Sample records for anti-factor xa activity

  1. 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.

  2. Antifactor Xa levels versus activated partial thromboplastin time for monitoring unfractionated heparin. (United States)

    Vandiver, Jeremy W; Vondracek, Thomas G


    Intravenous unfractionated heparin (UFH) remains an important therapeutic agent, particularly in the inpatient setting, for anticoagulation. Historically, the activated partial thromboplastin time (aPTT) has been the primary laboratory test used to monitor and adjust UFH. The aPTT test has evolved since the 1950s, and the historical goal range of 1.5-2.5 times the control aPTT, which first gained favor in the 1970s, has fallen out of favor due to a high degree of variability in aPTT readings from one laboratory to another, and even from one reagent to another. As a result, it is now recommended that the aPTT goal range be based on a corresponding heparin concentration of 0.2-0.4 unit/ml by protamine titration or 0.3-0.7 unit/ml by antifactor Xa assay. Given that several biologic factors can influence the aPTT independent of the effects of UFH, many institutions have transitioned to monitoring heparin with antifactor Xa levels, rather than the aPTT. Clinical data from the last 10-20 years have begun to show that a conversion from aPTT to antifactor Xa monitoring may offer a smoother dose-response curve, such that levels remain more stable, requiring fewer blood samples and dosage adjustments. Given the minimal increased acquisition cost of the antifactor Xa reagents, it can be argued that the antifactor Xa is a cost-effective method for monitoring UFH. In this review, we discuss the relative advantages and disadvantages of the aPTT, antifactor Xa, and protamine titration tests, and provide a clinical framework to guide practitioners who are seeking to optimize UFH monitoring within their own institutions.

  3. A novel prothrombin time assay for assessing the anticoagulant activity of oral factor Xa inhibitors. (United States)

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


    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.

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

    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


    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.

  5. Development and evaluation of PEGylated Enoxaparin: a novel approach for enhanced anti-Xa activity. (United States)

    Choubey, Anupam Kumar; Dora, Chander Parkash; Bhatt, Tara Dutt; Gill, Manjinder Singh; Suresh, Sarasija


    Enoxaparin (ENX) is one of the most widely prescribed low molecular weight heparin inprophylaxis and treatment of venous thromboembolism. In this study, Enoxaparin-PEG conjugate (P-ENX) was synthesized from Enoxaparin and polyethylene glycol (PEG) and evaluated for its potential for extended duration of action. The esterification of the carboxyl groups of the drug moiety with the hydroxyl groups of mPEG-2000 was done by employing carbodiimide coupling chemistry. P-ENX conjugate was purified by dialysis and characterized by Fourier transform infrared spectroscopy (FTIR), Proton-Nuclear magnetic resonance ((1)H NMR) and matrix-assisted laser desorption/ionization (MALDI) mass analysis techniques. FTIR analysis revealed frequency of the carbonyl group in accord with ester linkage formation between the drug and the PEG moiety. (1)H NMR of the conjugate showed significant change in the chemical shift further indicative of ENX and PEG chemical interaction. In MALDI spectra, small peaks at 12,907 and 16,137 m/z confirmed the probability of conjugation of ENX and PEG. P-ENX exhibited considerable enhancement in anti-Xa activity (by three-folds) in comparison to free ENX. Further, an increase in AUC (over four-folds) was observed in P-ENX. Thus, PEGylation of ENX is a novel approach for extended and enhanced activity of ENX with a potential for decreased dosing frequency.

  6. [Automatization of heparin determination using chronometric evaluation of anti-Xa activity of the AT III-heparin complex]. (United States)

    Sampol, J; Rossi, J M; Lejay, G


    The authors describe an adaptation on a semi- automatique coagulometer KC 10 of a manual assay of anti-Xa activity of the Heparin-Antithrombin III Complex close to the technique described by Yin and al. ( Hepaclot - Stago ). The results show a good linearity and a good reproducibility, with a better sensitivity than the manuel method. Freezing has no influence. Significant differences were observed between our assay and the manuel anti-IIa assay. These last results neither depend on the administration route nor on the heparin batches.

  7. The Xanthomonas oryzae pv. oryzae PhoPQ two-component system is required for AvrXA21 activity, hrpG expression, and virulence. (United States)

    Lee, Sang-Won; Jeong, Kyu-Sik; Han, Sang-Wook; Lee, Seung-Eun; Phee, Bong-Kwan; Hahn, Tae-Ryong; Ronald, Pamela


    The rice pathogen recognition receptor, XA21, confers resistance to Xanthomonas oryzae pv. oryzae strains producing the type one system-secreted molecule, AvrXA21. X. oryzae pv. oryzae requires a regulatory two-component system (TCS) called RaxRH to regulate expression of eight rax (required for AvrXA21 activity) genes and to sense population cell density. To identify other key components in this critical regulatory circuit, we assayed proteins expressed in a raxR gene knockout strain. This survey led to the identification of the phoP gene encoding a response regulator that is up-regulated in the raxR knockout strain. Next we generated a phoP knockout strain and found it to be impaired in X. oryzae pv. oryzae virulence and no longer able to activate the response regulator HrpG (hypersensitive reaction and pathogenicity G) in response to low levels of Ca2+. The impaired virulence of the phoP knockout strain can be partially complemented by constitutive expression of hrpG, indicating that PhoP controls a key aspect of X. oryzae pv. oryzae virulence through regulation of hrpG. A gene encoding the cognate putative histidine protein kinase, phoQ, was also isolated. Growth curve analysis revealed that AvrXA21 activity is impaired in a phoQ knockout strain as reflected by enhanced growth of this strain in rice lines carrying XA21. These results suggest that the X. oryzae pv. oryzae PhoPQ TCS functions in virulence and in the production of AvrXA21 in partnership with RaxRH.

  8. Coagulation Factor Xa inhibits cancer cell migration via Protease-activated receptor-1 activation

    NARCIS (Netherlands)

    Borensztajn, Keren; Bijlsma, Maarten F.; Reitsma, Pieter H.; Peppelenbosch, Maikel R.; Spek, C. Arnold


    Cell migration is critically important in (patho) physiological processes. The metastatic potential of cancer cells partly depends on activation of the coagulation cascade. The aim of the present study was to determine whether coagulation factor X (FXa) can regulate the migration and invasion of can

  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. Clinical Scenarios for Discordant Anti-Xa (United States)

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


    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

  11. Clinical Scenarios for Discordant Anti-Xa

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    Jesus Vera-Aguilera


    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.

  12. 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


    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

  13. A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa. (United States)

    Lu, Genmin; DeGuzman, Francis R; Hollenbach, Stanley J; Karbarz, Mark J; Abe, Keith; Lee, Gail; Luan, Peng; Hutchaleelaha, Athiwat; Inagaki, Mayuko; Conley, Pamela B; Phillips, David R; Sinha, Uma


    Inhibitors of coagulation factor Xa (fXa) have emerged as a new class of antithrombotics but lack effective antidotes for patients experiencing serious bleeding. We designed and expressed a modified form of fXa as an antidote for fXa inhibitors. This recombinant protein (r-Antidote, PRT064445) is catalytically inactive and lacks the membrane-binding γ-carboxyglutamic acid domain of native fXa but retains the ability of native fXa to bind direct fXa inhibitors as well as low molecular weight heparin-activated antithrombin III (ATIII). r-Antidote dose-dependently reversed the inhibition of fXa by direct fXa inhibitors and corrected the prolongation of ex vivo clotting times by such inhibitors. In rabbits treated with the direct fXa inhibitor rivaroxaban, r-Antidote restored hemostasis in a liver laceration model. The effect of r-Antidote was mediated by reducing plasma anti-fXa activity and the non-protein bound fraction of the fXa inhibitor in plasma. In rats, r-Antidote administration dose-dependently and completely corrected increases in blood loss resulting from ATIII-dependent anticoagulation by enoxaparin or fondaparinux. r-Antidote has the potential to be used as a universal antidote for a broad range of fXa inhibitors.

  14. 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.

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

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


    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. Complement inhibitory and anticoagulant activities of fractionated heparins

    NARCIS (Netherlands)

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


    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

  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


    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. The coagulation factor Xa/protease activated receptor-2 axis in the progression of liver fibrosis : a multifaceted paradigm

    NARCIS (Netherlands)

    Borensztajn, Keren; von der Thusen, Jan H.; Peppelenbosch, Maikel P.; Spek, C. Arnold


    Introduction Activation of the coagulation cascade during liver fibrosis: a puzzling paradox Protease-activated receptors: the link between coagulation cascade activation and liver fibrosis Expression and distribution of human PAR-2 in normal and pathological liver tissue FXa signalling on PAR-2 exp

  19. Kinetic characterization of factor Xa binding using a quenched fluorescent substrate based on the reactive site of factor Xa inhibitor from Bauhinia ungulata seeds. (United States)

    Oliva, M L V; Andrade, S A; Juliano, M A; Sallai, R C; Torquato, R J; Sampaio, M U; Pott, V J; Sampaio, C A M


    The specific Kunitz Bauhinia ungulata factor Xa inhibitor (BuXI) and the Bauhinia variegata trypsin inhibitor (BvTI) blocked the activity of trypsin, chymotrypsin, plasmin, plasma kallikrein and factor XIIa, and factor Xa inhibition was achieved only by BuXI (K(i) 14 nM). BuXI and BvTI are highly homologous (70%). The major differences are the methionine residues at BuXI reactive site, which are involved in the inhibition, since the oxidized protein no longer inhibits factor Xa but maintains the trypsin inhibition. Quenched fluorescent substrates based on the reactive site sequence of the inhibitors were synthesized and the kinetic parameters of the hydrolysis were determined using factor Xa and trypsin. The catalytic efficiency k(cat)/K(m) 4.3 x 10(7) M(-1)sec(>-1) for Abz-VMIAALPRTMFIQ-EDDnp (lead peptide) hydrolysis by factor Xa was 10(4)-fold higher than that of Boc-Ile-Glu-Gly-Arg-AMC, widely used as factor Xa substrate. Lengthening of the substrate changed its susceptibility to factor Xa hydrolysis. Both methionine residues in the substrate influence the binding to factor Xa. Serine replacement of threonine (P(1)') decreases the catalytic efficiency by four orders of magnitude. Factor Xa did not hydrolyze the substrate containing the reactive site sequence of BvTI, that inhibits trypsin inhibitor but not factor Xa. Abz-VMIAALPRTMFIQ-EDDnp prolonged both the prothrombin time and the activated partial thromboplastin time, and the other modified substrates used in this experiment altered blood-clotting assays.

  20. Blood coagulation factor Xa as an emerging drug target

    NARCIS (Netherlands)

    K. Borensztajn; C.A. Spek


    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

  1. Determination of rivaroxaban in patient’s plasma samples by anti-Xa chromogenic test associated to High Performance Liquid Chromatography tandem Mass Spectrometry (HPLC-MS/MS) (United States)

    Derogis, Priscilla Bento Matos; Sanches, Livia Rentas; de Aranda, Valdir Fernandes; Colombini, Marjorie Paris; Mangueira, Cristóvão Luis Pitangueira; Katz, Marcelo; Faulhaber, Adriana Caschera Leme; Mendes, Claudio Ernesto Albers; Ferreira, Carlos Eduardo dos Santos; França, Carolina Nunes; Guerra, João Carlos de Campos


    Rivaroxaban is an oral direct factor Xa inhibitor, therapeutically indicated in the treatment of thromboembolic diseases. As other new oral anticoagulants, routine monitoring of rivaroxaban is not necessary, but important in some clinical circumstances. In our study a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was validated to measure rivaroxaban plasmatic concentration. Our method used a simple sample preparation, protein precipitation, and a fast chromatographic run. It was developed a precise and accurate method, with a linear range from 2 to 500 ng/mL, and a lower limit of quantification of 4 pg on column. The new method was compared to a reference method (anti-factor Xa activity) and both presented a good correlation (r = 0.98, p < 0.001). In addition, we validated hemolytic, icteric or lipemic plasma samples for rivaroxaban measurement by HPLC-MS/MS without interferences. The chromogenic and HPLC-MS/MS methods were highly correlated and should be used as clinical tools for drug monitoring. The method was applied successfully in a group of 49 real-life patients, which allowed an accurate determination of rivaroxaban in peak and trough levels. PMID:28170419

  2. The Role of RaxST, a Prokaryotic Sulfotransferase, and RaxABC, a Putative Type I Secretion System, in Activation of the Rice XA21-Mediated Immune Response

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    Pamela C. Ronald


    Full Text Available Tyrosine sulfation is an important posttranslational modification that determines the outcome of serious diseases in plants and animals. We have recently demonstrated that the plant pathogen Xanthomonas oryzae pv. oryzae (Xoo carries a functional sulfotransferase (RaxST. raxST is required for activation of rice Xa21-mediated immunity indicating the critical, but unknown, function of raxST in mediating the Xoo/rice interaction. The raxST gene resides in the same operon (raxSTAB as components of a predicted type I secretion and processing system (RaxA and RaxB. These observations suggest a model where RaxST sulfates a molecule that contains a leader peptide, which is cleaved by the peptidase domain of the RaxB protein and secreted outside the bacterial cell by the RaxABC T1SS.

  3. Application of Molecular Modeling to Development of New Factor Xa Inhibitors

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    Vladimir B. Sulimov


    Full Text Available In consequence of the key role of factor Xa in the clotting cascade and absence of its activity in the processes that do not affect coagulation, this protein is an attractive target for development of new blood coagulation inhibitors. Factor Xa is more effective and convenient target for creation of anticoagulants than thrombin, inhibition of which may cause some side effects. This study is aimed at finding new inhibitors of factor Xa by molecular computer modeling including docking SOL and postdocking optimization DISCORE programs. After validation of molecular modeling methods on well-known factor Xa inhibitors the virtual screening of NCI Diversity and Voronezh State University databases of ready-made low molecular weight species has been carried out. Seventeen compounds selected on the basis of modeling results have been tested experimentally in vitro. It has been found that 12 of them showed activity against factor Xa (IC50 = 1.8–40 μM. Based on analysis of the results, the new original compound was synthesized and experimentally verified. It shows activity against factor Xa with IC50 value of 0.7 μM.

  4. Phenyltriazolinones as potent factor Xa inhibitors. (United States)

    Quan, Mimi L; Pinto, Donald J P; Rossi, Karen A; Sheriff, Steven; Alexander, Richard S; Amparo, Eugene; Kish, Kevin; Knabb, Robert M; Luettgen, Joseph M; Morin, Paul; Smallwood, Angela; Woerner, Francis J; Wexler, Ruth R


    We have discovered that phenyltriazolinone is a novel and potent P1 moiety for coagulation factor Xa. X-ray structures of the inhibitors with a phenyltriazolinone in the P1 position revealed that the side chain of Asp189 has reoriented resulting in a novel S1 binding pocket which is larger in size to accommodate the phenyltriazolinone P1 substrate.

  5. Mox: a novel modifier of the tomato Xa locus. (United States)

    Peterson, P W; Yoder, J I


    We have isolated a novel mutation that caused variegated leaf color in a tomato plant which had multiple maize Ac transposable elements and the tomato Xa allele. Xa is a previously characterized semi-dominant mutation that causes tomato leaves to be bright yellow when heterozygous (Xa/xa+). The mutation responsible for the new phenotype was named Mox (Modifier of Xa). The Mox mutation modified the Xa/xa+ yellow leaf phenotype in two ways: it compensated for the Xa allele resulting in a plant with a wildtype green color, and it caused somatic variegation which appeared as white and yellow sectors on the green background. Somatic variegation was visible only if the plant contained both the Mox and Xa loci. Genetic studies indicated that the Mox locus was linked in repulsion to Xa and that the Mox locus was genetically transmitted at a reduced frequency through the male gamete. Molecular characterization of the Ac elements in lines segregating for Mox identified an Ac insertion that appeared to cosegregate with Mox variegation. We propose a model in which the Mox mutation consists of a duplication of the xa+ allele and subsequent Ac-induced breakage of the duplicated region causes variegation.

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

    NARCIS (Netherlands)

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


    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

  7. The new factor Xa inhibitor: Apixaban

    Directory of Open Access Journals (Sweden)

    Sangeeta Bhanwra


    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. 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.

  9. Comparative nutritional compositions and proteomics analysis of transgenic Xa21 rice seeds compared to conventional rice. (United States)

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


    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.

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


    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.

  11. 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

  12. Theoretical Study of Molecular Structure and Physicochemical Properties of Novel Factor Xa Inhibitors and Dual Factor Xa and Factor IIa Inhibitors

    Directory of Open Access Journals (Sweden)

    Milan Remko


    Full Text Available The geometries and energies of factor Xa inhibitors edoxaban, eribaxaban, fidexaban, darexaban, letaxaban, and the dual factor Xa and thrombin inhibitors tanogitran and SAR107375 in both the gas-phase and aqueous solution were studied using the Becke3LYP/6-31++G(d,p or Grimme’s B97D/6-31++G(d,p method. The fully optimized conformers of these anticoagulants show a characteristic l-shape structure, and the water had a remarkable effect on the equilibrium geometry. According to the calculated pKa values eribaxaban and letaxaban are in neutral undissociated form at pH 7.4, while fidexaban and tanogitran exist as zwitterionic structures. The lipophilicity of the inhibitors studied lies within a large range of log P between 1 and 4. The dual inhibitor SAR107375 represents an improvement in structural, physicochemical and pharmacokinetic characteristics over tanogitran. At blood pH, SAR107375 predominantly exists in neutral form. In contrast with tanogitran, it is better absorbed and more lipophilic and active after oral application.

  13. Conformational analysis of XA and AX dipeptides in water by electronic circular dichroism and 1H NMR spectroscopy. (United States)

    Hagarman, Andrew; Measey, Thomas; Doddasomayajula, Ravi S; Dragomir, Isabelle; Eker, Fatma; Griebenow, Kai; Schweitzer-Stenner, Reinhard


    We measured the temperature-dependent electronic circular dichroism (ECD) spectra of AX, XA, and XG dipeptides in D2O. The spectra of all XA and AX peptides indicate a substantial population of the polyproline II (PPII) conformation, while the ECD spectra of LG, KG, PG, and AG were found to be quantitatively different from the alanine-based dipeptides. Additional UV absorption data indicate that the ECD spectra of the XG peptides stem from electronic coupling between the peptide and the C-terminal group, and that spectral differences reflect different orientations of the latter. We also measured the 1H NMR spectra of the investigated dipeptides to determine the 3JHalphaNH coupling constants for the C-terminal residue. The observed temperature dependence of the ECD spectra and the respective room-temperature 3JHalphaNH coupling constants were analyzed by a two-state model encompassing PPII and a beta-like conformation. The PPII propensity of alanine in the XA series is only slightly modulated by the N-terminal side chain, and is larger than 50%. As compared to AA, XA peptides containing L, P, S, K V, E, T, and I all cause a relative stabilization of the extended beta-strand conformation. The PPII fractions of XA peptides varied between 0.64 for AA and 0.58 for DA, whereas the PPII fractions of AX peptides were much lower. From the investigated AX peptides, only AL and AQ showed the expected PPII propensity. We found that AT, AI, and AV clearly prefer an extended beta-strand conformation. A quantitative comparison of AA, AAA, and AAAA revealed a hierarchy AAAA > AAA approximately AA for the PPII population, in agreement with predictions from MD calculations and results from Raman optical activity studies (McColl et al. J. Am. Chem. Soc. 2004, 126, 5076).

  14. 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


    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.

  15. Structure-based design of novel guanidine/benzamidine mimics: potent and orally bioavailable factor Xa inhibitors as novel anticoagulants. (United States)

    Lam, Patrick Y S; Clark, Charles G; Li, Renhua; Pinto, Donald J P; Orwat, Michael J; Galemmo, Robert A; Fevig, John M; Teleha, Christopher A; Alexander, Richard S; Smallwood, Angela M; Rossi, Karen A; Wright, Matthew R; Bai, Stephen A; He, Kan; Luettgen, Joseph M; Wong, Pancras C; Knabb, Robert M; Wexler, Ruth R


    As part of an ongoing effort to prepare orally active factor Xa inhibitors using structure-based drug design techniques and molecular recognition principles, a systematic study has been performed on the pharmacokinetic profile resulting from replacing the benzamidine in the P1 position with less basic benzamidine mimics or neutral residues. It is demonstrated that lowering the pK(a) of the P1 ligand resulted in compounds (3-benzylamine, 15a; 1-aminoisoquinoline, 24a; 3-aminobenzisoxazole, 23a; 3-phenylcarboxamide, 22b; and 4-methoxyphenyl, 22a) with improved pharmacokinetic features mainly as a result of decreased clearance, increased volume of distribution, and enhanced oral absorption. This work resulted in a series of potent and orally bioavailable factor Xa inhibitors that ultimately led to the discovery of SQ311, 24a. SQ311, which utilizes a 1-aminoisoquinoline as the P1 ligand, inhibits factor Xa with a K(i) of 0.33 nM and demonstrates both good in vivo antithrombotic efficacy and oral bioavailability.

  16. Anti-Factor V inhibitor in patients with autoimmune diseases: case report and literature review

    Directory of Open Access Journals (Sweden)

    Imashuku S


    Full Text Available Shinsaku Imashuku1, Takeshi Hasegawa2, Kagekatsu Kubo2, Masaki Nakato2, Midori Shima31Division of Pediatrics and Hematology, 2Division of Internal Medicine, Takasago-Seibu Hospital, Takasago, Hyogo; 3Department of Pediatrics, Nara Medical University, Kashihara, Nara, JapanAbstract: Acquired anti-Factor V deficiency caused by inhibitor production is a rare coagulation disorder. Although this is a well known entity in the literature, choice of optimal treatment for an individual patient is difficult, given that no standard therapeutic measures are available because of rare incidence and various underlying diseases occurring in the elderly. An 88 year-old man treated for Hashimoto's disease was found to exhibit prolongation of both prothrombin time and activated partial thromboplastin time. Detailed study of coagulation factors revealed a deficiency of Factor V. Our patient's coagulation disorder resolved in two weeks with intravenous administration of prednisolone 20 mg/day. Clinical features of autoimmune disease-related Factor V deficiency are discussed, along with eight previously reported cases over the past 20 years.Keywords: anti-Factor V inhibitor, Hashimoto's thyroiditis, autoimmune disease

  17. Mutation of the rice XA21 predicted nuclear localization sequence does not affect resistance to Xanthomonas oryzae pv. oryzae (United States)

    Ho, Yuen Ting


    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.

  18. 关于算子方程AX=XAX与AX=XA=XAX%On the Operator Equations AX=XAX and AX=XA=XAX

    Institute of Scientific and Technical Information of China (English)

    安桂梅; 白朝芳; 杜拴平


    用A的不变子空间作参数,给出了算子方程AX=XAX的全部解. 当A是单射或稠值域时,或者当A是正规算子时,给出了算子方程AX=XA=XAX的全部解. 我们还给出正规算子X是算子方程AX=XZ=XAX的解的充分必要条件.%In this paper, we give the representation of the solution set of the operator equation AX=XAX in terms of the invariant subspaces of A and the representation of solution set of AX=XA=XAX in the cases that A is a normal operator or an operator with dense range or with injectivity. We also give a sufficient and necessary condition for a normal operator X to be a solution of equation XAX=XA=XA.

  19. Investigating the enteroenteric recirculation of apixaban, a factor Xa inhibitor: administration of activated charcoal to bile duct-cannulated rats and dogs receiving an intravenous dose and use of drug transporter knockout rats. (United States)

    Zhang, Donglu; Frost, Charles E; He, Kan; Rodrigues, A David; Wang, Xiaoli; Wang, Lifei; Goosen, Theunis C; Humphreys, W Griffith


    The study described here investigated the impact of intestinal excretion (IE; excretion of drug directly from circulation to intestinal lumen), enteroenteric recirculation (EER), and renal tubule recirculation (RTR) on apixaban pharmacokinetics and disposition. The experimental approaches involve integrating apixaban elimination pathways with pharmacokinetic profiles obtained from bile duct-cannulated (BDC) rats and dogs receiving i.v. doses together with oral administration of activated charcoal (AC). Additionally, the role of P-gp (P-glycoprotein; abcb1) and BCRP (breast cancer resistance protein; abcg2) in apixaban disposition was evaluated in experiments using transporter inhibitors and transporter knockout (KO) rats. Approximately 20-50% of an apixaban i.v. dose was found in feces of BDC rats and dogs, suggesting IE leading to fecal elimination and intestinal clearance (IC). The fecal elimination, IC, and systemic clearance of apixaban were increased upon AC administration in both BDC rats and dogs and were decreased in BDC rats dosed with GF-120918, a dual BCRP and P-gp inhibitor). BCRP appeared to play a more important role for absorption and intestinal and renal elimination of apixaban than P-gp in transporter-KO rats after oral and i.v. dosing, which led to a higher level of active renal excretion in rat than other species. These data demonstrate that apixaban undergoes IE, EER, and RTR that are facilitated by efflux transporters. Intestinal reabsorption of apixaban could be interrupted by AC even at 3 hours post-drug dose in dogs (late charcoal effect). This study demonstrates that the intestine is an organ for direct clearance and redistribution of apixaban. The IE, EER, and RTR contribute to overall pharmacokinetic profiles of apixaban. IE as a clearance pathway, balanced with metabolism and renal excretion, helps decrease the impacts of intrinsic (renal or hepatic impairment) and extrinsic (drug-drug interactions) factors on apixaban disposition.

  20. 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))


    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.

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

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


    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.

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

    Lifescience Database Archive (English)



    Institute of Scientific and Technical Information of China (English)

    Laiyi Zhu; Zhiyong Huang


    We study the optimal order of approximation for |x|a (0 < a < 1) by Lagrange interpolation polynomials based on Chebyshev nodes of the first kind. It is proved that the Jackson order of approximation is attained.

  4. 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)


    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.

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

    Directory of Open Access Journals (Sweden)

    Sarah Yentz


    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.

  6. Protein-Templated Formation of an Inhibitor of the Blood Coagulation Factor Xa through a Background-Free Amidation Reaction. (United States)

    Jaegle, Mike; Steinmetzer, Torsten; Rademann, Jörg


    Protein-templated reactions enable the target-guided formation of protein ligands from reactive fragments, ideally with no background reaction. Herein, we investigate the templated formation of amides. A nucleophilic fragment that binds to the coagulation factor Xa was incubated with the protein and thirteen differentially activated dipeptides. The protein induced a non-catalytic templated reaction for the phenyl and trifluoroethyl esters; the latter was shown to be a completely background-free reaction. Starting from two fragments with millimolar affinity, a 29 nm superadditive inhibitor of factor Xa was obtained. The fragment ligation reaction was detected with high sensitivity by an enzyme activity assay and by mass spectrometry. The reaction progress and autoinhibition of the templated reaction by the formed ligation product were determined, and the structure of the protein-inhibitor complex was elucidated.

  7. Characterization and molecular marker screening of a rice bacteria-resistant gene Xa-min(t)

    Institute of Scientific and Technical Information of China (English)

    CHEN Yan; HU Jun; QIAN Wei; TIAN Yingchuan; HE Chaozu


    To test the resistant spectrum of the Xa-min(t) gene introgressed from Oryza minuta, thirty-four isolates of different bacterial blight pathogen, Xanthomonas oryzae pv. oryzae (Xoo), from 11 countries were used to inoculate the Xa-min(t) introgression line 78-15. Four rice cultivars, IR24, C64 (IRBB21), Nipponbare and Zhonghua 11 were used as controls. The results showed that the Xa-min(t) gene was broad-spectrum and highly resistant to diverse Xoo isolates. The methods of bulk segregant analysis (BSA), randomly amplified polymorphic DNA (RAPD) and sequence characterized amplified regions (SCAR) were used to analyze F2 individuals of the hybrid IR24×78-15 and molecular genetic markers linked to Xa-min(t) gene were identified. A total of 800 arbitrary decamer oligonucleotide primers were used for RAPD analysis. Two RAPD markers, BE05300 and BE061400, produced by primers BE05 and BE06 respectively, were closely linked to the Xa-min(t) gene. Based on the sequences of these two markers, sequence specific primers were designed and used to screen all F2 plants. One RAPD marker, BE05300, was converted into a stable SCAR marker (ScBE05300). Linkage analysis was carried out using markers ScBE05300 and BE061400 on 948 and 719 F2 individuals of the hybrid IR24×78-15. Our results indicate that the genetic distances from Xa-min(t) to ScBE05300 and BE061400 are 2.2 cM and 3.7 cM respectively on the same side. This study may facilitate the construction of the fine physical map of the Xa-min(t) gene.

  8. The tick-derived anticoagulant madanin is processed by thrombin and factor Xa.

    Directory of Open Access Journals (Sweden)

    Ana C Figueiredo

    Full Text Available The cysteine-less peptidic anticoagulants madanin-1 and madanin-2 from the bush tick Haemaphysalis longicornis are the founding members of the MEROPS inhibitor family I53. It has been previously suggested that madanins exert their functional activity by competing with physiological substrates for binding to the positively charged exosite I (fibrinogen-binding exosite of α-thrombin. We hereby demonstrate that competitive inhibition of α-thrombin by madanin-1 or madanin-2 involves binding to the enzyme's active site. Moreover, the blood coagulation factors IIa and Xa are shown to hydrolyze both inhibitors at different, although partially overlapping cleavage sites. Finally, the three-dimensional structure of the complex formed between human α-thrombin and a proteolytic fragment of madanin-1, determined by X-ray crystallography, elucidates the molecular details of madanin-1 recognition and processing by the proteinase. Taken together, the current findings establish the mechanism of action of madanins, natural anticoagulants that behave as cleavable competitive inhibitors of thrombin.

  9. 3D/3D registration of coronary CTA and biplane XA reconstructions for improved image guidance

    Energy Technology Data Exchange (ETDEWEB)

    Dibildox, Gerardo, E-mail:; 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)


    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.

  10. XA readout chip characteristics and CdZnTe spectral measurements

    Energy Technology Data Exchange (ETDEWEB)

    Barbier, L.M.; Birsa, F.; Odom, J. [NASA/Goddard Space Flight Center, Greenbelt, MD (United States)] [and others


    The authors report on the performance of a CdZnTe (CZT) array readout by an XA (X-ray imaging chip produced at the AMS foundry) application specific readout chip (ASIC). The array was designed and fabricated at NASA/Goddard Space Flight Center (GSFC) as a prototype for the Burst Arc-Second Imaging and Spectroscopy gamma-ray instrument. The XA ASIC was obtained from Integrated Detector and Electronics (IDE), in Norway. Performance characteristics and spectral data for {sup 241}Am are presented both at room temperature and at {minus}20 C. The measured noise ({sigma}) was 2.5 keV at 60 keV at room temperature. This paper represents a progress report on work with the XA ASIC and CZT detectors. Work is continuing and in particular, larger arrays are planned for future NASA missions.

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

    Directory of Open Access Journals (Sweden)

    Ali Zalpour


    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.

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

    Directory of Open Access Journals (Sweden)

    Gerald Bourgeois


    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.

  13. In vitro characterization of a novel factor Xa inhibitor, RPR 130737. (United States)

    Chu, V; Brown, K; Colussi, D; Choi, Y M; Green, D; Pauls, H W; Spada, A P; Perrone, M H; Leadley, R J; Dunwiddie, C T


    RPR 130737 inhibited factor Xa (FXa) with a Ki of 2.4 nM and also displayed excellent specificity toward FXa relative to other serine proteases. It showed selectivity of more than 1000-fold over thrombin, activated protein C, plasmin, tissue-plasminogen activator and trypsin. RPR 130737 prolonged plasma activated partial thromboplastin time and prothrombin time in a dose-dependent fashion. In the activated partial thromboplastin time assay, the concentrations required for doubling coagulation time were 0.32 microM (human), 0.61 microM (monkey), 0.44 microM (dog), 0.15 microM (rabbit), and 0.82 microM (rat). The concentrations required to double prothrombin time were 0.86 microM (human), and 1.26 microM (monkey), 1.15 microM (dog), 0.39 microM (rabbit) and 7.31 microM (rat). Kinetic studies revealed that RPR 130737 was a fast binding, reversible and competitive inhibitor for FXa when Spectrozyme FXa, a chromogenic substrate, was used. A coupled-enzyme assay measuring thrombin activity following prothrombinase conversion of prothrombin to thrombin indicated that RPR 130737 was a potent inhibitor for prothrombinase-bound FXa. In this assay, RPR 130737 showed IC50s of 17 nM and 35.9 nM, respectively when artificial phosphatidylserine/phosphatidylcholine (PS/PC) liposomes or gel-filtered platelets were used as the phospholipid source. An FX-deficient plasma clotting-time correction assay further demonstrated that RPR 130737 was a specific inhibitor of FXa. RPR 130737 showed no effect on platelet aggregation in vitro. These results indicate that RPR 130737 has the potential to be developed as an antithrombotic agent based on its potent and selective inhibitory effect against FXa.

  14. 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


    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.

  15. Characterization and expression analysis of two cDNAs encoding Xa1 and oxysterol binding proteins in sorghum (Sorghum bicolor) (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 ...

  16. 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)


    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.

  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)

    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


    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.

  18. Data of evolutionary structure change: 1DTGA-1B1XA [Confc[Archive

    Lifescience Database Archive (English)


  19. 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

  20. 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)



    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.

  1. Coagulation-induced shedding of platelet glycoprotein VI mediated by factor Xa. (United States)

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


    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.

