresis machines performed 27,675 donor apheresis procedures and 547 therapeutic procedures countrywide. We report the activity at the Metropolitan Blood Bank (the largest one of the country) in the period 1999-2003: 597 therapeutic procedures were performed in 171 patients, during 212 crisis episodes. The average age was 38 +/- 16 years, 65% male and 35% female. Most of the therapeutic procedures were therapeutic plasma exchange for hematology diseases (mainly thrombotic thrombocitopenic purpura and hemophilia inhibitors), including 184 therapeutic procedures with the Autopheresis-C (Baxter Healthcare Corp., Deerfield, IL). Most common adverse effects (3.9%) were hypotension and allergic reactions to the plasma. PMID:15880361

  13. Myofilament length dependent activation

    Energy Technology Data Exchange (ETDEWEB)

    de Tombe, Pieter P.; Mateja, Ryan D.; Tachampa, Kittipong; Mou, Younss Ait; Farman, Gerrie P.; Irving, Thomas C. (IIT); (Loyola)

    2010-05-25

    The Frank-Starling law of the heart describes the interrelationship between end-diastolic volume and cardiac ejection volume, a regulatory system that operates on a beat-to-beat basis. The main cellular mechanism that underlies this phenomenon is an increase in the responsiveness of cardiac myofilaments to activating Ca{sup 2+} ions at a longer sarcomere length, commonly referred to as myofilament length-dependent activation. This review focuses on what molecular mechanisms may underlie myofilament length dependency. Specifically, the roles of inter-filament spacing, thick and thin filament based regulation, as well as sarcomeric regulatory proteins are discussed. Although the 'Frank-Starling law of the heart' constitutes a fundamental cardiac property that has been appreciated for well over a century, it is still not known in muscle how the contractile apparatus transduces the information concerning sarcomere length to modulate ventricular pressure development.

  14. LANSCE Activity Report

    Energy Technology Data Exchange (ETDEWEB)

    Amy Robinson; Audrey Archuleta; Barbara Maes; Dan Strottman; Earl Hoffman; Garth Tietjen; Gene Farnum; Geoff Greene; Joyce Roberts; Ken Johnson; Paul Lewis; Roger Pynn; Stan Schriber; Steve Sterbenz; Steve Wender; Sue Harper

    1999-02-01

    The Los Alamos Neutron Science Center Activity Report describes scientific and technological progress and achievements in LANSCE Division during the period of 1995 to 1998. This report includes a message from the Division Director, an overview of LANSCE, sponsor overviews, research highlights, advanced projects and facility upgrades achievements, experimental and user program accomplishments, news and events, and a list of publications. The research highlights cover the areas of condensed-matter science and engineering, accelerator science, nuclear science, and radiography. This report also contains a compact disk that includes an overview, the Activity Report itself, LANSCE operations progress reports for 1996 and 1997, experiment reports from LANSCE users, as well as a search capability.

  15. Physical activity & depression

    OpenAIRE

    Tsiantoula E.; Tsiadoula L.; Patsiaouras A.; Kokaridas D.

    2012-01-01

    Depression is a major public health disorder. Clinical depression is the most frequent disability in North America among other countries and by 2020 it is estimated that it will represent the second most common disability worldwide. Physical activity can be used to prevent as well as treat depression. Its characteristics and structure should be individualized to the personality and special needs of the patient as well as to the severity of the disorder. Intensity, duration and the place of pe...

  16. Activity report 1993

    International Nuclear Information System (INIS)

    This activity report of the DSIN (Direction of Nuclear Installations Safety) is divided into 13 chapters bearing on: (1)Nuclear safety (2) Nuclear safety organisation (3) Regulations (4) Nuclear installations inspections (5) Crisis organisation (6) Information and communication (7) International relations (8) PWR (9)Other reactors (10) Experimental reactors, laboratories and other installations (11) Fuel cycle centers (12) Radioactive wastes storages (13) Nuclear installations definitively stopped

  17. Social media and activism

    OpenAIRE

    Cammaerts, Bart

    2015-01-01

    This entry provides an overview of the ways in which social media and digital networks are contextualized and examined in relation to social movements and activism. A number of communicative practices that activists deploy are identified and the ways in which information and communication technology (ICT)-mediated practices are embedded in roles and functions relevant to activists and social movements are addressed giving attention to the importance of social ties and networks online and offl...

  18. Business Activity Monitoring

    OpenAIRE

    Frühauf, Michal

    2009-01-01

    Main focus of the thesis lies in the corporate management decision support deploying and using IT / ICT. Specific technology described is Business Activity Monitoring. The contribution of the work lies primarily in two planes. The first plane is to create as far as the most comprehensive view of the BAM. The findings are collected from different directions and areas. The first direction of research is focused on the development of Business Intelligence and description of BAM as a trend of BI,...

  19. NPPCI activities in Finland

    International Nuclear Information System (INIS)

    Research activities at the Technical Research Centre of Finland in the control and instrumentation field have been directed both towards immediate needs and towards long term goals. The immediate needs have been connected to different ongoing investigations and to development projects in connection with process industry. Of the more long term projects the following can be explicitly mentioned: the Nordic project on human reliability; work on software reliability; design guides for digital CI systems; simulation of technical processes; artificial intelligence in nuclear power

  20. Diamond dipole active antenna

    OpenAIRE

    Bubnov, I. N.; Falkovych, I. S.; Gridin, A. A.; Stanislavsky, A. A.; Reznik, A. P.

    2015-01-01

    Advantages of the diamond dipole antenna as an active antenna are presented. Such an antenna is like an inverted bow-tie antenna, but the former has some advantages over the ordinary bow-tie antenna. It is shown that the diamond dipole antenna may be an effective element of a new antenna array for low-frequency radio astronomy as well as a communication antenna.

  1. Human telomerase activity regulation

    OpenAIRE

    Wojtyla, Aneta; Gladych, Marta; Rubis, Blazej

    2010-01-01

    Telomerase has been recognized as a relevant factor distinguishing cancer cells from normal cells. Thus, it has become a very promising target for anticancer therapy. The cell proliferative potential can be limited by replication end problem, due to telomeres shortening, which is overcome in cancer cells by telomerase activity or by alternative telomeres lengthening (ALT) mechanism. However, this multisubunit enzymatic complex can be regulated at various levels, including expression control b...

  2. Activity report for 1992

    International Nuclear Information System (INIS)

    ADEME means agency for defence of environment and for mastery of energy, these two aims are ADEME's mission; to serve its mission, this agency has to mobilize managers able to reduce tensions on natural resources and to limit impacts on environment; the concerned areas are transport, building, industry because of their weight in energy consumption, in pollutants emission and waste recovery. Here is the report of its activity for the year 1992

  3. Quality Of Construction Activity

    OpenAIRE

    LOREDANA VALENTINA HEDRE

    2010-01-01

    The problem of the quality works of building has a different importance because, as opposed to another activities of material productions here are not admitted bear of the quality in respect resistances, stability, durability, safeties in exploitation. The responsibility concerning assurance quality is not summed up just to the level of builders or beneficiaries, they became a national problem and last recently, European and even global issues. Implications are considered factors contributing...

  4. NEA activities in 1994

    International Nuclear Information System (INIS)

    This report deals with the activities in 1994 of the OECD Nuclear Energy Agency including : trends in nuclear power, nuclear development and fuel cycle (data, tools, methodologies, nuclear industry and its context, fuel cycle policy, energy policy reviews), reactor safety and regulation (exchange of operating experience and human factors, accident prevention activities, severe-accident phenomenology and management, structural integrity, probabilistic safety assessment, fuel cycle safety, regulatory approaches to severe-accident issues, inspection practices), radiation protection (radiation protection today and tomorrow, application of radiation protection standards, protection of workers, international emergency exercises), radioactive waste management (the philosophical and ethical basis of disposal, safety assessment and site investigations, other radiation waste management activities), nuclear science (scientific studies, validation of working methods, the NEA data bank, projects in support of other NEA programmes), joint projects (the Rasplav project, the Halden reactor project, information system on occupational exposure, decommissioning of nuclear facilities), legal affairs (liability and nuclear safety assistance to Eastern Europe, training seminar on nuclear law, information on nuclear law), information programme (review of Nea information programme, publications programme, a major information forum), and relations with nonmember countries (NEA relations with non-members countries, the Central and Eastern European Countries and New Independent States of the former Soviet Union programme of co-operation and assistance). (O.L.). 22 figs

  5. Sesterterpenoids with Anticancer Activity.

    Science.gov (United States)

    Evidente, Antonio; Kornienko, Alexander; Lefranc, Florence; Cimmino, Alessio; Dasari, Ramesh; Evidente, Marco; Mathieu, Véronique; Kiss, Robert