  2. Applying Retrospective Demographic Models to Assess Sustainable Use: the Maya Management of Xa'an Palms

    Directory of Open Access Journals (Sweden)

    Andrea Martínez-Ballesté


    Full Text Available Xa'an palm (Sabal yapa has been used to thatch traditional Maya houses for over 3000 years. In the Yucatan Peninsula, this palm has been introduced to pasturelands, maize fields (milpas, and homegardens. These and other traditional management systems are usually believed to be sustainable, but there is as yet little evidence to support this hypothesis. Demographic models have been used for this purpose, mainly focusing on population growth rate (λ. So far, retrospective analysis has not been applied, even though it examines how changes in the the life cycle of a species, caused by different management regimes, affect its λ. In this study, we assess whether ecologically sustainable use of xa'an occurs in homegardens, pasturelands, and milpas, and if so, how it is achieved. We constructed matrix population models for four populations of xa'an that were followed for 3 years, and then conducted a retrospective analysis on them. Management in homegardens seems to be oriented to increasing the availability of xa'an leaves, favoring the survival of seedlings, and increasing the density of harvestable-sized palms. However, in the milpa and the pastureland, the population size structure resembles that of unmanaged populations. Our λ values suggest that the traditional use of xa'an in all the studied management regimes is sustainable. Nevertheless, the processes that lead to sustainable use are different in each system, as shown by our retrospective analysis. Although fecundity contributes positively to λ only in homegardens, permanence and growth maintain palm populations at an equilibrium in the pastureland and in the milpa, respectively. Between-year climatic differences had a smaller impact on λ than management practices, which may vary from one year to another, leading to different balances in the sustainable use of the populations involved. Even though no significant differences were found in λ values, Maya achieve sustainable use of xa

  3. SAR and X-ray Structures of Enantiopure 1,2-cis-(1R,2S)-cyclopentyldiamine and Cyclohexyldiamine Derivativies as Inhibitors of Coagulation Factor Xa

    Energy Technology Data Exchange (ETDEWEB)

    Qiao,J.; Chang, C.; Cheney, D.; Morin, D.; Wang, P.; King, G.; Wang, S.; Rendina, T.; Luettgen, A.; et al.


    In the search of Factor Xa (FXa) inhibitors structurally different from the pyrazole-based series, we identified a viable series of enantiopure cis-(1R,2S)-cycloalkyldiamine derivatives as potent and selective inhibitors of FXa. Among them, cyclohexyldiamide 7 and cyclopentyldiamide 9 were the most potent neutral compounds, and had good anticoagulant activity comparable to the pyrazole-based analogs. Crystal structures of 7-FXa and 9-FXa illustrate binding similarities and differences between the five- and the six-membered core systems, and provide rationales for the observed SAR of P1 and linker moieties.

  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


    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


    Institute of Scientific and Technical Information of China (English)




  6. 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)


    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.

  7. 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


    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.

  8. 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


    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.

  9. Assessment of apixaban plasma levels by laboratory tests: suitability of three anti-Xa assays. A multicentre French GEHT study. (United States)

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


    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.

  10. 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


    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.

  11. 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


    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.

  12. Investigation of the terminal P4 domain in a series of D-phenylglycinamide-based factor Xa inhibitors. (United States)

    Franciskovich, Jeffry B; Masters, John J; Weber, Wayne W; Klimkowski, Valentine J; Chouinard, Michael; Sipes, Philip R; Johnson, Lea M; Snyder, David W; Chastain, Marcia K; Craft, Trelia J; Towner, Richard D; Gifford-Moore, Donetta S; Froelich, Larry L; Smallwood, Jeffrey K; Foster, Ronald S; Smith, Gerald F; Liebeschuetz, John W; Murray, Christopher W; Young, Stephen C


    Several P4 domain derivatives of the general d-phenylglycinamide-based scaffold (2) were synthesized and evaluated for their ability to bind to the serine protease factor Xa. Some of the more potent compounds were evaluated for their anticoagulant effects in vitro. A select subset containing various P1 indole constructs was further evaluated for their pharmacokinetic properties after oral administration to rats.

  13. XaNSoNS: GPU-accelerated simulator of diffraction patterns of nanoparticles (United States)

    Neverov, V. S.

    XaNSoNS is an open source software with GPU support, which simulates X-ray and neutron 1D (or 2D) diffraction patterns and pair-distribution functions (PDF) for amorphous or crystalline nanoparticles (up to ∼107 atoms) of heterogeneous structural content. Among the multiple parameters of the structure the user may specify atomic displacements, site occupancies, molecular displacements and molecular rotations. The software uses general equations nonspecific to crystalline structures to calculate the scattering intensity. It supports four major standards of parallel computing: MPI, OpenMP, Nvidia CUDA and OpenCL, enabling it to run on various architectures, from CPU-based HPCs to consumer-level GPUs.

  14. Survey of the anti-factor IX immunoglobulin profiles in patients with hemophilia B using a fluorescence-based immunoassay. (United States)

    Boylan, B; Rice, A S; Neff, A T; Manco-Johnson, M J; Kempton, C L; Miller, C H


    Essentials Studies characterizing neutralizing antibodies (inhibitors) in hemophilia B (HB) are lacking. The current study describes anti-factor (F) IX antibody profiles in 37 patients who have HB. Anti-FIX IgG4 levels exhibited a strong positive correlation with Nijmegen-Bethesda results. These data will help to more clearly define, predict, and treat alloantibody formation in HB.

  15. Biodegradation of Phenol by Using Immobilized Cells of Acinetobacter sp. XA05 and Sphingomonas sp. FG03%固定化Acinetobacter sp. XA05和Sphingomonas sp. FG03降解苯酚

    Institute of Scientific and Technical Information of China (English)

    李华; 刘永军; 刘金光


    从活性污泥和受苯酚污染的土壤中分离出的菌株XA05和FG03均具有很强的苯酚生物降解能力.16s rDNA序列分析表明,XA05和FG03菌株分别属于不动杆菌属(Acinetobacter sp.)和鞘氨醇单胞菌属(Sphingomonas sp.).实验结果表明,在苯酚初始质量浓度为800.0 mg/L、培养时间为35 h的条件下,自由悬浮细胞和固定化细胞的苯酚降解率均高于95.0%.

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


    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

  17. 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


    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...

  18. The Factor of Structure and Mechanical Properties in the Production of Critical Fixing Hardware 38XA

    Directory of Open Access Journals (Sweden)

    G.V. Pachurin


    Full Text Available Fixing hardware made of carbon, high-carbon, and alloyed wires is one of the widespread critical parts in mechanical engineering. The characteristics of fixtures and fasteners and their performance figures are assessed at all stages of steel-making operation, from the choice of burden stock for metal smelting to the method of preparing calibrated rolled metal parts and upsetting end products. Material used for producing long high-duty bolts must be both sufficiently strong and ductile, have homogeneous mechanical properties and chemistry, and no inner or surface defects. When manufacturing fasteners, hot-rolled metal is often plastically deformed by drafting before cold upsetting, and all unacceptable defects are removed by the expensive procedure of lathe-turning. Moreover, this technology of metal processing entails losses of up to 5.5 % in chips. This paper suggests a resource-efficient and environmentally friendlier fabrication method for calibrated rolled metal items made of steel 38XA, 9.65 mm diameter, for cold die-forging of high-duty bolts used in automotive engines, which helps spare expensive lathe-machining processes. Moreover, rolled steel produced using this technology is characterized by high resistance to plastic deformation when cold, which leads to increase n wear-resistance of tools in cold die-forging of bolts.

  19. 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


    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.

  20. 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)


    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.

  1. Discovery of 1-(4-Methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-4,5,6,7-tetrahydro- 1H-pyrazolo[3,4-c]pyridine-3-carboxamide (Apixaban, BMS-562247), a Highly Potent, Selective, Efficacious, and Orally Bioavailable Inhibitor of Blood Coagulation Factor Xa

    Energy Technology Data Exchange (ETDEWEB)

    Pinto, Donald J.P.; Orwat, Michael J.; Koch, Stephanie; Rossi, Karen A.; Alexander, Richard S.; Smallwood, Angela; Wong, Pancras C.; Rendina, Alan R.; Luettgen, Joseph M.; Knabb, Robert M.; He, Kan; Xin, Baomin; Wexler, Ruth R.; Lam, Patrick Y.S. (BMS)


    Efforts to identify a suitable follow-on compound to razaxaban (compound 4) focused on modification of the carboxamido linker to eliminate potential in vivo hydrolysis to a primary aniline. Cyclization of the carboxamido linker to the novel bicyclic tetrahydropyrazolopyridinone scaffold retained the potent fXa binding activity. Exceptional potency of the series prompted an investigation of the neutral P{sub 1} moieties that resulted in the identification of the p-methoxyphenyl P{sub 1}, which retained factor Xa binding affinity and good oral bioavailability. Further optimization of the C-3 pyrazole position and replacement of the terminal P{sub 4} ring with a neutral heterocycle culminated in the discovery of 1-(4-methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide (apixaban, compound 40). Compound 40 exhibits a high degree of fXa potency, selectivity, and efficacy and has an improved pharmacokinetic profile relative to 4.

  2. 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)



    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.

  3. ABB 800 xA 在水泥生产线原料磨车间中的应用%ABB 800 xA System in Raw Mill Plant of Cement Production Line

    Institute of Scientific and Technical Information of China (English)

    黄华潘; 周廷美; 莫易敏; 郑双


    针对某公司一条水泥生产线的控制需求,介绍了ABB 800xA系统在水泥原料磨生产线中的应用。在ABB 800xA系统的Control Builder M软件中进行编程,采用FBD功能块语言,在集成环境下进行硬件、软件和网络的组态。以ABB AC800M为主控制器,并在Graphic Builder软件中进行生产线画面的绘制。整个水泥生产线原料磨控制系统已经通过业主公司的FAT验证,实现了水泥原料磨生产线的全自动控制。%Aiming at control requirements in a cement production line , the ABB 800xA system applied in cement raw mill production line was introduced .Programming was realized by software of Control Builder M in ABB 800xA systems using FBD function block language .The hardware , software and networks were configured in an integrated environment .And the flow line was drawn in the software of Graphic Builder .The whole raw mill control system of cement production line was verified by the in -vestor company's FAT.The fully automatic control was achieved in raw mill cement production line .

  4. 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)


    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.

  5. X-ray structure of antistasin at 1.9 angstrom resolution and its modelled complex with blood coagulation factor Xa

    NARCIS (Netherlands)

    Lapatto, R; Krengel, U; Schreuder, HA; Arkema, A; deBoer, B; Kalk, KH; Hol, WGJ; Grootenhuis, PDJ; Mulders, JWM; Dijkema, R; Theunissen, HJM; Dijkstra, BW


    The three-dimensional structure of antistasin, a potent inhibitor of blood coagulation factor Xa, from the Mexican leech Haementeria officinalis was determined at 1.9 Angstrom resolution by X-ray crystallography, The structure reveals a novel protein fold composed of two homologous domains, each res

  6. Cloning and Genetic Transformation of the Candidate Genes for the Bacterial Blight Resistance Gene Xa31(t)in Rice%水稻白叶枯病抗性基因Xa31(t候选基因的克隆及遗传转化

    Institute of Scientific and Technical Information of China (English)

    杨青; 王春台; 刘学群; 谭艳平


    To construct the expression vector with the candidate genes of bacteria blight disease resistance gene Xa31(t) in rice, and to make the genetic transformation, the candidate genes Xa3l(t)-1 and Xa31(t)-2 of rice bacterial blight resistance gene Xa31(t) were obtained through the method of long segments PCR with the resistant variety 'Zachanglong' (ZCL) genomic DNA as the template. Then the target genes were cloned to the T-vector with the way of restriction endonuclease reaction and enzyme ligation reaction. After screening the positive clones and sequencing, the target genes were cloned to the expression vector of pCMABIA1300. Finally, the recombinant plasmids were transformed into the callus of the susceptible varieties ' Nipponbare' and 'Taibei309' respectively by agrobacterium-mediated approach and a lot of transformed rice seedlings were obtained. These work laid the foundation for cloning the bacterial blight resistance gene Xa31(t) and studied its function.%为了构建水稻白叶枯病抗性基因Xa31(t)候选基因的植物表达载体并对其进行遗传转化,以水稻白叶枯病抗性品种‘扎昌龙’(ZCL)的基因组DNA为模板,通过长片段PCR扩增得到水稻白叶枯病抗性基因Xa31(t)候选基因Xa31(t)-1和Xa31(t)-2的序列,采用酶切、连接的方法先将目的基因克隆至T载体,筛选正确的质粒后,再克隆至pCMABIA1300表达载体.以农杆菌介导法将构建好的重组质粒转入‘日本睛’和‘台北309’的愈伤后诱导成苗,获得了大量转基因植株,这些工作为克隆白叶枯病抗性基因并研究其功能奠定了基础.

  7. On the Equation $x^{2^l+1}+x+a=0$ over $\\mathrm{GF}(2^k)$ (Extended Version)

    CERN Document Server

    Helleseth, Tor


    In this paper, the polynomials $P_a(x)=x^{2^l+1}+x+a$ with $a\\in\\mathrm{GF}(2^k)$ are studied. New criteria for the number of zeros of $P_a(x)$ in $\\mathrm{GF}(2^k)$ are proved. In particular, a criterion for $P_a(x)$ to have exactly one zero in $\\mathrm{GF}(2^k)$ when $\\gcd(l,k)=1$ is formulated in terms of the values of permutation polynomials introduced by Dobbertin. We also study the affine polynomial $a^{2^l}x^{2^{2l}}+x^{2^l}+ax+1$ which is closely related to $P_a(x)$. In many cases, explicit expressions for calculating zeros of these polynomials are provided.

  8. On the Equation $x^{2^l+1}+x+a=0$ over $\\mathrm{GF}(2^k)$ (Extended Version)


    Helleseth, Tor; Kholosha, Alexander


    In this paper, the polynomials $P_a(x)=x^{2^l+1}+x+a$ with $a\\in\\mathrm{GF}(2^k)$ are studied. New criteria for the number of zeros of $P_a(x)$ in $\\mathrm{GF}(2^k)$ are proved. In particular, a criterion for $P_a(x)$ to have exactly one zero in $\\mathrm{GF}(2^k)$ when $\\gcd(l,k)=1$ is formulated in terms of the values of permutation polynomials introduced by Dobbertin. We also study the affine polynomial $a^{2^l}x^{2^{2l}}+x^{2^l}+ax+1$ which is closely related to $P_a(x)$. In many cases, ex...

  9. Factor Xa induces tissue factor expression in endothelial cells by P44/42 MAPK and NF-κB-dependent pathways (United States)

    Jiang, Rong; Wang, Ning-Ping; Tanaka, Kenichi A.; Levy, Jerrold H.; Guyton, Robert A.; Zhao, Zhi-Qing; Vinten-Johansen, Jakob


    Summary Background Tissue factor (TF) is an initiator of coagulation. The serine protease factor Xa (FXa) is the convergence point of the extrinsic and intrinsic components of the coagulation cascade. In addition to its hemostatic function, FXa elicits inflammatory responses in endothelial cells that may be important in surgical procedures in which inflammation is triggered. This study tested the hypothesis that FXa can upregulate TF on vascular endothelial cells by a MAPK- and NF-κB- dependent pathway. Methods and results Incubation of cultured human umbilical vein endothelial cells (HUVECs) with FXa increased TF protein expression and activity in a dose–dependent manner. Pre-incubation of HUVECs with the serine protease inhibitor antithrombin, which targets not only thrombin but also FXa and FIXa, inhibited FXa-induced TF expression, but the selective thrombin inhibitor hirudin did not inhibit FXa-induced TF expression, ruling out a thrombin-mediated pathway. After 10 min incubation with HUVECs, FXa rapidly induced P44/42 MAPK activation (immunoblotting of phosphorylated P44/42 MAPK) with a peak at 30 minutes. The MEK 1/2 inhibitor PD98059 partially reduced FXa-induced TF expression and activity (3.82±0.11 vs 6.54±0.08 fmol/min/cm2, P<0.05). NF-κB was activated by FXa, confirmed by cytoplasmic IkB α degradation and increased NF-κB P65 nuclear translocation. Interruption of the NF-κB pathway by the IkB α phosphorylation inhibitor Bay 11-7802 abrogated FXa-induced TF protein expression and activity (1.93± 0.02 vs 6.54±0.08 fmol/min/cm2, P<0.05). However, inhibition of PI3 kinase by LY 294002 did not attenuate FXa-induced TF protein expression and activity. Conclusions 1) FXa upregulates TF protein expression and activity in HUVECs 2) FXa-induced upregulation of TF is independent of the thrombin-PAR1 pathway, and 3) the MAPK and NF-kB pathways, but not PI3 kinase pathway, are involved in FXa-induced TF expression on human umbilical endothelial cells. FXa

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


    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.

  11. 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


    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.

  12. 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


    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.

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

    Directory of Open Access Journals (Sweden)

    Pavlović Svetlana


    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

  14. Influence of red algal sulfated polysaccharides on blood coagulation and platelets activation in vitro. (United States)

    Sokolova, Ekaterina V; Byankina, Anna O; Kalitnik, Alexandra A; Kim, Yong H; Bogdanovich, Larisa N; Solov'eva, Tamara F; Yermak, Irina M


    The influence of sulfated polysaccharides (λ-, κ-, and κ/β-carrageenan and porphyran) - on platelet activation was studied. Carrageenans were much weaker inhibitors of a coagulation process than heparin, while porphyran had not that effect. Results of the aPTT and PT assays suppose that carrageenans affected mostly intrinsic pathway of coagulation, while their effect on the extrinsic pathway is extremely low (λ and κ/β) or absent (κ, LMW derivative of κ-carrageenan). λ-Carrageenan was the most potent anticoagulant agent in TT, aPTT, PT, and anti-factor Xa activity. This sample was also the strongest inhibitor of collagen-induced platelet aggregation in PRP. Generally, the correlation of anticoagulant and antithrombotic action in PRP is preserved for carrageenans but not for heparin. Carrageenans and porphyran affected platelet adhesion to collagen by influencing glycoprotein VI. Low molecular weight κ-carrageenan had a similar effect on platelet adhesion mediated with both major collagen receptors: integrin α2 β1 and glycoprotein VI as native polysaccharide had. Carrageenans resulted in activation of platelets under platelet adhesion mediated by integrin αIIb β3 with less degree than heparin. The least sulfated κ/β-carrageenan that possessed an inhibiting effect on thrombin- and collagen-induced aggregation of washed platelets and on the PT test but it had no significant effect on TT was the weakest promoter of integrin αIIb β3 mediated platelet activation. In summary, our study showed that the polysaccharide action was complex, since it depended on its molecular mass, sulfation degree, and monosaccharide contents (3,6-anhydrogalactose).

  15. 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;


    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)....

  16. Human plasma kallikrein and tissue kallikrein binding to a substrate based on the reactive site of a factor Xa inhibitor isolated from Bauhinia ungulata seeds. (United States)

    Oliva, M L; Andrade, S A; Batista, I F; Sampaio, M U; Juliano, M; Fritz, H; Auerswald, E A; Sampaio, C A


    Kunitz type Bauhinia ungulata factor Xa inhibitor (BuXI) was purified from B. ungulata seeds. BuXI inactivates factor Xa and human plasma kallikrein (HuPK) with Ki values of 18.4 and 6.9 nM, respectively. However, Bauhinia variegata trypsin inhibitor (BvTI) which is 70% homologous to BuXI does not inhibit factor Xa and is less efficient on HuPK (Ki = 80 nM). The comparison between BuXI and BvTI reactive site structure indicates differences at Met59, Thr66 and Met67 residues. The hydrolysis rate of quenched fluorescence peptide substrates based on BuXI reactive site sequence, Abz-VMIAALPRTMFIQ-EDDnp (leading peptide), by HuPK and porcine pancreatic kallikrein (PoPK) is low, but hydrolysis is enhanced with Abz-VMIAALPRTMQ-EDDnp, derived from the leading peptide shortened by removing the dipeptide Phe-Ileu from the C-terminal portion, for HuPK (Km = 0.68 microM, k(cat)/Km = 1.3 x 10(6) M(-1) s(-1)), and the shorter substrate Abz-LPRTMQ-EDDnp is better for PoPK (Km = 0.66 microM, k(cat)/Km = 2.2 x 10(3) M(-1) s(-1)). The contribution of substrate methionine residues to HuPK and PoPK hydrolysis differs from that observed with factor Xa. The determined Km and k(cat) values suggest that the substrates interact with kallikreins the same as an enzyme and inhibitor interacts to form complexes.

  17. Microfluidic Chip-Based Online Screening Coupled to Mass Spectrometry: Identification of Inhibitors of Thrombin and Factor Xa. (United States)

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


    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.

  18. Coagulation factor Xa signaling : the link between coagulation and inflammatory bowel disease?

    NARCIS (Netherlands)

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


    Inflammatory bowel disease (IBD) is characterized by activation of the coagulation cascade and it has long been suspected that coagulation is an essential component of this still largely idiopathic group of diseases. The realization that coagulation factors are not only passive mediators in the prop

  19. Independent anti-angiogenic capacities of coagulation factors X and Xa. (United States)

    Lange, Soledad; Gonzalez, Ibeth; Pinto, Mauricio P; Arce, Maximiliano; Valenzuela, Rodrigo; Aranda, Evelyn; Elliot, Matias; Alvarez, Marjorie; Henriquez, Soledad; Velasquez, Ethel V; Orge, Felipe; Oliva, Barbara; Gonzalez, Pamela; Villalon, Manuel; Cautivo, Kelly M; Kalergis, Alexis M; Pereira, Karla; Mendoza, Camila; Saez, Claudia; Kato, Sumie; Cuello, Mauricio A; Parborell, Fernanda; Irusta, Griselda; Palma, Veronica; Allende, Miguel L; Owen, Gareth I


    Knockout models have shown that the coagulation system has a role in vascular development and angiogenesis. Herein, we report for the first time that zymogen FX and its active form (FXa) possess anti-angiogenic properties. Both the recombinant FX and FXa inhibit angiogenesis in vitro using endothelial EA.hy926 and human umbilical cord vascular endothelial cells (HUVEC). This effect is dependent on the Gla domain of FX. We demonstrate that FX and FXa use different mechanisms: the use of Rivaroxaban (RX) a specific inhibitor of FXa attenuated its anti-angiogenic properties but did not modify the anti-angiogenic effect of FX. Furthermore, only the anti-angiogenic activity of FXa is PAR-1dependent. Using in vivo models, we show that FX and FXa are anti-angiogenic in the zebrafish intersegmental vasculature (ISV) formation and in the chick embryo chorioallantoic membrane (CAM) assays. Our results provide further evidence for the non-hemostatic functions of FX and FXa and demonstrate for the first time a biological role for the zymogen FX.

  20. Construction of A Bacterial Artificial Chromosome (BAC) Contig Encompassing the Bacterial Blight Resistance Gene Xa4 Locus in Rice%水稻抗白叶枯病基因Xa4位点跨叠BAC克隆群的构建

    Institute of Scientific and Technical Information of China (English)

    江光怀; 王文明; 谢兵; 翟文学; 鲁润龙; 朱立煌


    The gene Xa4 confers dominantly resistance to rice bacterialblight, which has been finely mapped between RFLP markers G181 and L1044, and co-segregated with the resistance gene homologues sequence marker RS13. The three markers were used to screen a rice Bacterial Artificial Chromosome (BAC) library constructed from IRBB56, a Xa4-harborring indica variety, resulting in the detection of totally 128 positive clones. Of the 18 positive clones picked out by RS13, 4 and 6 clones were simultaneously detected by G181 and L1044, respectively. Based on their Hindrestriction patterns, 12 clones were selected out to construct a contig that spanned about 420 kb covering the Xa4 locus, which is a solid base for the isolation of Xa4 gene.%水稻白叶枯病抗性基因Xa4已被定位于第11染色体长臂末端的分子标记G181和L1044之间,并与抗性基因同源序列片段RS13共分离。利用这3个标记筛选IRBB56的BAC文库,共得到128个阳性BAC克隆,其中RS13获得18个阳性克隆,这18个克隆中有4个和6个克隆分别同时为G181和L1044的阳性克隆。选其中的12个克隆进行分析,构建了一个从G181到L1044区间的BAC跨叠克隆群,全长420kb,并且56M22、106P13和104B153个BAC克隆可覆盖整个跨叠克隆群。这一研究结果为进一步分离Xa4基因打下了基础。

  1. Absolute and comparative subcutaneous bioavailability of ardeparin sodium, a low molecular weight heparin. (United States)

    Troy, S; Fruncillo, R; Ozawa, T; Mammen, E; Holloway, S; Chiang, S


    Ardeparin sodium (Normiflo, Wyeth-Ayerst) is a low molecular weight heparin undergoing clinical evaluation as an antithrombotic agent. The objective of this study was to evaluate the absolute and comparative bioavailability of ardeparin following subcutaneous administration of three different formulations [two formulations of ardeparin at 10,000 anti-factor Xa (aXa) U/ml, but with different preservatives, and a 20,000 aXa U/ml formulation]. The study was conducted using a randomized 4-period crossover design (three subcutaneous treatments and one intravenous treatment) in 24 healthy subjects, and the pharmacokinetics of ardeparin were characterized by plasma anti-factor IIa (aIIa) and anti-factor Xa (aXa) activities. The mean absolute bioavailability of ardeparin based on aIIa activity ranged from 62% to 64% and the mean absolute bioavailability based on aXa activity ranged from 88% to 97%. Based on bioequivalence testing criteria, the three ardeparin formulations were bioequivalent.

  2. Evaluation of Selective Efficiency of Molecular Markers Linked with a Novel Gene Xa39 Resistant to Bacterial Blight in Rice%水稻抗白叶枯病新基因Xa39分子标记有效性的评价

    Institute of Scientific and Technical Information of China (English)

    卓大龙; 胡丹丹; 张帆; 张帆; 石英尧; 高用明; 周永力; 黎志康


    Xa39是一个对水稻白叶枯病具有广谱抗性的显性新基因,在水稻抗白叶枯病育种中具有良好的应用价值和前景。在前期研究中,我们将该基因定位在水稻第11染色体上。本研究利用携带Xa39基因的供体亲本FF329与受体亲本 BT4、BT6、BT12、BT18杂交培育出4FL10、4FL14、4FL17、4FL21四个育种 F2分离群体,结合人工接种抗病性鉴定,对3个与Xa39紧密连锁的分子标记进行分子标记辅助选择(MAS)有效性比较,筛选高效的PCR分子标记。结果表明,标记RM26985和RM206在上述4个群体中的MAS准确率分别达到95.81%和93.61%,同时使用两者其准确率达到95.59%,上述2个标记在水稻白叶枯病抗性改良育种中可以提高Xa39的选择效率。%Xa39 is a novel and dominant resistance gene with broad spectrum for bacterial leaf blight in rice. In previous study, this gene was mapped on chromosome 11. In present study, FF329 carrying Xa39 gene as donor parent and BT4, BT6, BT12, BT18 as recipients were used to develop four F2 segregation populations (4FL10, 4FL14, 4FL17, 4FL21). Combining artificial inoculation with phenotype identification of bacterial leaf blight, the validity of three molecular markers tightly linked with Xa39, and two co-dominant molecular markers was investigated for marker-assisted selection (MAS). The results showed that the accu-racy of marker RM26985 for MAS was 95.81%and that of marker RM206 was 93.61%in the four populations. The accuracy of two markers RM26985 and RM206 used simultaneously for MAS was up to 95.35%. Therefore, RM26985 and RM206 can be used as effective markers in MAS for Xa39 in rice breeding program.

  3. 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


    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......, 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...

  4. 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


    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.

  5. 携有抗白叶枯病新基因Xa23水稻近等基因系的构建及应用%Development of Near-Isogenic Line CBB23 with a New Resistance Gene to Bacterial Blight in Rice and Its Application

    Institute of Scientific and Technical Information of China (English)

    章琦; 王春连; 赵开军; 杨文才; 乔枫; 周永力; 江祺祥; 刘古春


    1993~1998年,构建了携有抗稻白叶枯病新基因Xa23的近等基因系,命名为CBB23.以全生育期高度感病并具有改良株型的籼稻品种JG30为轮回亲本,与携有Xa23的抗性供体H4杂交,JG30/H4的F1通过回交、自交直至B5F4,各世代均用与目标基因Xa23相对应的专化小种菌系P6人工接种鉴定,同步进行株型和农艺性状选择,直至抗性稳定和农艺性状类似其轮回亲本.比较了CBB23 (携Xa23) 和IRBB21 (携Xa21) 对20个菌系包括10个菲律宾小种、3个日本小种和7个中国病原型代表菌系的抗谱, Xa23抗所有20 个菌系;Xa21 抗19个菌系,对菲律宾10号小种则高度感病.用近等基因系CBB23构建了JG30/CBB23组合的F2分离群体,通过SSR标记筛选,初步将Xa23定位于水稻第11染色体.进一步筛选出3 个与Xa23更紧密连锁的AFLP标记.其中的APKj23与Xa23之间的图距约为1.0 cM.并报道了在抗病育种中已有效的应用了携有Xa23的近等基因系 CBB23.%The near-isogenic line (NIL) with a new gene Xa23 for resistance to bacterial blight (BB) was developed and designated as CBB23 in 1993-1998. A susceptible indica variety JG30 with improved plant type was used as a recurrent parent. The progenies derived from the cross JG30/H4 harboring the gene Xa23 were developed by back-cross until BC5, and selfing for 4 times. Evaluation of the resistance gene Xa23 with specific strain P6 and selection of plant type successively were carried out till the line showing stable resistance and agronomic characters similar to the recurrent parent. Comparison of reaction for resistance spectrum to 20 strains including 10 Philippine races, 3 Japanese races, and 7 Chinese pathotypes between CBB23(carrying Xa23 )and IRBB21(carrying Xa21) was made. Xa23 is resistant to all 20 strains, and Xa21 is resistant to 19 strains and highly susceptible to the Philippine race 10. The NIL CBB23 was used to establish segregation populations of JG30/CBB23 for mapping the

  6. In vivo expansion of regulatory T cells with IL-2/IL-2 mAb complexes prevents anti-factor VIII immune responses in hemophilia A mice treated with factor VIII plasmid-mediated gene therapy. (United States)

    Liu, Chao-Lien; Ye, Peiqing; Yen, Benjamin C; Miao, Carol H


    Generation of transgene-specific immune responses can constitute a major complication following gene therapy treatment. An in vivo approach to inducing selective expansion of Regulatory T (Treg) cells by injecting interleukin-2 (IL-2) mixed with a specific IL-2 monoclonal antibody (JES6-1) was adopted to modulate anti-factor VIII (anti-FVIII) immune responses. Three consecutive IL-2 complexes treatments combined with FVIII plasmid injection prevented anti-FVIII formation and achieved persistent, therapeutic-level of FVIII expression in hemophilia A (HemA) mice. The IL-2 complexes treatment expanded CD4(+)CD25(+)Foxp3(+) Treg cells five- to sevenfold on peak day, and they gradually returned to normal levels within 7-14 days without changing other lymphocyte populations. The transiently expanded Treg cells are highly activated and display suppressive function in vitro. Adoptive transfer of the expanded Treg cells protected recipient mice from generation of high-titer antibodies following FVIII plasmid challenge. Repeated plasmid transfer is applicable in tolerized mice without eliciting immune responses. Mice treated with IL-2 complexes mounted immune responses against both T-dependent and T-independent neoantigens, indicating that IL-2 complexes did not hamper the immune system for long. These results demonstrate the important role of Treg cells in suppressing anti-FVIII immune responses and the potential of developing Treg cell expansion therapies that induce long-term tolerance to FVIII.

  7. Identification of microsatellite markers (SSR linked to a new bacterial blight resistance gene xa33(t in rice cultivar ‘Ba7’

    Directory of Open Access Journals (Sweden)

    Theerayut Toojinda


    Full Text Available This study attempts to identify a new source of bacterial blight (BB resistance gene and microsatellite makers (SSR linked to it. A total number of 139 F2 progenies generated from a cross between the resistant donor ‘Ba7’and ‘Pin Kaset’ were developed and used for this study. A Thai Xoo isolate, TXO16, collected from Phitsanulok province, was used to evaluate the resistance reaction in the F2 population. The segregation ratio of resistance (R and susceptibility (S was statistically fitted to 1R:3S model indicating single recessive gene segregation. Twenty F2 individuals consisting of 10 resistant and 10 susceptible plants were chosen for DNA analysis. Sixty-two polymorphic markers covering all rice chromosomes were used to identify the location and linked markers of the resistance gene. Four SSR markers, viz. RM30, RM7243, RM5509 and RM400, located on the long arm of rice chromosome 6, could clearly discriminate between resistant and susceptible phenotypes, and 161 BC2F2:3 individuals carrying BB resistance gene were developed through MAS using these SSR markers. This population was inoculated with TXO16 to validate and confirm the location of the gene and linked markers. The segregation ratio was statistically fitted to 1R:3S model confirming a recessive nature of the gene action in this germplasm. Phenotypic-genotypic association including five additional markers suggested that RM20590 was tightly linked to this resistance gene (R2=59.12 %. The BB phenotype was controlled by a recessive gene with incomplete dominance of susceptible allele providing intermediate resistance to Xoo pathogen in heterozygotes. The location of the gene was in the vicinity of a dominant gene, Xa7, which was previously reported. However, the resistance gene identified here was different from Xa7 because of the different nature of gene action. Consequently, this gene was tentatively designated as xa33(t. The resistance gene from rice cultivar ‘Ba7’ and the

  8. Rivaroxaban-once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation: rationale and design of the ROCKET AF study

    DEFF Research Database (Denmark)

    NN, NN


    BACKGROUND: Atrial fibrillation (AF), the most common significant cardiac arrhythmia, increases the risk of stroke, particularly in the elderly. Warfarin is effective in reducing stroke risk but is burdensome to patients and is difficult to control. Rivaroxaban is an oral direct factor Xa inhibit...

  9. Investigations on Preparation, Crystal Structure and Thermal Stability of Bis(O-ethylcarbonodithiolato-S ,S′) (1,10-phenanthroline-N1,N10)cobalt(Ⅱ) Complex: [Co(Et-XA)2·phen] ·H2O (XA = xanthate)

    Institute of Scientific and Technical Information of China (English)

    JIAN, Fang-Fang; LI, Yan; WANG, Huan-Xiang; JIAO, Kui


    [Co(Et-XA)2-phen]· H2O was prepared by adding 1,10-phenanthroline to the EtOH solution of bis (O-ethylcarbonodithiolato)cobalt(H) [Co(Et-XA)2]. The single crystal structure has been determined by X-ray diffraction analysis. The compound is orthorhombic with space group Pna21 and unit-cell parameters a = 1.0290(2) nm, b = 1.4550(3) nm and c = 1.4860(3)nm. The geometry of each Co atom which coordinates with four S atoms from two xanthate anions and two N atoms from phenanthroline ligand, is a distorted octahedron. The brown crystals were examined by elemental analysis, FT-IR, UV spectra and thermogravimetric-differential thermal analysis (TGDTA). Thermal decomposition of the compound takes place in several steps. In the first step, the compound releases 1, 10-phenanthroline ligand, then loses the H2O molecules. In the second step, the complex decomposes to CoS3. The final product of thermal decomposition is CoS. Elemental analysis, Irand UV spectra are in agreement with the proposd structure.