    2015-01-01

    Terpenes have received a great deal of attention in the scientific literature due to complex, synthetically challenging structures and diverse biological activities associated with this class of natural products. Based on the number of C5 isoprene units they are generated from, terpenes are classified as hemi- (C5), mono- (C10), sesqui- (C15), di- (C20), sester- (C25), tri (C30), and tetraterpenes (C40). Among these, sesterterpenes and their derivatives known as sesterterpenoids, are ubiquitous secondary metabolites in fungi, marine organisms, and plants. Their structural diversity encompasses carbotricyclic ophiobolanes, polycyclic anthracenones, polycyclic furan-2-ones, polycyclic hydroquinones, among many other carbon skeletons. Furthermore, many of them possess promising biological activities including cytotoxicity and the associated potential as anticancer agents. This review discusses the natural sources that produce sesterterpenoids, provides sesterterpenoid names and their chemical structures, biological properties with the focus on anticancer activities and literature references associated with these metabolites. A critical summary of the potential of various sesterterpenoids as anticancer agents concludes the review. PMID:26295461

  6. Active inference and learning.

    Science.gov (United States)

    Friston, Karl; FitzGerald, Thomas; Rigoli, Francesco; Schwartenbeck, Philipp; O'Doherty, John; Pezzulo, Giovanni

    2016-09-01

    This paper offers an active inference account of choice behaviour and learning. It focuses on the distinction between goal-directed and habitual behaviour and how they contextualise each other. We show that habits emerge naturally (and autodidactically) from sequential policy optimisation when agents are equipped with state-action policies. In active inference, behaviour has explorative (epistemic) and exploitative (pragmatic) aspects that are sensitive to ambiguity and risk respectively, where epistemic (ambiguity-resolving) behaviour enables pragmatic (reward-seeking) behaviour and the subsequent emergence of habits. Although goal-directed and habitual policies are usually associated with model-based and model-free schemes, we find the more important distinction is between belief-free and belief-based schemes. The underlying (variational) belief updating provides a comprehensive (if metaphorical) process theory for several phenomena, including the transfer of dopamine responses, reversal learning, habit formation and devaluation. Finally, we show that active inference reduces to a classical (Bellman) scheme, in the absence of ambiguity. PMID:27375276

  7. Antimicrobial activity of antiproteinases.

    Science.gov (United States)

    Sallenave, J M

    2002-04-01

    Low-molecular-mass neutrophil elastase inhibitors have been shown to be important in the control of lung inflammation. In addition to inhibiting the enzyme neutrophil elastase, these low-molecular-mass compounds (10 kDa) have been shown to have other activities. For example, secretory leucocyte proteinase inhibitor (SLPI) and elastase-specific inhibitor/SKALP (skin-derived antileucoproteinase)/elafin have also been shown to have "defensin"-like antimicrobial activities. Indeed, these inhibitors have antimicrobial properties in vitro against bacteria, fungi and, potentially, HIV. In addition, we have shown, using an adenovirus-mediated gene transfer overexpression strategy, that elafin is also active against Pseudomonas aeruginosa infection in mice in vivo. The mechanism of action is currently under investigation. In addition to these direct or indirect effects on microbes, it has been shown that lipopolysaccharide is able to up-regulate SPLI production in macrophages in vitro, and that the addition of recombinant SLPI to human monocytes or the transfection of macrophages with SPLI can down-regulate pro-inflammatory mediators such as tumour necrosis factor, presumably to limit self-damaging excessive inflammation. Using viral gene transfer vectors, we are currently investigating the potential of these inhibitors in various models of inflammation in vivo. PMID:12023836

  8. Cooperatively active sensing system

    International Nuclear Information System (INIS)

    Aiming at development of a strong and flexible sensing system, a study on a sensing technology prepared with cooperativity, activity, and real time workability has been promoted. In the former period, together with preparation of plural moving robot group with real time processing capacity of a lot of sensor informations composing of platform, a parallel object direction language Eus Lisp effectively capable of describing and executing cooperative processing and action therewith was developed. And, it was also shown that capacity to adaptively act even at dynamic environment could be learnt experientially. And, on processing of individual sensor information, application of a photographing system with multiple resolution property similar to human visual sense property was attempted. In the latter period, together with intending of upgrading on adaptability of sensing function, by using moving robot group in center of a moving robot loaded with active visual sense, a cooperative active sensing prototype system was constructed to show effectiveness of this study through evaluation experiment of patrolling inspection at plant simulating environment. (G.K.)

  9. Active quantum plasmonics.

    Science.gov (United States)

    Marinica, Dana Codruta; Zapata, Mario; Nordlander, Peter; Kazansky, Andrey K; M Echenique, Pedro; Aizpurua, Javier; Borisov, Andrei G

    2015-12-01

    The ability of localized surface plasmons to squeeze light and engineer nanoscale electromagnetic fields through electron-photon coupling at dimensions below the wavelength has turned plasmonics into a driving tool in a variety of technological applications, targeting novel and more efficient optoelectronic processes. In this context, the development of active control of plasmon excitations is a major fundamental and practical challenge. We propose a mechanism for fast and active control of the optical response of metallic nanostructures based on exploiting quantum effects in subnanometric plasmonic gaps. By applying an external dc bias across a narrow gap, a substantial change in the tunneling conductance across the junction can be induced at optical frequencies, which modifies the plasmonic resonances of the system in a reversible manner. We demonstrate the feasibility of the concept using time-dependent density functional theory calculations. Thus, along with two-dimensional structures, metal nanoparticle plasmonics can benefit from the reversibility, fast response time, and versatility of an active control strategy based on applied bias. The proposed electrical manipulation of light using quantum plasmonics establishes a new platform for many practical applications in optoelectronics. PMID:26824066

  10. Adaptable typologies for active roofs

    NARCIS (Netherlands)

    Quanjel, E.M.C.J.; Zeiler, W.

    2006-01-01

    The main objective of this part of the 6th framework Pan-European EUR-ACTIVE ROOF-er project is to improve the interaction between design participants of dynamic adaptable Active Roofs in product development and Active Roofs from an architects/ customers perspective. Improvements in Active Roof desi

  11. Spontaneous Plasticity of Multineuronal Activity Patterns in Activated Hippocampal Networks

    Directory of Open Access Journals (Sweden)

    Atsushi Usami

    2008-01-01

    Full Text Available Using functional multineuron imaging with single-cell resolution, we examined how hippocampal networks by themselves change the spatiotemporal patterns of spontaneous activity during the course of emitting spontaneous activity. When extracellular ionic concentrations were changed to those that mimicked in vivo conditions, spontaneous activity was increased in active cell number and activity frequency. When ionic compositions were restored to the control conditions, the activity level returned to baseline, but the weighted spatial dispersion of active cells, as assessed by entropy-based metrics, did not. Thus, the networks can modify themselves by altering the internal structure of their correlated activity, even though they as a whole maintained the same level of activity in space and time.

  12. Enzyme Activities in Waste Water and Activated Sludge

    DEFF Research Database (Denmark)

    Nybroe, Ole; Jørgensen, Per Elberg; Henze, Mogens

    1992-01-01

    The purpose of the present study was to evaluate the potential of selected enzyme activity assays to determine microbial abundance and heterotrophic activity in waste water and activated sludge. In waste water, esterase and dehydrogenase activities were found to correlate with microbial abundance...... measured as colony forming units of heterotrophic bacteria. A panel of four enzyme activity assays, α-glucosidase, alanine-aminopeptidase, esterase and dehydrogenase were used to characterize activated sludge and anaerobic hydrolysis sludge from a pilot scale plant. The enzymatic activity profiles were...... distinctly different, suggesting that microbial populations were different, or had different physiological properties, in the two types of sludge. Enzyme activity profiles in activated sludge from four full-scale plants seemed to be highly influenced by the composition of the inlet. Addition of hydrolysed...

  13. Advances in Activity Cliff Research.

    Science.gov (United States)

    Dimova, Dilyana; Bajorath, Jürgen

    2016-05-01

    Activity cliffs, i.e. similar compounds with large potency differences, are of interest from a chemical and informatics viewpoint; as a source of structure-activity relationship information, for compound optimization, and activity prediction. Herein, recent highlights of activity cliff research are discussed including studies that have further extended our understanding of activity cliffs, yielded unprecedented insights, or paved the way for practical applications.