  10. Unfractionated and low-molecular-weight heparin and the phosphodiesterase inhibitors, IBMX and cilostazol, block ex vivo Equid Herpesvirus type-1-induced platelet activation

    Directory of Open Access Journals (Sweden)

    Tracy Stokol


    Full Text Available Equid herpes virus type-1 (EHV-1 is a major pathogen of horses, causing abortion storms and outbreaks of herpes virus myeloencephalopathy. These clinical syndromes are partly attributed to ischemic injury from thrombosis in placental and spinal vessels. The mechanism of thrombosis in affected horses is unknown. We have previously shown that EHV-1 activates platelets through virus-associated tissue factor-initiated thrombin generation. Activated platelets participate in thrombus formation by providing a surface to localize coagulation factor complexes that amplify and propagate thrombin generation. We hypothesized that coagulation inhibitors that suppress thrombin generation (heparins or platelet inhibitors that impede post-receptor thrombin signaling (phosphodiesterase [PDE] antagonists would inhibit EHV-1-induced platelet activation ex vivo. We exposed platelet-rich plasma collected from healthy horses to the RacL11 abortigenic and Ab4 neuropathogenic strains of EHV-1 at 1 plaque forming unit/cell in the presence or absence of unfractionated heparin (UFH, low-molecular-weight (LMWH heparin or the PDE inhibitors, 3-isobutyl-1methylxanthine (IBMX and cilostazol. We assessed platelet activation status in flow cytometric assays by measuring P-selectin expression. We found that all of the inhibitors blocked EHV-1- and thrombin-induced platelet activation in a dose-dependent manner. Platelet activation in PRP was maximally inhibited at concentrations of 0.05 U/mL UFH and 2.5 μg/mL LMWH. These concentrations represented 0.1 to 0.2 U/mL anti-Factor Xa activity measured in chromogenic assays. Both IBMX and cilostazol showed maximal inhibition of platelet activation at the highest tested concentration of 50 μM but inhibition was lower than that seen with UFH and LMWH. Our results indicate that heparin anticoagulants and strong non-selective (IBMX or isoenzyme-3 selective (cilostazol PDE antagonists inhibit ex vivo EHV-1-induced platelet activation

  11. 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


      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。

  12. Comparative evaluation of direct thrombin and factor Xa inhibitors with antiplatelet agents under flow and static conditions: an in vitro flow chamber model. (United States)

    Hosokawa, Kazuya; Ohnishi, Tomoko; Sameshima, Hisayo; Miura, Naoki; Koide, Takehiko; Maruyama, Ikuro; Tanaka, Kenichi A


    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.

  13. 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.

  14. 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


    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.

  15. A novel protease activity assay using a protease-responsive chaperone protein

    Energy Technology Data Exchange (ETDEWEB)

    Sao, Kentaro [Graduate School of Systems Life Sciences, Kyushu University, 744 Motooka Nishi-ku, Fukuoka 819-0395 (Japan); Murata, Masaharu, E-mail: [Department of Advanced Medical Initiatives, Faculty of Medical Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku Fukuoka 812-8582 (Japan); Fujisaki, Yuri; Umezaki, Kaori [Department of Advanced Medical Initiatives, Faculty of Medical Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku Fukuoka 812-8582 (Japan); Mori, Takeshi; Niidome, Takuro; Katayama, Yoshiki [Graduate School of Systems Life Sciences, Kyushu University, 744 Motooka Nishi-ku, Fukuoka 819-0395 (Japan); Department of Applied Chemistry, Faculty of Engineering, Kyushu University, Nishi-ku Fukuoka 819-0395 (Japan); Center for Future Chemistry, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395 (Japan); Hashizume, Makoto [Department of Advanced Medical Initiatives, Faculty of Medical Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku Fukuoka 812-8582 (Japan)


    Protease activity assays are important for elucidating protease function and for developing new therapeutic agents. In this study, a novel turbidimetric method for determining the protease activity using a protease-responsive chaperone protein is described. For this purpose, a recombinant small heat-shock protein (sHSP) with an introduced Factor Xa protease recognition site was synthesized in bacteria. This recombinant mutant, FXa-HSP, exhibited chaperone-like activity at high temperatures in cell lysates. However, the chaperone-like activity of FXa-HSP decreased dramatically following treatment with Factor Xa. Protein precipitation was subsequently observed in the cell lysates. The reaction was Factor Xa concentration-dependent and was quantitatively suppressed by a specific inhibitor for Factor Xa. Protein aggregation was detected by a simple method based on turbidimetry. The results clearly demonstrate that this assay is an effective, easy-to-use method for determining protease activities without the requirement of labeling procedures and the use of radioisotopes.

  16. 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;


    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....

  17. Comparison of prothrombin time tests used in the monitoring of edoxaban and their evaluation as indicators of the reversal effect. (United States)

    Iba, Toshiaki; Emmi, Mari; Hiki, Makoto; Nagayama, Masataka; Aihara, Koichiro; Tabe, Yoko; Yuri, Maiko; Ohsaka, Akimichi


    Clinical demand for the prompt assessment of the activity of direct-acting factor Xa inhibitors in the emergency care setting is increasing. In the present study, we examined whether prothrombin time (PT) tests can serve as a clinically useful indicator of anti-factor Xa activity. In the first series, the in vitro effect of edoxaban on PT was evaluated by spiking human plasma with edoxaban and measuring PT using three different commercial PT tests. In the second series, the reversal effect of prothrombin complex concentrates (PCC) and activated PCC (aPCC) in edoxaban-spiked plasma was evaluated. In the third series, PT of plasma samples from patients administered either 15 or 30 mg/day of edoxaban was assessed, and the results were compared with edoxaban concentrations determined by a calibrated anti-factor Xa activity assay. The spike test revealed that all PT reagents positively correlated with edoxaban. The sensitivity to edoxaban varied among the three reagents and Triniclot(®) Excel S showed the best performance. Prolonged PT by edoxaban was reversed by PCC and aPCC in a dose-dependent manner; however, complete reversal was not achieved. Positive correlation between anti-factor Xa activity and PT was shown in the clinical samples at the edoxaban range from 0 to >300 ng/mL.

  18. Low molecular weight heparin impairs tendon repair. (United States)

    Virchenko, O; Aspenberg, P; Lindahl, T L


    Thrombin has many biological properties similar to those of growth factors. In a previous study, we showed that thrombin improves healing of the rat tendo Achillis. Low molecular weight heparin (LMWH) inhibits the activity and the generation of thrombin. We therefore considered that LMWH at a thromboprophylactic dose might inhibit tendon repair. Transection of the tendo Achillis was carried out in 86 rats and the healing tested mechanically. Low molecular weight heparin (dalateparin) was either injected a few minutes before the operation and then given continuously with an osmotic mini pump for seven days, or given as one injection before the operation. In another experiment ,we gave LMWH or a placebo by injection twice daily. The anti-factor Xa activity was analysed. Continuous treatment with LMWH impaired tendon healing. After seven days, this treatment caused a 33% reduction in force at failure, a 20% reduction in stiffness and a 67% reduction in energy uptake. However, if injected twice daily, LMWH had no effect on tendon healing. Anti-factor Xa activity was increased by LMWH treatment, but was normal between intermittent injections. Low molecular weight heparin delays tendon repair if given continuously, but not if injected intermittently, probably because the anti-factor Xa activity between injections returns to normal, allowing sufficient thrombin stimulation for repair. These findings indicate the need for caution in the assessment of long-acting thrombin and factor Xa inhibitors.

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


    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.

  20. Crystal Structures and Spectra Characterizations of Ethylxanthic Bis(triphenylphosphine) Metal (Ⅰ) Complex: M(Et-XA) (PPh3)2 [M = Au (Ⅰ), Cu (Ⅰ)]%二(三苯基膦)乙基黄原酸金属配合物的晶体结构和谱学表征

    Institute of Scientific and Technical Information of China (English)

    建方方; 李艳; 肖海连; 焦奎


    The crystal structures of the complexes of [Au(Et-XA) (PPh3)2] (1), and [Cu(Et-XA) (PPh3)2] (2), havebeen determined by X-ray crystallography. They are isomorphous. The crystal structures are very similar and consistof discrete molecules of [Au(Et-XA)(PPh3)2] and [Cu(Et-XA)(PPh3)2], respectively. They all display distortedtetrahedral geometry around the central metal atom. In the complexes, the ethylxanthate ions act as bidentate lig-ands with their S atoms coordinated to metal. Each forms a four-member chelate ring. The P atoms from twotriphenylphosphine ligands are coordinated to the metal atom. The Au-P bond lengths are 0. 2295(2) nm and0. 2329(2)nm, and the Au-S bond lengths are 0. 2620 (3)nm and 0. 2846 (3)nm, respectively. The Cu-P and Cu-Sbond lengths are 0. 2254(1) nm, 0. 2273(2) nm, and 0. 2375(1) nm, 0. 2495(2) nm, respectively. Elementalanalysis, electronic and IR spectra are in agreement with the structural data. CCDC: 1, 208728; 2, 208903.

  1. 1-[3-Aminobenzisoxazol-5'-yl]-3-trifluoromethyl-6-[2'-(3-(R)-hydroxy-N-pyrrolidinyl)methyl-[1,1']-biphen-4-yl]-1,4,5,6-tetrahydropyrazolo-[3,4-c]-pyridin-7-one (BMS-740808) a highly potent, selective, efficacious, and orally bioavailable inhibitor of blood coagulation factor Xa. (United States)

    Pinto, Donald J P; Orwat, Michael J; Quan, Mimi L; Han, Qi; Galemmo, Robert A; Amparo, Eugene; Wells, Brian; Ellis, Christopher; He, Ming Y; Alexander, Richard S; Rossi, Karen A; Smallwood, Angela; Wong, Pancras C; Luettgen, Joseph M; Rendina, Alan R; Knabb, Robert M; Mersinger, Lawrence; Kettner, Charles; Bai, Steven; He, Kan; Wexler, Ruth R; Lam, Patrick Y S


    Attempts to further optimize the pyrazole factor Xa inhibitors centered on masking the aryl aniline P4 moiety. Scaffold optimization resulted in the identification of a novel bicyclic pyrazolo-pyridinone scaffold which retained fXa potency. The novel bicyclic scaffold preserved all binding interactions observed with the monocyclic counterpart and importantly the carboxamido moiety was integrated within the scaffold making it less susceptible to hydrolysis. These efforts led to the identification of 1-[3-aminobenzisoxazol-5'-yl]-3-trifluoromethyl-6-[2'-(3-(R)-hydroxy-N-pyrrolidinyl)methyl-[1,1']-biphen-4-yl]-1,4,5,6-tetrahydropyrazolo-[3,4-c]-pyridin-7-one 6f (BMS-740808), a highly potent (fXa Ki=30 pM) with a rapid onset of inhibition (2.7x10(7) M-1 s-1) in vitro, selective (>1000-fold over other proteases), efficacious in the AVShunt thrombosis model, and orally bioavailable inhibitor of blood coagulation factor Xa.

  2. Studies of Chemical Constituents and Their Antioxidant Activities From Astragalus mongholicus Bunge

    Institute of Scientific and Technical Information of China (English)



    Objective To evaluate the antioxidant activities of different chemical constituents from Astragalus mongholicus Bunge and their protection against xanthine (XA)/xanthine oxidase (XO)-induced toxicity in PC12 cells. Methods The compounds of Astragalus mongholicus Bunge were isolated by chromatography and the structures were elucidated on the basis of spectral data interpretation. Their antioxidant activities were detected by 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activities in a cell-free system. Meanwhile, the effects against XA/XO-induced toxicity were assessed using MTT assay in PC12 cells. Results Ten principal constituents were isolated and identified as formononetin (I), ononin (II), calycosin (III), calycosin-7-O-β-D-glucoside (IV), 9,10-dimethoxypterocarpan-3-O-β-D-glucoside (V), adenosine (VI), pinitol (VII), daucosterol (VIII), β-sitoster (IX) and saccharose (X) from Astragalus mongholicus Bunge. The compounds I, III, and IV scavenged DPPH free radicals in vitro. Formononetin and calycosin were found to inhibit XA/XO-induced cell injury significantly, with an estimated EC50 of 50 ng/mL. Conclusion Compound Ⅱ, Ⅵ, and Ⅶ are first reported in this plant. Calycosin exhibits the most potent antioxidant activity both in the cell-free system and in the cell system.

  3. 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


    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.

  4. Assisting in Providing Pre-Employment and In-Plant Training. Self-Paced Instructional Module, Module Number X-A. (United States)

    Simmons, Kenneth L.; Brooks, Kent

    One of 33 self-paced instructional modules for training industry services leaders, this module contains three sequential learning activities on assisting in providing pre-employment and inplant training in an industry services program. (Industry services are manpower services provided by public agencies to new or expanding private industries.) The…

  5. Histones Differentially Modulate the Anticoagulant and Profibrinolytic Activities of Heparin, Heparin Derivatives, and Dabigatran. (United States)

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Mulhall Kevin J


    Full Text Available 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. 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


    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.

  8. Preparation, characterization, and antitumor activity of new ethylenediamine platinum(IV) complexes containing mixed carboxylate ligands. (United States)

    Khokhar, A R; Deng, Y; Kido, Y; Siddik, Z H


    A series of ethylenediamine platinum(IV) complexes of the type PtIV(en)XA2 and PtIV(en)X'2A2, where X = 1,1-cyclobutanedicarboxylato or malonato, X' = chloro, cyclobutanecarboxylato, cyclopentanecarboxylato, or cyclohexanecarboxylato, and A = acetato or trifluoroacetato were synthesized and characterized by elemental analysis, infrared, and NMR (13C and 195Pt) spectroscopic techniques. These compounds had good to excellent antitumor activity against murine leukemia L1210 cells. Complexes with axial trifluoroacetate groups were superior to those with acetate ligands. Those possessing both axial trifluoroacetate groups and monodentate bis-carboxylate ligands in the equatorial positions were the most active in the series investigated.

  9. 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


    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.

  10. A sulfated fucan from the brown alga Laminaria cichorioides has mainly heparin cofactor II-dependent anticoagulant activity. (United States)

    Yoon, Seon-Joo; Pyun, Yu-Ryang; Hwang, Jae-Kwan; Mourão, Paulo A S


    The major acidic polysaccharide from the brown alga Laminaria cichorioides is a complex and heterogeneous sulfated fucan. Its preponderant structure is a 2,3-disulfated, 4-linked alpha-fucose unit. The purified polysaccharide has a potent anticoagulant activity, as estimated by APTT assay ( approximately 40 IU/mg), which is mainly mediated by thrombin inhibition by heparin cofactor II. It also accelerates thrombin and factor Xa inhibition by antithrombin but at a lower potency. Sulfated fucan from L. cichorioides is a promising anticoagulant polysaccharide and a possible alternative for an antithrombotic compound due to its preferential heparin cofactor II-dependent activity.

  11. Comparative effects of enoxaparin and heparin on arterial and venous clot lysis with alteplase in dogs. (United States)

    Stassen, J M; Rapold, H J; Vanlinthout, I; Collen, D


    The effects of Enoxaparin with a specific anti-thrombin (anti-IIa) activity of 32 U/mg and a specific anti-factor-XA (anti-Xa) activity of 96 U/mg, and of heparin with a specific anti-IIa and anti-Xa activity of 192 U/mg, on thrombolysis with alteplase (Actilyse) were compared in a randomized blinded study using a combined arterial and venous thrombosis model in the dog. All dogs received an intravenous bolus of 5 mg/kg lysine-acetyl salicylate and 0.5 mg/kg alteplase over 60 min. Twenty-eight dogs were randomly assigned to seven treatment groups: placebo, Enoxaparin 1.5, 3 or 6 mg/kg, or heparin 0.5, 1 or 2 mg/kg, given as a 50% intravenous bolus and a 50% infusion over 2 h. Steady-state plasma levels ranged from 0.37 to 1.0 anti-IIa U/ml and 0.9 to 3.1 anti-Xa U/ml for Enoxaparin and from 0.4 to 2.3 anti-IIa U/ml and 0.42 to 3.2 anti-Xa U/ml for heparin. The activated thromboplastin time with 6 mg/kg Enoxaparin prolonged to 94 +/- 19 s and with 2 mg/kg heparin to > 150 s. The time to reflow was 120 +/- 36 min with placebo, 19 +/- 5 min with 6 mg/kg Enoxaparin (p = 0.03 vs control), and 22 +/- 5 min with 2 mg/kg of heparin (p = 0.03 vs control). Arterial patency, expressed in min reflow during the 180 min observation period correlated significantly with the dose of anticoagulant given (r = 0.73, p = 0.003 for Enoxaparin and r = 0.61, p = 0.012 for heparin).(ABSTRACT TRUNCATED AT 250 WORDS)

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


    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.

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


    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.

  14. 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 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

  15. 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


    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

  16. 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


    INTRODUCTION: Critically ill patients are predisposed to venous thromboembolism. We hypothesized that higher doses of enoxaparin would improve thromboprophylaxis without increasing the risk of bleeding. Peak anti-factor Xa (anti-Xa) levels of 0.1- 0.4 IU/ml, reflect adequate thromboprophylaxis...... for general ward patients. Studies conducted in orthopaedic patients demonstrated a statistically significant relationship between anti-Xa levels and wound haematoma and thrombosis. Corresponding levels for critically ill patients may well be higher, but have never been validated in large studies. METHODS: 80...

  17. 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


    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

  18. 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


    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

  19. 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


    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......-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......: The safety and efficacy results of this study suggest that a AVE5026 dose of between 20 and 40 mg presents an adequate benefit-to-risk ratio....

  20. 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


    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......-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......: The safety and efficacy results of this study suggest that a AVE5026 dose of between 20 and 40 mg presents an adequate benefit-to-risk ratio....

  1. Factor XI and contact activation as targets for antithrombotic therapy. (United States)

    Gailani, D; Bane, C E; Gruber, A


    The most commonly used anticoagulants produce therapeutic antithrombotic effects either by inhibiting thrombin or factor Xa (FXa) or by lowering the plasma levels of the precursors of these key enzymes, prothrombin and FX. These drugs do not distinguish between thrombin generation contributing to thrombosis from thrombin generation required for hemostasis. Thus, anticoagulants increase bleeding risk, and many patients who would benefit from therapy go untreated because of comorbidities that place them at unacceptable risk for hemorrhage. Studies in animals demonstrate that components of the plasma contact activation system contribute to experimentally induced thrombosis, despite playing little or no role in hemostasis. Attention has focused on FXII, the zymogen of a protease (FXIIa) that initiates contact activation when blood is exposed to foreign surfaces, and FXI, the zymogen of the protease FXIa, which links contact activation to the thrombin generation mechanism. In the case of FXI, epidemiologic data indicate this protein contributes to stroke and venous thromboembolism, and perhaps myocardial infarction, in humans. A phase 2 trial showing that reduction of FXI may be more effective than low molecular weight heparin at preventing venous thrombosis during knee replacement surgery provides proof of concept for the premise that an antithrombotic effect can be uncoupled from an anticoagulant effect in humans by targeting components of contact activation. Here, we review data on the role of FXI and FXII in thrombosis and results of preclinical and human trials for therapies targeting these proteins.

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

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    Hadil A. Al Otair


    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

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

    LENUS (Irish Health Repository)

    Ni Ainle, Fionnuala


    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.

  4. Cotiarinase is a novel prothrombin activator from the venom of Bothrops cotiara. (United States)

    Kitano, Eduardo S; Garcia, Thalita C; Menezes, Milene C; Tashima, Alexandre K; Zelanis, André; Serrano, Solange M T


    Snake venom serine proteinases (SVSPs) may affect hemostatic pathways by specifically activating components involved in coagulation, fibrinolysis and platelet aggregation or by unspecific proteolytic degradation. In this study, we purified and characterized an SVSP from Bothrops cotiara venom, named cotiarinase, which generated thrombin upon incubation with prothrombin. Cotiarinase was isolated by a two-step procedure including gel-filtration and cation-exchange chromatographies and showed a single protein band with a molecular mass of 29 kDa by SDS-polyacrylamide gel electrophoresis under reducing conditions. Identification of cotiarinase by mass spectrometric analysis revealed peptides that matched sequences of viperid SVSPs. Cotiarinase did not show fibrinogen-clotting, platelet-aggregating, fibrinogenolytic and factor X activating activities. Upon incubation with prothrombin the generation of thrombin was detected using the peptide substrate d-Phe-Pip-Arg-pNA. Moreover, mass spectrometric identification of prothrombin fragments generated by cotiarinase in the absence of co-factors (phospholipids, factor Va, factor Xa and Ca(2+) ions), indicated the limited proteolysis of this protein to release prothrombin 1, fragment 1 and thrombin. Cotiarinase is a novel SVSP that acts on prothrombin to release active thrombin that does not match any group of the current classification of snake venom prothrombin activators.

  5. Purification and characterization of a prothrombin-activating protease from Nephila clavata. (United States)

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


    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.

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

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    Jonathan H. Foley


    Full Text Available 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.

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


    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

  8. 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


    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.

  9. Impact of autoclave sterilization on the activity and structure of formulated heparin. (United States)

    Beaudet, Julie M; Weyers, Amanda; Solakyildirim, Kemal; Yang, Bo; Takieddin, Majde; Mousa, Shaker; Zhang, Fuming; Linhardt, Robert J


    The stability of a formulated heparin was examined during its sterilization by autoclaving. A new method to follow loss in heparin binding to the serine protease inhibitor, antithrombin III, and the serine protease, thrombin, was developed using a surface plasmon resonance competitive binding assay. This loss in binding affinity correlated well with loss in antifactor IIa (thrombin) activity as well as antifactor Xa activity as measured using conventional amidolytic assays. Autoclaving also resulted in a modest breakdown of the heparin backbone as confirmed by a slight reduction in number-averaged and weight-averaged molecular weight and an increase in polydispersity. Although no clear changes were observed by nuclear magnetic resonance spectroscopy, disaccharide composition analysis using high-performance liquid chromatography-electrospray ionization-mass spectrometry suggested that loss of selected sulfo groups had taken place. It is this sulfo group loss that probably accounts for a decrease in the binding of autoclaved heparin to antithrombin III and thrombin as well as the observed decrease in its amidolytic activity.

  10. Studies on prekallikrein of bovine plasma. II. Activation of prekallikrein with proteinases and properties of kallikrein activated by bovine Hageman factor. (United States)

    Takahashi, H; Nagasawa, S; Suzuki, T


    Activation of bovine plasma prekallikrein was investigated with several proteinases. Highly purified bovine plasma prekallikrein was rapidly activated to kallikrein [EC] by bovine activated Hageman factor, trypsin [EC] and Pronase P (proteinases from Streptomyces griseus) and more gradually by papain [EC] and ficin [EC]. Activation of prekallikrein was also observed with bovine plasmin [EC], but not with bovine clotting factors Xa (Stuart factor) [EC] and IXa (Christmas factor) or thrombin [EC]. Urokinase [EC], Reptilase, collagenase [EC], elastase [EC], alpha-chymotrypsin [EC], Nagarse [EC], 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.

  11. 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;


    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....

  12. Heparins and heparinoids: occurrence, structure and mechanism of antithrombotic and hemorrhagic activities. (United States)

    Nader, Helena B; Lopes, Carla C; Rocha, Hugo A O; Santos, Elizeu A; Dietrich, Carl P


    The correlation between structure, anticlotting, antithrombotic and hemorrhagic activities of heparin, heparan sulfate, low molecular weight heparins and heparin-like compounds from various sources that are in used in clinical practice or under development is briefly reviewed. Heparin-like molecules composed exclusively of iduronic acid 2-O-sulfate residues have weak anticlotting activities, whereas molecules that contain both iduronic acid 2-O sulfate, iduronic acid and small amounts of glucuronic acid, such as heparin, or mixed amounts of glucuronic and iduronic acids (mollusk heparins) possess high anticlotting and anti-Xa activities. These results also suggest that a proper combination of these elements might produce a strong antithrombotic agent. Heparin isolated from shrimp mimics the pharmacological activities of low molecular weight heparins. A heparan sulfate derived from bovine pancreas and a sulfated fucan from brown algae have a potent antithrombotic activity in arterial and venous thrombosis model "in vivo" with a negligible activity upon the serine-proteases of the coagulation cascade "in vitro". These and other results led to the hypothesis that antithrombotic activity of heparin and other antithrombotic agents is due at least in part by their action on endothelial cells stimulating the synthesis of an antithrombotic heparan sulfate. All the antithrombotic agents derived from heparin and other heparinoids have hemorrhagic activity. Exceptions to this are a heparan sulfate from bovine pancreas and a sulfated fucan derived from brown algae, which have no hemorrhagic activity but have high antithrombotic activities "in vivo". Once the structure of these compounds are totally defined it will be possible to design an ideal antithrombotic.

  13. Rare earth activated yttrium aluminate phosphors with modulated luminescence. (United States)

    Muresan, L E; Popovici, E J; Perhaita, I; Indrea, E; Oro, J; Casan Pastor, N


    Yttrium aluminate (Y3 A5 O12 ) was doped with different rare earth ions (i.e. Gd(3+) , Ce(3+) , Eu(3+) and/or Tb(3+) ) in order to obtain phosphors (YAG:RE) with general formula,Y3-x-a Gdx REa Al5 O12 (x = 0; 1.485; 2.97 and a = 0.03). The synthesis of the phosphor samples was done using the simultaneous addition of reagents technique. This study reveals new aspects regarding the influence of different activator ions on the morpho-structural and luminescent characteristics of garnet type phosphor. All YAG:RE phosphors are well crystallized powders containing a cubic-Y3 Al5 O12 phase as major component along with monoclinic-Y4 Al2 O9 and orthorhombic-YAlO3 phases as the impurity. The crystallites dimensions of YAG:RE phosphors vary between 38 nm and 88 nm, while the unit cell slowly increase as the ionic radius of the activator increases. Under UV excitation, YAG:Ce exhibits yellow emission due to electron transition in Ce(3+) from the 5d level to the ground state levels ((2) F5/2 , (2) F7/2 ). The emission intensity of Ce(3+) is enhanced in the presence of the Tb(3+) ions and is decreased in the presence of Eu(3+) ions due to some radiative or non-radiative processes that take place between activator ions. By varying the rare earth ions, the emission colour can be modulated from green to white and red. Copyright © 2015 John Wiley & Sons, Ltd.

  14. 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. (United States)

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


    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.

  15. 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

  16. Matriptase activation connects tissue factor-dependent coagulation initiation to epithelial proteolysis and signaling. (United States)

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


    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.

  17. Anticoagulant activity of native and partially degraded glycoglucuronomannan after chemical sulfation. (United States)

    de Oliveira Barddal, Helyn Priscila; Gracher, Ana Helena Pereira; Simas-Tosin, Fernanda Fogagnoli; Iacomini, Marcello; Cipriani, Thales Ricardo


    Heparin has great clinical importance as anticoagulant and antithrombotic agent. However, because of its risks of causing bleeding and contamination by animal pathogens, several studies aim to obtain alternatives to heparin. In the search for anticoagulant and antithrombotic agents from a non-animal source, a glycoglucuronomannan from the gum exudate of the plant Vochysia thyrsoidea was partially hydrolyzed, and both native and partially degraded polysaccharides were chemically sulfated, yielding VThS and Ph-VThS respectively. Methylation analysis indicated that sulfation occurred preferentially at the O-5 position of arabinose units in the VThS and at the O-6 position of mannose units in Ph-VThS. In vitro aPTT assay showed that VThS and Ph-VThS have anticoagulant activity, which could be controlled by protamine, and ex vivo aPTT assay demonstrated that Ph-VThS is absorbed by subcutaneous route. Like heparin, they were able to inhibit α-thrombin and factor Xa by a serpin-dependent mechanism. In vivo, VThS and Ph-VThS reduced thrombus formation by approximately 50% at a dose of 40 IU/kg, similarly to heparin. The results demonstrated that the chemically sulfated polysaccharides are promising anticoagulant and antithrombotic agents.

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

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


    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).

  19. 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


    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.

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


    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.

  1. Isolation, purification, and characterization of fucose-containing sulfated polysaccharides from the brown seaweed Ecklonia kurome and their blood-anticoagulant activities. (United States)

    Nishino, T; Yokoyama, G; Dobashi, K; Fujihara, M; Nagumo, T


    A sulfated polysaccharide fraction, obtained from the hot-water extract of the brown seaweed, Ecklonia kurome by removing laminaran and the major part of alginic acid, gave sulfated polysaccharides (B-I, B-II, C-I, and C-II) by both anion-exchange chromatography on a column of Ecteola-cellulose and by fractional precipitation with ethanol containing 0.3% calcium acetate, and then by gel-filtration chromatography on a Sepharose 4B column. B-I and B-II are composed of fucose, galactose, mannose, xylose, glucuronic acid, and ester sulfate in the approximate molar ratios of 1.00:0.36:0.48:1.08:1.85:2.35 and 1.00:0.81:0.18:0.45:0.61:2.00, respectively. C-I and C-II are composed of fucose, galactose, glucuronic acid, and ester sulfate in approximate molar ratios of 1.00:0.03:0.03:1.61 and 1.00:0.19:0.07:1.48, respectively. Blood-anticoagulant activities with respect to activated partial thromboplastin time (APTT) were approximately 24, 19, 81, and 85% of that of heparin for B-I, B-II, C-I, and C-II, respectively. All the polysaccharides showed slight antithrombin activity. No antifactor Xa activity was observed for any of the polysaccharides.

  2. Low molecular weight heparin for the prevention of deep venous thrombosis: a suitable monitoring in elderly patients? (United States)

    Mahé, Isabelle; Drouet, Ludovic; Chassany, Oliver; Grenard, Anne-Sophie; Caulin, Charles; Bergmann, Jean-François


    Monitoring of anti-Xa activity (aXa) levels is not routinely required in patients receiving enoxaparine at prophylactic dosages, since aXa is supposed to stay below the manufacturer's recommended range in patients treated for venous thrombosis (0.5-1 IU/ml). In order to aXa in elderly subjects receiving prophylactic enoxaparin, 68 consecutive patients (mean age 82.5 +/- 10.7 years) hospitalized in a medical department receiving 4000 IU enoxaparin daily subcutaneously for the prevention of venous thromboembolic disease were studied. After the first injection of enoxaparin, the aXa of 57.4% patients was superior to 0.5 IU/ml while 69.4% had an aXa higher than 0.5 after 8.4 +/- 1.2 days. A negative relationship between aXa and body weight and a trend towards a positive correlation between aXa and age but not with creatinine clearance were noted. Our findings question the opportunity to monitor aXa in elderly patients receiving 4000 IU enoxaparin as antithrombotic prophylaxis.

  3. Performance of coagulation tests in patients on therapeutic doses of rivaroxaban. A cross-sectional pharmacodynamic study based on peak and trough plasma levels. (United States)

    Francart, Suzanne J; Hawes, Emily M; Deal, Allison M; Adcock, Dorothy M; Gosselin, Robert; Jeanneret, Cheryl; Friedman, Kenneth D; Moll, Stephan


    Knowledge of anticoagulation status during rivaroxaban therapy is desirable in certain clinical situations. It was the study objective to determine coagulation tests most useful for assessing rivaroxaban's anticoagulant effect. Peak and trough blood samples from 29 patients taking rivaroxaban 20 mg daily were collected. Mass spectrometry and various coagulation assays were performed. "On-therapy range" was defined as the rivaroxaban concentrations determined by LC-MS/MS. A "misprediction percentage" was calculated based on how often results of each coagulation assay were in the normal reference range, while the rivaroxaban concentration was in the "on-therapy" range. The on-therapy range was 8.9-660 ng/ml. The misprediction percentages for prothrombin time (PT) and activated partial thromboplastin time (aPTT), using multiple reagents and coagulometers, ranged from 10%-52% and 31%-59%, respectively. PT, aPTT and activated clotting time (ACT) were insensitive to trough rivaroxaban: 59%, 62%, and 80% of samples had a normal result, respectively. Over 95% of PT and ACT values were elevated at peak. Four different rivaroxaban calibrated anti-Xa assays had R² values >0.98, demonstrating strong correlations with rivaroxaban drug levels. In conclusion, PT, aPTT and ACT are often normal in patients on therapeutic doses of rivaroxaban. However, PT and ACT may have clinical utility at higher drug plasma levels. Rivaroxaban calibrated anti-factor Xa assays can accurately identify low and high on-therapy rivaroxaban drug levels and, therefore, have superior utility in all clinical situations where assessment of anticoagulation status may be beneficial.

  4. Impact of nonsynonymous mutations of factor X on the functions of factor X and anticoagulant activity of edoxaban. (United States)

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


    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.

  5. A model ternary heparin conjugate by direct covalent bond strategy applied to drug delivery system. (United States)

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


    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.

  6. Nonclinical evaluation of novel cationically modified polysaccharide antidotes for unfractionated heparin.

    Directory of Open Access Journals (Sweden)

    Bartlomiej Kalaska

    Full Text Available Protamine, the only registered antidote of unfractionated heparin (UFH, may produce a number of adverse effects, such as anaphylactic shock or serious hypotension. We aimed to develop an alternative UFH antidote as efficient as protamine, but safer and easier to produce. As a starting material, we have chosen generally non-toxic, biocompatible, widely available, inexpensive, and easy to functionalize polysaccharides. Our approach was to synthesize, purify and characterize cationic derivatives of dextran, hydroxypropylcellulose, pullulan and γ-cyclodextrin, then to screen them for potential heparin-reversal activity using an in vitro assay and finally examine efficacy and safety of the most active polymers in Wistar rat and BALB/c mouse models of experimentally induced arterial and venous thrombosis. Efficacy studies included the measurement of thrombus formation, activated partial thromboplastin time, bleeding time, and anti-factor Xa activity; safety studies included the measurement of hemodynamic, hematologic and immunologic parameters. Linear, high molecular weight dextran substituted with glycidyltrimethylammonium chloride groups at a ratio of 0.65 per glucose unit (Dex40-GTMAC3 is the most potent and the safest UFH inhibitor showing activity comparable to that of protamine while possessing lower immunogenicity. Cationic polysaccharides of various structures neutralize UFH. Dex40-GTMAC3 is a promising and potentially better UFH antidote than protamine.