  14. Asthma and physical activity.

    Science.gov (United States)

    Oseid, S

    1982-01-01

    Physical activity regularly leads to a decline in lung function in children and adolescents with asthma. This decline is a consequence of what is known as exercise-induced asthma (EIA), and can be determined and graded with the help of lung function tests before and after submaximal workloads on the ergometer cycle or the treadmill. Typical EIA appears in asthmatic individuals with entirely normal lung function before the effort, but EIA may also become clinically manifest with exercise in patients who have a subclinical degree of obstruction. The grade of EIA is essentially dependent on the duration and intensity of effort but also on the type of exercise. For example, free running causes much greater bronchoconstriction than swimming. The temperature and humidity of the inspired air may partially explain this difference. At the Voksentoppen Allergy Institute we find that about 85% of children develop a fall in lung function of 15% or more after a six minute ergometer cycle test. With typical EIA the fall may be totally or partially abolished by prophylactic medication 10 minutes before the start of the test. Disodium cromoglycate (Intal) and/or beta-adrenergic drugs are regularly used before all physical activity. Training programmes must be based on the interval principle. Swimming, ball games, relay races and dancing are examples of useful activities in the training and rehabilitation of children and adolescents with asthma. Through prophylactic medication and physical training, the aerobic work capacity, muscle strength and lung function in asthmatic children is improved. Training also leads to a significant mobilisation of mental resources and an increase in social integration. PMID:6958045

  15. Access and Fishing Activities

    DEFF Research Database (Denmark)

    Høst, Jeppe Engset

    2015-01-01

    a detailed ethnographic description of five different fishing operations and then compare them on a number of different fronts. This will direct us to some general differences in their modes of operation in relation to the vessel quota share (VQS) system and lead us to the next chapter, where the principal......In this chapter, I look at the implications of transferable quotas on the organization of production; that is, how fishing activities are structured around access to the individual and transferable quotas and how, in turn, the quotas structure the production. Therefore, this chapter will give...

  16. Crew Activity Analyzer

    Science.gov (United States)

    Murray, James; Kirillov, Alexander

    2008-01-01

    The crew activity analyzer (CAA) is a system of electronic hardware and software for automatically identifying patterns of group activity among crew members working together in an office, cockpit, workshop, laboratory, or other enclosed space. The CAA synchronously records multiple streams of data from digital video cameras, wireless microphones, and position sensors, then plays back and processes the data to identify activity patterns specified by human analysts. The processing greatly reduces the amount of time that the analysts must spend in examining large amounts of data, enabling the analysts to concentrate on subsets of data that represent activities of interest. The CAA has potential for use in a variety of governmental and commercial applications, including planning for crews for future long space flights, designing facilities wherein humans must work in proximity for long times, improving crew training and measuring crew performance in military settings, human-factors and safety assessment, development of team procedures, and behavioral and ethnographic research. The data-acquisition hardware of the CAA (see figure) includes two video cameras: an overhead one aimed upward at a paraboloidal mirror on the ceiling and one mounted on a wall aimed in a downward slant toward the crew area. As many as four wireless microphones can be worn by crew members. The audio signals received from the microphones are digitized, then compressed in preparation for storage. Approximate locations of as many as four crew members are measured by use of a Cricket indoor location system. [The Cricket indoor location system includes ultrasonic/radio beacon and listener units. A Cricket beacon (in this case, worn by a crew member) simultaneously transmits a pulse of ultrasound and a radio signal that contains identifying information. Each Cricket listener unit measures the difference between the times of reception of the ultrasound and radio signals from an identified beacon

  17. Reuse of activated alumina

    Energy Technology Data Exchange (ETDEWEB)

    Hobensack, J.E. [Martin Marietta Energy Systems, Inc., Piketon, OH (United States)

    1991-12-31

    Activated alumina is used as a trapping media to remove trace quantities of UF{sub 6} from process vent streams. The current uranium recovery method employs concentrated nitric acid which destroys the alumina pellets and forms a sludge which is a storage and disposal problem. A recently developed technique using a distilled water rinse followed by three dilute acid rinses removes on average 97% of the uranium, and leaves the pellets intact with crush strength and surface area values comparable with new material. Trapping tests confirm the effectiveness of the recycled alumina as UF{sub 6} trapping media.

  18. Rationales for regulatory activity

    Energy Technology Data Exchange (ETDEWEB)

    Perhac, R.M. [Univ. of Tennessee, Knoxville, TN (United States)

    1997-02-01

    The author provides an outline which touches on the types of concerns about risk evaluation which are addressed in the process of establishing regulatory guides. Broadly he says regulatory activity serves three broad constituents: (1) Paternalism (private risk); (2) Promotion of social welfare (public risks); (3) Protection of individual rights (public risks). He then discusses some of the major issues encountered in reaching a decision on what is an acceptable level of risk within each of these areas, and how one establishes such a level.

  19. Flipped Classroom, active Learning?

    DEFF Research Database (Denmark)

    Andersen, Thomas Dyreborg; Levinsen, Henrik; Philipps, Morten;

    2015-01-01

    Action research is conducted in three physics classes over a period of eighteen weeks with the aim of studying the effect of flipped classroom on the pupils agency and learning processes. The hypothesis is that flipped classroom teaching will potentially allocate more time to work actively...... are conducted in three different phases corresponding to different teaching sequences During the first phase the classes are taught as they are usually taught. During the next two phases classes are taught on the basis of a common understanding of the flipped classroom teaching model obtained during a 4 day...

  20. Agrice 2002. Activity report

    International Nuclear Information System (INIS)

    Renewable raw materials derived from agricultural crops are used to manufacture bio-products in energy, chemicals and materials industries. Renewable feedstocks address a double need. On the one hand, they offer alternatives to fossil resources, and on the other hand, they are a response to today's environmental challenges: mitigation of the greenhouse affect, reduction of air, soil and water pollution, innocuousness and biodegradability of products. A new chemistry must be created. Large-scale and ongoing research work must be committed to this goal. The research effort implies active coordination of all the various actors involved - multidisciplinary research teams, agro-industrial enterprises, user industries (petrochemicals, chemicals, materials), and specific agricultural branches. With these ends in mind the scientific interest group AGRICE - Agriculture for Chemicals and Energy - was established by public authorities and eight partners in France in 1994. The AGRICE consortium was renewed for six years in 2001, with a broader membership base. AGRICE now includes the following partners: - the research arms of the Commissariat a l'Energie Atomique (CEA), the Institut Francais du Petrole (IFP), and the Institut National de Recherche Agronomique (INRA), - professional organisations representing producers of oilseeds (ONIDOL), grains (AGPB) and beets (CGB), - corporate members ATOFINA, AUTOBAR PACKAGING France, BAYER CROP SCIENCE, CERESTAR France, LIMAGRAIN Agro-Industrie, RHODIA, TOTAL FINA ELF, - the French ministries of Agriculture, Industry, Research, and the Environment, - the French Agency for the Environment and Energy Management (ADEME), - the French Agency for Innovation (ANVAR). ADEME is responsible for managing AGRICE. The consortium is involved in major international undertakings, notably through the European Renewable Resources and Materials Association (ERRMA). This report presents: 1 - the AGRICE profile, scope of activity, structure and Operations

  1. Athena: Assessment Phase Activities

    Science.gov (United States)

    Lumb, David; Ayre, Mark

    2015-09-01

    The Athena mission concept has been proposed by the community in response to science themes of the Hot and Energetic Universe. Unlike other, competitive, mission selection exercises this "Large" class observatory mission has essentially been pre-selected. Nevertheless it has to be demonstrated that Athena meets the programmatic constraints of 1Bn euro cost cap, and a readiness level appropriate for formal mission adoption by the end 2019. This should be confirmed through a Phase A study conducted with two parallel industry activities. We describe the technical and programmatic content of these and latest progress in space and ground segment definition.

  2. Physical activity in elderly

    Directory of Open Access Journals (Sweden)

    Jan Cvecka

    2015-08-01

    Full Text Available Aging is a multifactorial irreversible process associated with significant decline in muscle mass and neuromuscular functions. One of the most efficient methods to counteract age-related changes in muscle mass and function is physical exercise. An alternative effective intervention to improve muscle structure and performance is electrical stimulation. In the present work we present the positive effects of physical activity in elderly and a study where the effects of a 8-week period of functional electrical stimulation and strength training with proprioceptive stimulation in elderly are compared.

  3. Active galactic nuclei

    CERN Document Server

    Blandford, RD; Woltjer, L

    1990-01-01

    Starting with this volume, the Lecture Notes of the renowned Advanced Courses of the Swiss Society for Astrophysics and Astronomy will be published annually. In each course, three extensive lectures given by leading experts in their respective fields cover different and essential aspects of the subject. The 20th course, held at Les Diablerets in April 1990, dealt with current research on active galactic nuclei; it represents the most up-to-date views on the subject, presented with particular regard for clarity. The previous courses considered a wide variety of subjects, beginning with ""Theory

  4. Regulating prefrontal cortex activation

    DEFF Research Database (Denmark)

    Aznar, Susana; Klein, Anders Bue

    2013-01-01

    pharmacological effect of elevating serotonin levels in anxiety regulation. Recent animal and human functional magnetic resonance studies have pointed to a specific involvement of the 5-hydroxytryptamine (5-HT)2A serotonin receptor in the PFC feedback regulatory projection onto the amygdala. This receptor...... of emotion-based actions, such as addiction and other impulse-related behaviors. In this review, we give an overview of the 5-HT2A receptor distribution (neuronal, intracellular, and anatomical) along with its functional and physiological effect on PFC activation, and how that relates to more recent findings...... of a regulatory effect of the PFC on the emotional control of our actions....