  7. Nonclinical evaluation of novel cationically modified polysaccharide antidotes for unfractionated heparin. (United States)

    Kalaska, Bartlomiej; Kaminski, Kamil; Sokolowska, Emilia; Czaplicki, Dominik; Kujdowicz, Monika; Stalinska, Krystyna; Bereta, Joanna; Szczubialka, Krzysztof; Pawlak, Dariusz; Nowakowska, Maria; Mogielnicki, Andrzej


    Protamine, the only registered antidote of unfractionated heparin (UFH), may produce a number of adverse effects, such as anaphylactic shock or serious hypotension. We aimed to develop an alternative UFH antidote as efficient as protamine, but safer and easier to produce. As a starting material, we have chosen generally non-toxic, biocompatible, widely available, inexpensive, and easy to functionalize polysaccharides. Our approach was to synthesize, purify and characterize cationic derivatives of dextran, hydroxypropylcellulose, pullulan and γ-cyclodextrin, then to screen them for potential heparin-reversal activity using an in vitro assay and finally examine efficacy and safety of the most active polymers in Wistar rat and BALB/c mouse models of experimentally induced arterial and venous thrombosis. Efficacy studies included the measurement of thrombus formation, activated partial thromboplastin time, bleeding time, and anti-factor Xa activity; safety studies included the measurement of hemodynamic, hematologic and immunologic parameters. Linear, high molecular weight dextran substituted with glycidyltrimethylammonium chloride groups at a ratio of 0.65 per glucose unit (Dex40-GTMAC3) is the most potent and the safest UFH inhibitor showing activity comparable to that of protamine while possessing lower immunogenicity. Cationic polysaccharides of various structures neutralize UFH. Dex40-GTMAC3 is a promising and potentially better UFH antidote than protamine.

  8. Apixaban versus enoxaparin for thromboprophylaxis after hip replacement

    DEFF Research Database (Denmark)

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


    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...

  9. Parasin Ⅰ : Prokaryotic Expression, Purification and Antimicrobial Activity Analysis of a Recombination Catfish Antimicrobial Peptide%重组鲢鱼抗菌肽parasin Ⅰ原核表达、纯化与抗菌活性

    Institute of Scientific and Technical Information of China (English)

    赵华; 张艳艳; 汤加勇; 李珂; 周继昌; 王康宁


    This study was conducted to construct parasin I expression vector, produce the recombinant peptide in the E. coli expression system, and analyze the antibacterial activity of the recombinant parasin I . According to the amino acid sequence of mature peptide of parasin I and codon bias of E. coli, a 57 bp cDNA fragment was synthesized. The recombinant vector p£7B2-Para I in E. coli was constructed by PCR, and a sequence encoding endonuclease site of Xa factor was cloned into the 5'-upstream of the parasin I gene. The recombinant vector was delivered into E. coli Rosetta ( DE3) cells and isopropyl (3-D-thiogalactoside (IPTG) was used to induce recombinant fusion protein under different temperatures (37 and 20 t). The results showed that the recombinant fusion protein reached about 45% to 50% of the total protein in E. coli, which had a molecular mass of 21 ku. The fusion protein induced under low temperature (20 t) mainly existed in dissolvable form. After purified by affinity chromatography, the recombinant parasin I showed potent anti-Staphylococ-cus aureus activity after digested by Xa fator. An efficient expression system in E. coli for the production of a recombinant parasin I with high yield are successfully constructed in this study, and the recombinant protein shows potent anti-bacterial activity after digested by Xa fator. [ Chinese Journal of Animal Nutrition, 2012, 24(9) : 1731-1736]%本文旨在构建抗菌肽parasin Ⅰ大肠杆菌重组表达载体,表达人工重组parasin Ⅰ,并检测其抑菌活性.根据parasin Ⅰ的成熟肽序列和大肠杆菌密码子偏好性,人工合成1段57 bp的基因编码cDNA,通过PCR技术构建大肠杆菌重组表达质粒pET32-Para Ⅰ,并在parasin Ⅰ基因5′-端引入Xa因子酶切位点.重组载体转化大肠杆菌Rosetta(DE3)菌株后,在不同温度(37和20℃)条件下对阳性转化子进行异丙基硫代半乳糖苷(IPTG)诱导表达.结果表明:IPTG成功诱导了1个21 ku的融合蛋白表达,

  10. Factor XI and Contact Activation as Targets for Antithrombotic Therapy


    Gailani, David; Bane, Charles E.; Gruber, Andras


    The most commonly used anticoagulants produce therapeutic antithrombotic effects either by inhibiting thrombin or factor Xa, or by lowering the plasma levels of the precursors of these key enzymes, prothrombin and factor X. These drugs do not distinguish between thrombin generation contributing to thrombosis from thrombin generation required for hemostasis. Thus, anticoagulants increase bleeding risk, and many patients who would benefit from therapy go untreated because of comorbidities that ...

  11. The solution properties of mefenamic acid and a closely related analogue are indistinguishable in polar solvents but significantly different in nonpolar environments. (United States)

    Lee, Eun Hee; Byrn, Stephen R; Pinal, Rodolfo


    This study investigates the cosolute effects of mefenamic acid (XA) and flufenamic acid (FA). These compounds serve as model of a drug discovery lead compound and a structural analogue. The activity coefficients of XA and FA in different solvents were obtained from solubility measurements at 25°C. The effect of varying concentrations of FA on the solubility of XA in four different solvents, including toluene, cyclohexane, ethanol, and an ethanol-water mixture (80:20, v/v), was investigated. The magnitude of change in the activity coefficient of XA in the presence of FA in different solvents was used to elucidate the thermodynamic effect of FA on the solubility of XA. Nuclear magnetic resonance and Fourier-transform infrared spectroscopy were used to obtain molecular level information about the interactions of the compounds in solution. The presence of FA increases XA solubility in toluene and in cyclohexane as much as seven-fold. Conversely, in ethanol and the ethanol-water mixture, similar levels of FA have essentially no effect on the solubility of XA. The solution properties investigated show that despite the close structural similarity between XA and FA, the two compounds are strongly distinguishable in nonpolar solvents. Conversely, the solution properties of the same two solutes are indistinguishable in polar solvents. A solubilization model based on solute-cosolute interactions is presented.

  12. Bioengineered Chinese hamster ovary cells with Golgi-targeted 3-O-sulfotransferase-1 biosynthesize heparan sulfate with an antithrombin-binding site. (United States)

    Datta, Payel; Li, Guoyun; Yang, Bo; Zhao, Xue; Baik, Jong Youn; Gemmill, Trent R; Sharfstein, Susan T; Linhardt, Robert J


    HS3st1 (heparan sulfate 3-O-sulfotransferase isoform-1) is a critical enzyme involved in the biosynthesis of the antithrombin III (AT)-binding site in the biopharmaceutical drug heparin. Heparin is a highly sulfated glycosaminoglycan that shares a common biosynthetic pathway with heparan sulfate (HS). Although only granulated cells, such as mast cells, biosynthesize heparin, all animal cells are capable of biosynthesizing HS. As part of an effort to bioengineer CHO cells to produce heparin, we previously showed that the introduction of both HS3st1 and NDST2 (N-deacetylase/N-sulfotransferase isoform-2) afforded HS with a very low level of anticoagulant activity. This study demonstrated that untargeted HS3st1 is broadly distributed throughout CHO cells and forms no detectable AT-binding sites, whereas Golgi-targeted HS3st1 localizes in the Golgi and results in the formation of a single type of AT-binding site and high anti-factor Xa activity (137 ± 36 units/mg). Moreover, stable overexpression of HS3st1 also results in up-regulation of 2-O-, 6-O-, and N-sulfo group-containing disaccharides, further emphasizing a previously unknown concerted interplay between the HS biosynthetic enzymes and suggesting the need to control the expression level of all of the biosynthetic enzymes to produce heparin in CHO cells.

  13. The activity of gastric ghrelin positive cells in obese patients treated surgically.

    Directory of Open Access Journals (Sweden)

    Artur Bossowski


    Full Text Available Ghrelin is a 28 amino acid peptide hormone regulating food intake and stimulating releasement of growth hormone. It is produced in a distinct endocrine call known as X/A - like cells. The most abundant source of this very important factor in energy homeostasis is gastric fundus. Regulatory mechanisms of ghrelin synthesis and secretion in physiological and pathological states are not discovered completely. The aim of our study was evaluation of the activity of gastric X/A-like cells in obese patients before and after the most popular surgical bariatric procedures - Roux - Y Gastric Bypass (RYGB and Laparoscopic Adjustable Gastric Banding (LAGB. Obese patients in number 18 took part in the study. LAGB was performed in 7 patients and RYGB in 11 patients. Peripheral blood was taken from each patient before operation and first day, seventh day, one month and three months after surgery. Ghrelin level was determined by RIA technique. The specimen of stomach was taken from circular stapler after gastrojejunostomy during RYGB and immunohistochemical study of gastric mucosa, using the EnVision method and specific monoclonal antybodies against ghrelin was performed. The intensity of ghrelin-immunoreactivity in X/A-like cells was analyzed using Olympus Cell D image analysis system. Efficiency of bariatric procedures was estimated by EWL- excess weight loss. We observed very strong immunohistochemical reactions of gastric X/A-like cells, accompanied by lower ghrelin plasma concentration, in comparison to the control group. LAGB procedure induced increase of ghrelin plasma level while RYGB procedure induced decrease of this hormone. The main finding of the present study is the hypoactivity of gastric X/A-like cells in obese patients in comparison to the control group.

  14. Structure and anticoagulant activity of sulfated galactans. Isolation of a unique sulfated galactan from the red algae Botryocladia occidentalis and comparison of its anticoagulant action with that of sulfated galactans from invertebrates. (United States)

    Farias, W R; Valente, A P; Pereira, M S; Mourão, P A


    We have characterized the structure of a sulfated d-galactan from the red algae Botryocladia occidentalis. The following repeating structure (-4-alpha-d-Galp-1-->3-beta-d-Galp-1-->) was found for this polysaccharide, but with a variable sulfation pattern. Clearly one-third of the total alpha-units are 2,3-di-O-sulfated and another one-third are 2-O-sulfated. The algal sulfated d-galactan has a potent anticoagulant activity (similar potency as unfractionated heparin) due to enhanced inhibition of thrombin and factor Xa by antithrombin and/or heparin cofactor II. We also extended the experiments to several sulfated polysaccharides from marine invertebrates with simple structures, composed of a single repeating structure. A 2-O- or 3-O-sulfated l-galactan (as well as a 2-O-sulfated l-fucan) has a weak anticoagulant action when compared with the potent action of the algal sulfated d-galactan. Possibly, the addition of two sulfate esters to a single alpha-galactose residue has an "amplifying effect" on the anticoagulant action, which cannot be totally ascribed to the increased charge density of the polymer. These results indicate that the wide diversity of polysaccharides from marine alga and invertebrates is a useful tool to elucidate structure/anticoagulant activity relationships.

  15. Physical activity (United States)

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

  16. Ex vivo effects of low-dose rivaroxaban on specific coagulation assays and coagulation factor activities in patients under real life conditions. (United States)

    Mani, Helen; Hesse, Christian; Stratmann, Gertrud; Lindhoff-Last, Edelgard


    Global coagulation assays display variable effects at different concentrations of rivaroxaban. The aim of this study is to quantify the ex vivo effects of low-dose rivaroxaban on thrombophilia screening assays and coagulation factor activities based on the administration time, and to show how to mask possible interferences. Plasma samples from 40 patients receiving rivaroxaban 10 mg daily were investigated to measure activities of clotting factor II, V, VII, VIII, IX, XI, XII and XIII; protein C- and protein S-levels; lupus anticoagulants; anticardiolipin IgG and IgM; D-dimer, heparin-platelet factor 4 (HPF4) antibodies and screening tests for von Willebrand disease (VWD). Two hours after rivaroxaban administration, the activities of clotting factors were significantly decreased to different extents, except for factor XIII. Dilution of plasma samples resulted in neutralisation of these interferences. The chromogenic protein C activity assay was not affected by rivaroxaban. Depending on the timing of tablet intake in relation to blood sampling protein S activity was measured falsely high when a clotting assay was used. False-positive results for lupus anticoagulants were observed depending on the assay system used and the administration time of rivaroxaban. ELISA-based assays such as anticardiolipin IgG and IgM, D-dimer, HPF4-antibodies and the turbidimetric assays for VWD were not affected by rivaroxaban. Specific haemostasis clotting tests should be performed directly prior to rivaroxaban intake. Assay optimisation in the presence of rivaroxaban can be achieved by plasma dilution. Immunologic assays are not influenced by rivaroxaban, while chromogenic assays can be used, when they do not depend on factor Xa.

  17. Thrombin generation and low-molecular-weight heparin prophylaxis in pregnant women with thrombophilia. (United States)

    Selmeczi, Anna; Roach, Rachel E J; Móré, Csaba; Batta, Zoltán; Hársfalvi, Jolán; van der Bom, Johanna G; Boda, Zoltán; Oláh, Zsolt


    Pregnancy is associated with increased risk of venous thromboembolism, especially in the presence of thrombophilia. However, there is no consensus on the optimal approach for thromboprophylaxis in this population. Recent evidence suggests that thrombin generation correlates with the overall procoagulant state of the plasma. Our aim was to evaluate thrombin generation in a prospective cohort of thrombophilic pregnant women, and investigate the effectiveness of low-molecular-weight heparin (LMWH) prophylaxis in pregnancy. Women with severe (n=8), mild (n=47) and no (n=15) thrombophilia were followed throughout their pregnancies. Thrombin generation was evaluated in each trimester as well as five days and eight weeks postpartum (as a reference category). In women undergoing LMWH prophylaxis, thrombin generation and anti-Factor-Xa activity were measured just before and 4 hours after administration (peak effect). Thrombin generation was determined using Technothrombin TGA assay system. For the analysis, median peak thrombin and endogenous thrombin potential were used. Peak thrombin and endogenous thrombin potential were increased during pregnancy compared to the non-pregnant state with the highest results in the severe thrombophilia group. In women receiving LMWH prophylaxis a decrease was observed in thrombin generation at peak effect but over the progression of pregnancy the extent of this decrease reduced in a stepwise fashion. Our results show that thrombin generation demonstrates the hypercoagulable state in thrombophilic pregnancies. In addition, we found the effect of LMWH prophylaxis to progressively decrease with advancing stages of pregnancy.

  18. 76 FR 51947 - Small Takes of Marine Mammals Incidental to Specified Activities; Pile Driving in the Columbia... (United States)


    ... Northwest, originating in Canada's Rocky Mountains and flowing approximately 1,200 mi (1,931 km) to the... National Oceanic and Atmospheric Administration RIN 0648-XA289 Small Takes of Marine Mammals Incidental to... marine mammals, by harassment, incidental to pile driving during construction of the Terminal 5...

  19. Antiviral cationic peptides as a strategy for innovation in global health therapeutics for dengue virus: high yield production of the biologically active recombinant plectasin peptide. (United States)

    Rothan, Hussin A; Mohamed, Zulqarnain; Suhaeb, Abdulrazzaq M; Rahman, Noorsaadah Abd; Yusof, Rohana


    Dengue virus infects millions of people worldwide, and there is no vaccine or anti-dengue therapeutic available. Antimicrobial peptides have been shown to possess effective antiviral activity against various viruses. One of the main limitations of developing these peptides as potent antiviral drugs is the high cost of production. In this study, high yield production of biologically active plectasin peptide was inexpensively achieved by producing tandem plectasin peptides as inclusion bodies in E. coli. Antiviral activity of the recombinant peptide towards dengue serotype-2 NS2B-NS3 protease (DENV2 NS2B-NS3pro) was assessed as a target to inhibit dengue virus replication in Vero cells. Single units of recombinant plectasin were collected after applying consecutive steps of refolding, cleaving by Factor Xa, and nickel column purification to obtain recombinant proteins of high purity. The maximal nontoxic dose (MNTD) of the recombinant peptide against Vero cells was 20 μM (100 μg/mL). The reaction velocity of DENV2 NS2B-NS3pro decreased significantly after increasing concentrations of recombinant plectasin were applied to the reaction mixture. Plectasin peptide noncompetitively inhibited DENV2 NS2B-NS3pro at Ki value of 5.03 ± 0.98 μM. The percentage of viral inhibition was more than 80% at the MNTD value of plectasin. In this study, biologically active recombinant plectasin which was able to inhibit dengue protease and viral replication in Vero cells was successfully produced in E. coli in a time- and cost- effective method. These findings are potentially important in the development of potent therapeutics against dengue infection.

  20. Activated Charcoal (United States)

    Activated Carbon, Animal Charcoal, Carbo Vegetabilis, Carbon, Carbón Activado, Charbon Actif, Charbon Activé, Charbon Animal, Charbon Médicinal, Charbon Végétal, Charbon Végétal Activé, Charcoal, Gas Black, Lamp Black, Medicinal Charcoal, Noir de Gaz, ...

  1. Conformation analysis of a surface loop that controls active site access in the GH11 xylanase A from Bacillus subtilis. (United States)

    Vieira, Davi Serradella; Ward, Richard John


    Xylanases (EC 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.

  2. Physical Activity

    DEFF Research Database (Denmark)

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


    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....

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

    Directory of Open Access Journals (Sweden)

    Norwood Thomas H


    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.

  4. Activity Theory. (United States)

    Koschmann, Timothy; Roschelle, Jeremy; Nardi, Bonnie A.


    Includes three articles that discuss activity theory, based on "Context and Consciousness." Topics include human-computer interaction; computer interfaces; hierarchical structuring; mediation; contradictions and development; failure analysis; and designing educational technology. (LRW)

  5. Structural investigation of zymogenic and activated forms of human blood coagulation factor VIII: a computational molecular dynamics study

    Directory of Open Access Journals (Sweden)

    Venkateswarlu Divi


    Full Text Available Abstract Background Human blood coagulation factor VIII (fVIII is a large plasma glycoprotein with sequential domain arrangement in the order A1-a1-A2-a2-B-a3-A3-C1-C2. The A1, A2 and A3 domains are interconnected by long linker peptides (a1, a2 and a3 that possess the activation sites. Proteolysis of fVIII zymogen by thrombin or factor Xa results in the generation of the activated form (fVIIIa which serves as a critical co-factor for factor IXa (fIXa enzyme in the intrinsic coagulation pathway. Results In our efforts to elucidate the structural differences between fVIII and fVIIIa, we developed the solution structural models of both forms, starting from an incomplete 3.7 Å X-ray crystal structure of fVIII zymogen, using explicit solvent MD simulations. The full assembly of B-domainless single-chain fVIII was built between the A1-A2 (Ala1-Arg740 and A3-C1-C2 (Ser1669-Tyr2332 domains. The structural dynamics of fVIII and fVIIIa, simulated for over 70 ns of time scale, enabled us to evaluate the integral motions of the multi-domain assembly of the co-factor and the possible coordination pattern of the functionally important calcium and copper ion binding in the protein. Conclusions MD simulations predicted that the acidic linker peptide (a1 between the A1 and A2 domains is largely flexible and appears to mask the exposure of putative fIXa enzyme binding loop (Tyr555-Asp569 region in the A2 domain. The simulation of fVIIIa, generated from the zymogen structure, predicted that the linker peptide (a1 undergoes significant conformational reorganization upon activation by relocating completely to the A1-domain. The conformational transition led to the exposure of the Tyr555-Asp569 loop and the surrounding region in the A2 domain. While the proposed linker peptide conformation is predictive in nature and warrants further experimental validation, the observed conformational differences between the zymogen and activated forms may explain and support the

  6. Changing trends in anti-coagulant therapies. Are heparins and oral anti-coagulants challenged? (United States)

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


    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

  7. Identifying Activity

    CERN Document Server

    Lewis, Adrian S


    Identification of active constraints in constrained optimization is of interest from both practical and theoretical viewpoints, as it holds the promise of reducing an inequality-constrained problem to an equality-constrained problem, in a neighborhood of a solution. We study this issue in the more general setting of composite nonsmooth minimization, in which the objective is a composition of a smooth vector function c with a lower semicontinuous function h, typically nonsmooth but structured. In this setting, the graph of the generalized gradient of h can often be decomposed into a union (nondisjoint) of simpler subsets. "Identification" amounts to deciding which subsets of the graph are "active" in the criticality conditions at a given solution. We give conditions under which any convergent sequence of approximate critical points finitely identifies the activity. Prominent among these properties is a condition akin to the Mangasarian-Fromovitz constraint qualification, which ensures boundedness of the set of...

  8. Activating schoolyards

    DEFF Research Database (Denmark)

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


    BACKGROUND: The aim of the Activating Schoolyards Study is to develop, implement, document and assess a comprehensive schoolyard intervention to promote physical activity (PA) during school recess for primary school children (grade 4-8). The intervention is designed to implement organizational...... to 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...... as well as quantitative methods can be seen as a strength, as the different types of data complement each other and results of one part of the study informed the following parts. A unique aspect of our study is the use of accelerometers in combination with GPS and GIS in the effect evaluation...

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


    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.

  10. Activated protein C resistance in patients following venous thromboembolism receiving rivaroxaban versus vitamin K antagonists: assessment using Russell viper venom time-based assay. (United States)

    Goralczyk, Tadeusz; Wojtowicz, Katarzyna B; Undas, Anetta


    Activated protein C resistance (APC-R) is assessed as part of thrombophilia screening, preferably in patients not taking oral anticoagulants. Rivaroxaban is known to alter some APC-R assays. To our knowledge, there have been no reports on the effect of rivaroxaban on the Russell viper venom time (RVVT)-based APC-R assay in real-life patients. In 168 consecutive outpatients suspected of having venous thromboembolism because of thrombophilia, APC-R was determined using the RVVT-based ProC Ac R assay (Siemens, Marburg, Germany). Patients receiving rivaroxaban or vitamin K antagonists were eligible. We measured rivaroxaban concentrations using the anti-Xa Biophen DiXal assay (Hyphen Biomed, Neuville-Sur-Oise, France) and factor V Leiden using the real-time PCR. APC-R was detected in 23 (28%) patients on rivaroxaban (n = 81) administrated 2-48 h since the blood draw, 15 (28%) patients on vitamin K antagonists (n = 54), and in four (12%) patients off anticoagulation (n = 33). Compared with nonanticoagulated patients, APC-R ratios were similar in patients on rivaroxaban, without any correlation with rivaroxaban concentrations (from 0 to 303 μg/l). None of the patients on rivaroxaban were found to have false-negative or false-positive APC-R ratios. Rivaroxaban concentrations up to 300 μg/l do not affect results of the ProC Ac R RVVT-based assay, which could be recommended in patients referred to a clinic for thrombophilia screening in whom the time since the last dose of rivaroxaban is uncertain.

  11. Active house

    DEFF Research Database (Denmark)

    Eriksen, Kurt Emil; Olesen, Gitte Gylling Hammershøj


    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...

  12. Get Active (United States)

    ... Have fun with your family. If you have children, you can be a role model for making healthy choices. Encourage your whole family to get active outside . Go for a hike or organize a family soccer game. If someone you know has trouble making ...

  13. 含有FXa切割位点的抗菌肽X在大肠杆菌中的融合表达%Fusion Expression of Cecropin X Including the Cleavage of FXa in Escherichia coli

    Institute of Scientific and Technical Information of China (English)

    袁榴娣; 窦非; 梁玉璞; 谢维; 王芳; 张双全; 戴祝英


    PCR method was used to introduce the code sequence of Factor Xa cleavage site to the 5′ end of cecropin CMIV mutant gene X, then the gene was cloned into the expression vector pGEX-KG, and was highly expressed in E. coli BL21 by IPTG induction. The fusion protein was purified by affinity-chromatography and was cleaved by Factor Xa. Cecropin X with antibacterial activity was obtained after purified by ion-exchange chromatography.

  14. Active particles

    CERN Document Server

    Degond, Pierre; Tadmor, Eitan


    This volume collects ten surveys on the modeling, simulation, and applications of active particles using methods ranging from mathematical kinetic theory to nonequilibrium statistical mechanics. The contributing authors are leading experts working in this challenging field, and each of their chapters provides a review of the most recent results in their areas and looks ahead to future research directions. The approaches to studying active matter are presented here from many different perspectives, such as individual-based models, evolutionary games, Brownian motion, and continuum theories, as well as various combinations of these. Applications covered include biological network formation and network theory; opinion formation and social systems; control theory of sparse systems; theory and applications of mean field games; population learning; dynamics of flocking systems; vehicular traffic flow; and stochastic particles and mean field approximation. Mathematicians and other members of the scientific commu...

  15. Laboratory Activities

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Christopher F.; Serne, R. Jeffrey


    This chapter summarizes the laboratory activities performed by PNNL’s Vadose Zone Characterization Project in support of the Tank Farm Vadose Zone Program, led by CH2M HILL Hanford Group, Inc. The results of these studies are contained in numerous reports (Lindenmeier et al. 2002; Serne et al. 2002a, 2002b, 2002c, 2002d, 2002e; Lindenmeier et al. 2003; Serne et al. 2004a, 2004b; Brown et al. 2005, 2006a, 2007; Serne et al. 2007) and have generated much of the data reported in Chapter 22 (Geochemistry-Contaminant Movement), Appendix G (Geochemistry-Contaminant Movement), and Cantrell et al. (2007, SST WMA Geochemistry Data Package – in preparation). Sediment samples and characterization results from PNNL’s Vadose Zone Characterization Project are also shared with other science and technology (S&T) research projects, such as those summarized in Chapter 12 (Associated Science Activities).

  16. Antimicrobial Activity. (United States)


    Natural products of higher plants may possess a new source of antimicrobial agents with possibly novel mechanisms of action. They are effective in the treatment of infectious diseases while simultaneously mitigating many of the side effects that are often associated with conventional antimicrobials. A method using scanning electron microscope (SEM) to study the morphology of the bacterial and fungal microbes and thus determining antimicrobial activity is presented in the chapter.

  17. Fumarase activity

    DEFF Research Database (Denmark)

    Nielsen, Per Mose; Eldirdiri, Abubakr; Bertelsen, Lotte Bonde


    ]fumarate conversion to [1,4-(13)C2]malate by fumarase has been proposed as a measure of necrosis in rat tumor models and in chemically induced AKI rats. Here we show that the degradation of cell membranes in connection with necrosis leads to elevated fumarase activity in plasma and urine and secondly...... that hyperpolarized [1,4-(13)C2]malate production 24 h after reperfusion correlates with renal necrosis in a 40-min unilateral ischemic rat model. Fumarase activity screening on bio-fluids can detect injury severity, in bilateral as well as unilateral AKI models, differentiating moderate and severe AKI as well...... as short- and long-term AKI. Furthermore after verification of renal injury by bio-fluid analysis the precise injury location can be monitored by in vivo measurements of the fumarase activity non-invasively by hyperpolarized [1,4-(13)C]fumarate MR imaging. The combined in vitro and in vivo biomarker of AKI...

  18. Glucokinase activators. (United States)

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Frost C


    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

  20. Active instruments

    DEFF Research Database (Denmark)

    Lim, Miguel Antonio; Ørberg, Jakob Williams


    themselves. We draw on two multi-year field studies of India and Denmark to investigate how national reforms and developments within the ranking industry interact in often surprising ways. Rankings do not always do what policy makers expect. We (1) highlight the activity of rankers in these two countries, (2......) show the dynamic nature of policy processes, and (3) consider the search for policy reference points among the different actors. We present rankers in motion, policies in motion, and finally the complex nature of the ranking device that needs to be both a relevant and malleable policy instrument...

  1. Active packaging with antifungal activities. (United States)

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


    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.

  2. 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.

  3. Complejos bihidrogenoides confinados en pozos cuánticos GaAs-Ga1-XaLxAS


    Marìn Cadavid, Jairo Humberto


    Hace alrededor de dos décadas, las investigaciones de punta en la fabricación de dispositivos electrónicos, se basaban en el crecimiento de películas delgadas con espesores del orden de los micrones, los cuales tenían al Silicio como material más importante. Teniendo presente que la mayoría de propiedades de interés, relacionadas con sistemas de electrones, son fuertemente dependientes de la dimensionalidad, varios físicos se dieron a la tarea de fabricar nuevos materiales basados en capas de...

  4. Fusion of CTA and XA data using 3D centerline registration for plaque visualization during coronary intervention (United States)

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


    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.

  5. TaXA21-A1 on chromosome 5AL is associated with resistance to multiple pests in wheat (United States)

    A quantitative trait locus QYr.osu-5A on the long arm of chromosome 5A in bread wheat (Triticum aestivum L., 2n=6x=42; AABBDD) was previously reported to confer consistent resistance in adult plants to predominant stripe rust races, but the gene causing the quantitative trait locus (QTL) is not know...

  6. 77 FR 17323 - Special Conditions: XtremeAir GmbH, XA42; Acrobatic Category Aerodynamic Stability (United States)


    ... maintain a 3 degree angle of descent. (D) In place of 14 CFR part 23, Sec. 23.177, Static directional and... unusual design feature associated with its static stability. This airplane can perform at the highest...: April 25, 2012. FOR FURTHER INFORMATION CONTACT: Mr. Ross Schaller, Federal Aviation...

  7. BAM! Physical Activity (United States)

    ... Smarts Links Fuel Up for Fun Power Packing Physical Activity Xpert Opinion Activity Calendar Activity Cards Ballet Baseball ... Disaster - Are You at Risk? Disaster - Helping Hands Physical Activity - Questions Physical Activity - Active or Not, Here it ...

  8. Intangible activities

    DEFF Research Database (Denmark)

    Hermansen, Jonathan


    ‘Informal helping’ is often associated with other types of prosocial behaviour such as formal voluntary work. Therefore, one could jump to the conclusion that it would be the same factors driving both types of activities. This article demonstrates that this is not the case. The study relies...... on a population survey on informal helping and volunteering in Denmark. The two contributions of this article are as follows: (1) it demonstrates that the sociodemographic indicators that are closely linked to formal volunteering are not related to informal helping in the same manner and (2) it demonstrates...... that it is necessary to separate the decision to help and the amount of hours that people help, a distinction that previous empirical studies on this topic fail to include. The results show that informal helping may not simply be compared to other instances of prosocial behaviour. In particular, the socio...

  9. Assessment of the effects of dalteparin on coagulation variables and determination of a treatment schedule for use in cats. (United States)

    Schönig, Jette C; Mischke, Reinhard H


    OBJECTIVE To determine a treatment protocol for SC administration of dalteparin to cats on the basis of currently available detailed pharmacokinetic data and to assess the effect of SC administration of dalteparin to cats on coagulation variables such as activated partial thromboplastin time (aPTT), thrombin time, and results for thromboelastometry, compared with effects on anti-activated coagulation factor X (anti-Xa) activity. ANIMALS 6 healthy domestic shorthair cats. PROCEDURES Cats received 14 injections of dalteparin (75 anti-Xa U/kg, SC) at 6-hour intervals. Blood samples were collected before and 2 hours after the first and second injections on days 1, 2, and 4. Anti-Xa activity was measured by use of a chromogenic substrate assay, aPTT and thrombin time were measured by use of an automated coagulometer, and viscoelastic measurements were obtained with thromboelastrometry. RESULTS 2 hours after the second injection, the target peak anti-Xa activity range of 0.5 to 1.0 U/mL was achieved in all cats, whereas median trough values remained below this range. Peak anti-Xa activity had only minimal effects on coagulation variables; the maximum median ratio for aPTT (in relationship to the value before the first dalteparin injection) was 1.23. CONCLUSIONS AND CLINICAL RELEVANCE Results of this study indicated that this treatment protocol resulted in reproducible anti-Xa activity in cats that was mostly within the targeted peak range of anti-Xa activity recommended for humans. Treatment in accordance with this protocol may not require routine coagulation monitoring of cats, but this must be confirmed in feline patients.

  10. 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 (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.


    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

  11. Active sharing

    CERN Multimedia


    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...

  12. DAVIC activities (United States)

    Fujiwara, Hiroshi


    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.

  13. Survival of heparins, oral anticoagulants, and aspirin after the year 2010. (United States)

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


    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

  14. IASS Activity (United States)

    Hojaev, Alisher S.; Ibragimova, Elvira M.


    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.

  15. Activation Energy (United States)

    Gadeken, Owen


    Teaming is so common in today's project management environment that most of us assume it comes naturally. We further assume that when presented with meaningful and challenging work, project teams will naturally engage in productive activity to complete their tasks. This assumption is expressed in the simple (but false) equation: Team + Work = Teamwork. Although this equation appears simple and straightforward, it is far from true for most project organizations whose reality is a complex web of institutional norms based on individual achievement and rewards. This is illustrated by the very first successful team experience from my early Air Force career. As a young lieutenant, I was sent to Squadron Officer School, which was the first in the series of Air Force professional military education courses I was required to complete during my career. We were immediately formed into teams of twelve officers. Much of the course featured competition between these teams. As the most junior member of my team, I quickly observed the tremendous pressure to show individual leadership capability. At one point early in the course, almost everyone in our group was vying to become the team leader. This conflict was so intense that it caused us to fail miserably in our first outdoor team building exercise. We spent so much time fighting over leadership that we were unable to complete any of the events on the outdoor obstacle course. This complete lack of success was so disheartening to me that I gave our team little hope for future success. What followed was a very intense period of bickering, conflict, and even shouting matches as our dysfunctional team tried to cope with our early failures and find some way to succeed. British physician and researcher Wilfred Bion (Experiences in Groups, 1961) discovered that there are powerful psychological forces inherent in all groups that divert from accomplishing their primary tasks. To overcome these restraining forces and use the potential


    Directory of Open Access Journals (Sweden)

    Chaitanya Gadiko*, Satyanarayana Thota and Sudhakar K. Tippabotla


    Full Text Available Bioequivalence needs to be established on healthy human volunteers for Low Molecular Weight Heparins (LMWHs such as Dalteparin, Enoxaparin, Tinzaparin and Fondaparinux using Pharmacodynamic marker(s for generic approval. Anti-Xa and anti-IIa activity are used to determine the activity of LMWHs (Dalteparin, Enoxaparin and Tinzaparin and anti-Xa activity for Fondaparinux in biological samples for the assessment of its bioavailability. These are selected based on the pharmacodynamic activities of LMWHs. LMWHs exhibit their antithrombotic activity preferentially by inhibiting clotting Factor Xa, and to a lesser extent Factor IIa. On the other hand Fondaparinux is a synthetic and specific inhibitor of Factor-Xa and hencebioequivalence needs to be established for only anti-Xa activity. The pharmacodynamic data of anti-IIa activity need to be submitted for regulatory agency as supportive data of comparable therapeutic outcome for all LMWHs except Fondaparinux. In addition to the above, pharmacokinetic data of Heptest (Heparin clotting assay and activated Partial Thromboplastin Time (aPTT may also serve as a supportive evidence for establishing bioequivalence of LMWH formulations as there were no clear recommendations available.

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

    Directory of Open Access Journals (Sweden)

    Ramadan A


    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

  18. 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.

  19. TAL nucleases (TALNs): hybrid proteins composed of TAL effectors and FokI DNA-cleavage domain. (United States)

    Li, Ting; Huang, Sheng; Jiang, Wen Zhi; Wright, David; Spalding, Martin H; Weeks, Donald P; Yang, Bing


    DNA double-strand breaks enhance homologous recombination in cells and have been exploited for targeted genome editing through use of engineered endonucleases. Here we report the creation and initial characterization of a group of rare-cutting, site-specific DNA nucleases produced by fusion of the restriction enzyme FokI endonuclease domain (FN) with the high-specificity DNA-binding domains of AvrXa7 and PthXo1. AvrXa7 and PthXo1 are members of the transcription activator-like (TAL) effector family whose central repeat units dictate target DNA recognition and can be modularly constructed to create novel DNA specificity. The hybrid FN-AvrXa7, AvrXa7-FN and PthXo1-FN proteins retain both recognition specificity for their target DNA (a 26 bp sequence for AvrXa7 and 24 bp for PthXo1) and the double-stranded DNA cleaving activity of FokI and, thus, are called TAL nucleases (TALNs). With all three TALNs, DNA is cleaved adjacent to the TAL-binding site under optimal conditions in vitro. When expressed in yeast, the TALNs promote DNA homologous recombination of a LacZ gene containing paired AvrXa7 or asymmetric AvrXa7/PthXo1 target sequences. Our results demonstrate the feasibility of creating a tool box of novel TALNs with potential for targeted genome modification in organisms lacking facile mechanisms for targeted gene knockout and homologous recombination.

  20. Staying Active: Physical Activity and Exercise (United States)

    ... Examples of muscle-strengthening activities include lifting weights, yoga, push-ups, and sit-ups. A “repetition” is one complete movement of an activity. To get health benefits, do muscle-strengthening activities until it is hard ...

  1. Physical Activity Assessment (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.

  2. 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


    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.

  3. Immunizations: Active vs. Passive (United States)

    ... Prevention > Immunizations > Immunizations: Active vs. Passive Safety & Prevention Listen Español Text Size Email Print Share Immunizations: Active vs. Passive Page Content Article Body Pediatricians can ...

  4. Political activity for physical activity: health advocacy for active transport. (United States)

    Richards, Rosalina; Murdoch, Linda; Reeder, Anthony I; Amun, Qa-t-a


    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 sustainability, transport and urban

  5. Criminalisation of Activism

    DEFF Research Database (Denmark)

    Uldam, Julie

    Different forms of political participation involve different challenges. This paper focuses on challenges to radical activism and particularly the criminalisation of activism.......Different forms of political participation involve different challenges. This paper focuses on challenges to radical activism and particularly the criminalisation of activism....

  6. Active commuting to school (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...

  7. 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. (United States)

    Nakamura, S; Iwanaga, S; Suzuki, T


    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], Factor XIIa, kallikreins [EC], urokinase [EC], trypsin [EC], ficin [EC], papain [EC], and bromelain [EC]. Among these enzymes, only bromelain and trypsin showed clear activating effects.

  8. Physical Activity During School

    DEFF Research Database (Denmark)

    Østergaard, Lars Domino

    It is important, not only on health grounds, to exercise and to be physically active. In school, physical activities have shown to improve the students’ academic behaviour resulting in improved attention and information processing as well as enhanced coping. To stimulate and motivate students...... to be even more active during school hours further enhancing their academic behaviour, it is important to know when, why and how they are active, and their attitude towards different types of physical activities. Therefore, the aim of this study was to categorize the physical activities attended by students...... during school hours and to elucidate their attitude towards the different types of activities. The data consisted of observations of lessons followed by group interviews. Analyses of the observations revealed six categories of physical activities, varying from mandatory physical activities, activities...

  9. Análisis de los efectos de anti-factor de crecimiento endotelial vascular (anti-VEGF)sobre el desprendimiento del epitelio pigmentario asociado a DMAE exudativa


    Karandiuk, Nataliia


    La degeneración macular asociada a la edad (DMAE) representa, en la actualidad, un importante problema de salud pública en todos los países desarrollados. Está considerada como la principal causa de ceguera legal por encima de los 50 años y una de las primeras causas de mala visión. La implicación del factor de crecimiento vascular endotelial (VEGF) en su patogenia y la llegada de la terapia antiangiogénica han cambiado su pronóstico funcional, si bien es cierto que la eficacia de la misma...

  10. 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


    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.

  11. Anti-CD3 antibodies modulate anti-factor VIII immune responses in hemophilia A mice after factor VIII plasmid-mediated gene therapy. (United States)

    Peng, Baowei; Ye, Peiqing; Rawlings, David J; Ochs, Hans D; Miao, Carol H


    One major obstacle in gene therapy is the generation of immune responses directed against transgene product. Five consecutive anti-CD3 treatments concomitant with factor VIII (FVIII) plasmid injection prevented the formation of inhibitory antibodies against FVIII and achieved persistent, therapeutic levels of FVIII gene expression in treated hemophilia A mice. Repeated plasmid gene transfer is applicable in tolerized mice without eliciting immune responses. Anti-CD3 treatment significantly depleted both CD4+ and CD8+ T cells, whereas increased transforming growth factor-beta levels in plasma and the frequency of both CD4+CD25+FoxP3+ and CD4+CD25-Foxp3+ regulatory T cells in the initial few weeks after treatment. Although prior depletion of CD4+CD25+ cells did not abrogate tolerance induction, adoptive transfer of CD4+ cells from tolerized mice at 6 weeks after treatment protected recipient mice from anti-FVIII immune responses. Anti-CD3-treated mice mounted immune responses against both T-dependent and T-independent neo-antigens, indicating that anti-CD3 did not hamper the immune systems in the long term. Concomitant FVIII plasmid + anti-CD3 treatment induced long-term tolerance specific to FVIII via a mechanism involving the increase in transforming growth factor-beta levels and the generation of adaptive FVIII-specific CD4+Foxp3+ regulatory T cells at the periphery. Furthermore, anti-CD3 can reduce the titers of preexisting anti-FVIII inhibitory antibodies in hemophilia A mice.

  12. Characterization of the anti-factor VIII immunoglobulin profile in patients with hemophilia A by use of a fluorescence-based immunoassay (United States)

    Boylan, Brian; Rice, Anne S.; Dunn, Amy L.; Tarantino, Michael D.; Brettler, Doreen B.; Barrett, John C.; Miller, Connie H.


    Summary Background The development of neutralizing antibodies, referred to as inhibitors, against factor VIII (FVIII) is a major complication associated with FVIII infusion therapy for the treatment of hemophilia A (HA). Previous studies have shown that a subset of HA patients and a low percentage of healthy individuals harbor non-neutralizing anti-FVIII antibodies that do not elicit the clinical manifestations associated with inhibitor development. Objective Assess HA patients' anti-FVIII antibody profiles as potential predictors of clinical outcomes. Methods A fluorescence immunoassay (FLI) was used to detect anti-FVIII antibodies in 491 samples from 371 HA patients. Results Assessments of antibody profiles showed that the presence of anti-FVIII IgG1, IgG2, or IgG4 correlated qualitatively and quantitatively with the presence of a FVIII inhibitor as reported by the Nijmegen-Bethesda assay (NBA). Forty-eight patients with a negative inhibitor history contributed serial samples to the study, including seven patients who had negative NBA titers initially and later converted to NBA-positive. The FLI detected anti-FVIII IgG1 in five of those seven patients prior to their conversion to NBA-positive. Five of 15 serial-sample patients who had a negative inhibitor history and a positive anti-FVIII IgG1 later developed an inhibitor, compared to 2 of 33 patients with a negative inhibitor history without anti-FVIII IgG1. Conclusions These data provide a rationale for future studies designed both to monitor the dynamics of anti-FVIII antibody profiles in HA patients as a potential predictor of future inhibitor development and to assess the value of the anti-FVIII FLI as a supplement to traditional inhibitor testing. PMID:25354263

  13. 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.

  14. Cultural Activation of Consumers. (United States)

    Siegel, Carole E; Reid-Rose, Lenora; Joseph, Adriana M; Hernandez, Jennifer C; Haugland, Gary


    This column discusses "cultural activation," defined as a consumer's recognition of the importance of providing cultural information to providers about cultural affiliations, challenges, views about, and attitudes toward behavioral health and general medical health care, as well as the consumer's confidence in his or her ability to provide this information. An aid to activation, "Cultural Activation Prompts," and a scale that measures a consumer's level of activation, the Cultural Activation Measurement Scale, are described. Suggestions are made about ways to introduce cultural activation as a component of usual care.

  15. Anticoagulation after subcutaneous enoxaparin is time sensitive in STEMI patients treated with tenecteplase. (United States)

    Welsh, Robert C; Westerhout, Cynthia M; Buller, Christopher E; O'Neill, Blair; Gordon, Phillip; Armstrong, Paul W


    The adequacy of anticoagulation with enoxaparin as an adjuvant to fibrinolytic therapy for STEMI is unclear and has implications for both efficacy and safety; especially in patients undergoing a pharmacoinvasive reperfusion strategy. A subset of fibrinolytic-treated patients in the WEST study was enrolled in a systematic anti-Xa substudy. All received ASA and subcutaneous (SQ) enoxaparin 1 mg/kg followed by TNK-tPA. Incremental IV dosing of enoxaparin (0.3-0.5 mg/kg) was allowed prior to percutaneous coronary intervention (PCI). Anti-Xa blood samples were drawn prior and after angiography. Data are presented as percentages, medians and IQRs. Forty-five patients underwent angiography 2.8 h (2.5-14.6) after fibrinolytic. The pre-angiography median anti-Xa acquired 179 min (153-875) after SQ enoxaparin was 0.48 U/ml (0.42-0.65); a relationship between anti-Xa activity and time from administration was evident (r = 0.418, p < 0.007). Without supplemental IV enoxaparin the 2nd anti-Xa acquired 218 min (195-930) after SQ enoxaparin was 0.48 U/ml (0.41-0.80, n = 29). After supplemental IV enoxaparin, the 2nd anti-Xa was 0.92 U/ml (0.72-1.10, n = 16). An incremental IV enoxaparin dose and anti-Xa relationship was demonstrated (r = 0.59, p = 0.001) i.e. no IV 0.48 U/ml (0.41-0.80, n = 29), 0.3 mg/kg IV 0.81 U/ml (0.63-1.00, n = 12), and 0.5 mg/kg IV 1.34 U/ml (1.16-1.54, n = 4). Most fibrinolytic treated STEMI patients receiving weight-adjusted SQ enoxaparin (1 mg/kg) had subtherapeutic anti-Xa levels (<0.5 U/ml) after ~3 h. A strategy of supplemental 0.3 mg/kg IV enoxaparin at time of PCI reliably achieved anti-Xa ≥ 0.5 U/ml. Our findings provide a rational novel strategy for anti-thrombotic management in STEMI patients undergoing a pharmacoinvasive reperfusion strategy.

  16. Major operations and activities

    Energy Technology Data Exchange (ETDEWEB)

    Black, D.G.


    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.

  17. ACS Community Activities Contests (United States)

    Burgener, Marisa


    The Committee on Community Activities and the Office of Community Activities announce the winners of the Illustrated Haiku Contest, Earth Day 2007 and the Poster Contest, National Chemistry Week 2006.

  18. Active Marine Station Metadata (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...

  19. USAID Activity Locatons (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 magnetic regenerator (United States)

    Barclay, John A.; Steyert, William A.


    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.

  1. Physical Activity (Exercise) (United States)

    ... page Subscribe to ePublications email updates. Enter email address Submit Home > ePublications > Our ePublications > Physical activity (exercise) fact sheet ePublications Physical activity (exercise) ...

  2. Guide to Physical Activity (United States)

    ... minutes Stairwalking for 15 minutes Sporting Activities Playing volleyball for 45–60 minutes Playing touch football for ... strenuous activities. Competitive sports, such as tennis and volleyball, can provide an enjoyable form of exercise for ...

  3. Italian active volcanoes

    Institute of Scientific and Technical Information of China (English)

    RobertoSantacroce; RenawCristofolini; LuigiLaVolpe; GiovanniOrsi; MauroRosi


    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.

  4. Facts about Physical Activity (United States)

    ... Nutrition Physical Activity Overweight & Obesity Healthy Weight Breastfeeding Micronutrient Malnutrition State and Local Programs Facts about Physical ... Nutrition Physical Activity Overweight & Obesity Healthy Weight Breastfeeding Micronutrient Malnutrition State and Local Programs File Formats Help: ...

  5. Family Activities for Fitness (United States)

    Grosse, Susan J.


    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.

  6. Activity Theory and Ontology (United States)

    Peim, Nick


    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…

  7. Measurement of Physical Activity. (United States)

    Dishman, Rod K.; Washburn, Richard A.; Schoeller, Dale A.


    Valid assessment of physical activity must be unobtrusive, practical to administer, and specific about physical activity type, frequency, duration, and intensity. Assessment methods can be categorized according to whether they provide direct or indirect (e.g., self-report) observation of physical activity, body motion, physiological response…

  8. Ras activation by SOS

    DEFF Research Database (Denmark)

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


    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 ...

  9. Proteolytic activities in yeast. (United States)

    Saheki, T; Holzer, H


    Studies on the mechanism and time course of the activation of proteinases A (EC, B (EC and C (EC 3.4.12.--) in crude yeast extracts at pH 5.1 and 25 degrees C showed that the increase in proteinase B activity is paralleled with the disappearance of proteinase B inhibitor. Addition of purified proteinase A to fresh crude extracts accelerates the inactivation of the proteinase B inhibitor and the appearance of maximal activities of proteinases B and C. The decrease of proteinase B inhibitor activity and the increase of proteinase B activity are markedly retarded by the addition of pepstatin. Because 10-minus 7 M pepstatin completely inhibits proteinase A without affecting proteinase B activity, this is another indication for the role of proteinase A during the activation of proteinase B. Whereas extracts of yeast grown on minimal medium reached maximal activation of proteinases B and C after 20 h of incubation at pH 5.1 and 25 degrees C, extracts of yeast grown on complete medium had to be incubated for about 100 h. In the latter case, the addition of proteinas A results in maximal activation of proteinases B and C and disappearance of proteinase B inhibitor activity only after 10--20 h of incubation. With the optimal conditions, the maximal activities of proteinases A, B and C, as well as of the proteinase B inhibitor, were determined in crude extracts of yeast that had been grown batchwise for different lengths of time either on minimal or on complete medium. Upon incubation, all three proteinases were activated by several times their initial activity. This reflects the existence of proteolytically degradable inhibitors of the three proteinases and together with the above mentioned observations it demonstrates that the "activation" of yeast proteinases A, B and C upon incubation results from the proteolytic digestion of inhibitors rather than from activation of inactive zymogens by limited proteolysis.

  10. Recurrent radio activity in active galactic nuclei

    Directory of Open Access Journals (Sweden)

    Jamrozy M.


    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.

  11. Active ageing technologies

    DEFF Research Database (Denmark)

    Lassen, Aske Juul

    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...... ‘sites of active aging’ in Denmark. By presenting three technologies of active aging (billiards at an activity center for elderly persons, dancing tiles for rehabilitation after falls and an online fitness community for elderly persons) the paper suggests that active aging is more than regimes...

  12. Accessibility, activity participation and location of activities

    DEFF Research Database (Denmark)

    Næss, Petter


    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...... outweigh each other. However, differences in trip distances due to the location of the dwelling relative to concentrations of facilities translate into substantially longer total travelling distances among suburbanites than among inner-city residents....... 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...

  13. Expression and characterization of the N-terminal half of antistasin, an anticoagulant protein derived from the leech Haementeria officinalis. (United States)

    Palladino, L O; Tung, J S; Dunwiddie, C; Alves, K; Lenny, A B; Przysiecki, C; Lehman, D; Nutt, E; Cuca, G C; Law, S W


    Antistasin, a 15-kDa anticoagulant protein isolated from the salivary glands of the Mexican leech Haementeria officinalis, has been shown to be a potent inhibitor of factor Xa in the blood coagulation cascade. Antistasin possesses a twofold internal homology between the N- and C-terminal halves of the molecule, suggesting a gene duplication event in the evolution of the antistasin gene. This structural feature also suggests that either or both halves of the protein may possess biological activity if expressed as separate domains. Because the N-terminal domain contains a factor Xa P1-reactive site, we chose to express this domain in an insect cell baculovirus expression system. Characterization of this recombinant half antistasin molecule reveals that the N-terminal domain inhibits factor Xa in vitro, with a K(i) of 1.7 nM.

  14. Marine Biology Activities. Ocean Related Curriculum Activities. (United States)

    Pauls, John

    The ocean affects all of our lives. Therefore, awareness of and information about the interconnections between humans and oceans are prerequisites to making sound decisions for the future. Project ORCA (Ocean Related Curriculum Activities) has developed interdisciplinary curriculum materials designed to meet the needs of students and teachers…

  15. Active knee joint flexibility and sports activity

    DEFF Research Database (Denmark)

    Hahn, Thomas; Foldspang, Anders; Vestergaard, E


    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...

  16. [Biomedical activity of biosurfactants]. (United States)

    Krasowska, Anna


    Biosurfactants, amphiphilic compounds, synthesized by microorganisms have surface, antimicrobial and antitumor properties. Biosurfactants prevent adhesion and biofilms formation by bacteria and fungi on various surfaces. For many years microbial surfactants are used as antibiotics with board spectrum of activity against microorganisms. Biosurfactants act as antiviral compounds and their antitumor activities are mediated through induction of apoptosis. This work presents the current state of knowledge related to biomedical activity of biosurfactants.

  17. CDBG Economic Development Activity (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...

  18. CDBG Housing Activity (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...

  19. CDBG Public Services Activity (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, food...

  20. 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


    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.

  1. Study on the separation and purification of chlorogenic acid and its antioxidant activity from Eucommia ulmoides Oliv.leaves%杜仲叶绿原酸分离纯化工艺比较及其抗氧化性研究

    Institute of Scientific and Technical Information of China (English)

    李文娜; 肖苑; 陈阳


    Objective: To optimize the separation and purification method of chlorogenic acid from leaves of Eucommia ulmoides Oliv. And study its antioxidant activities. Methods: The extraction effects of chlorogenic acid from leaves of Eucommia ulmoides Oliv. Was used as evaluation index. The optimum separation conditions were designed by using lime precipitation, solvent extraction, precipitation of lead acetate and chitosan to separate chlorogenic acid. Seven types of macroporous resin, including NKA-9, NKA-Ⅱ, D101, XA-8, DA-8, HPD100 and HPD826 were compared the purification efficiency. The antioxidant activity of extracts was evaluated. Results: Chitosan and NKA-9 macroporous resin can be used in the separation and purification of crude extracs of chlorogenic acid from leaves of Eucommia ulmoides Oliv. The chlorogenic acid in stock solution was 2.54%.The purity of the product after the resin purification was 42.43%, which was for increased 16 times. Conclusion: Chitosan and NKA-9 was suitable to separate and purify the chlorogenic acid. The extract of chlorogenic acid from Eucommia ulmoides leaves has more effective antioxidant activity than chlorogenic acid.%目的:优化杜仲叶中绿原酸的分离纯化工艺,并探讨其抗氧化活性.方法:以绿原酸提取率为指标,比较铅沉淀、石灰乳沉淀、溶剂萃取、壳聚糖絮凝除杂对粗提物的分离效率,并考察7种大孔树脂对绿原酸的吸附性能,还研究了杜仲叶绿原酸提取物的抗氧化活性.结果:最佳分离除杂方法为壳聚糖絮凝除杂法,最佳树脂为NKA-9型大孔树脂,上柱前粗提物绿原酸含量为2.54%,经大孔树脂纯化后产品中绿原酸含量达到42.43%,提高了16倍.结论:壳聚糖絮凝除杂法能很好分离除杂,NKA-9型大孔树脂对杜仲叶绿原酸有较好纯化效果.杜仲叶绿原酸提取物抗氧化活性强于绿原酸标准品.

  2. Activity Book: Ocean Ecology. (United States)

    Learning, 1992


    Presents a collection of activities to help elementary students study ocean ecology. The activities have students investigate ocean inhabitants, analyze animal adaptations, examine how temperature and saltiness affect ocean creatures, and learn about safeguarding the sea. Student pages offer reproducible learning sheets. (SM)

  3. Reflections on Activity Theory (United States)

    Bakhurst, David


    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…

  4. The Activity of Play

    DEFF Research Database (Denmark)

    Pichlmair, Martin


    This paper presents Activity Theory as a framework for understanding the action of playing games with the intention of building a foundation for the creation of new game design tools and methods. Activity Theory, an epistemological framework rooted in Soviet psychology of the first half of the 20...

  5. Physical Activity Questionnaire

    Directory of Open Access Journals (Sweden)

    Kostencka Alicja


    Full Text Available Study aim: The aim of the study was to determine the weekly energy expenditure measuring MET/min/week based on data collected through the Canada Fitness Survey (CFS, according to the classification used in the International Physical Activity Questionnaire (IPAQ, and to verify the adopted method to assess the level of physical activity in students of physical education.

  6. Active and Healthy Schools (United States)

    Ball, Stephen; Kovarik, Jessica; Leidy, Heather


    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…

  7. Activating Event Knowledge (United States)

    Hare, Mary; Jones, Michael; Thomson, Caroline; Kelly, Sarah; McRae, Ken


    An increasing number of results in sentence and discourse processing demonstrate that comprehension relies on rich pragmatic knowledge about real-world events, and that incoming words incrementally activate such knowledge. If so, then even outside of any larger context, nouns should activate knowledge of the generalized events that they denote or…

  8. Emotionally Intense Science Activities (United States)

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


    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…

  9. Peak Longevity Physical Activity (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.

  10. Activities of the ILO. (United States)

    Labour Education, 1984


    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)

  11. Choreography of AMPK activation. (United States)

    Langendorf, Christopher G; Kemp, Bruce E


    A recent study published in Cell Research by Li and colleagues reports a detailed biophysical and structural study of AMPK's intra-molecular interactions during activation. By employing subunit tagging and proximity analysis with the aid of AlphaScreen instrumentation, Li et al. add to our understanding of the choreography of activation of AMPK by both nucleotides and phosphorylation.

  12. Obesity, Physical Activity - Children. (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…

  13. Active at Any Size (United States)

    ... go to the gym all the time to benefit from being active. To make physical activity more fun, try something you enjoy doing, such as dancing to the radio or taking a yoga class with friends. Many people find they start ...

  14. Global physical activity levels

    DEFF Research Database (Denmark)

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


    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-old) ...

  15. Biomedical activity of biosurfactants


    Anna Krasowska


    Biosurfactants, amphiphilic compounds, synthesized by microorganisms have surface, antimicrobial and antitumor properties. Biosurfactants prevent adhesion and biofilms formation by bacteria and fungi on various surfaces. For many years microbial surfactants are used as antibiotics with board spectrum of activity against microorganisms. Biosurfactants act as antiviral compounds and their antitumor activities are mediated through induction of apoptosis. This work presents the current state of k...

  16. Activity-based design

    DEFF Research Database (Denmark)

    Andersen, Peter Bøgh


    : what you can do depends upon where you are. Finally, human and automatic machinery alternate in filling certain roles in the activity: sometime the officer maintains the course, sometimes the autopilot. Such activities require us to rethink the traditional oppositions between communication...

  17. A designated centre for people with disabilities operated by Health Service Executive, Westmeath

    LENUS (Irish Health Repository)

    Quinlan, Catherine


    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.

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

    LENUS (Irish Health Repository)

    Quinlan, Catherine


    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.

  19. Determinants of Physical Activity in Active and Low-Active, Sixth Grade African-American Youth. (United States)

    Trost, Stewart G.; Pate, Russell R.; Ward, Dianne S.; Saunders, Ruth; Riner, William


    Compared determinants of physical activity in active and low-active African-American sixth graders, surveying students and making objective assessments of physical activity over seven days. Results indicated that physical activity self-efficacy, beliefs about physical activity outcomes, involvement in community-based physical activity, perception…

  20. Intracellular light-activation of riboswitch activity. (United States)

    Walsh, Steven; Gardner, Laura; Deiters, Alexander; Williams, Gavin J


    By combining a riboswitch with a cell-permeable photocaged small-molecule ligand, an optochemical gene control element was constructed that enabled spatial and temporal control of gene expression in bacterial cells. The simplicity of this strategy, coupled with the ability to create synthetic riboswitches with tailored ligand specificities and output in a variety of microorganisms, plants, and fungi might afford a general strategy to photocontrol gene expression in vivo. The ability to activate riboswitches by using light enables the interrogation and manipulation of a wide range of biological processes with high precision, and will have broad utility in the regulation of artificial genetic circuits.

  1. Biological activities of alginate. (United States)

    Ueno, Mikinori; Oda, Tatsuya


    To gain insight into the structure-activity relationship of alginate, we examined the effect of alginates with varying molecular weights and M/G ratio on murine macrophage cell line, RAW264.7 cells in terms of induction of tumor necrosis factor-α (TNF-α) secretion. Among the alginates tested, alginate with the highest molecular weight (MW 38,000, M/G 2.24) showed the most potent TNF-α-inducing activity. Alginates having higher M/G ratio tended to show higher activity. These results suggest that molecular size and M/G ratio are important structural parameters influencing the TNF-α-inducing activity. Interestingly, enzymatic depolymerization of alginate with bacterial alginate lyase resulted in dramatic increase in the TNF-α-inducing activity. The higher activity of enzymatically digested alginate oligomers to induce nitric oxide production from RAW264.7 cells than alginate polymer was also observed. On the other hand, alginate polymer and oligomer showed nearly equal hydroxyl radical scavenging activities.

  2. Emotionally Intense Science Activities (United States)

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


    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.

  3. Active optical zoom system (United States)

    Wick, David V.


    An active optical zoom system changes the magnification (or effective focal length) of an optical imaging system by utilizing two or more active optics in a conventional optical system. The system can create relatively large changes in system magnification with very small changes in the focal lengths of individual active elements by leveraging the optical power of the conventional optical elements (e.g., passive lenses and mirrors) surrounding the active optics. The active optics serve primarily as variable focal-length lenses or mirrors, although adding other aberrations enables increased utility. The active optics can either be LC SLMs, used in a transmissive optical zoom system, or DMs, used in a reflective optical zoom system. By appropriately designing the optical system, the variable focal-length lenses or mirrors can provide the flexibility necessary to change the overall system focal length (i.e., effective focal length), and therefore magnification, that is normally accomplished with mechanical motion in conventional zoom lenses. The active optics can provide additional flexibility by allowing magnification to occur anywhere within the FOV of the system, not just on-axis as in a conventional system.

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

    Institute of Scientific and Technical Information of China (English)


    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.

  5. Anticoagulant and antithrombotic activities of modified xylofucan sulfate from the brown alga Punctaria plantaginea. (United States)

    Ustyuzhanina, Nadezhda E; Bilan, Maria I; Gerbst, Alexey G; Ushakova, Natalia A; Tsvetkova, Eugenia A; Dmitrenok, Andrey S; Usov, Anatolii I; Nifantiev, Nikolay E


    Selectively and totally sulfated (1 → 3)-linked linear homofucans bearing ∼ 20 monosaccharide residues on average have been prepared from the branched xylofucan sulfate isolated from the brown alga Punctaria plantaginea. Anticoagulant and antithrombotic properties of the parent biopolymer and its derivatives were assessed in vitro. Highly sulfated linear fucan derivatives were shown to inhibit clot formation in APTT assay and ristocetin induced platelets aggregation, while the partially sulfated analogs were inactive. In the experiments with purified proteins, fucan derivatives with degree of sulfation of ∼ 2.0 were found to enhance thrombin and factor Xa inhibition by antithrombin III. The effect of sulfated fucans on thrombin inhibition, which was similar to those of heparinoid Clexane(®) (enoxaparin) and of a fucoidan from the brown alga Saccharina latissima studied previously, can be explained by the multicenter interaction and formation of a ternary complex thrombin-antithrombin III-polysaccharide. The possibility of such complexation was confirmed by computer docking study.

  6. A universe of activities (United States)

    Armentia, J.; Jáuregui, F.; Gordón, N.; Manzanal, R.

    Since its opening back in november 1993 the Planetarium of Pamplona has gone a long way creating activities related to teaching and communicating Astronomy, Science and other areas of what we call Culture. In this poster we present a summary of some of the most relevant activities that have had an special relevance throughout these years. We will refer to our “School of Stars” in which more than 400 000 students have already been involved and other activities that have been very appreciated by our visitors.

  7. Physics of solar activity (United States)

    Sturrock, Peter A.


    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.

  8. China's Space Activities

    Institute of Scientific and Technical Information of China (English)

    China National Space Administration


    @@ 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.

  9. Active Directory cookbook

    CERN Document Server

    Hunter, Laura


    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

  10. Creative activity and inclusion

    Directory of Open Access Journals (Sweden)

    Shemanov A.Yu.


    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.

  11. Active Packaging Coatings

    Directory of Open Access Journals (Sweden)

    Luis J. Bastarrachea


    Full Text Available Active food packaging involves the packaging of foods with materials that provide an enhanced functionality, such as antimicrobial, antioxidant or biocatalytic functions. This can be achieved through the incorporation of active compounds into the matrix of the commonly used packaging materials, or by the application of coatings with the corresponding functionality through surface modification. The latter option offers the advantage of preserving the packaging materials’ bulk properties nearly intact. Herein, different coating technologies like embedding for controlled release, immobilization, layer-by-layer deposition, and photografting are explained and their potential application for active food packaging is explored and discussed.

  12. In-vitro suppression of IL-6 and IL-8 release from human pulmonary epithelial cells by non-anticoagulant fraction of enoxaparin.

    Directory of Open Access Journals (Sweden)

    Madhur D Shastri

    Full Text Available Enoxaparin, a mixture of anticoagulant and non-anticoagulant fractions, is widely used as an anticoagulant agent. However, it is also reported to possess anti-inflammatory properties. Our study indicated that enoxaparin inhibits the release of IL-6 and IL-8 from A549 pulmonary epithelial cells. Their release causes extensive lung tissue damage. The use of enoxaparin as an anti-inflammatory agent is hampered due to the risk of bleeding associated with its anticoagulant fractions. Therefore, we aimed to identify the fraction responsible for the observed anti-inflammatory effect of enoxaparin and to determine the relationship between its structure and biological activities.A549 pulmonary epithelial cells were pre-treated in the presence of enoxaparin and its fractions. The levels of IL-6 and IL-8 released from the trypsin-stimulated cells were measured by ELISA. The anticoagulant activity of the fraction responsible for the effect of enoxaparin was determined using an anti-factor-Xa assay. The fraction was structurally characterised using nuclear magnetic resonance. The fraction was 2-O, 6-O or N-desulfated to determine the position of sulfate groups required for the inhibition of interleukins. High-performance size-exclusion chromatography was performed to rule out that the observed effect was due to the interaction between the fraction and trypsin or interleukins.Enoxaparin (60 μg/mL inhibited the release of IL-6 and IL-8 by >30%. The fraction responsible for this effect of enoxaparin was found to be a disaccharide composed of α-L-iduronic-acid and α-D-glucosamine-6-sulfate. It (15 μg/mL inhibited the release of interleukins by >70%. The 6-O sulphate groups were responsible for its anti-inflammatory effect. The fraction did not bind to trypsin or interleukins, suggesting the effect was not due to an artefact of the experimental model.The identified disaccharide has no anticoagulant activity and therefore eliminates the risk of bleeding

  13. 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;


    , 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...

  14. Clinical decision-making for vitamin K-1 and K-2 deficiency and coronary artery calcification with warfarin therapy: are diet, factor Xa inhibitors or both the answer? (United States)

    Wahlqvist, Mark L; Tanaka, Kiyoshi; Tzeng, Bing-Hsiean


    Coronary artery calcification is a recognised risk factor for ischaemic heart disease and mortality. Evidence is now strong that Mönckeberg's arteriosclerosis, a form of vascular calcification, can be attributable to vitamin K deficiency, but that vitamin K-2, especially the MK-4 form from foods like cheese can be protective. Warfarin blocks the recycling of hepatic and peripheral vitamin K leading to secondary vitamin K deficiency with adverse effects on vasculature, bone, kidneys, brain and other tissues and systems (inflammatory, immune function and neoplasia at least). There is individual susceptibility to vitamin K deficiency and warfarin sensitivity, partly explicable in terms of genetic polymorphisms, epigenetics, diet and pharmacotherapy. The emergence of extensive coronary calcification in a man with atrial fibrillation treated for a decade with warfarin is described by way of illustration and to raise the present clinical management conundrums. Finally, a putative set of recommendations is provided.

  15. 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


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


    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...

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


    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

  17. Creating Art Appreciation Activities. (United States)

    Heidt, Ann H.


    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)

  18. Active flows on trees

    CERN Document Server

    Forrow, Aden; Dunkel, Jörn


    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...

  19. Tanzania - Kigoma Solar Activity (United States)

    Millennium Challenge Corporation — The performance evaluation of the Kigoma solar activity was designed to answer questions about the implementation of the program and about outcomes that may have...

  20. Physical activity: genes & health

    CERN Multimedia


    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.

  1. Homebuyer Activities Report (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,...

  2. Math Lab Activities (United States)

    Brumbaugh, Douglas K.; Hynes, Michael C.


    The goals, objects, materials and grade levels are specified in this description of a laboratory activity involving analytic geometry concepts. Students mark out bicycle gymkhana courses in which directions to participants are given by Cartesian coordinates. (JP)

  3. PRCR Classes and Activities (United States)

    Town of Cary, North Carolina — This data is specific to Parks and Recreation classes, workshops, and activities within the course catalog. It contains an entry for upcoming classes.*This data set...

  4. Habitats, activities, and signs

    DEFF Research Database (Denmark)

    Andersen, Peter Bøgh; Brynskov, Martin


    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......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...