  5. WFIRST Project Science Activities

    Science.gov (United States)

    Gehrels, Neil

    2012-01-01

    The WFIRST Project is a joint effort between GSFC and JPL. The project scientists and engineers are working with the community Science Definition Team to define the requirements and initial design of the mission. The objective is to design an observatory that meets the WFIRST science goals of the Astr02010 Decadal Survey for minimum cost. This talk will be a report of recent project activities including requirements flowdown, detector array development, science simulations, mission costing and science outreach. Details of the interim mission design relevant to scientific capabilities will be presented.

  6. Direct Activation Of Methane

    KAUST Repository

    Basset, Jean-Marie

    2013-07-15

    Heteropolyacids (HPAs) can activate methane at ambient temperature (e.g., 20.degree. C.) and atmospheric pressure, and transform methane to acetic acid, in the absence of any noble metal such as Pd). The HPAs can be, for example, those with Keggin structure: H.sub.4SiW.sub.12O.sub.40, H.sub.3PW.sub.12O.sub.40, H.sub.4SiMo.sub.12O.sub.40, or H.sub.3PMo.sub.12O.sub.40, can be when supported on silica.

  7. COMPANY ACTIVITY FINANCIAL RISK

    Directory of Open Access Journals (Sweden)

    Caruntu Genu Alexandru

    2012-12-01

    Full Text Available In economic and financial activity, risk is an inherent financial decisions, encountered in daily agenda of managers of companies. Unexpected changes in the price of a product development not only affect the financial results of a company, but can cause even bankruptcy. In fact, the nature of financial decisions involve uncertainty. Financial decisions are made based on cash flows under future contracts, which are par excellence incerte.Activitatea an enterprise that holds any weight in the industry is subject to risks, since it can not predict with certainty different components of its outcome (cost, quantity, price and operating cycle (purchase, processing, sales.

  8. Active galactic nuclei

    CERN Document Server

    Beckmann, Volker

    2012-01-01

    This AGN textbook includes phenomena based on new results in the X-Ray domain from new telescopes such as Chandra and XMM Newton not mentioned in any other book. Furthermore, it considers also the Fermi Gamma Ray Space Telescope with its revolutionary advances of unprecedented sensitivity, field of view and all-sky monitoring. Those and other new developments as well as simulations of AGN merging events and formations, enabled through latest super-computing capabilities. The book gives an overview on the current knowledge of the Active Galacitc Nuclei phenomenon. The spectral energy d

  9. FY 1996 activity summary

    International Nuclear Information System (INIS)

    The US Department of Energy Office of Nuclear and Facility Safety provides nuclear safety policy, independent technical evaluation, and technical support. A summary of these activities is provided in this report. These include: (1) changing the mission of the former production facilities to storage and waste management; (2) stabilizing nuclear materials not recycled due to production cessation or interruptions; (3) reformulating the authorization basis for existing facilities to convert to a standards based approach for operations consistent with modern expectations; and (4) implementing a modern regulatory framework for nuclear facilities. Enforcement of the Price-Anderson Amendments Act is also reported

  10. Activity report 1978

    International Nuclear Information System (INIS)

    The research and development (R and D) work of the Reactor Research Centre at Kalpakkam for the calendar year 1978 is reported in the form of individual summaries under the headings: reactor physics, reactor engineering, FBTR construction/commissioning, reprocessing, reactor chemistry, metallurgy of reactor materials, materials science, instrumentation. The major thrust of the R and D activities is on reactor technology of fast breeders, and at present, primarily directed to the problems associated with the Fast Breeder Test Reactor which is under construction. (M.G.B.)

  11. LeActiveMath

    OpenAIRE

    Gross, Christian

    2005-01-01

    LeActiveMath (Language-Enhanced, User-Adaptive, Interactive e-Learning for Mathematics) ist ein von der EU finanziertes dreijähriges Projekt (2004 - 2006), an dem sich britische, spanische, niederländische und deutsche Universitäten, Firmen und Institute beteiligen, zum Zwecke der Entwicklung und Evaluation einer innovativen Mathematik-Lernsoftware für Differentialrechnung. Diese soll sich für die Oberstufe wie auch für die ersten Semester mathematisch ausgerichteter Studiengänge eignen und s...

  12. Stellar magnetic activity

    International Nuclear Information System (INIS)

    The stellar emission in the chromospheric Ca II H+K lines is compared with the coronal soft X-ray emission, measuring the effects of non-radiative heating in the outer atmosphere at temperatures differing two orders of magnitude. The comparison of stellar flux densities in Ca II H+K and X-rays is extended to fluxes from the transition-region and the high-temperature chromosphere. The stellar magnetic field is probably generated in the differentially rotating convective envelope. The relation between rotation rate and the stellar level of activity measured in chromospheric, transition-region, and coronal radiative diagnostics is discovered. X-ray observations of the binary λ Andromedae are discussed. The departure of M-type dwarfs from the main relations, and the implications for the structure of the chromospheres of these stars are discussed. Variations of the average surface flux densities of the Sun during the 11-year activity cycle agree with flux-flux relations derived for other cool stars, suggesting that the interpretation of the stellar relations may be furthered by studying the solar analogue in more detail. (Auth.)

  13. Involvement in Physical Activity

    Directory of Open Access Journals (Sweden)

    James Gavin

    2013-04-01

    Full Text Available A total of 1,096 adolescents participated in 123 focus groups regarding the perceived outcomes of their involvement in sports and physical activity (PA. The groups, segmented by grade level, sex, and school types, were conducted in both public and private high schools in Montreal, Quebec. We sought to understand, through the participants’ own words, their perception of the outcome matrix of involvement in sports and PA. Focus group questions emphasized changes that adolescents associated with such engagement. In particular, participants were asked how sports and PA might influence behaviors, emotional states, personal characteristics, and other outcomes. Twelve themes were identified in the responses: Positive Health and Physical Changes (18.5%, Activity-Related Positive Emotions (15.6%, and Personal Learning (11.3% were most prevalent in the discussions. A cluster of deeper personal changes thematically described as Self-Identity, Autonomy, and Positive Character Development accounted for another 16.5% of the responses. Relatively few commentaries emphasized negative effects (7.1%. Converting the proportions of qualitative data into a quantitative index allowed us to analyze potential differences in emphasis according to sex, age, and school type. Though a few significant findings emerged, the larger pattern was of a uniform perceptual map across the variables for this adolescent sample. Implications drawn from this investigation highlight the need to clearly articulate concrete pathways to positive nonphysical changes (e.g., mood states, autonomy, positive character development from engagements in sports and PA.

  14. Active Astronomy Roadshow Haiti

    Science.gov (United States)

    Laycock, Silas; Oram, Kathleen; Alabre, Dayana; Douyon, Ralph; UMass Lowell Haiti Development Studies Center

    2016-01-01

    College-age Haitian students working with advisors and volunteers from UMass Lowell in 2015 developed and tested an activity-based K-8 curriculum in astronomy, space, and earth science. Our partner school is located in Les Cayes, Haiti a city where only 65% of children attend school, and only half of those will complete 6th grade. Astronomy provides an accessible and non-intimidating entry into science, and activity-based learning contrasts with the predominant traditional teaching techniques in use in Haiti, to reach and inspire a different cohort of learners. Teachers are predominantly women in Haiti, so part of the effort involves connecting them with scientists, engineers and teacher peers in the US. As a developing nation, it is vital for Haitian (as for all) children to grow up viewing women as leaders in science. Meanwhile in the US, few are aware of the reality of getting an education in a 3rd world nation (i.e. most of the world), so we also joined with teachers in Massachusetts to give US school children a peek at what daily life is like for their peers living in our vibrant but impoverished neighbor. Our Haitian partners are committed to helping their sister-schools with curriculum and educator workshops, so that the overall quality of education can rise, and not be limited to the very few schools with access to resources. We will describe the activites, motivation, and and the lessons learned from our first year of the project.

  15. Microbiologically active nanocomposite media

    Science.gov (United States)

    Petranovskii, Vitalii; Panina, Lyudmila; Bogomolova, Eugenia; Belostotskaya, Galina

    2003-07-01

    The most recent approach to the development of novel antimicrobial and antifungal agents is based on the application of synthetic and natural zeolites, because zeolites are known to be the carrier and slow releaser of the heavy metals with olygodynamic properties. The microbiological activity of the ion-exchanged zeolites is attributed to the ionic state of the metal sreleased from the zeolites by ion re-exchange. In the present work we used low cost natural clinoptilolite (Cli) as a substrate for copper and silver in different states. The state of oxidation of the exchanged metal in zeolite with supported Cu and Ag species (in the form of cations, small clusters, sub-coloidal particles, large particles) in order to fit them to fulfill the following criteria: to demonstrate their high protective abilities against fungi and long-term stability. The study of structure of samples with XRD, UV-visible spectroscopy, FTIR, their stability with temperature and during storage was carried out for obtaining the correct correlation with microbiological activity.