  5. 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...... due to photonic crystal dispersion. The observations are explained by the enhancement of net gain by light slow down. Another application based on active photonic crystal waveguides is micro lasers. Measurements on quantum dot micro laser cavities with different mirror configurations and photonic...

  6. CDBG Public Improvements Activity (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, fire...

  7. Extravehicular activity technology discipline (United States)

    Webbon, Bruce W.


    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.


    Loewe, S


    Cannabinol, generally believed to be an inert component of hemp oil, is shown to have marihuana activity. The significance of this observation with regard to the relationship between structure and mamactivity in the class of cannabinols is discussed.

  9. OTI Activity Database (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. Vessel Activity Record (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...

  11. RAVEN Quality Assurance Activities

    Energy Technology Data Exchange (ETDEWEB)

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


    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.

  12. Intercreativity: Mapping Online Activism (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. TPR And TPR Activities

    Institute of Scientific and Technical Information of China (English)



    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.

  14. Toroidal optical activity

    CERN Document Server

    Raybould, T A; Papasimakis, N; Kuprov, I; Youngs, I; Chen, W T; Tsai, D P; Zheludev, N I


    Optical activity is ubiquitous across natural and artificial media and is conventionally understood in terms of scattering from electric and magnetic moments. Here we demonstrate experimentally and confirm numerically a type of optical activity that cannot be attributed to electric and magnetic multipoles. We show that our observations can only be accounted for by the inclusion of the toroidal dipole moment, the first term of the recently established peculiar family of toroidal multipoles.

  15. Phytase activity in lichens. (United States)

    Higgins, Niall F; Crittenden, Peter D


    Phytase activity was investigated in 13 lichen species using a novel assay method. The work tested the hypothesis that phytase is a component of the suite of surface-bound lichen enzymes that hydrolyse simple organic forms of phosphorus (P) and nitrogen (N) deposited onto the thallus surface. Hydrolysis of inositol hexaphosphate (InsP6 , the substrate for phytase) and appearance of lower-order inositol phosphates (InsP5 -InsP1 ), the hydrolysis products, were measured by ion chromatography. Phytase activity in Evernia prunastri was compared among locations with contrasting rates of N deposition. Phytase activity was readily measurable in epiphytic lichens (e.g. 11.3 μmol InsP6 hydrolysed g(-1)  h(-1) in Bryoria fuscescens) but low in two terricolous species tested (Cladonia portentosa and Peltigera membranacea). Phytase and phosphomonoesterase activities were positively correlated amongst species. In E. prunastri both enzyme activities were promoted by N enrichment and phytase activity was readily released into thallus washings. InsP6 was not detected in tree canopy throughfall but was present in pollen leachate. Capacity to hydrolyse InsP6 appears widespread amongst lichens potentially promoting P capture from atmospheric deposits and plant leachates, and P cycling in forest canopies. The enzyme assay used here might find wider application in studies on plant root-fungal-soil systems.

  16. Antimicrobial activity of flavonoids. (United States)

    Cushnie, T P Tim; Lamb, Andrew J


    Flavonoids are ubiquitous in photosynthesising cells and are commonly found in fruit, vegetables, nuts, seeds, stems, flowers, tea, wine, propolis and honey. For centuries, preparations containing these compounds as the principal physiologically active constituents have been used to treat human diseases. Increasingly, this class of natural products is becoming the subject of anti-infective research, and many groups have isolated and identified the structures of flavonoids possessing antifungal, antiviral and antibacterial activity. Moreover, several groups have demonstrated synergy between active flavonoids as well as between flavonoids and existing chemotherapeutics. Reports of activity in the field of antibacterial flavonoid research are widely conflicting, probably owing to inter- and intra-assay variation in susceptibility testing. However, several high-quality investigations have examined the relationship between flavonoid structure and antibacterial activity and these are in close agreement. In addition, numerous research groups have sought to elucidate the antibacterial mechanisms of action of selected flavonoids. The activity of quercetin, for example, has been at least partially attributed to inhibition of DNA gyrase. It has also been proposed that sophoraflavone G and (-)-epigallocatechin gallate inhibit cytoplasmic membrane function, and that licochalcones A and C inhibit energy metabolism. Other flavonoids whose mechanisms of action have been investigated include robinetin, myricetin, apigenin, rutin, galangin, 2,4,2'-trihydroxy-5'-methylchalcone and lonchocarpol A. These compounds represent novel leads, and future studies may allow the development of a pharmacologically acceptable antimicrobial agent or class of agents.

  17. Hypoglycemic Activity of Jatrorrhizine

    Institute of Scientific and Technical Information of China (English)


    The hypoglycemic activity and its mechanism of Jatrorrhizine (Jat) were studied. The normal mice and alloxan-induced hyperglycemic mice were given with different doses of Jat. Blood glucose and liver glycogen levels were determined by spectrophotometry with glucose-oxidase and iodine reagents respectively. The levels of blood lactic acid (LC) and liver lactate dehydrogenase (LDH) activity were measured to explore the effect of Jat on anaerobic glycolysis. Succinate dehydrogenase (SDH) activity in liver was measured to evaluate the effect of Jat on aerobic glycolysis in liver. It was found that Jat (50 mg/kg, 100 mg/kg) could significantly decrease blood glucose level in a dose- and time-dependent manner in both normal and alloxan-diabetic mice, increase the activity of SDH, but had no significant effects on the LC level and LDH activity. Jat could significantly reduce the content of liver glycogen in normal mice. Moreover, Jat could inhibit the platelet aggregation in rabbits in vitro in a dose-effect relationship. It was concluded that Jat induced the pronounced decrease in blood glucose in normal and hyperglycemic mice. The hypoglycemic activity of Jat may be attributed to the enhancement of aerobic glycolysis.

  18. Reversal Strategies for NOACs

    DEFF Research Database (Denmark)

    Husted, Steen; Verheugt, Freek; Comuth, Willemijn


    antidotes for NOACs are expected to be on the market soon. Phase III clinical trials with a humanized antibody fragment directed against dabigatran (idarucizumab) and recombinant, modified factor Xa (andexanet alfa) are ongoing. A molecule (aripazine) with broad activity against various anticoagulants...

  19. SwissProt search result: AK112119 [KOME

    Lifescience Database Archive (English)

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

  20. SwissProt search result: AK109059 [KOME

    Lifescience Database Archive (English)

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

  1. SwissProt search result: AK061101 [KOME

    Lifescience Database Archive (English)

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

  2. SwissProt search result: AK112005 [KOME

    Lifescience Database Archive (English)

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

  3. Psychomotor activities with seniors

    Directory of Open Access Journals (Sweden)

    Jitka Kopřivová


    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

  4. Antimutagenic activity of spearmint. (United States)

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


    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).


    Institute of Scientific and Technical Information of China (English)

    LI Xiang; LI Zhong; XI Hongxia; LUO Lingai


    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.

  6. Interpreting EEG alpha activity. (United States)

    Bazanova, O M; Vernon, D


    Exploring EEG alpha oscillations has generated considerable interest, in particular with regards to the role they play in cognitive, psychomotor, psycho-emotional and physiological aspects of human life. However, there is no clearly agreed upon definition of what constitutes 'alpha activity' or which of the many indices should be used to characterize it. To address these issues this review attempts to delineate EEG alpha-activity, its physical, molecular and morphological nature, and examine the following indices: (1) the individual alpha peak frequency; (2) activation magnitude, as measured by alpha amplitude suppression across the individual alpha bandwidth in response to eyes opening, and (3) alpha "auto-rhythmicity" indices: which include intra-spindle amplitude variability, spindle length and steepness. Throughout, the article offers a number of suggestions regarding the mechanism(s) of alpha activity related to inter and intra-individual variability. In addition, it provides some insights into the various psychophysiological indices of alpha activity and highlights their role in optimal functioning and behavior.

  7. Active flows on trees (United States)

    Forrow, Aden; Woodhouse, Francis G.; Dunkel, Jörn


    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 can interact 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. Our analytical predictions agree well 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 1 / 4 the number of edges. More broadly, these results suggest that the macroscopic response of active networks, from actin-myosin networks in cells to flow networks in Physarum polycephalum, can be dominated by a few select modes.

  8. Active noise control primer

    CERN Document Server

    Snyder, Scott D


    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...

  9. Software Activation Using Multithreading

    Directory of Open Access Journals (Sweden)

    Jianrui Zhang


    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.

  10. Chromatin as active matter (United States)

    Agrawal, Ankit; Ganai, Nirmalendu; Sengupta, Surajit; Menon, Gautam I.


    Active matter models describe a number of biophysical phenomena at the cell and tissue scale. Such models explore the macroscopic consequences of driving specific soft condensed matter systems of biological relevance out of equilibrium through ‘active’ processes. Here, we describe how active matter models can be used to study the large-scale properties of chromosomes contained within the nuclei of human cells in interphase. We show that polymer models for chromosomes that incorporate inhomogeneous activity reproduce many general, yet little understood, features of large-scale nuclear architecture. These include: (i) the spatial separation of gene-rich, low-density euchromatin, predominantly found towards the centre of the nucleus, vis a vis. gene-poor, denser heterochromatin, typically enriched in proximity to the nuclear periphery, (ii) the differential positioning of individual gene-rich and gene-poor chromosomes, (iii) the formation of chromosome territories, as well as (iv), the weak size-dependence of the positions of individual chromosome centres-of-mass relative to the nuclear centre that is seen in some cell types. Such structuring is induced purely by the combination of activity and confinement and is absent in thermal equilibrium. We systematically explore active matter models for chromosomes, discussing how our model can be generalized to study variations in chromosome positioning across different cell types. The approach and model we outline here represent a preliminary attempt towards a quantitative, first-principles description of the large-scale architecture of the cell nucleus.

  11. [Inflammasome: activation mechanisms]. (United States)

    Suárez, Raibel; Buelvas, Neudo


    Inflammation is a rapid biologic response of the immune system in vascular tissues, directed to eliminate stimuli capable of causing damage and begin the process of repair. The macromolecular complexes known as "inflammasomes" are formed by a receptor, either NOD (NLR) or ALR, the receptor absent in melanoma 2 (AIM2). In addition, the inflammasome is formed by the speck-like protein associated to apoptosis (ASC) and procaspase-1, that may be activated by variations in the ionic and intracellular and extracellular ATP concentrations; and the loss of stabilization of the fagolisosomme by internalization of insoluble crystals and redox mechanisms. As a result, there is activation of the molecular platform and the processing of inflammatory prointerleukins to their active forms. There are two modalities of activation of the inflammasome: canonical and non-canonical, both capable of generating effector responses. Recent data associate NLRP 3, IL-1β and IL-18 in the pathogenesis of a variety of diseases, including atherosclerosis, type II diabetes, hyperhomocysteinemia, gout, malaria and hypertension. The inflammasome cascade is emerging as a new chemotherapeutic target in these diseases. In this review we shall discuss the mechanisms of activation and regulation of the inflammasome that stimulate, modulate and resolve inflammation.

  12. Regulating prefrontal cortex activation

    DEFF Research Database (Denmark)

    Aznar, Susana; Klein, Anders Bue


    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......The prefrontal cortex (PFC) is involved in mediating important higher-order cognitive processes such as decision making, prompting thereby our actions. At the same time, PFC activation is strongly influenced by emotional reactions through its functional interaction with the amygdala...... is highly expressed in the prefrontal cortex areas, playing an important role in modulating cortical activity and neural oscillations (brain waves). This makes it an interesting potential pharmacological target for the treatment of neuropsychiatric modes characterized by lack of inhibitory control...

  13. IHY activities in Brazil (United States)

    Dal Lago, Alisson

    The International Heliophysical Year is a program of international scientific colaboration planned to be held in the period from 2007-2009. Many brazilian institutions have shown interest in participating in the IHY activities. All of them provided information about their instrumental facilities and contact person. A list of institutions and their information is shown in the Latin-American IHY webpage (, hosted by the Latin American Association on Space Geophysics - ALAGE. IHY Brazilian activities are being conducted in close colaboration with Latin-American Institutions. Five Coordinated Investigation programs (CIPs) have been proposed by scientists from brazilian institutions. Recentely, in February 2008, there has been the Latin American IHY School in Sao Paulo (Brazil), with the participation of 80 students from Brazil, Argentina, Peru, Mexico and Cuba. In this work, a report on the brazilian activities will be presented.

  14. Lesion activity assessment

    DEFF Research Database (Denmark)

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


    . 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......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...... in 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...

  15. Active Elbow Orthosis

    Directory of Open Access Journals (Sweden)

    Tomas Ripel


    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.

  16. Adapted Active Appearance Models

    Directory of Open Access Journals (Sweden)

    Renaud Séguier


    Full Text Available Active Appearance Models (AAMs are able to align efficiently known faces under duress, when face pose and illumination are controlled. We propose Adapted Active Appearance Models to align unknown faces in unknown poses and illuminations. Our proposal is based on the one hand on a specific transformation of the active model texture in an oriented map, which changes the AAM normalization process; on the other hand on the research made in a set of different precomputed models related to the most adapted AAM for an unknown face. Tests on public and private databases show the interest of our approach. It becomes possible to align unknown faces in real-time situations, in which light and pose are not controlled.

  17. Correlates of physical activity

    DEFF Research Database (Denmark)

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


    that age, sex, health status, self-efficacy, and motivation are associated with physical activity. Ecological models take a broad view of health behaviour causation, with the social and physical environment included as contributors to physical inactivity, particularly those outside the health sector......Physical inactivity is an important contributor to non-communicable diseases in countries of high income, and increasingly so in those of low and middle income. Understanding why people are physically active or inactive contributes to evidence-based planning of public health interventions, because......, 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...

  18. General human activity patterns

    CERN Document Server

    Mollgaard, Anders; Mathiesen, Joachim


    We investigate the dynamics and interplay between human communication, movement, and social proximity by analyzing data collected from smartphones distributed among 638 individuals. The main question we consider is: to what extent do individuals act according to patterns shared across an entire population? Based on statistics of the entire population, we successfully predict 71\\% of the activity and 85\\% of the inactivity involved in communication, movement, and social proximity. We find that individual level statistics only result in marginally better predictions, indicating a high degree of shared activity patterns across the population. Finally, we predict short-term activity patterns using a generalized linear model, which suggests that a simple linear description might be sufficient to explain a wide range of actions, whether they be of social or of physical character.

  19. SCOR announces new activities (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.

  20. Actively coupled optical waveguides


    Alexeeva, N. V.; Barashenkov, I. V.; Rayanov, K.; Flach, S.


    We consider light propagation through a pair of nonlinear optical waveguides with absorption, placed in a medium with power gain. The active medium boosts the in-phase component of the overlapping evanescent fields of the guides, while the nonlinearity of the guides couples it to the damped out-of-phase component creating a feedback loop. As a result, the structure exhibits stable stationary and oscillatory regimes in a wide range of gain-loss ratios. We show that the pair of actively-coupled...

  1. Actively coupled optical waveguides (United States)

    Alexeeva, N. V.; Barashenkov, I. V.; Rayanov, K.; Flach, S.


    We consider light propagation through a pair of nonlinear optical waveguides with absorption, placed in a medium with power gain. The active medium boosts the in-phase component of the overlapping evanescent fields of the guides, while the nonlinearity of the guides couples it to the damped out-of-phase component creating a feedback loop. As a result, the structure exhibits stable stationary and oscillatory regimes in a wide range of gain-loss ratios. We show that the pair of actively coupled (AC) waveguides can act as a stationary or integrate-and-fire comparator sensitive to tiny differences in their input powers.

  2. Antibacterial Activity of Grepafloxacin

    Directory of Open Access Journals (Sweden)

    B Wiedemann


    Full Text Available 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 kills Gram-positive bacteria at concentrations little above the MIC. Its pharmacodynamic profile against pneumococci is promising, favouring use of this drug for respiratory tract infections.

  3. Measuring children's physical activity

    DEFF Research Database (Denmark)

    Schneller, Mikkel Bo; Bentsen, Peter; Nielsen, Glen


    INTRODUCTION: Accelerometer-based physical activity monitoring has become the method of choice in many large-scale physical activity (PA) studies. However, there is an ongoing debate regarding the placement of the device, the determination of device wear time, and how to solve a lack of participant...... on the thigh (n=903) and one on the lower back (n= 856), for up to ten consecutive days. Participants were instructed not to reattach an accelerometer should it fall off. Simple and multiple linear regression were used to determine associations between accelerometer wear time and age, sex, BMI percentiles...

  4. Antifungal activity of diethyldithiocarbamate. (United States)

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


    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.

  5. Atherosclerosis and Physical Activity


    Al-Mamari, Ali


    Atherosclerosis and coronary heart disease have been considered as major health problem worldwide. Abnormalities in lipids and lipoprotein metabolism and impairment of endothelial function have been implicated as the main contributing factors in atherosclerosis and its progression. Physical activity has been recognized as a preventive measure for atherosclerosis.

  6. Bonus Activity Book. (United States)

    Learning, 1993


    Elementary level activity book presents suggestions for teaching students about endangered and threatened species worldwide. Students learn about what is causing the rapid extinction rate and what needs to be done. They also discover the value of rainforests and why conservationists are fighting to save them. (SM)

  7. Asteroseismic stellar activity relations

    CERN Document Server

    Bonanno, A; Karoff, C


    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 ...

  8. [Biological activity of Spirulina]. (United States)

    Blinkova, L P; Gorobets, O B; Baturo, A P


    In this review information of Spirulina platensis (SP), a blue-green alga (photosynthesizing cyanobacterium) having diverse biological activity is presented. Due to high content of highly valuable proteins, indispensable amino acids, vitamins, beta-carotene and other pigments, mineral substances, indispensable fatty acids and polysaccharides, PS has been found suitable for use as bioactive additive. SP produces an immunostimulating effect by enhancing the resistance of humans, mammals, chickens and fish to infections, the capacity of influencing hemopoiesis, stimulating the production of antibodies and cytokines. Under the influence of SP macrophages, T and B cells are activated. SP sulfolipids have proved to be effective against HIV. Preparations obtained from SP biomass have also been found active against herpesvirus, cytomegalovirus, influenza virus, etc. SP extracts are capable in inhibiting cancerogenesis. SP preparations are regarded as functional products contributing to the preservation of the resident intestinal microflora, especially lactic acid bacilli and bifidobacteria, and to a decrease in the level of Candida albicans. The biological activity of SP with respect to microorganisms holds good promise for using these microalgae as components of culture media.

  9. Activation force splines

    DEFF Research Database (Denmark)

    Engell-Nørregård, Morten Pol; Erleben, Kenny

    dimensional 2D/3D deformable model. Our activation splines are easy to set up and can be used for physics based animation of deformable models such as snake motion and locomotion of characters. Our approach generalises easily to both 2D and 3D simulations and is applicable in physics based games or animations...

  10. Mechanism of charity activity

    Directory of Open Access Journals (Sweden)

    Roman B. Golovkin


    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

  11. Active surveillance: Oncologic outcome

    NARCIS (Netherlands)

    L.D.F. Venderbos (Lionne); L.P. Bokhorst (Leonard); C.H. Bangma (Chris); M.J. Roobol-Bouts (Monique)


    textabstractPURPOSE OF REVIEW: To give insight into recent literature (during the past 12-18 months) reporting on oncologic outcomes of men on active surveillance. RECENT FINDINGS: From recent published trials comparing radical prostatectomy vs. watchful waiting, we learn that radical treatment only

  12. Low activity aluminum blanket

    Energy Technology Data Exchange (ETDEWEB)

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


    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)

  13. Seismology of active stars

    NARCIS (Netherlands)

    Hekker, S.; García, R.A.


    In this review we will discuss the current standing and open questions of seismology in active stars. With the longer photometric time series data that are, and will become, available from space-missions such as Kepler we foresee significant progress in our understanding of stellar internal structur

  14. 'Active' Thin Sections

    NARCIS (Netherlands)

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


    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

  15. Sexual activity and aging. (United States)

    Ni Lochlainn, Mary; Kenny, Rose Anne


    Sexuality is an important component of emotional and physical intimacy that men and women experience throughout their lives. Research suggesting that a high proportion of men and women remain sexually active well into later life refutes the prevailing myth that aging and sexual dysfunction are inexorably linked. Age-related physiological changes do not render a meaningful sexual relationship impossible or even necessarily difficult. Many of these physiological changes are modifiable. There are various therapeutic options available to patients to achieve maximum sexual capacity in old age. This article reviews the prevalence of sexual activity among older adults, the problems these adults encounter with sexual activity, and the role of the health care professional in addressing these problems. The physiological sex-related changes that occur as part of the normal aging process in men and women are reviewed, as well as the effect of age-related physical and psychological illness on sexual function. The attitudes and perceptions of the media and general public toward sexual activity and aging are summarized. An understanding of the sexual changes that accompany the aging process may help general practitioners and other doctors to give practical and useful advice on sexuality as well as refute the misconception that aging equates to celibacy. A thorough awareness of this aspect of older people's quality of life can raise meaningful expectations for aging patients.

  16. 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


    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

  17. Activated Sludge Rheology

    DEFF Research Database (Denmark)

    Ratkovich, Nicolas Rios; Horn, Willi; Helmus, Frank


    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 filtr...

  18. Regional Activities Division. Papers. (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…

  19. 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...

  20. Marketing coprovided activities. (United States)

    Dickerson, Pamela S


    Coproviding is a wonderful way for two or more organizations to work together to provide continuing nursing education. To be transparent to the learners, marketing materials identify the parties involved and prominently note the name of the organization accountable for developing the activity and awarding the contact hours.

  1. An electrochemical active valve

    NARCIS (Netherlands)

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


    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

  2. Access and Fishing Activities

    DEFF Research Database (Denmark)

    Høst, Jeppe Engset


    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...

  3. Grooming. Learning Activity Package. (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…

  4. CMMs Development Activities

    Institute of Scientific and Technical Information of China (English)

    HU Jun; HU Yefa; HUANG Anyi


    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.

  5. Shark Tagging Activities. (United States)

    Current: The Journal of Marine Education, 1998


    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…

  6. Antimalarial activity of cedronin. (United States)

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


    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).

  7. Interdisciplinary Astronomy Activities (United States)

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


    On November 9th, 2015, three didactical hours were dedicated to Interdisciplinary Astronomy Activities ( 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 (, (b) watching the following videos: Journey to the end of the universe (, Rosetta update (, The Solar System (, Ambition the film ( 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 (, 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 Moreover, we discussed about Big Ideas of Science ( 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.

  8. Activities. Inductive and Deductive Reasoning. (United States)

    O'Daffer, Phares G.; And Others


    Provided are the activity sheets for students and the teaching guide for this middle school geometry activity. Materials, prerequisites, objectives, and procedures are listed. Extension activities are suggested. An answer key is included. (CW)

  9. Is Enhanced Physical Activity Possible Using Active Videogames?


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


    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.

  10. Is Enhanced Physical Activity Possible Using Active Videogames? (United States)

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


    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.

  11. Integration of Active Video Games in Extracurricular Activity at Schools (United States)

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


    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…

  12. X-chromosome inactivation in monkey embryos and pluripotent stem cells. (United States)

    Tachibana, Masahito; Ma, Hong; Sparman, Michelle L; Lee, Hyo-Sang; Ramsey, Cathy M; Woodward, Joy S; Sritanaudomchai, Hathaitip; Masterson, Keith R; Wolff, Erin E; Jia, Yibing; Mitalipov, Shoukhrat M


    Inactivation of one X chromosome in female mammals (XX) compensates for the reduced dosage of X-linked gene expression in males (XY). However, the inner cell mass (ICM) of mouse preimplantation blastocysts and their in vitro counterparts, pluripotent embryonic stem cells (ESCs), initially maintain two active X chromosomes (XaXa). Random X chromosome inactivation (XCI) takes place in the ICM lineage after implantation or upon differentiation of ESCs, resulting in mosaic tissues composed of two cell types carrying either maternal or paternal active X chromosomes. While the status of XCI in human embryos and ICMs remains unknown, majority of human female ESCs show non-random XCI. We demonstrate here that rhesus monkey ESCs also display monoallelic expression and methylation of X-linked genes in agreement with non-random XCI. However, XIST and other X-linked genes were expressed from both chromosomes in isolated female monkey ICMs indicating that ex vivo pluripotent cells retain XaXa. Intriguingly, the trophectoderm (TE) in preimplantation monkey blastocysts also expressed X-linked genes from both alleles suggesting that, unlike the mouse, primate TE lineage does not support imprinted paternal XCI. Our results provide insights into the species-specific nature of XCI in the primate system and reveal fundamental epigenetic differences between in vitro and ex vivo primate pluripotent cells.

  13. [Peri- and postoperative use of low molecular weight heparin in peripheral vascular surgery]. (United States)

    Samama, C M; Mouren, S; Bridel, M P; Combe, S; Koskas, F; Kieffer, E; Viars, P


    A pilot study has been conducted in ten consecutive patients undergoing femoro-popliteal reconstruction or distal vascular surgery under epidural anaesthesia. Immediately before arterial cross-clamping, enoxaparin (E) (75 anti-Xa was injected intravenously (i.v.). During surgery, washing of the saphenous or polytetrafluoroethylene (PTFE) graft has been performed using enoxaparin. Enoxaparin (75 anti-Xa was administered subcutaneously (S.C.) 8 hours after the i.v. injection, and then every 12 hours during 10 days. The patency of the vascular reconstruction and the side-effects of E administration were evaluated clinically before and during surgery, then by a daily clinical examination. Echo-Doppler and/or arteriography were also performed preoperatively and on the 10th postoperative day. Haematocrit, platelet count, activated partial thromboplastin time, prothrombin time, thrombin time, fibrinogen and anti-Xa activity were assessed. None of the patients developed venous or arterial thrombosis and all the by-pass grafts remained patient. Only one minor surgical bleeding occurred on the first post operative day, despite anti-Xa levels in the expected range. One patient developed minor haematomas at the injection site. No bleeding was observed. Further randomized studies comparing LMWH and UH are required in order to substantiate these preliminary clinical and biological findings.

  14. Active microchannel heat exchanger (United States)

    Tonkovich, Anna Lee Y [Pasco, WA; Roberts, Gary L [West Richland, WA; Call, Charles J [Pasco, WA; Wegeng, Robert S [Richland, WA; Wang, Yong [Richland, WA


    The present invention is an active microchannel heat exchanger with an active heat source and with microchannel architecture. The microchannel heat exchanger has (a) an exothermic reaction chamber; (b) an exhaust chamber; and (c) a heat exchanger chamber in thermal contact with the exhaust chamber, wherein (d) heat from the exothermic reaction chamber is convected by an exothermic reaction exhaust through the exhaust chamber and by conduction through a containment wall to the working fluid in the heat exchanger chamber thereby raising a temperature of the working fluid. The invention is particularly useful as a liquid fuel vaporizer and/or a steam generator for fuel cell power systems, and as a heat source for sustaining endothermic chemical reactions and initiating exothermic reactions.

  15. Nematicidal activity of terpenoids. (United States)

    Abdel-Rahman, Fawzia H; Alaniz, Nina M; Saleh, Mahmoud A


    Thirty four phytoterpenoids were evaluated for their nematicidal effect using the model nematode Caenorhabditis elegans. Nematicidal activities of the tested compounds at concentrations of 50 μg/mL showed wide variation in their effects ranging from no effect, weak, moderate and strong effects. Terpenoids exerting 50% or higher mortality at 50 μg/mL were further tested at five different concentrations to calculate the concentration that will kill 50% of the nematode population (LC(50)). Among the most effective terpenoids were carvacrol, thymol, nerolidol, α-terpinene, geraniol, citronellol, farnesol, limonene, pseudoionone and eugenol in a descending order. These compounds exhibited a dose-dependent effect. The results suggest that the selected monoterpenoids and essential oils with a high concentration of these compounds mayprovide potential natural nematicides and merit further study as botanical nematicides for the control of both plant and animal parasitic nematodes. In general, oxygenated terpenoids and phenolic terpenoids exhibited higher nematicidal activity than hydrocarbons terpenoids.

  16. Apheresis activity in Venezuela. (United States)

    Saltiel, Christiane


    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.

  17. Active optical clock

    Institute of Scientific and Technical Information of China (English)

    CHEN JingBiao


    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.

  18. 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


    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.

  19. Stellar Chromospheric Activity

    Directory of Open Access Journals (Sweden)

    Hall Jeffrey C.


    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.

  20. Techniques for active passivation

    Energy Technology Data Exchange (ETDEWEB)

    Roscioli, Joseph R.; Herndon, Scott C.; Nelson, Jr., David D.


    In one embodiment, active (continuous or intermittent) passivation may be employed to prevent interaction of sticky molecules with interfaces inside of an instrument (e.g., an infrared absorption spectrometer) and thereby improve response time. A passivation species may be continuously or intermittently applied to an inlet of the instrument while a sample gas stream is being applied. The passivation species may have a highly polar functional group that strongly binds to either water or polar groups of the interfaces, and once bound presents a non-polar group to the gas phase in order to prevent further binding of polar molecules. The instrument may be actively used to detect the sticky molecules while the passivation species is being applied.

  1. Cisplatin triggers platelet activation. (United States)

    Togna, G I; Togna, A R; Franconi, M; Caprino, L


    Clinical observations suggest that anticancer drugs could contribute to the thrombotic complications of malignancy in treated patients. Thrombotic microangiopathy, myocardial infarction, and cerebrovascular thrombotic events have been reported for cisplatin, a drug widely used in the treatment of many solid tumours. The aim of this study is to explore in vitro cisplatin effect on human platelet reactivity in order to define the potentially active role of platelets in the pathogenesis of cisplatin-induced thrombotic complications. Our results demonstrate that cisplatin increases human platelet reactivity (onset of platelet aggregation wave and thromboxane production) to non-aggregating concentrations of the agonists involving arachidonic acid metabolism. Direct or indirect activation of platelet phospholipase A(2) appears to be implicated. This finding contributes to a better understanding of the pathogenesis of thrombotic complications occurring during cisplatin-based chemotherapy.

  2. The Active Asteroids

    CERN Document Server

    Jewitt, Dave


    Some asteroids eject dust, unexpectedly producing transient, comet-like comae and tails. First ascribed to the sublimation of near-surface water ice, mass losing asteroids (also called "main-belt comets") can in fact be driven by a surprising diversity of mechanisms. In this paper, we consider eleven dynamical asteroids losing mass, in nine of which the ejected material is spatially resolved. We address mechanisms for producing mass loss including rotational instability, impact ejection, electrostatic repulsion, radiation pressure sweeping, dehydration stresses and thermal fracture, in addition to the sublimation of ice. In two objects (133P and 238P) the repetitive nature of the observed activity leaves ice sublimation as the only reasonable explanation while, in a third ((596) Scheila), a recent impact is the cause. Another impact may account for activity in P/2010 A2 but this tiny object can also be explained as having shed mass after reaching rotational instability. Mass loss from (3200) Phaethon is proba...

  3. 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)


    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.

  4. Sesterterpenoids with Anticancer Activity. (United States)

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


    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.

  5. Human neutrophil antimicrobial activity. (United States)

    Thomas, E L; Lehrer, R I; Rest, R F


    Polymorphonuclear neutrophilic leukocytes (PMNs) take up opsonized microorganisms into phagosomes that fuse with secretory granules in the PMN cytoplasm to form phagolysosomes. Killing and digestion of microorganisms take place within phagolysosomes. Antimicrobial activities in phagolysosomes are divided into two classes. Oxygen (O2)-dependent mechanisms are expressed when PMNs undergo the "respiratory burst." An NADPH oxidase in the phagolysosome membrane is activated and reduces O2 to superoxide (O2-). O2 reduction is the first step in a series of reactions that produce toxic oxidants. For example, .O2- dismutases to hydrogen peroxide (H2O2), and the azurophil granule enzyme myeloperoxidase catalyzes the oxidation of Cl- by H2O2 to yield hypochlorous acid (HOCl). The reaction of HOCl with ammonia and amines modulates the toxicity of this oxidant. O2-independent antimicrobial mechanisms include the activities of lysosomal proteases, other hydrolytic enzymes, and proteins and peptides that bind to microorganisms and disrupt essential processes or structural components. For example, the bactericidal/permeability-increasing protein, cathepsin G, and the defensins are released into phagolysosomes from the azurophil granules. Proposed mechanisms of action of neutrophil antimicrobial agents, their range of microbial targets, and their possible interactions within phagolysosomes are discussed.

  6. Amphoteric surface active agents

    Directory of Open Access Journals (Sweden)

    Eissa, A.M. F.


    Full Text Available 2-[trimethyl ammonium, triethyl ammonium, pyridinium and 2-amino pyridinium] alkanoates, four series of surface active agents containing carbon chain C12, C14, C16 and C18carbon atoms, were prepared. Their structures were characterized by microanalysis, infrared (IR and nuclear magnetic resonance (NMR. Surface and interfacial tension, Krafft point, wetting time, emulsification power, foaming height and critical micelle concentration (cmc were determined and a comparative study was made between their chemical structure and surface active properties. Antimicrobial activity of these surfactants was also determined.

    Se prepararon cuatro series de agentes tensioactivos del tipo 2-[trimetil amonio, trietil amonio, piridinio y 2-amino piridinio] alcanoatos, que contienen cadenas carbonadas con C12, C14, C16 y C18 átomos de carbono.
    Se determinaron la tensión superficial e interfacial, el punto de Krafft, el tiempo humectante, el poder de emulsionamiento, la altura espumante y la concentración critica de miscela (cmc y se hizo un estudio comparativo entre la estructura química y sus propiedades tensioactivas. Se determinó también la actividad antimicrobiana de estos tensioactivos. Estas estructuras se caracterizaron por microanálisis, infrarrojo (IR y resonancia magnética nuclear (RMN.

  7. Thermal activity on Enceladus (United States)

    Tobie, G.; Besserer, J.; Behounkova, M.; Cadek, O.; Choblet, G.; Sotin, C.