  16. The Active Solid Earth

    Science.gov (United States)

    Ebinger, Cynthia

    2016-04-01

    Dynamic processes in Earth's crust, mantle and core shape Earth's surface and magnetic field over time scales of seconds to millennia, and even longer time scales as recorded in the ca. 4 Ga rock record. Our focus is the earthquake-volcano deformation cycles that occur over human time scales, and their comparison with time-averaged deformation studies, with emphasis on mantle plume provinces where magma and volatile release and vertical tectonics are readily detectable. Active deformation processes at continental and oceanic rift and back arc zones provide critical constraints on mantle dynamics, the role of fluids (volatiles, magma, water), and plate rheology. For example, recent studies of the East African rift zone, which formed above one of Earth's largest mantle upwellings reveal that magma production and volatile release rates are comparable to those of magmatic arcs, the archetypal zones of continental crustal creation. Finite-length faults achieve some plate deformation, but magma intrusion in the form of dikes accommodates extension in continental, back-arc, and oceanic rifts, and intrusion as sills causes permanent uplift that modulates the local time-space scales of earthquakes and volcanoes. Volatile release from magma intrusion may reduce fault friction and permeability, facilitating aseismic slip and creating magma pathways. We explore the implications of active deformation studies to models of the time-averaged structure of plume and extensional provinces in continental and oceanic plate settings.

  17. Agrice 2001. Activity report

    International Nuclear Information System (INIS)

    AGRICE was created in 1994 to support research on new renewable plant-based products other than foodstuffs, to open up new markets for agriculture, and to take action on today's environmental challenges: fighting the greenhouse effect, curbing pollution (VOCs, effluents, etc.), eco-toxics, preservation of health, and depletion of fossil energy supplies. The scope of AGRICE's activity covers primarily the industrial conversion of crop production to chemicals (lubricants, surfactants, solvents, etc.), energy (liquid and solid biofuels) and materials (agro-materials, biopolymers). AGRICE's brief is to stimulate applied technological research. The consortium first tackled work aimed at substituting plant-based products for products derived from fossil resources. This strategy has been progressively widened to take into account the inherent characteristics of plant-based products in order to meet new needs. In addition to research focusing on industrial products and processes, this action spans the study of agronomic improvements, project economics, markets, and energy and environmental assessments. This report presents: 1 - the AGRICE profile, scope of activity (Biofuels (vehicles and non-vehicles), Biomolecules, Biomaterials), structure and Operations, and sectors of focus; 2 - the year 2001: Toward a new golden age of renewable plant based resources?, Financial Report and Applications, Noteworthy Achievements in 2001, Events in 2001, European Joint Undertakings; 3 - appendixes: Breakdown of AGRICE grants by sector 1994-2001, Financial report 1994-2001, Partners, The ADEME / AGRICE team, Projects initiated and completed in 2001

  18. Forensic Activation Analysis

    International Nuclear Information System (INIS)

    The high sensitivity of high-flux (reactor) thermal-neutron activation analysis (NAA) for the detection and quantitative measurement of a large number of elements has led, in recent years, to a considerable degree of application of the method in the area of scientific crime investigation (criminalistics). Thus, in a Forensic Activation Analysis Bibliography recently compiled by the author, some 135 publications in this field are listed - and more are appearing quite rapidly. The nondestructive character of the purely-instrumental form of the method is an added advantage in forensic work, since evidence samples involved in actual criminal cases are not destroyed during analysis, but are preserved intact for possible presentation in court. Quite aside from, or in addition to, use in court, NAA results can be very helpful in the investigative stage of particular criminal cases. The ultra sensitivity of the method often enables one to analyze evidence specimens that are too tiny for meaningful analysis by more conventional elemental analysis methods. Also, this high sensitivity often enables one to characterize, or individualize, evidence specimens as to the possibility of common origin - via the principle of multi-element trace-constituent characterization

  19. Leadership Development Activities

    Directory of Open Access Journals (Sweden)

    Malikeh Beheshtifar

    2012-07-01

    Full Text Available Nowadays, human resource development is considered as a developed concept in HR field. It is a process for helping personnel to conduct their duties better. Most organizations tend to leadership development as a separable subject and as areas of responsibility within organization. Whereas the leadership development plans have been unsuccessful. This article aim to draw attention to the fact that leadership development is crucial in organizations. A literature review was conducted by searching journal databases, textbooks, and relevant reports. A categorization of the evidence allowed informed discussions on the key themes surrounding leadership development activities. Leadership development is caused to employees' promotion and progress via nurture of new talents, stimulus in employees by persuade to do individual development, save time and cost, and increase customers' satisfaction by relations improvement. Accordingly, the development systems can cover a wide scope in organization. They are effective to career management, training and development, performance management, strategic human resource planning, recruitment and selection, and succession planning activities. Despite the need for further scientific and validated studies, organizations should be urged to devote sufficient resources and attention towards leadership development for promoting long-term survival and prosperity.

  20. Active Optics in LAMOST

    Institute of Scientific and Technical Information of China (English)

    Ding-Qiang Su; Xiang-Qun Cui

    2004-01-01

    Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST)is one of the major national projects under construction in China. Active optics is one of the most important technologies for new large telescopes. It is used for correcting telescope errors generated by gravitational and thermal changes. Here,however, we use this technology to realize the configuration of LAMOST, -a task that cannot be done in the traditional way. A comprehensive and intensive research on the active optics used in LAMOST is also reported, including an open-loop control method and an auxiliary closed-loop control method. Another important development is in our pre-calibration method of open-loop control, which is with some new features: simultaneous calculation of the forces and displacements of force actuators and displacement actuators; the profile of mirror can be arbitrary;the mirror surface shape is not expressed by a fitting polynomial, but is derived from the mirror surface shape formula which is highly accurate; a proof is given that the solution of the pre-calibration method is the same as the least squares solution.

  1. Intergovernmental organisation activities

    International Nuclear Information System (INIS)

    This section treats of the following Intergovernmental organisation activities: 1 - European Atomic Energy Community: Non-legally binding instruments - Communication from the European Commission 'Towards an Integrated Strategic Energy Technology (SET) Plan: Accelerating the European Energy System Transformation'; 2014 Annual Report of the Euratom Supply Agency; Report of June 2015 from the Euratom Supply Agency to the European Commission on the Security of Supply of Medical Radioisotopes; 2 - International Atomic Energy Agency (IAEA): Convention on Nuclear Safety (CNS); 59. regular session of the IAEA General Conference (Resolutions of the Conference, Measures to Strengthen International Cooperation in Nuclear, Radiation, Transport and Waste Safety (GC(59)/RES/9): conventions, regulatory frameworks and supporting non-legally-binding instruments for safety, Nuclear liability, National infrastructures, Nuclear installation safety, Safe management of radioactive sources, Nuclear and radiological incident and emergency preparedness and response); Nuclear Security (GC(59)/RES/10); IAEA Treaty Event; Legislative assistance activities; Nuclear Law Institute; 3 - OECD Nuclear Energy Agency (NEA): European Nuclear Energy Tribunal (ENET) Inaugural Session for the 9. mandate; New signatories to the extension of the Generation IV International Forum (GIF) Framework Agreement; Joint Declaration on the Security of Supply of Medical Radioisotopes; International Framework for Nuclear Energy Cooperation (IFNEC); 15. session of the International School of Nuclear Law (ISNL); 2016 session of the International Nuclear Law Essentials (INLE)

  2. INFLUENCE OF SELECTED PHARMACEUTICALS ON ACTIVATED SLUDGE DEHYDROGENASE ACTIVITY

    Directory of Open Access Journals (Sweden)

    Agnieszka Tomska

    2016-06-01

    The aim of this work was to evaluate the effect of selected antibiotics - sulfanilamide and erythromycin on activated sludge dehydrogenase activity with use of trifenyltetrazolinum chloride (TTC test. Dehydrogenases activity is an indicator of biochemical activity of microorganisms present in activated sludge or the ability to degrade organic compounds in waste water. TTC test is particularly useful for the regularity of the course of treatment, in which the presence of inhibitors of biochemical reactions and toxic compounds are present. It was observed that the dehydrogenase activity decreases with the increase of a antibiotics concentration. The lowest value of the dehydrogenase activity equal to 32.4 μmol TF / gMLSS obtained at sulfanilamide concentration 150mg / l. For this sample, an inhibition of dehydrogenase activity was 31%.

  3. CBP Active Dumping and Active Countervailing (AD/CVD) Cases

    Data.gov (United States)

    Department of Homeland Security — The datasets provide information from CBP's reference files on active anti-dumping and active countervailing cases. This data includes associated case numbers (if...