    Observations by Cassini have revealed that Enceladus' souh pole is highly active, with jets of icy particles and water vapour emanated from narrow tectonic ridges, called "tiger stripes". This jet activity is associated to a very high thermal emission mainly focused along the tectonic ridges. Heat power required to sustain such an activity is probably related to the dissipation of mechanical energy due to tidal forces exerted by Saturn. However, the dissipation process and its relation to the tectonic features are not clearly established. Both shear heating along the tectonic ridges and viscous dissipation in the convective part of the ice shell could contribute to the energy budget (Nimmo et al. 2007, Tobie et al. 2008). Tobie et al. (2008) pointed out that only interior models with a liquid water layer at depth, covering at least ~2/3 of the southern hemisphere, can explain the observed magnitude of dissipation and its particular location at the south pole. However, the long term stability of such a liquid reservoir remains problematic (Roberts and Nimmo 2007) and the possible link between the liquid reservoir and the surface activities is unknown. Concentration of tidal stresses along the tiger ridges have also been invoked as a mechanism to trigger the eruptive processes (Hurtford et al. 2007, Smith-Konter et al. 2008). However, those models do not take into account a realistic rheological structure for the ice shell when computing the fluctuating stress field. Moreover, the effect of the faults on the background tidal stress is neglected. In particular, low viscosity values are expected to be associated with the shear zone along the tiger stripes and may have a significant impact of the global tidal stress field. In order to self-consistently determine the tidal deformation and its impact on the thermal activity on Enceladus, we are currently developing a 3D model that combines a thermal convection code in spherical geometry (Choblet et al. 2007) and a

  8. Adaptable typologies for active roofs

    NARCIS (Netherlands)

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


    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

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

    Directory of Open Access Journals (Sweden)

    Atsushi Usami


    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.

  10. Enzyme Activities in Waste Water and Activated Sludge

    DEFF Research Database (Denmark)

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


    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...

  11. Advances in Activity Cliff Research. (United States)

    Dimova, Dilyana; Bajorath, Jürgen


    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.

  12. AMS Prototyping Activities (United States)

    Burleigh, Scott


    This slide presentation reviews the activity around the Asynchronous Message Service (AMS) prototype. An AMS reference implementation has been available since late 2005. It is aimed at supporting message exchange both in on-board environments and over space links. The implementation incoroporates all mandatory elements of the draft recommendation from July 2007: (1) MAMS, AMS, and RAMS protocols. (2) Failover, heartbeats, resync. (3) "Hooks" for security, but no cipher suites included in the distribution. The performance is reviewed, and a Benchmark latency test over VxWorks Message Queues is shown as histograms of a count vs microseconds per 1000-byte message

  13. Athena: Assessment Phase Activities (United States)

    Lumb, David; Ayre, Mark


    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.

  14. Topological Active Volumes

    Directory of Open Access Journals (Sweden)

    Barreira N


    Full Text Available The topological active volumes (TAVs model is a general model for 3D image segmentation. It is based on deformable models and integrates features of region-based and boundary-based segmentation techniques. Besides segmentation, it can also be used for surface reconstruction and topological analysis of the inside of detected objects. The TAV structure is flexible and allows topological changes in order to improve the adjustment to object's local characteristics, find several objects in the scene, and identify and delimit holes in detected structures. This paper describes the main features of the TAV model and shows its ability to segment volumes in an automated manner.

  15. System of Volcanic activity

    Directory of Open Access Journals (Sweden)



    Full Text Available A comparison is made among the systems of B. G.
    Escher (3, of R. W. van Bemmelen (1 and that of the author (4. In this
    connection, on the basis of Esclier's classification, the terms of "constructiv
    e " and "destructive" eruptions are introduced into the author's system and
    at the same time Escher's concept on the possible relation between the depth
    of magma-chamber and the measure of the gas-pressure is discussed briefly.
    Three complementary remarks to the first paper (4 011 the subject of system
    of volcanic activity are added.


    Directory of Open Access Journals (Sweden)

    Caruntu Genu Alexandru


    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.

  17. Active galactic nuclei

    CERN Document Server

    Blandford, RD; Woltjer, L


    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

  18. Active terahertz metamaterials

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Hou-tong [Los Alamos National Laboratory; O' Hara, John F [Los Alamos National Laboratory; Taylor, Antoinette J [Los Alamos National Laboratory


    In this paper we present an overview of research in our group in terahertz (THz) metamaterials and their applications. We have developed a series of planar metamaterials operating at THz frequencies, all of which exhibit a strong resonant response. By incorporating natural materials, e.g. semiconductors, as the substrates or as critical regions of metamaterial elements, we are able to effectively control the metamaterial resonance by the application of external stimuli, e.g., photoexcitation and electrical bias. Such actively controllable metamaterials provide novel functionalities for solid-state device applications with unprecedented performance, such as THz spectroscopy, imaging, and many others.

  19. Reuse of activated alumina

    Energy Technology Data Exchange (ETDEWEB)

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


    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.

  20. Diagramming Complex Activities

    DEFF Research Database (Denmark)

    Andersen, Peter Bøgh


    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...... aspect. The paper suggests thematic roles as a semantics for actions, argues that a selection of well-known diagramming techniques can be defined within this theory, and uses the theory to discuss new issues related to process control and mobile technology....

  1. Miscarriage and occupational activity

    DEFF Research Database (Denmark)

    Bonde, Jens Peter; Jørgensen, Kristian Tore; Bonzini, Matteo


    . METHODS: A search in Medline and EMBASE 1966-2012 identified 30 primary papers reporting the relative risk (RR) of miscarriage according to ≥1 of 5 occupational activities of interest. Following an assessment of completeness of reporting, confounding, and bias, each risk estimate was characterized as more......, N=10). RR for working hours and standing became smaller when analyses were restricted to higher quality studies. CONCLUSIONS: These largely reassuring findings do not provide a strong case for mandatory restrictions in relation to shift work, long working hours, occupational lifting, standing...

  2. Physical activity in elderly

    Directory of Open Access Journals (Sweden)

    Jan Cvecka


    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. Physical Activity in Elderly (United States)

    Tirpakova, Veronika; Sedliak, Milan; Kern, Helmut; Mayr, Winfried; Hamar, Dušan


    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. PMID:26913164

  4. The Active Muon Shield

    CERN Document Server

    Bezshyiko, Iaroslava


    In the SHiP beam-dump of the order of 1011 muons will be produced per second. An active muon-shield is used to magnetically deflect these muons out of the acceptance of the spectrom- eter. This note describes how this shield is modelled and optimized. The SHiP spectrometer is being re-optimized using a conical decay-vessel, and utilizing the possibility to magnetize part of the beam-dump shielding iron. A shield adapted to these new conditions is presented which is significantly shorter and lighter than the shield used in the Technical Proposal (TP), while showing a similar performance.

  5. Active galactic nuclei

    CERN Document Server

    Beckmann, Volker


    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

  6. Direct Activation Of Methane

    KAUST Repository

    Basset, Jean-Marie


    Heteropolyacids (HPAs) can activate methane at ambient temperature (e.g., 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. Rationales for regulatory activity

    Energy Technology Data Exchange (ETDEWEB)

    Perhac, R.M. [Univ. of Tennessee, Knoxville, TN (United States)


    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.

  8. Microbiologically active nanocomposite media (United States)

    Petranovskii, Vitalii; Panina, Lyudmila; Bogomolova, Eugenia; Belostotskaya, Galina


    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.

  9. The Active Solid Earth (United States)

    Ebinger, Cynthia


    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.

  10. Active Optics in LAMOST

    Institute of Scientific and Technical Information of China (English)

    Ding-Qiang Su; Xiang-Qun Cui


    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.

  11. Active Astronomy Roadshow Haiti (United States)

    Laycock, Silas; Oram, Kathleen; Alabre, Dayana; Douyon, Ralph; UMass Lowell Haiti Development Studies Center


    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.

  12. Leadership Development Activities

    Directory of Open Access Journals (Sweden)

    Malikeh Beheshtifar


    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.

  13. Involvement in Physical Activity

    Directory of Open Access Journals (Sweden)

    James Gavin


    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. Stable X Chromosome Reactivation in Female Human Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Tahsin Stefan Barakat


    Full Text Available In placental mammals, balanced expression of X-linked genes is accomplished by X chromosome inactivation (XCI in female cells. In humans, random XCI is initiated early during embryonic development. To investigate whether reprogramming of female human fibroblasts into induced pluripotent stem cells (iPSCs leads to reactivation of the inactive X chromosome (Xi, we have generated iPSC lines from fibroblasts heterozygous for large X-chromosomal deletions. These fibroblasts show completely skewed XCI of the mutated X chromosome, enabling monitoring of X chromosome reactivation (XCR and XCI using allele-specific single-cell expression analysis. This approach revealed that XCR is robust under standard culture conditions, but does not prevent reinitiation of XCI, resulting in a mixed population of cells with either two active X chromosomes (Xas or one Xa and one Xi. This mixed population of XaXa and XaXi cells is stabilized in naive human stem cell medium, allowing expansion of clones with two Xas.

  15. CBP Active Dumping and Active Countervailing (AD/CVD) Cases (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...

  16. Sedentary activity associated with metabolic syndrome independent of physical activity

    DEFF Research Database (Denmark)

    Bankoski, Andrea; Harris, Tamara B; McClain, James J


    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....

  17. Characterization and distribution of esterase activity in activated sludge

    NARCIS (Netherlands)

    Boczar, BA; Forney, LJ; Begley, WM; Larson, RJ; Federle, TW


    The location and activity of esterase enzymes in activated Sludge from three Municipal wastewater treatment plants were characterized using model Substrate, and denaturing and nondenaturing polyacrylamide gel electrophoresis (PAGE) Of particulate, freeze thaw (primarily periplasmic enzymes and those

  18. The active video games' narrative impact on children's physical activities (United States)

    Active video games (AVGs) capable of inducing physical activity offer an innovative approach to combating childhood obesity. Unfortunately, children's AVG game play decreases quickly, underscoring the need to identify novel methods for player engagement. Narratives have been demonstrated to influenc...


    Directory of Open Access Journals (Sweden)

    Agnieszka Tomska


    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%.

  20. How Active Are Older Americans?

    Directory of Open Access Journals (Sweden)

    Judy Kruger, PhD


    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

  1. 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)


    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

  2. Examining Activism in Practice: A Qualitative Study of Archival Activism (United States)

    Novak, Joy Rainbow


    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. Youth Physical Activity Resource Use and Activity Measured by Accelerometry (United States)

    Maslow, Andra L.; Colabianchi, Natalie


    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…

  4. Project origami activities for exploring mathematics

    CERN Document Server

    Hull, Thomas


    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

  5. Active Ageing: An Analysis

    Directory of Open Access Journals (Sweden)

    Alina-Cristina Nuta


    Full Text Available The problem of ageing is a highly topical for Romania and for European Union. In this framework, to create and implement some strategies for active ageing is an important objective. The international and regional forums set (supported by official statistics that the number of older people growing rapidly. Romania needs some programmes (with labour, social, economic, health care aspects to deal with the demographic changes, programs that will reform the existing working life structures and legislation. Despite the actual pension reform, which tries to close the opportunity of early retirement (by penalizing the total pension flows, or increasing the retirement age, etc., the labour system does not sets some important targets for this area.

  6. DPAL activities in Japan (United States)

    Endo, Masamori; Wani, Fumio


    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.


    Directory of Open Access Journals (Sweden)



    Full Text Available Sports and economy have discovered each other, hoping to serve common interests. In view of transferring in a more efficient way the information about their products or services to consumers, the business operator finances sports activities for advertising purposes. A company involved in sports sponsorship can instantly transmit the message about its products to millions of potential buyers, thus increasing the market share and hence the profit that it generates. By sponsoring sport it is meant any agreement / convention, under which one party the sponsor makes available to the beneficiary the material resources, financial and / or other benefits in exchange for its association with a sport or sportsman and especially the promise to use this association with sport or sportsman for the purpose of advertising, especially TV advertising. The growing use of athletes as spokespersons for a product is largely due to the ability of athletes to attract public attention and the credibility they enjoy

  8. The sound of activism. (United States)

    Sandstrom, B; Vetter, C


    ABSTRACT A longtime advocate for female empowerment and equality, Boden Sandstrom has worked for political change in many arenas. In the 1960s, she began a career as a librarian, but soon made activism her full-time job, working for feminist, leftist and socialist causes. In the 1970s, she found a way to turn her lifelong passion for music into a career as a sound engineer. Once established in that profession, she began donating her services to political events, marches, demonstrations, and rallies. After thirteen years of running her own company, called Woman Sound,Inc. (later City Sound Productions,Inc.), she turned to the study of ethnomusicology. She is now Program Manager and Lecturer for the Ethnomusicology Program at the University of Maryland, where she is also working on her doctorate in that subject. She continues to freelance as a sound engineer and serve as a technical producer for major events.

  9. Actively stressed marginal networks

    CERN Document Server

    Sheinman, M; MacKintosh, F C


    We study the effects of motor-generated stresses in disordered three dimensional fiber networks using a combination of a mean-field, effective medium theory, scaling analysis and a computational model. We find that motor activity controls the elasticity in an anomalous fashion close to the point of marginal stability by coupling to critical network fluctuations. We also show that motor stresses can stabilize initially floppy networks, extending the range of critical behavior to a broad regime of network connectivities below the marginal point. Away from this regime, or at high stress, motors give rise to a linear increase in stiffness with stress. Finally, we demonstrate that our results are captured by a simple, constitutive scaling relation highlighting the important role of non-affine strain fluctuations as a susceptibility to motor stress.

  10. Actively stressed marginal networks. (United States)

    Sheinman, M; Broedersz, C P; MacKintosh, F C


    We study the effects of motor-generated stresses in disordered three-dimensional fiber networks using a combination of a mean-field theory, scaling analysis, and a computational model. We find that motor activity controls the elasticity in an anomalous fashion close to the point of marginal stability by coupling to critical network fluctuations. We also show that motor stresses can stabilize initially floppy networks, extending the range of critical behavior to a broad regime of network connectivities below the marginal point. Away from this regime, or at high stress, motors give rise to a linear increase in stiffness with stress. Finally, we demonstrate that our results are captured by a simple, constitutive scaling relation highlighting the important role of nonaffine strain fluctuations as a susceptibility to motor stress.

  11. Active Flow Control (United States)



    This paper considers the two-dimensional problem of a plane vortex sheet disturbed by an impulsive line source. A previous incorrect treatment of this problem is examined in detail. Instabilities of the vortex sheet are triggered by the source and grow exponentially in space and time. The Green function is constructed for the problem and it is shown that a point source properly positioned and delayed will induce a field that cancels the unstable growing modes. The resulting displacement of the vortex sheet is expressed in simple terms. The instabilities are checked by the anti-source which combines with the field of the primary source into a vortex sheet response which decays with time at large time. This paper is a contribution to the study of active control of shear layer instabilities, the main contribution being to clear up a previous paper with peculiar results that are, in fact, wrong.

  12. Respiratory active mitochondrial supercomplexes. (United States)

    Acín-Pérez, Rebeca; Fernández-Silva, Patricio; Peleato, Maria Luisa; Pérez-Martos, Acisclo; Enriquez, Jose Antonio


    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.

  13. Plasminogen activation and cancer

    DEFF Research Database (Denmark)

    Danø, Keld; Behrendt, N.; Hoyer-Hansen, G.


    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...

  14. Physical activity among adolescents

    DEFF Research Database (Denmark)

    Henriksen, P W; Ingholt, L; Rasmussen, M


    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...... during leisure time. We used logistic regression analyses to estimate the associations for girls and boys separately, adjusted by age group, parents' occupational social class, family structure, and migration status. There were significant and graded associations between adolescents' PA and all four...... 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...

  15. Existing chemicals: international activities. (United States)

    Purchase, J F


    The standards of care used in the protection of the health and safety of people exposed to chemicals has increased dramatically in the last decade. Standards imposed by regulation and those adopted by industry have required a greater level of knowledge about the hazards of chemicals. In the E.E.C., the 6th amendment of the dangerous substances directive imposed the requirement that al new chemicals should be tested according to prescribed programme before introduction on to the market. The development of a European inventory of existing chemicals was an integral part of the 6th amendment. It has now become clear that increased standards of care referred to above must be applied to the chemicals on the inventory list. There is, however, a considerable amount of activity already under way in various international agencies. The OECD Chemicals Programme has been involved in considering the problem of existing chemicals for some time, and is producing a priority list and action programme. The International Programme on Chemical Safety produces international chemical safety cards, health and safety guides and environmental health criteria documents. The international register of potentially toxic compounds (part of UNEP) has prepared chemical data profiles on 990 compounds. The International Agency for Research on Cancer prepared monographs on the carcinogenic risk of chemicals to man. So far 42 volumes have been prepared covering about 900 substances. IARC and IPCS also prepare periodic reports on ongoing research on carcinogenicity or toxicity (respectively) of chemicals. The chemical industry through ECETOC (the European Chemical Industry Ecology and Toxicology Centre) has mounted a major initiative on existing chemicals. Comprehensive reviews of the toxicity of selected chemicals are published (Joint Assessment of Commodity Chemicals). In its technical report no. 30 ECETOC lists reviews and evaluations by major national and international organisations, which provides

  16. Diabetes Diet, Eating, & Physical Activity (United States)

    ... Disease, & Other Dental Problems Diabetes & Sexual & Urologic Problems Diabetes Diet, Eating, & Physical Activity Nutrition and physical activity ... What foods can I eat if I have diabetes? You may worry that having diabetes means going ...

  17. Consolidated Human Activities Database (CHAD) (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...

  18. Motivating Kids to Be Active (United States)

    ... set healthy patterns that will last into adulthood. Benefits of Being Active When kids are active, their ... school sports to after-school interests, such as yoga or skateboarding. It's important to remember that physical ...

  19. Physical Activity and Your Heart (United States)

    ... more energy than resting. Walking, running, dancing, swimming, yoga, and gardening are a few examples of physical activity. According to the Department of Health and Human Services' 2008 Physical Activity Guidelines for ...

  20. Physical activity extends life expectancy (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.

  1. Advanced Active Acoustics Lab (AAAL) (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...

  2. Physical active rest in education of active personality of students

    Directory of Open Access Journals (Sweden)

    Zaycev V.P.


    Full Text Available Meaningfulness of physical recreation is rotined in education of active personality of students. Research material is literary sources on this issue. Factors which influence on an educate function of personality of students are considered. Application of physical recreation is grounded for education of active personality of students. It is marked that physical recreation in pedagogical process decides educate, educational, health and social tasks. It positively influences on education of active personality of students. It is rotined that in education of active personality of students an important role is played by their research activity.

  3. Automated activity-aware prompting for activity initiation. (United States)

    Holder, Lawrence B; Cook, Diane J


    Performing daily activities without assistance is important to maintaining an independent functional lifestyle. As a result, automated activity prompting systems can potentially extend the period of time that adults can age in place. In this paper we introduce AP, an algorithm to automate activity prompting based on smart home technology. AP learns prompt rules based on the time when activities are typically performed as well as the relationship between activities that normally occur in a sequence. We evaluate the AP algorithm based on smart home datasets and demonstrate its ability to operate within a physical smart environment.

  4. Writing clear animal activity proposals. (United States)

    Pinson, David M


    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.

  5. Danish Labour Market Activation Policies

    DEFF Research Database (Denmark)

    Kvist, Jon; Pedersen, LIsbeth


    transformation over the past fifteen years. From the initial curbing of unemployment among the insured unemployed through standard activation offers, the aim today is also to increase labour supply among non-economic active groups using individually tailored programmes. Danish activation policies this embrace...

  6. Assessing and Increasing Physical Activity (United States)

    Van Camp, Carole M.; Hayes, Lynda B.


    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.

  7. Water-Related Teaching Activities. (United States)

    Coon, Herbert L.; Price, Charles L.

    This publication is designed to provide interested teachers with teaching activities for all grade levels and subject areas that can be used to help students learn about water resources. For each activity, the purpose, level, subject, and concept are given. Activities are organized by grade level. Most of these water related learning activities…

  8. Optically active quantum dots (United States)

    Gerard, Valerie; Govan, Joseph; Loudon, Alexander; Baranov, Alexander V.; Fedorov, Anatoly V.; Gun'ko, Yurii K.


    The main goal of our research is to develop new types of technologically important optically active quantum dot (QD) based materials, study their properties and explore their biological applications. For the first time chiral II-VI QDs have been prepared by us using microwave induced heating with the racemic (Rac), D- and L-enantiomeric forms of penicillamine as stabilisers. Circular dichroism (CD) studies of these QDs have shown that D- and L-penicillamine stabilised particles produced mirror image CD spectra, while the particles prepared with a Rac mixture showed only a weak signal. It was also demonstrated that these QDs show very broad emission bands between 400 and 700 nm due to defects or trap states on the surfaces of the nanocrystals. These QDs have demonstrated highly specific chiral recognition of various biological species including aminoacids. The utilisation of chiral stabilisers also allowed the preparation of new water soluble white emitting CdS nano-tetrapods, which demonstrated circular dichroism in the band-edge region of the spectrum. Biological testing of chiral CdS nanotetrapods displayed a chiral bias for an uptake of the D- penicillamine stabilised nano-tetrapods by cancer cells. It is expected that this research will open new horizons in the chemistry of chiral nanomaterials and their application in nanobiotechnology, medicine and optical chemo- and bio-sensing.

  9. [Active management of labor]. (United States)

    Ruiz Ortiz, E; Villalobos Román, M; Flores Murrieta, G; Sotomayor Alvarado, L


    Eighty three primigravidae patients at the end of latency labor, erased cervix, 3 cm dilation, vertex presentation and adequate pelvis, were studied. Two groups were formed: 53 patients in the study group, who received active management of labor, and 30 patients in the control group, treated in the traditional way. In all the patients a graphic recording of labor, was carried out; it included all the events, and as labor advanced, a signoidal curve of cervical dilatation, was registered, as well as the hyperbolic one for presentation descent. The study group received the method in a systematized manner, as follows: 1. Peridular block. 2. Amniotomy. 3. IV oxytocin one hour after amniotomy. 4. FCR monitoring. 5. Detection of dystocia origin. Materno-fetal morbidity was registered in both groups, as well as cesarean section rate, instrumental delivery and its indications, labor duration, and time of stay in labor room. Diminution of above intems and opportune detection of dystocia, were determined. It was concluded that a constructive action plan, starting at hospital admission in most healthy women, allows a normal delivery of brief duration.

  10. Surface Active Components: Review

    Directory of Open Access Journals (Sweden)

    Z. Shafiei


    Full Text Available Biosurfactant or surface active components are produced by many different microorganisms. Biosurfactants are amphiphilic molecules with both hydrophilic and hydrophobic (generally hydrocarbon moieties that partition preferentially a within the interface between fluid phases with some other degrees of polarity and hydrogen bonding including oil/water or air/water interfaces. These properties render surfactants able to reducing surface and interfacial tension and forming microemulsion where hydrocarbons can solubilize in water or where water can solubilize in hydrocarbons, the majority of surfactants have gained importance in the fields of enhanced oil recovery, environmental bioremediation, food processing and pharmaceuticals. However, large-scale production of these molecules has not been realized as a result of low yields in production processes and high recovery and purification costs. This review article represents a classification of biosurfactant in addition to their microbial origin and effect of some nutrition and environmental factor for high production of biosurfactant. The nitrogen, carbon sources and environmental factors can make a difference key to the regulating biosurfactants synthesis Fascination with microbial surfactants have been steadily increasing recently because of advantages over the chemical surfactants for example environmentally friendly nature, lower toxicity, higher biodegradability, higher selectivity and specific gravity at extreme temperature, pH and salinity. For this reason the demand of biosurfactant are increasing day by day.

  11. Elusive Active Galactic Nuclei

    CERN Document Server

    Maiolino, R; Gilli, R; Nagar, N M; Bianchi, S; Böker, T; Colbert, E; Krabbe, A; Marconi, A; Matt, G; Salvati, M


    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 obtain a first estimate of the fraction of elusive AGN in local galaxies and to constrain their nature. Our results suggest that elusive AGN have a local density comparable to or even higher than optically classified Seyfert nuclei. Most elusive AGN are heavily absorbed in the X-rays, with gas column densities exceeding 10^24 cm^-2, suggesting that their peculiar nature is associated with obscuration. It is likely that in elusive AGN, the nuclear UV source is completely embedded and the ionizing photons cannot escape, which prevents the formation of a classical Narrow Line Region. Elusive AGN may contribute significantly to the 30 keV bump of the X-ray background.

  12. ADASY (Active Daylighting System) (United States)

    Vázquez-Moliní, Daniel; González-Montes, Mario; Fernández-Balbuena, Antonio Á.; Bernabéu, Eusebio; García-Botella, Ángel; García-Rodríguez, Lucas; Pohl, Wilfried


    The main objective of ADASY (Active Daylighting System) work is to design a façade static daylighting system oriented to office applications, mainly. The goal of the project is to save energy by guiding daylight into a building for lighting purpose. With this approach we can reduce the electrical load for artificial lighting, completing it with sustainable energy. The collector of the system is integrated on a vertical façade and its distribution guide is always horizontal inside of the false ceiling. ADASY is designed with a specific patent pending caption system, a modular light-guide and light extractor luminaire system. Special care has been put on the final cost of the system and its building integration purpose. The current ADASY configuration is able to illuminate 40 m2 area with a 300lx-400lx level in the mid time work hours; furthermore it has a good enough spatial uniformity distribution and a controlled glare. The data presented in this study are the result of simulation models and have been confirmed by a physical scaled prototype. ADASY's main advantages over regular illumination systems are: -Low maintenance; it has not mobile pieces and therefore it lasts for a long time and require little attention once installed. - No energy consumption; solar light continue working even if there has been a power outage. - High quality of light: the colour rendering of light is very high - Psychological benefits: People working with daylight get less stress and more comfort, increasing productivity. - Health benefits

  13. Barriers for recess physical activity

    DEFF Research Database (Denmark)

    Pawlowski, Charlotte Skau; Tjørnhøj-Thomsen, Tine; Schipperijn, Jasper


    BACKGROUND: Many children, in particular girls, do not reach the recommended amount of daily physical activity. School recess provides an opportunity for both boys and girls to be physically active, but barriers to recess physical activity are not well understood. This study explores gender...... differences in children's perceptions of barriers to recess physical activity. Based on the socio-ecological model four types of environmental barriers were distinguished: natural, social, physical and organizational environment. METHODS: Data were collected through 17 focus groups (at 17 different schools...... this study, we recommend promoting recess physical activity through a combination of actions, addressing barriers within the natural, social, physical and organizational environment....

  14. Perspectives in active liquid crystals. (United States)

    Majumdar, Apala; Cristina, Marchetti M; Virga, Epifanio G


    Active soft matter is a young, growing field, with potential applications to a wide variety of systems. This Theme Issue explores this emerging new field by highlighting active liquid crystals. The collected contributions bridge theory to experiment, mathematical theories of passive and active nematics, spontaneous flows to defect dynamics, microscopic to continuum levels of description, spontaneous activity to biological activation. While the perspectives offered here only span a small part of this rapidly evolving field, we trust that they might provide the interested reader with a taste for this new class of non-equilibrium systems and their rich behaviour.

  15. In vivo imaging of protease activity by Probody therapeutic activation. (United States)

    Wong, Kenneth R; Menendez, Elizabeth; Craik, Charles S; Kavanaugh, W Michael; Vasiljeva, Olga


    Probody™ therapeutics are recombinant, proteolytically-activated antibody prodrugs, engineered to remain inert until activated locally by tumor-associated proteases. Probody therapeutics exploit the fundamental dysregulation of extracellular protease activity that exists in tumors relative to healthy tissue. Leveraging the ability of a Probody therapeutic to bind its target at the site of disease after proteolytic cleavage, we developed a novel method for profiling protease activity in living animals. Using NIR optical imaging, we demonstrated that a non-labeled anti-EGFR Probody therapeutic can become activated and compete for binding to tumor cells in vivo with a labeled anti-EGFR monoclonal antibody. Furthermore, by inhibiting matriptase activity in vivo with a blocking-matriptase antibody, we show that the ability of the Probody therapeutic to bind EGFR in vivo was dependent on protease activity. These results demonstrate that in vivo imaging of Probody therapeutic activation can be used for screening and characterization of protease activity in living animals, and provide a method that avoids some of the limitations of prior methods. This approach can improve our understanding of the activity of proteases in disease models and help to develop efficient strategies for cancer diagnosis and treatment.

  16. Global optogenetic activation of inhibitory interneurons during epileptiform activity. (United States)

    Ledri, Marco; Madsen, Marita Grønning; Nikitidou, Litsa; Kirik, Deniz; Kokaia, Merab


    Optogenetic techniques provide powerful tools for bidirectional control of neuronal activity and investigating alterations occurring in excitability disorders, such as epilepsy. In particular, the possibility to specifically activate by light-determined interneuron populations expressing channelrhodopsin-2 provides an unprecedented opportunity of exploring their contribution to physiological and pathological network activity. There are several subclasses of interneurons in cortical areas with different functional connectivity to the principal neurons (e.g., targeting their perisomatic or dendritic compartments). Therefore, one could optogenetically activate specific or a mixed population of interneurons and dissect their selective or concerted inhibitory action on principal cells. We chose to explore a conceptually novel strategy involving simultaneous activation of mixed populations of interneurons by optogenetics and study their impact on ongoing epileptiform activity in mouse acute hippocampal slices. Here we demonstrate that such approach results in a brief initial action potential discharge in CA3 pyramidal neurons, followed by prolonged suppression of ongoing epileptiform activity during light exposure. Such sequence of events was caused by massive light-induced release of GABA from ChR2-expressing interneurons. The inhibition of epileptiform activity was less pronounced if only parvalbumin- or somatostatin-expressing interneurons were activated by light. Our data suggest that global optogenetic activation of mixed interneuron populations is a more effective approach for development of novel therapeutic strategies for epilepsy, but the initial action potential generation in principal neurons needs to be taken in consideration.

  17. Evaluating Active U: an internet-mediated physical activity program

    Directory of Open Access Journals (Sweden)

    Goodrich David E


    Full Text Available Abstract Background Engaging in regular physical activity can be challenging, particularly during the winter months. To promote physical activity at the University of Michigan during the winter months, an eight-week Internet-mediated program (Active U was developed providing participants with an online physical activity log, goal setting, motivational emails, and optional team participation and competition. Methods This study is a program evaluation of Active U. Approximately 47,000 faculty, staff, and graduate students were invited to participate in the online Active U intervention in the winter of 2007. Participants were assigned a physical activity goal and were asked to record each physical activity episode into the activity log for eight weeks. Statistics for program reach, effectiveness, adoption, and implementation were calculated using the Re-Aim framework. Multilevel regression analyses were used to assess the decline in rates of data entry and goal attainment during the program, to assess the likelihood of joining a team by demographic characteristics, to test the association between various predictors and the number of weeks an individual met his or her goal, and to analyze server load. Results Overall, 7,483 individuals registered with the Active U website (≈16% of eligible, and 79% participated in the program by logging valid data at least once. Staff members, older participants, and those with a BMI P Conclusion Internet-mediated physical activity interventions that focus on physical activity logging and goal setting while incorporating team competition may help a significant percentage of the target population maintain their physical activity during the winter months.

  18. Resources Management in Active Networks

    Institute of Scientific and Technical Information of China (English)


    In an active network, users can insert customized active codes into active nodes to execute. Thus it needs more resources than those required by conventional networks, and these resources must be effectively monitored and managed. Management policies in existing OSs are too complicated to apply to simple active packets. In this paper, we present new resources management policies that are mainly adoped to manage CPU, storage and transmission bandwidth. Namely, we use SPF algorithm to schedule and process active packets, and import an interval queue method to allocate transmission bandwidth, and use feedback mechanism to control congestion. At the same time, we design some experiments on prototype systems with and without resources management policies respectively. The experiments results show that management policies presented by us can effectively manage resources in active nodes and can improve the performance of active networks.

  19. Activity cliffs and activity cliff generators based on chemotype-related activity landscapes. (United States)

    Pérez-Villanueva, Jaime; Méndez-Lucio, Oscar; Soria-Arteche, Olivia; Medina-Franco, José L


    Activity cliffs have large impact in drug discovery; therefore, their detection and quantification are of major importance. This work introduces the metric activity cliff enrichment factor and expands the previously reported activity cliff generator concept by adding chemotype information to representations of the activity landscape. To exemplify these concepts, three molecular databases with multiple biological activities were characterized. Compounds in each database were grouped into chemotype classes. Then, pairwise comparisons of structure similarities and activity differences were calculated for each compound and used to construct chemotype-based structure-activity similarity (SAS) maps. Different landscape distributions among four major regions of the SAS maps were observed for different subsets of molecules grouped in chemotypes. Based on this observation, the activity cliff enrichment factor was calculated to numerically detect chemotypes enriched in activity cliffs. Several chemotype classes were detected having major proportion of activity cliffs than the entire database. In addition, some chemotype classes comprising compounds with smooth structure activity relationships (SAR) were detected. Finally, the activity cliff generator concept was applied to compounds grouped in chemotypes to extract valuable SAR information.

  20. Atmospheric neutrino data Active-Active x Active-Sterile oscillations

    CERN Document Server

    Peres, O L G


    I summarize here the results of a global fit to the full data set corresponding to 33.0 kt-yr of data of the Super-Kamiokande experiment as well as to all other experiments in order to compare the active-active and active-sterile neutrinos oscillation channels to the atmospheric neutrino anomaly.

  1. UV activity indicators (United States)

    Buccino, A. P.; Mauas, P. J. D.

    In Order to continue the work displayed in Buccino & Mauas(2003) and Buccino (2003), we have calculated the index Mg II (Xhk) on 1640 high resolution IUE spectra of 269 main sequence stars of spectral classes F, G and K. From this set of observations, we found an exponential relation between the continuum UV flux and the color (B-V). Contrary to Schrijver et al (1989), who assumed that the continuum UV flux depended on the color following the relation found by Rutten (1984) for the visible one, i.e. the logarithm of the flux is proportional to a polynomial of third order with the color. Nevertheless, the exponential relation flux in the continuous UV and the color (B-V) fits far better to our data that the given one by Rutten (1984). Obtained this dependency for the ultraviolet continuum flux, the index Xhk can be obtained from the single flux in the lines core, allowing to calculate the index of Mg II for those spectra where the continuum is very dark and so the relation signal noise is very low. As it were already reported in previous works (Rutten (1991), Schrijver (1992)), we found a minimum basal flux in the Mg II h and k lines core due to the cromospheric heating by disipation of acustics waves. From this minimum flux, we calculated minimum index of activity that satisfactorily fits to the minimum values of the indexes calculated on the 1640 spectra like quotient between the flux in the line core and the continuous one.

  2. Strategy as active waiting. (United States)

    Sull, Donald N


    Successful executives who cut their teeth in stable industries or in developed countries often stumble when they face more volatile markets. They falter, in part, because they assume they can gaze deep into the future and develop a long-term strategy that will confer a sustainable competitive advantage. But visibility into the future of volatile markets is sharply limited because so many different variables are in play. Factors such as technological innovation, customers' evolving needs, government policy, and changes in the capital markets interact with one another to create unexpected outcomes. Over the past six years, Donald Sull, an associate professor at London Business School, has led a research project examining some of the world's most volatile markets, from national markets like China and Brazil to industries like enterprise software, telecommunications, and airlines. One of the most striking findings from this research is the importance of taking action during comparative lulls in the storm. Huge business opportunities are relatively rare; they come along only once or twice in a decade. And, for the most part, companies can't manufacture those opportunities; changes in the external environment converge to make them happen. What managers can do is prepare for these golden opportunities by managing smart during the comparative calm of business as usual. During these periods of active waiting, leaders must probe the future and remain alert to anomalies that signal potential threats or opportunities; exercise restraint to preserve their war chests; and maintain discipline to keep the troops battle ready. When a golden opportunity or"sudden death"threat emerges, managers must have the courage to declare the main effort and concentrate resources to seize the moment.

  3. Genotoxic activity of praziquantel. (United States)

    Montero, R; Ostrosky, P


    Praziquantel is a synthetic drug with a remarkable activity against parasites, particularly treamatodes and cestodes. Initial genotoxicity tests used a spectrum of endpoints including tests in bacteria, yeasts, mammalian cells and Drosophila and each one gave negative results. Effects on reproductive cells of mice were negative as well. However, host mediated studies in mice and humans were contradictory and a comutagenic effect with several mutagens and carcinogens was found. Later studies, including monitoring in humans and pigs have shown that Praziquantel induces a greater frequency of hyperploid lymphocytes as well as structural chromosomal aberrations, but not in all the individuals treated. In vitro studies have demonstrated that Praziquantel can induce micronuclei in syrian hamster embryonic (SHE) cells and in lymphocytes of some individuals. The same was found about structural chromosomal aberrations. Fetal death and fetal resorption were found when Praziquantel was administered in high doses to pregnant rats between the 6th and 10th day of gestation. Due to its efficiency as a parasiticide, Praziquantel is in use in Latin-American, Asiatic, African and East-European countries where infections by trematodes and cestodes are frequent. However, the extensive use of Praziquantel in multiple reinfections, in non-infected and non-diagnosed individuals for prevention, in higher doses or repeated doses for cysticercosis treatment and in individuals exposed to environmental mutagens, in conjunction with new findings about its metabolism and genotoxic properties, make it necessary to further evaluate the potential of this drug not only to be mutagenic per se, but to contribute in the development of neoplasm.

  4. Active Beam Spectroscopy (United States)

    von Hellermann, M. G.; Delabie, E.; Jaspers, R. J. E.; Biel, W.; Marchuk, O.; Summers, H. P.; Whiteford, A.; Giroud, C.; Hawkes, N. C.; Zastrow, K. D.


    Charge eXchange Recombination Spectroscopy (CXRS) plays a pivotal role in the diagnostics of hot fusion plasmas and is implemented currently in most of the operating devices. In the present report the main features of CXRS are summarized and supporting software packages encompassing "Spectral Analysis Code CXSFIT", "Charge Exchange Analysis Package CHEAP", and finally "Forward Prediction of Spectral Features" are described. Beam Emission Spectroscopy (BES) is proposed as indispensable cross-calibration tool for absolute local impurity density measurements and also for the continuous monitoring of the neutral beam power deposition profile. Finally, a full exploitation of the `Motional Stark Effect' pattern is proposed to deduce local pitch angles, total magnetic fields and possibly radial electric fields. For the proposed active beam spectroscopy diagnostic on ITER comprehensive performance studies have been carried out. Estimates of expected spectral signal-to-noise ratios are based on atomic modelling of neutral beam stopping and emissivities for CXRS, BES and background continuum radiation as well as extrapolations from present CXRS diagnostic systems on JET, Tore Supra, TEXTOR and ASDEX-UG. Supplementary to thermal features a further promising application of CXRS has been proposed recently for ITER, that is a study of slowing-down alpha particles in the energy range up to 2 MeV making use of the 100 keV/amu DNB (Diagnostic Neutral Beam) and the 500 keV/amu HNB (Heating Neutral Beam). Synthetic Fast Ion Slowing-Down spectra are evaluated in terms of source rates and slowing-down parameters


    DEFF Research Database (Denmark)

    Hansen, Aviaja Anna; Le-Quy, Vang; Nielsen, Kåre Lehmann;

    and when external carbon sources were supplemented to the activated sludge the composition of the denitrifying communities was significantly affected. Transcriptome profiling provided detailed insight in the metabolic pathways in several of the active denitrifiers in activated sludge. In conclusion...... reactor studies. To obtain better identification of active denitrifying communities in full-scale wastewater treatment plants (WWTPs) we applied DNA-SIP with 13C-labelled substrates, and RT-PCR of expressed denitrification genes (nirS, nirK and nosZ) upon various substrate-inductions. To come around...... were determined with quantitative FISH, while their active metabolic pathways were investigated directly in activated sludge with a tag-based metatranscriptomic approach under acetate-utilizing and denitrifying conditions. The different methods revealed a majority of denitrifiers in all WWTPs belonging...

  6. Fluidization and Active Thinning by Molecular Kinetics in Active Gels. (United States)

    Oriola, David; Alert, Ricard; Casademunt, Jaume


    We derive the constitutive equations of an active polar gel from a model for the dynamics of elastic molecules that link polar elements. Molecular binding kinetics induces the fluidization of the material, giving rise to Maxwell viscoelasticity and, provided that detailed balance is broken, to the generation of active stresses. We give explicit expressions for the transport coefficients of active gels in terms of molecular properties, including nonlinear contributions on the departure from equilibrium. In particular, when activity favors linker unbinding, we predict a decrease of viscosity with activity-active thinning-of kinetic origin, which could explain some experimental results on the cell cortex. By bridging the molecular and hydrodynamic scales, our results could help understand the interplay between molecular perturbations and the mechanics of cells and tissues.

  7. Negotiating active ageing at a Danish activity centre

    DEFF Research Database (Denmark)

    Lassen, Aske Juul

    and practices active ageing. The paper uses an activity centre in Copenhagen as its site of negotiation. Methods: These questions have been explored with the use of ethnographic fieldwork and through a documentary study. The ethnographic fieldwork has been conducted at an activity centre with 4 months...... of participatory observation in 2011 and 2012, as well as 11 semi-structured, in-depth interviews with users of the centre. 4 of these users have been followed around during everyday activities such as doing groceries, picking up grandchildren, etc. The documentary study consists of documents and statements...

  8. Activated coconut shell charcoal carbon using chemical-physical activation (United States)

    Budi, Esmar; Umiatin, Nasbey, Hadi; Bintoro, Ridho Akbar; Wulandari, Futri; Erlina


    The use of activated carbon from natural material such as coconut shell charcoal as metal absorbance of the wastewater is a new trend. The activation of coconut shell charcoal carbon by using chemical-physical activation has been investigated. Coconut shell was pyrolized in kiln at temperature about 75 - 150 °C for about 6 hours in producing charcoal. The charcoal as the sample was shieved into milimeter sized granule particle and chemically activated by immersing in various concentration of HCl, H3PO4, KOH and NaOH solutions. The samples then was physically activated using horizontal furnace at 400°C for 1 hours in argon gas environment with flow rate of 200 kg/m3. The surface morphology and carbon content of activated carbon were characterized by using SEM/EDS. The result shows that the pores of activated carbon are openned wider as the chemical activator concentration is increased due to an excessive chemical attack. However, the pores tend to be closed as further increasing in chemical activator concentration due to carbon collapsing.

  9. Production and characterization of granular activated carbon from activated sludge

    Directory of Open Access Journals (Sweden)

    Z. Al-Qodah


    Full Text Available In this study, activated sludge was used as a precursor to prepare activated carbon using sulfuric acid as a chemical activation agent. The effect of preparation conditions on the produced activated carbon characteristics as an adsorbent was investigated. The results indicate that the produced activated carbon has a highly porous structure and a specific surface area of 580 m²/g. The FT-IR analysis depicts the presence of a variety of functional groups which explain its improved adsorption behavior against pesticides. The XRD analysis reveals that the produced activated carbon has low content of inorganic constituents compared with the precursor. The adsorption isotherm data were fitted to three adsorption isotherm models and found to closely fit the BET model with R² equal 0.948 at pH 3, indicating a multilayer of pesticide adsorption. The maximum loading capacity of the produced activated carbon was 110 mg pesticides/g adsorbent and was obtained at this pH value. This maximum loading was found experimentally to steeply decrease as the solution pH increases. The obtained results show that activated sludge is a promising low cost precursor for the production of activated carbon.

  10. Silicon active photonic devices (United States)

    Dimitropoulos, Dimitrios

    Active photonic devices utilizing the optical nonlinearities of silicon have emerged in the last 5 years and the effort for commercial photonic devices in the material that has been the workhorse of electronics has been building up since. This dissertation presents the theory for some of these devices. We are concerned herein with CW lasers, amplifiers and wavelength converters that are based on the Raman effect. There have already been cursory experimental demonstrations of these devices and some of their limitations are already apparent. Most of the limitations observed are because of the appearance of effects that are competing with stimulated Raman scattering. Under the high optical powers that are necessary for the Raman effect (tens to hundrends of mW's) the process of optical two-photon (TPA) absorption occurs. The absorption of optical power that it causes itself is weak but in the process electrons and holes are generated which can further absorb light through the free-carrier absorption effect (FCA). The effective "lifetime" that these carriers have determines the magnitude of the FCA loss. We present a model for the carrier lifetime in Silicon-On-Insulator (SOI) waveguides and numerical simulations to understand how this critical parameter varies and how it can be controlled. A p-i-n junction built along SOI waveguides can help achieve lifetime of the order of 20--100 ps but the price one has to pay is on-chip electrical power consumption on the order of 100's of mWs. We model CW Raman lasers and we find that the carrier lifetime reduces the output power. If the carrier lifetime exceeds a certain "critical" value optical losses become overwhelming and lasing is impossible. As we show, in amplifiers, the nonlinear loss does not only result in diminished gain, but also in a higher noise figure. Finally the effect of Coherent anti-Stokes Raman scattering (CARS) is examined. The effect is important because with a pump frequency at 1434nm coherent power

  11. Permanent active longitudes and activity cycles on RS CVn stars (United States)

    Berdyugina, Svetlana V.; Tuominen, Ilkka


    A new analysis of the published long-term photometric observations has revealed permanent active-longitude structures in four RS CVn stars: EI Eri, II Peg, sigma Gem, and HR 7275. Two active longitudes separated by half of the period are found to dominate on the surface during all available seasons. The positions of the longitudes on three stars (EI Eri, II Peg, HR 7275) are migrating in the orbital reference frame, and there is no preferred orientation with respect to the line of centres in the binaries. The rate of migration is approximately constant. In case of sigma Gem the active longitude migration is synchronized with the orbital motion in the direction of the line of centres in the binary. The active region lifetimes can be longer than the time span of the observations (>=15 yr). The periods of the active longitude rotation are determined: for EI Eri 1fd 9510, for II Peg 6fd 7066, for sigma Gem 19fd 604, for HR 7275 28fd 263. Long-term activity cycles of the stars are discovered from the analysis of the relative contribution of the two longitudes to the photometric variability. One longitude is found to be usually more active than the other at a given moment, and the change of the activity level between the longitudes is cyclic with periods of years. The switch of the activity takes a much shorter time, about a few months, similar to the ``flip-flop'' phenomenon found for FK Com stars. Moments of switching are regarded as new tracers of the activity, and total cycles, which return activity to the same longitude, are found to be for EI Eri 9.0 yr, for II Peg 9.3 yr, for sigma Gem 14.9 yr, for HR 7275 17.5 yr.

  12. Tyrosine phosphorylation of NEDD4 activates its ubiquitin ligase activity. (United States)

    Persaud, Avinash; Alberts, Philipp; Mari, Sara; Tong, Jiefei; Murchie, Ryan; Maspero, Elena; Safi, Frozan; Moran, Michael F; Polo, Simona; Rotin, Daniela


    Ligand binding to the receptor tyrosine kinase fibroblast growth factor (FGF) receptor 1 (FGFR1) causes dimerization and activation by transphosphorylation of tyrosine residues in the kinase domain. FGFR1 is ubiquitylated by the E3 ligase NEDD4 (also known as NEDD4-1), which promotes FGFR1 internalization and degradation. Although phosphorylation of FGFR1 is required for NEDD4-dependent endocytosis, NEDD4 directly binds to a nonphosphorylated region of FGFR1. We found that activation of FGFR1 led to activation of c-Src kinase-dependent tyrosine phosphorylation of NEDD4, enhancing the ubiquitin ligase activity of NEDD4. Using mass spectrometry, we identified several FGF-dependent phosphorylated tyrosines in NEDD4, including Tyr(43) in the C2 domain and Tyr(585) in the HECT domain. Mutating these tyrosines to phenylalanine to prevent phosphorylation inhibited FGF-dependent NEDD4 activity and FGFR1 endocytosis and enhanced cell proliferation. Mutating the tyrosines to glutamic acid to mimic phosphorylation enhanced NEDD4 activity. Moreover, the NEDD4 C2 domain bound the HECT domain, and the presence of phosphomimetic mutations inhibited this interaction, suggesting that phosphorylation of NEDD4 relieves an inhibitory intra- or intermolecular interaction. Accordingly, activation of FGFR1 was not required for activation of NEDD4 that lacked its C2 domain. Activation of c-Src by epidermal growth factor (EGF) also promoted tyrosine phosphorylation and enhanced the activity of NEDD4. Thus, we identified a feedback mechanism by which receptor tyrosine kinases promote catalytic activation of NEDD4 and that may represent a mechanism of receptor crosstalk.

  13. CDPK Activation in PRR Signaling. (United States)

    Seybold, Heike; Boudsocq, Marie; Romeis, Tina


    Calcium-dependent protein kinases undergo a rapid biochemical activation in response to an intracellular Ca increase induced by the PRR-dependent perception of a pathogen-related stimulus. Based on SDS gel resolution, the in-gel kinase assay allows the analysis of multiple in vivo protein samples in parallel, combining the advantage of protein separation according to molecular mass with the activity read-out of a protein kinase assay. It thus enables to follow the transient CDPK activation and inactivation in response to in vivo elicitation with a time-wise resolution. In addition, changes of CDPK phosphorylation activity often correlate with slight shifts in the enzyme's apparent molecular mass, indicating posttranslational modifications and a conformational change of the active enzyme compared to its inactive resting form. These band shifts can be detected by a simple immunoblotting to monitor CDPK activation.

  14. Swim pressure of active matter (United States)

    Takatori, Sho; Yan, Wen; Brady, John; Caltech Team


    Through their self-motion, all active matter systems generate a unique ``swim pressure'' that is entirely athermal in origin. This new source for the active stress exists at all scales in both living and nonliving active systems, and also applies to larger organisms where inertia is important (i.e., the Stokes number is not small). Here we explain the origin of the swim stress and develop a simple thermodynamic model to study the self-assembly and phase separation in active soft matter. Our new swim stress perspective can help analyze and exploit a wide class of active soft matter, from swimming bacteria and catalytic nanobots, schools of fish and birds, and molecular motors that activate the cellular cytoskeleton.

  15. Enhanced NIF neutron activation diagnostics. (United States)

    Yeamans, C B; Bleuel, D L; Bernstein, L A


    The NIF neutron activation diagnostic suite relies on removable activation samples, leading to operational inefficiencies and a fundamental lower limit on the half-life of the activated product that can be observed. A neutron diagnostic system measuring activation of permanently installed samples could remove these limitations and significantly enhance overall neutron diagnostic capabilities. The physics and engineering aspects of two proposed systems are considered: one measuring the (89)Zr/(89 m)Zr isomer ratio in the existing Zr activation medium and the other using potassium zirconate as the activation medium. Both proposed systems could improve the signal-to-noise ratio of the current system by at least a factor of 5 and would allow independent measurement of fusion core velocity and fuel areal density.

  16. Catalytic activity of Au nanoparticles

    DEFF Research Database (Denmark)

    Larsen, Britt Hvolbæk; Janssens, Ton V.W.; Clausen, Bjerne;


    Au is usually viewed as an inert metal, but surprisingly it has been found that Au nanoparticles less than 3–5 nm in diameter are catalytically active for several chemical reactions. We discuss the origin of this effect, focusing on the way in which the chemical activity of Au may change with par......Au is usually viewed as an inert metal, but surprisingly it has been found that Au nanoparticles less than 3–5 nm in diameter are catalytically active for several chemical reactions. We discuss the origin of this effect, focusing on the way in which the chemical activity of Au may change...... with particle size. We find that the fraction of low-coordinated Au atoms scales approximately with the catalytic activity, suggesting that atoms on the corners and edges of Au nanoparticles are the active sites. This effect is explained using density functional calculations....

  17. Social activity and healthy aging

    DEFF Research Database (Denmark)

    McGue, Matt; Christensen, Kaare


    with late-life physical functioning, cognitive functioning, and depression symptomatology using data from 1112 pairs of like-sex twins who participated in the Longitudinal Study of Aging Danish Twins. Consistent with previous research, we found that social activity was significantly correlated with overall...... level of physical functioning, cognitive functioning, and depression symptomatology. We also found that social activity was significantly and moderately heritable (estimate of .36), raising the possibility that its association with late-life functioning might reflect selection processes. Further, social...... activity did not predict change in functioning and in monozygotic twin pairs discordant on level of social activity, the more socially active twin was not less susceptible to age decreases in physical and cognitive functioning and increases in depression symptomatology than the less socially active twin...

  18. Activated sludge inhibition capacity index

    Directory of Open Access Journals (Sweden)

    V. Surerus


    Full Text Available Toxic compounds in sewage or industrial wastewater may inhibit the biological activity of activated sludge impairing the treatment process. This paper evaluates the Inhibition Capacity Index (ICI for the assessment of activated sludge in the presence of toxicants. In this study, activated sludge was obtained from industrial treatment plants and was also synthetically produced. Continuous respirometric measurements were carried out in a reactor, and the oxygen uptake rate profile obtained was used to evaluate the impact of inhibiting toxicants, such as dissolved copper, phenol, sodium alkylbenzene sulfonate and amoxicillin, on activated sludge. The results indicate that ICI is an efficient tool to quantify the intoxication capacity. The activated sludge from the pharmaceutical industry showed higher resistance than the sludge from other sources, since toxicants are widely discharged in the biological treatment system. The ICI range was from 58 to 81% when compared to the synthetic effluent with no toxic substances.

  19. Japanese activities in refrigeration technology (United States)

    Fujita, T.; Ohtsuka, T.; Ishizaki, Y.

    This paper reviews recent activities in refrigeration technology in Japan. The projects described are stimulated by growing industrial needs or form part of large national projects. The JNR project on the MAGLEV train is currently the most powerful activity and it demands knowledge in all the different disciplines of cryogenics in particular on various scales of refrigeration. Research activities are also directed towards the development of Stirling cycle and magnetic refrigerators for applications in a wider area.

  20. L3 Study Team Activities (United States)

    Shoemaker, David; L3ST Team


    The NASA-Chartered L3 Study Team is working to develop the US community participation and to support NASA's contribution to the ESA-led LISA mission to observe gravitational waves via space-based detectors. The present activities of the L3ST will be described, and the next steps for the Study Team will also be given. NASA supports travel activities and support for the Study Team activities.


    Directory of Open Access Journals (Sweden)

    V. S. Novikov


    Full Text Available Fundamental and applied innovations impact activities in the tourist industry and evolution thereof. More and more sophisticated technologies and communication techniques are practically used to serve tourists. Basically, innovative tourist activity development concept represents innovation of values and in particular means that tourist’s impression is taken into account to higher extent and tourist product personification changes the products’ consumer value. Discussed in the article are tourist activity, tourist cluster, destination and glocalization development prospects.

  2. Activity Recognition in Social Media (United States)


    activity is splitting. 6 Crowd video classification Ability to identify crowd behavior enables crowd management systems to design and manage public...characterize group activities . We then showed the effectiveness of group level features in crowd video classification . 9 List of Publications 1. N. Bhargava, S...AFRL-AFOSR-JP-TR-2016-0044 Activity Recognition in Social Media Subhasis Chaudhuri INDIAN INSTITUTE OF TECHNOLOGY BOMBAY Final Report 05/09/2016

  3. Activating Teaching for Quality Learning

    DEFF Research Database (Denmark)

    Zhurbenko, Vitaliy


    Activating teaching is an educational concept which is based on active participation of students in the study process. It is becoming an alternative to more typical approach where the teacher will just lecture and the students will take notes. The study described in this paper considers student...... activating teaching methods focusing on those based on knowledge dissemination. The practical aspects of the implemented teaching method are considered, and employed assessment methods and tools are discussed....

  4. Spanish Young Generation (JJNN) Activities

    Energy Technology Data Exchange (ETDEWEB)

    Millan, Miguel [INITEC Nuclear- Westinghouse, Padilla 17, 28006 Madrid (Spain)


    Spanish Young Generation has been very active during 2006-2008. JJNN have mainly focused on communication activities, as conferences at universities, schools and nuclear companies. Lately, becoming in referent of the young politics, journalist and the young people in Nuclear Subjects is the new and most challenging target of the Spanish Young Generation. In order to accomplish with their objects and commitments with their members, JJNN are developing all kinds of activities focused in the young people and the JJNN members. (authors)

  5. Architectural Design Activities for JAS

    CERN Document Server

    Khaled, Lena


    The critical part for building any software system is its architecture. Architectural design is a design at a higher level of abstraction. A good architecture ensures that software will satisfy its requirement. This paper defines the most important activities of architectural design that used through building any software; also it applies these activities on one type of Electronic Commerce (EC) applications that is Job Agency System(JAS) to show how these activities can work through these types of applications.

  6. Biological Activities of Hydrazone Derivatives

    Directory of Open Access Journals (Sweden)

    S. Güniz Küçükgüzel


    Full Text Available There has been considerable interest in the development of novel compounds with anticonvulsant, antidepressant, analgesic, antiinflammatory, antiplatelet, antimalarial, antimicrobial, antimycobacterial, antitumoral, vasodilator, antiviral and antischistosomiasis activities. Hydrazones possessing an azometine -NHN=CH- proton constitute an important class of compounds for new drug development. Therefore, many researchers have synthesized these compounds as target structures and evaluated their biological activities. These observations have been guiding for the development of new hydrazones that possess varied biological activities.

  7. Active Combustion Control Valve Project (United States)

    National Aeronautics and Space Administration — Over the past decade, research into active combustion control has yielded impressive results in suppressing thermoacoustic instabilities and widening the...

  8. Studies in geophysics: Active tectonics (United States)


    Active tectonics is defined within the study as tectonic movements that are expected to occur within a future time span of concern to society. Such movements and their associated hazards include earthquakes, volcanic eruptions, and land subsidence and emergence. The entire range of geology, geophysics, and geodesy is, to some extent, pertinent to this topic. The needs for useful forecasts of tectonic activity, so that actions may be taken to mitigate hazards, call for special attention to ongoing tectonic activity. Further progress in understanding active tectonics depends on continued research. Particularly important is improvement in the accuracy of dating techniques for recent geologic materials.

  9. Physical Activity in the Classroom

    DEFF Research Database (Denmark)

    Réol, Lise Andersen


    physical activity during each school day from 0th to 10th school year, as a tool to facilitate health, motivation and academic performance. A qualitative study on pupils in 6th grade (N=8) and teachers’ (N=3) experience of movement and physical activities in school gives support to the idea, that physical...... activities in school enhance positive emotions and support an inclusive and safe learning environment. Thought it does also point to the fact, that it is indeed not that simple. Teachers’ sport-specific educational competences, their own experience of well-being and fun related to physical activities...


    Institute of Scientific and Technical Information of China (English)


    Papain (Papainase, EC was immobilized on porous silica beads by cross linking with glutaraldehyde. The thermal activation of this immobilized papain in aqueous system was found at a temperature range from 50 to 90℃. The higher the temperature, the more active the immobilized papain will possess. At the same time,the durability of the immobilized papain on heating was greatly improved. The effect of additives and salts on the activity of the immobilized papain were also studied. The results showed that the additives and some of the salts studied could markedly enhance the activity of the immobilized papain at elevated temperature.

  11. CDBG Activity Funding by Tract (United States)

    Department of Housing and Urban Development — All CDBG activities in the categories of acquisition, economic development, housing, public improvements, public services, and other summarized by Census Tract.

  12. Physical activity and human health

    Directory of Open Access Journals (Sweden)

    Paulina Wojciechowska


    Full Text Available Introduction: The dynamic development of the automotive industry, transport, and the media means that human life has become much easier. At the same time, the comfortable living conditions have decreased physical activity. Biologically conditioned, the need of activity has been minimised by the ever-increasing pace of life. As a result, it may lead to the loss of physical and mental health. Active recreation is not only an excellent source of activity, but also a source of satisfaction. Youths and adults should therefore spend their free time primarily on various forms of physical activity. Aim of the research : To evaluate the physical fitness of students who regularly practice physical exercise, those who occasionally practice, and those not practicing any form of physical activity. Material and methods : In the research we used a questionnaire of the Ruffier test and an orthostatic test. The study involved a group of 15 people aged 20–25 years. Participation in the study was entirely voluntary and anonymous. The study group consisted only of women. Results obtained from the questionnaire survey were fully reflected during exercise tests performed. Results and conclusions: Only regularly practiced physical activity has an effect on our body. Regular exercise increases our body’s physical capacity. Activity is the best means of prevention of lifestyle diseases. Youths and adults should spend their free time mainly doing various forms of physical activity.

  13. Active Combustion Control Valve Project (United States)

    National Aeronautics and Space Administration — Over the past decade, research into active combustion control has yielded impressive results in suppressing thermoacoustic instabilities and widening the operational...

  14. Active Gas Regenerative Liquefier Project (United States)

    National Aeronautics and Space Administration — We offer a novel liquefier that has the potential to simultaneously increase thermodynamic efficiency and significantly reduce complexity. The ?active gas...

  15. Active Directory Designing, Deploying, and Running Active Directory

    CERN Document Server

    Desmond, Brian


    By giving you a thorough grounding in Active Directory, this bestselling book teaches you how to design, manage, and maintain an AD infrastructure, whether it's for a small business network or a multinational enterprise with thousands of resources, services, and users. The fourth edition covers Active Directory from Windows 2000 through Windows Server 2008 in an easy-to-understand narrative style.

  16. Incorporation of Socio-scientific Content into Active Learning Activities (United States)

    King, D. B.; Lewis, J. E.; Anderson, K.; Latch, D.; Sutheimer, S.; Webster, G.; Moog, R.


    Active learning has gained increasing support as an effective pedagogical technique to improve student learning. One way to promote active learning in the classroom is the use of in-class activities in place of lecturing. As part of an NSF-funded project, a set of in-class activities have been created that use climate change topics to teach chemistry content. These activities use the Process Oriented Guided Inquiry Learning (POGIL) methodology. In this pedagogical approach a set of models and a series of critical thinking questions are used to guide students through the introduction to or application of course content. Students complete the activities in their groups, with the faculty member as a facilitator of learning. Through assigned group roles and intentionally designed activity structure, process skills, such as teamwork, communication, and information processing, are developed during completion of the activity. Each of these climate change activities contains a socio-scientific component, e.g., social, ethical and economic data. In one activity, greenhouse gases are used to explain the concept of dipole moment. Data about natural and anthropogenic production rates, global warming potential and atmospheric lifetimes for a list of greenhouse gases are presented. The students are asked to identify which greenhouse gas they would regulate, with a corresponding explanation for their choice. They are also asked to identify the disadvantages of regulating the gas they chose in the previous question. In another activity, where carbon sequestration is used to demonstrate the utility of a phase diagram, students use economic and environmental data to choose the best location for sequestration. Too often discussions about climate change (both in and outside the classroom) consist of purely emotional responses. These activities force students to use data to support their arguments and hypothesize about what other data could be used in the corresponding discussion to

  17. Active vibration and noise control by hybrid active acoustic panels

    Energy Technology Data Exchange (ETDEWEB)

    Stoebener, U.; Gaul, L. [Stuttgart Univ. (Germany). Inst. A fuer Mechanik


    In the present paper a hybrid passive and active treatment for vibration and noise reduction of plate type structures is proposed. The treatment is manufactured as sandwich structure and is called hybrid active acoustic panel. The passive component is used to reduce the vibration and sound radiation for high frequencies whereas the active part of the system is designed for the low frequency range. By selecting the thickness of the passive damping layer a certain frequency limit is defined, which divides the high and low frequency range. The actuator and sensor layout of the active component is evaluated by using the mode shapes of the low frequency range. According to the evaluated layout a hybrid active acoustic panel is manufactured and experimentally tested. The experimental results validate the proposed concept. (orig.)

  18. Protease activities of rumen protozoa. (United States)

    Forsberg, C W; Lovelock, L K; Krumholz, L; Buchanan-Smith, J G


    Intact, metabolically active rumen protozoa prepared by gravity sedimentation and washing in a mineral solution at 10 to 15 degrees C had comparatively low proteolytic activity on azocasein and low endogenous proteolytic activity. Protozoa washed in 0.1 M potassium phosphate buffer (pH 6.8) at 4 degrees C and stored on ice autolysed when they were warmed to 39 degrees C. They also exhibited low proteolytic activity on azocasein, but they had a high endogenous proteolytic activity with a pH optimum of 5.8. The endogenous proteolytic activity was inhibited by cysteine proteinase inhibitors, for example, iodoacetate (63.1%) and the aspartic proteinase inhibitor, pepstatin (43.9%). Inhibitors specific for serine proteinases and metalloproteinases were without effect. The serine and cysteine proteinase inhibitors of microbial origin, including antipain, chymostatin, and leupeptin, caused up to 67% inhibition of endogenous proteolysis. Hydrolysis of casein by protozoa autolysates was also inhibited by cysteine proteinase inhibitors. Some of the inhibitors decreased endogenous deamination, in particular, phosphoramidon, which had little inhibitory effect on proteolysis. Protozoal and bacterial preparations exhibited low hydrolytic activities on synthetic proteinase and carboxypeptidase substrates, although the protozoa had 10 to 78 times greater hydrolytic activity (per milligram of protein) than bacteria on the synthetic aminopeptidase substrates L-leucine-p-nitroanilide, L-leucine-beta-naphthylamide, and L-leucinamide. The aminopeptidase activity was partially inhibited by bestatin. It was concluded that cysteine proteinases and, to a lesser extent, aspartic proteinases are primarily responsible for proteolysis in autolysates of rumen protozoa. The protozoal autolysates had high aminopeptidase activity; low deaminase activity was observed on endogenous amino acids. PMID:6364968

  19. NSLS 2009 Activity Report

    Energy Technology Data Exchange (ETDEWEB)

    Nasta K.; Mona R.


    2009 was an incredibly exciting year for light sources at Brookhaven. The National Synchrotron Light Source (NSLS) hosted more than 2,200 visiting researchers, who, along with the about 50 members of our scientific staff, produced a total of 957 publications - about 20 percent of which appeared in premier journals. Covering topics ranging from Alzheimer's disease detection to ethanol-powered fuel cells, a sampling of these findings can be found in this Activity Report. We've also seen the resurfacing of some of our long-time users hard work. I was very proud to hear that two of the three recipients of the 2009 Nobel Prize in Chemistry have ties to the NSLS. Venki Ramakrishnan, a former employee in Brookhaven's biology department and long-time user of the NSLS, now at Cambridge University, and Thomas A. Steitz of Yale University, also a long-time NSLS user, shared the prize with Ada E. Yonath of the Weizmann Institute of Science for their work on the structure and function of the ribosome. In the late 1990s, Ramakrishnan and Steitz used protein crystallography at the NSLS to gather atomic-level images of two ribosome subunits: 30S (Ramakrishnan) and 50S (Steitz). Both laureates solved the high-resolution structures for these subunits based on this data. After struggling with a rough budget for several years, we received excellent funding, and then some, this year. In addition to NSLS operations funding, we received $3 million in funds from the American Recovery and Reinvestment Act (ARRA). We used that additional money for two exciting projects: construction of a full-field x-ray microscope and acquisition of several advanced x-ray detectors. The x-ray microscope will be able to image objects with a targeted spatial resolution of 30 nanometers. This capability will be particularly important for new initiatives in energy research and will prepare our users for the projected 1-nanometer resolution benchmark at the National Synchrotron Light Source II

  20. NSLS 2009 Activity Report

    Energy Technology Data Exchange (ETDEWEB)

    Nasta K.; Mona R.


    2009 was an incredibly exciting year for light sources at Brookhaven. The National Synchrotron Light Source (NSLS) hosted more than 2,200 visiting researchers, who, along with the about 50 members of our scientific staff, produced a total of 957 publications - about 20 percent of which appeared in premier journals. Covering topics ranging from Alzheimer's disease detection to ethanol-powered fuel cells, a sampling of these findings can be found in this Activity Report. We've also seen the resurfacing of some of our long-time users hard work. I was very proud to hear that two of the three recipients of the 2009 Nobel Prize in Chemistry have ties to the NSLS. Venki Ramakrishnan, a former employee in Brookhaven's biology department and long-time user of the NSLS, now at Cambridge University, and Thomas A. Steitz of Yale University, also a long-time NSLS user, shared the prize with Ada E. Yonath of the Weizmann Institute of Science for their work on the structure and function of the ribosome. In the late 1990s, Ramakrishnan and Steitz used protein crystallography at the NSLS to gather atomic-level images of two ribosome subunits: 30S (Ramakrishnan) and 50S (Steitz). Both laureates solved the high-resolution structures for these subunits based on this data. After struggling with a rough budget for several years, we received excellent funding, and then some, this year. In addition to NSLS operations funding, we received $3 million in funds from the American Recovery and Reinvestment Act (ARRA). We used that additional money for two exciting projects: construction of a full-field x-ray microscope and acquisition of several advanced x-ray detectors. The x-ray microscope will be able to image objects with a targeted spatial resolution of 30 nanometers. This capability will be particularly important for new initiatives in energy research and will prepare our users for the projected 1-nanometer resolution benchmark at the National Synchrotron Light Source II