  4. Sedentary activity associated with metabolic syndrome independent of physical activity

    DEFF Research Database (Denmark)

    Bankoski, Andrea; Harris, Tamara B; McClain, James J;

    2011-01-01

    This study examined the association between objectively measured sedentary activity and metabolic syndrome among older adults.......This study examined the association between objectively measured sedentary activity and metabolic syndrome among older adults....

  5. Negotiating active ageing at a Danish activity centre

    DEFF Research Database (Denmark)

    Lassen, Aske Juul

    aging means in the everyday live of the elderly. Active aging is formed in many arenas and takes a variety of forms with different actors focusing on physical, occupational, social and mental activity. This paper focuses on how the elderly takes part in this forming, by asking how the elderly negotiates...... produced by the EU and a Danish municipality, as well as reports and articles published by mainstream media. Results: The elderly at the activity centres perceives of active ageing differently than how it is formed in the documents explored. Active ageing is situated and contextualised in practice......, and becomes a subject of dispute when the elderly feel subjected to specific activities. In this way active ageing is negotiable, and is simultaneously internalized and rejected in the practice of the elderly at the activity centre....

  6. Active Magnetic Regenerative Liquefier

    Energy Technology Data Exchange (ETDEWEB)

    Barclay, John A. [Heracles Energy Corporation d.b.a. Prometheus Energy, Washington, DC (United States); Oseen-Send, Kathryn [Heracles Energy Corporation d.b.a. Prometheus Energy, Washington, DC (United States); Ferguson, Luke [Heracles Energy Corporation d.b.a. Prometheus Energy, Washington, DC (United States); Pouresfandiary, Jamshid [Heracles Energy Corporation d.b.a. Prometheus Energy, Washington, DC (United States); Cousins, Anand [Heracles Energy Corporation d.b.a. Prometheus Energy, Washington, DC (United States); Ralph, Heather [Heracles Energy Corporation d.b.a. Prometheus Energy, Washington, DC (United States); Hampto, Tom [Heracles Energy Corporation d.b.a. Prometheus Energy, Washington, DC (United States)

    2016-01-12

    This final report for the DOE Project entitled Active Magnetic Regenerative Liquefier (AMRL) funded under Grant DE-FG36-08GO18064 to Heracles Energy Corporation d.b.a. Prometheus Energy (Heracles/Prometheus) describes an active magnetic regenerative refrigerator (AMRR) prototype designed and built during the period from July 2008 through May 2011. The primary goal of this project was to make significant technical advances toward highly efficient liquefaction of hydrogen. Conventional hydrogen liquefiers at any scale have a maximum FOM of ~0.35 due primarily to the intrinsic difficulty of rapid, efficient compression of either hydrogen or helium working gases. Numerical simulation modeling of high performance AMRL designs indicates certain designs have promise to increase thermodynamic efficiency from a FOM of ~0.35 toward ~0.5 to ~0.6. The technical approach was the use of solid magnetic working refrigerants cycled in and out of high magnetic fields to build an efficient active regenerative magnetic refrigeration module providing cooling power for AMRL. A single-stage reciprocating AMRR with a design temperature span from ~290 K to ~120 K was built and tested with dual magnetic regenerators moving in and out of the conductively-cooled superconducting magnet subsystem. The heat transfer fluid (helium) was coupled to the process stream (refrigeration/liquefaction load) via high performance heat exchangers. In order to maximize AMRR efficiency a helium bypass loop with adjustable flow was incorporated in the design because the thermal mass of magnetic refrigerants is higher in low magnetic field than in high magnetic field. Heracles/Prometheus designed experiments to measure AMRR performance under a variety of different operational parameters such as cycle frequency, magnetic field strength, heat transfer fluid flow rate, amount of bypass flow of the heat transfer fluid while measuring work input, temperature span, cooling capability as a function of cold temperature

  7. Antibacterial activity of Pterocarpus santalinus

    Directory of Open Access Journals (Sweden)

    Manjunatha B

    2006-01-01

    Full Text Available Antibacterial activity of leaf and stem bark of Pterocarpus santalinus (Fabaceae was investigated. The antibacterial activity was tested against both Gram-positive and Gram-negative organisms. Among the two extracts tested, stem bark extract exhibited broad-spectrum antibacterial activity against the tested organisms. The stem bark extract showed maximum activity against Enterobacter aerogenes, Alcaligenes faecalis, Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris, Bacillus cereus, Bacillus subtilis, Staphylococcus aureus . The leaf extract showed maximum activity against Escherichia coli, Alcaligenes faecalis, Enterobacter aerogenes and Pseudomonas aeruginosa . Both extracts exhibited concentration dependent activity.

  8. How Active Are Older Americans?

    Directory of Open Access Journals (Sweden)

    Judy Kruger, PhD

    2007-07-01

    Full Text Available IntroductionRegular physical activity can reduce age-related functional decline, as well people’s risk for chronic diseases such as coronary heart disease, hypertension, colon cancer, and diabetes. The objective of this study was to estimate the level of participation in aerobic, muscle-strengthening, and flexibility activities among Americans aged 50 years or older.MethodsUsing population-based data from the 2001 National Health Interview Survey, we classified qualified respondents (N = 11,969 according to whether they met the activity criteria used in Healthy People 2010 goals for leisure-time participation in regular aerobic physical activity, vigorous-intensity aerobic activity, strength-training activity, and flexibility activity. We also classified respondents according to their level of aerobic activity (i.e., inactive, insufficiently active, and regularly active.ResultsWe estimated that 46.4% of older Americans engaged in no leisure-time aerobic activity; that 26.1% were regularly active (participated in light- to moderate-intensity aerobic activities at least 5 days per week for at least 30 minutes or vigorous-intensity activities at least 3 days per week for at least 20 minutes; that 16.2% participated in vigorous-intensity aerobic activities at least 3 days per week for at least 20 minutes; that 13.7% participated in strength-training activities at least 2 days per week; and that 24.5% participated in flexibility activities at least 1 day per week. Among the 26.1% of older Americans who were regularly active, 30.5% engaged in strengthen-training activities at least 2 days per week. Overall, only 8.2% of older Americans met the criteria for both aerobic and strength-training activity.ConclusionAs of 2001, the percentage of older Americans who met recommended activity levels of physical activity were well below the goals for U.S. adults in Healthy People 2010. Further efforts are needed to encourage older Americans to engage in

  9. RELAXIN ACTIVATES PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR GAMMA

    OpenAIRE

    Singh, Sudhir; Bennett, Robert G

    2009-01-01

    Relaxin is a polypeptide hormone that triggers multiple signaling pathways through its receptor RXFP1. Many of relaxin’s functions, including vascular and antifibrotic effects, are similar to those induced by activation of PPARγ. In this study, we tested the hypothesis that relaxin signaling through RXFP1 would activate PPARγ activity. In cells overexpressing RXFP1 (HEK-RXFP1), relaxin increased transcriptional activity through a PPAR response element (PPRE) in a concentration-dependent manne...

  10. Denitrifying activity of activated sludge in suspension and in biofilm

    OpenAIRE

    Cortez, Susana; Teixeira, P.; Oliveira, Rosário; Mota, M.

    2008-01-01

    A method based on measuring substrate depletion rate was developed to evaluate the denitrifying activity of activated sludge in suspension and in biofilm form in anoxic serum flasks. The adapted activated sludge inoculum was grown as biofilm in an anoxic rotating biological contactor (RBC). Acetate was used as external carbon source to obtain a carbon to nitrogen ratio (C/N) of 2. The results showed that the specific activity of cells in biofilm form was higher than in planktonic for...

  11. Activated Sludge Rheology

    DEFF Research Database (Denmark)

    Ratkovich, Nicolas Rios; Horn, Willi; Helmus, Frank;

    2013-01-01

    Rheological behaviour is an important fluid property that severely impacts its flow behaviour and many aspects related to this. In the case of activated sludge, the apparent viscosity has an influence on e.g. pumping, hydrodynamics, mass transfer rates, sludge-water separation (settling...... and filtration). It therefore is an important property related to process performance, including process economics. To account for this, rheological behaviour is being included in process design, necessitating its measurement. However, measurements and corresponding protocols in literature are quite diverse...... rheological measurements. Moreover, the rheological models are not very trustworthy and remain very “black box”. More insight in the physical background needs 30 to be gained. A model-based approach with dedicated experimental data collection is the key to address this....

  12. RTE - Activity report 2011

    International Nuclear Information System (INIS)

    RTE, an independent subsidiary of EDF, is the French electricity transmission system operator. It is a public service company responsible for operating, maintaining and developing the high and extra high voltage network. It guarantees the reliability and proper operation of the power network. RTE transports electricity between electricity suppliers (French and European) and consumers, whether they are electricity distributors or industrial consumers directly connected to the transmission system. The mission of RTE is to balance the electricity supply and demand in real time. This publication gathers in a single document the 2011 Activity and Sustainable development report of RTE, the Management report with the consolidated financial statements, and the Report from the chairman of the supervisory board

  13. Activity report 2004

    International Nuclear Information System (INIS)

    Constituted by a public and commercial establishment, the French National Radioactive Waste Management Agency (ANDRA) is responsible for the long term management of radioactive waste. This activity report presents the three missions of the ANDRA during the year 2004. The industrial mission deals with the Aube center disposal and the Manche center disposal facilities and the collection effort concerning the diffuse nuclear waste. The research mission focuses on the presentation of several topics: the repository design by studying various potential architectures, the reversibility and the safety assessment under operating conditions and the description of the behavior of repository at various space and time scales. The last mission concerns the information and the communication program. (A.L.B.)

  14. Plasminogen activation and cancer

    DEFF Research Database (Denmark)

    Danø, Keld; Behrendt, N.; Hoyer-Hansen, G.;

    2005-01-01

    Breakdown of the extracellular matrix is crucial for cancer invasion and metastasis. It is accomplished by the concerted action of several proteases, including the serine protease plasmin and a number of matrix metalloproteases.The activity of each of these proteases is regulated by an array......, the regulation of extracellular proteolysis in cancer involves a complex interplay between cancer cells and non-malignant stromal cells in the expression of the molecular components involved. For some types of cancer, this cellular interplay mimics that observed in the tissue of ori- gin during non......-neoplastic tissue remodelling processes.We propose that cancer invasion can be considered as uncontrolled tissue remodelling. Inhibition of extracellular proteases is an attractive approach to cancer therapy. Because proteases have many different functions in the normal organism, efficient inhibition will have...

  15. Physical activity among adolescents

    DEFF Research Database (Denmark)

    Henriksen, P W; Ingholt, L; Rasmussen, M;

    2015-01-01

    The objectives of this study were (a) to examine the association between various kinds of parental social support and adolescents' physical activity (PA) and (b) to examine whether various kinds of social support from mothers and fathers were differently associated with boys' and girls' PA. Data...... dimensions of parental support for PA. The association patterns were similar for mothers' and fathers' social support and similar for girls and boys. Social processes in the family are important for adolescents' participation in PA. It is important to continue to explore these social processes in order...... came from the Aarhus School Survey that included 2100 schoolchildren at 11, 13, and 15 years of age. Parental social support for PA was measured by items about encouragement to do PA, doing joint PA, parents watching PA, and talking about PA. PA was measured as at least 4 h of vigorous PA per week...

  16. Uranium management activities

    International Nuclear Information System (INIS)

    One of the missions of the Department of Energy's (DOE) Oak Ridge Office (ORO) has been the management of the Department's uranium materials. This mission has been accomplished through successful integration of ORO's uranium activities with the rest of the DOE complex. Beginning in the 1980's, several of the facilities in that complex have been shut down and are in the decommissioning process. With the end of the Cold War, the shutdown of many other facilities is planned. As a result, inventories of uranium need to be removed from the Department facilities. These inventories include highly enriched uranium (HEU), low enriched uranium (LEU), normal uranium (NU), and depleted uranium (DU). The uranium materials exist in different chemical forms, including metals, oxides, solutions, and gases. Much of the uranium in these inventories is not needed to support national priorities and programs. (author)

  17. RTE - Activity report 2010

    International Nuclear Information System (INIS)

    RTE, an independent subsidiary of EDF, is the French electricity transmission system operator. It is a public service company responsible for operating, maintaining and developing the high and extra high voltage network. It guarantees the reliability and proper operation of the power network. RTE transports electricity between electricity suppliers (French and European) and consumers, whether they are electricity distributors or industrial consumers directly connected to the transmission system. The mission of RTE is to balance the electricity supply and demand in real time. This publication gathers in a single document the 2010 Activity and Sustainable development report of RTE, the Management report with the consolidated financial statements, and the Report from the chairman of the supervisory board

  18. DPAL activities in Japan

    Science.gov (United States)

    Endo, Masamori; Wani, Fumio

    2015-02-01

    Activities on diode pumped alkali laser (DPAL) in Japan is reviewed. We have started alkali laser works in 2011, and currently, we are the only players in Japan. Our interests are application oriented, and it is not only defense but also industrial. DPAL is a good candidate as a source of remote laser machining, thanks to its scalability and extremely good beam quality. We are studying on scientific and engineering problems of Cs DPAL with a small-scale apparatus. A commercial diode laser with volume Bragg grating outcoupler is used to pump the gain cell longitudinally. A 6.5 W continuous-wave output with optical to optical efficiency of 56% (based on the absorbed power) has been achieved. Numerical simulation codes are developed to understand the physics of DPAL and to help future developments.

  19. Respiratory active mitochondrial supercomplexes.

    Science.gov (United States)

    Acín-Pérez, Rebeca; Fernández-Silva, Patricio; Peleato, Maria Luisa; Pérez-Martos, Acisclo; Enriquez, Jose Antonio

    2008-11-21

    The structural organization of the mitochondrial respiratory complexes as four big independently moving entities connected by the mobile carriers CoQ and cytochrome c has been challenged recently. Blue native gel electrophoresis reveals the presence of high-molecular-weight bands containing several respiratory complexes and suggesting an in vivo assembly status of these structures (respirasomes). However, no functional evidence of the activity of supercomplexes as true respirasomes has been provided yet. We have observed that (1) supercomplexes are not formed when one of their component complexes is absent; (2) there is a temporal gap between the formation of the individual complexes and that of the supercomplexes; (3) some putative respirasomes contain CoQ and cytochrome c; (4) isolated respirasomes can transfer electrons from NADH to O(2), that is, they respire. Therefore, we have demonstrated the existence of a functional respirasome and propose a structural organization model that accommodates these findings.

  20. Is enhanced physical activity possible using active videogames?

    Science.gov (United States)

    Our research indicated that 10– to 12-year-old children receiving two active Wii (TM)(Nintendo (R); Nintendo of America, Inc., Redmond, WA) console videogames were no more physically active than children receiving two inactive videogames. Research is needed on how active videogames may increase phys...

  1. Youth Physical Activity Resource Use and Activity Measured by Accelerometry

    Science.gov (United States)

    Maslow, Andra L.; Colabianchi, Natalie

    2011-01-01

    Objectives: To examine whether use of physical activity resources (e.g., parks) was associated with daily physical activity measured by accelerometry. Methods: One hundred eleven adolescents completed a travel diary with concurrent accelerometry. The main exposure was self-reported use of a physical activity resource (none /1 resources). The main…

  2. Examining Activism in Practice: A Qualitative Study of Archival Activism

    Science.gov (United States)

    Novak, Joy Rainbow

    2013-01-01

    While archival literature has increasingly discussed activism in the context of archives, there has been little examination of the extent to which archivists in the field have accepted or incorporated archival activism into practice. Scholarship that has explored the practical application of archival activism has predominately focused on case…

  3. Small Active Radiation Monitor

    Science.gov (United States)

    Badhwar, Gautam D.

    2004-01-01

    A device, named small active radiation monitor, allows on-orbit evaluations during periods of increased radiation, after extravehicular activities, or at predesignated times for crews on such long-duration space missions as on the International Space Station. It also permits direct evaluation of biological doses, a task now performed using a combination of measurements and potentially inaccurate simulations. Indeed the new monitor can measure a full array of radiation levels, from soft x-rays to hard galactic cosmic-ray particles. With refinement, it will benefit commercial (nuclear power-plant workers, airline pilots, medical technicians, physicians/dentists, and others) and military personnel as well as the astronauts for whom thermoluminescent dosimeters are inadequate. Civilian and military personnel have long since graduated from film badges to thermoluminescent dosimeters. Once used, most dosimeters must be returned to a central facility for processing, a step that can take days or even weeks. While this suffices for radiation workers for whom exposure levels are typically very low and of brief duration, it does not work for astronauts. Even in emergencies and using express mail, the results can often be delayed by as much as 24 hours. Electronic dosimeters, which are the size of electronic oral thermometers, and tattlers, small electronic dosimeters that sound an alarm when the dose/dose rate exceeds preset values, are also used but suffer disadvantages similar to those of thermoluminescent dosimeters. None of these devices fully answers the need of rapid monitoring during the space missions. Instead, radiation is monitored by passive detectors, which are read out after the missions. Unfortunately, these detectors measure only the absorbed dose and not the biologically relevant dose equivalent. The new monitor provides a real-time readout, a time history of radiation exposures (both absorbed dose and biologically relevant dose equivalent), and a count of the

  4. Report of Activity, 1997

    International Nuclear Information System (INIS)

    The Institute of Nuclear Protection and Safety (Institut de Protection et de Surete Nucleaire) - IPSN carries out research and expert studies needed in managing nuclear risk and consequences of nuclear events on population and environment, i.e. supervises the safety of installations, the prevention and study of accidents, the human health and environmental conditions, the safety of transport and has also the task of organizing the management of the crisis situations. IPSN has the mission of informing the public and participates in numerous international actions. Thus, since 1989 IPSN and its German counterpart, GRS, co-operate towards improving of the nuclear safety in Europe and developing a common approach of international issues. As acting for public authorities (government departments in charge with industry, environment, health or labor), IPSN grants technical authorizations on request of DSIN exploiters. The IPSN personnel amounts up to 1300 employees of whom around two thirds are engineers, researchers, physicians, agronomists, and veterinarians. This IPSN annual report contains in the 'Free Tribune' section two general papers entitled: 'The federalist role of research at IPSN' by Catherine Lecompte and 'The dose, a central issue in radioprotection debates' by Annie Sugier. Then five sub-reports follow: 1.The safety of nuclear facilities and radioactive wastes; 2.Crisis management; 3. The management of sensitive materials (protection and control of sensitive materials and safety analysis of the radioactive materials transport); 4.Protection of human health; 5.Environment protection. The report also presents the international activities, the cooperation IPSN/GRS, the budget, the staff and the human resource policy and the communication activity

  5. Project origami activities for exploring mathematics

    CERN Document Server

    Hull, Thomas

    2012-01-01

    IntroductionActivity 1 Folding Equilateral Triangles in a Square Activity 2 Origami Trigonometry Activity 3 Dividing a Length into Equal Nths: Fujimoto Approximation Activity 4 Dividing a Length into Equal Nths Exactly Activity 5 Origami Helix Activity 6 Folding a Parabola Activity 7 Can Origami Trisect an Angle?Activity 8 Solving Cubic Equations Activity 9 Lill's Method Activity 10 Folding Strips into Knots Activity 11 Haga's ""Origamics"" Activity 12 Modular Star Ring Activity 13 Folding a Butterfly Bomb Activity 14 Molly's Hexahedron Activity 15 Business Card Modulars Activity 16 Five Inter

  6. Physical activity - preventive medicine (image)

    Science.gov (United States)

    Physical activity contributes to health by reducing the heart rate, decreasing the risk for cardiovascular disease, and reducing ... loss that is associated with age and osteoporosis. Physical activity also helps the body use calories more efficiently, ...

  7. Consolidated Human Activities Database (CHAD)

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Consolidated Human Activity Database (CHAD) contains data obtained from human activity studies that were collected at city, state, and national levels. CHAD is...

  8. [Antibiotic activity of some fungi].

    Science.gov (United States)

    Savchuk, Ia I; Tsyganenko, K S; Zaĭchenko, O M

    2013-01-01

    Biological activity of pure extracts of cultural filtrates of Aspergillus niveus 2411, Myrothecium cinctum 910, Ulocladium consortiale 960, Penicillium sp. 10-51 concerning wide spectrum of test-organisms was investigated. It was shown that the extracts had high levels of antibacterial activity against Gram-positive microorganisms, especially against Bacillus genus. But their activity against Gram-negative bacteria was a bit lower. On the other hand, metabolites of M. cinctum 910 and Penicillium sp. 10-51 did show the activity concerning phytopathogenic bacteria. Extracts of fungi showed fungistatic activity against yeasts, but they were not so active concerning fungal test-cultures. Extracts of A. niveus 2411, Penicillium sp. 10-51 suppressed the growth of Phoma betae. The highest level of fungistatic activity was shown by metabolites of M. cinctum 910. They showed activity against Aspergillus genus strains and phytopathogenic isolates of Fusarium lactis, Rhizoctonia solani and Botrytis cinerea. PMID:24479314

  9. Physical activity extends life expectancy

    Science.gov (United States)

    Leisure-time physical activity is associated with longer life expectancy, even at relatively low levels of activity and regardless of body weight, according to a study by a team of researchers led by the NCI.

  10. Physical Activity and Psoriatic Arthritis

    Science.gov (United States)

    ... out more! Email * Zipcode Physical Activity and Psoriatic Arthritis Physical activity plays an important role in overall well-being. If you have psoriatic arthritis, moderate exercise may offer specific benefits, including improved ...

  11. Advanced Active Acoustics Lab (AAAL)

    Data.gov (United States)

    Federal Laboratory Consortium — The Advanced Active Acoustics Lab (AAAL) is a state-of-the-art Undersea Warfare (USW) acoustic data analysis facility capable of both active and passive underwater...

  12. Activities for Teaching Solar Energy.

    Science.gov (United States)

    Mason, Jack Lee; Cantrell, Joseph S.

    1980-01-01

    Plans and activities are suggested for teaching elementary children about solar energy. Directions are included for constructing a flat plate collector and a solar oven. Activities for a solar field day are given. (SA)

  13. Environmental Education Tips: Weather Activities.

    Science.gov (United States)

    Brainard, Audrey H.

    1989-01-01

    Provides weather activities including questions, on weather, heating the earth's surface, air, tools of the meteorologist, clouds, humidity, wind, and evaporation. Shows an example of a weather chart activity. (RT)

  14. Antibacterial activity of Pterocarpus santalinus

    OpenAIRE

    Manjunatha B

    2006-01-01

    Antibacterial activity of leaf and stem bark of Pterocarpus santalinus (Fabaceae) was investigated. The antibacterial activity was tested against both Gram-positive and Gram-negative organisms. Among the two extracts tested, stem bark extract exhibited broad-spectrum antibacterial activity against the tested organisms. The stem bark extract showed maximum activity against Enterobacter aerogenes, Alcaligenes faecalis, Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris, Bacillus cere...

  15. Writing clear animal activity proposals.

    Science.gov (United States)

    Pinson, David M

    2011-06-01

    Although IACUC-related topics are frequently discussed in the literature, there is little published information about how to write animal activity proposals. In this article, the author discusses key considerations in the writing and review of animal activity proposals. The author then describes a framework for developing and writing clear animal activity proposals that highlight animal welfare concerns. Though these recommendations are aimed at individuals writing and reviewing research proposals, the framework can be modified for other types of animal activity proposals.

  16. Audit Activities and Their Comparison

    OpenAIRE

    Hudcová, Michaela

    2013-01-01

    This work deals with audit activities and assurance engagements. So it deals with similar issues from Czech and international perspective. It describes the types of audit activities and assurance engagements. It also describes related legislation, standards and regulatory authorities. The work contains information about persons, who perform audit activities and assurance engagements. This thesis compares audit activities and assurance engagements. The comparison shows a great similarity. This...

  17. Organic active materials for batteries

    Energy Technology Data Exchange (ETDEWEB)

    Abouimrane, Ali; Weng, Wei; Amine, Khalil

    2016-08-16

    A rechargeable battery includes a compound having at least two active sites, R.sup.1 and R.sup.2; wherein the at least two active sites are interconnected by one or more conjugated moieties; each active site is coordinated to one or more metal ions M.sup.a+ or each active site is configured to coordinate to one or more metal ions; and "a" is 1, 2, or 3.

  18. Preparation of activated carbon by chemical activation under vacuum.

    Science.gov (United States)

    Juan, Yang; Ke-Qiang, Qiu

    2009-05-01

    Activated carbons especially used for gaseous adsorption were prepared from Chinesefir sawdust by zinc chloride activation under vacuum condition. The micropore structure, adsorption properties, and surface morphology of activated carbons obtained under atmosphere and vacuum were investigated. The prepared activated carbons were characterized by SEM, FTIR, and nitrogen adsorption. It was found that the structure of the starting material is kept after activation. The activated carbon prepared under vacuum exhibited higher values of the BET surface area (up to 1079 m2 g(-1)) and total pore volume (up to 0.5665 cm3 g(-1)) than those of the activated carbon obtained under atmosphere. This was attributed to the effect of vacuum condition that reduces oxygen in the system and limits the secondary reaction of the organic vapor. The prepared activated carbon has well-developed microstructure and high microporosity. According to the data obtained, Chinese fir sawdust is a suitable precursor for activated carbon preparation. The obtained activated carbon could be used as a low-cost adsorbent with favorable surface properties. Compared with the traditional chemical activation, vacuum condition demands less energy consumption, simultaneity, and biomass-oil is collected in the procedure more conveniently. FTIR analysis showed that heat treatment would result in the aromatization of the carbon structure. PMID:19534162

  19. Assessing and Increasing Physical Activity

    Science.gov (United States)

    Van Camp, Carole M.; Hayes, Lynda B.

    2012-01-01

    Increasing physical activity is a crucial component of any comprehensive approach to combat the growing obesity epidemic. This review summarizes recent behavioral research on the measurement of physical activity and interventions aimed at increasing physical activity and provides directions for future research.

  20. Physical Activity and Your Heart

    Science.gov (United States)

    ... page from the NHLBI on Twitter. What Is Physical Activity? Español Physical activity is any body movement that works your muscles ... yoga, and gardening are a few examples of physical activity. According to the Department of Health and Human ...