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Sample records for factor vwf multimers

  1. Shear-induced unfolding and enzymatic cleavage of full-length VWF multimers

    CERN Document Server

    Lippok, Svenja; Obser, Tobias; Kleemeier, Lars; Schneppenheim, Reinhard; Budde, Ulrich; Netz, Roland R; Rädler, Joachim O

    2015-01-01

    Proteolysis of the multimeric blood coagulation protein von Willebrand Factor (VWF) by ADAMTS13 is crucial for prevention of microvascular thrombosis. ADAMTS13 cleaves VWF within the mechanosensitive A2 domain, which is believed to open under shear flow. Here, we combine Fluorescence Correlation Spectroscopy (FCS) and a microfluidic shear cell to monitor real-time kinetics of full-length VWF proteolysis as a function of shear stress. For comparison, we also measure the Michaelis-Menten kinetics of ADAMTS13 cleavage of wild-type VWF in the absence of shear but partially denaturing conditions. Under shear, ADAMTS13 activity on full-length VWF arises without denaturing agent as evidenced by FCS and gel-based multimer analysis. In agreement with Brownian hydrodynamics simulations, we find a sigmoidal increase of the enzymatic rate as a function of shear at a threshold shear rate 5522/s. The same flow-rate dependence of ADAMTS13 activity we also observe in blood plasma, which is relevant to predict hemostatic dysf...

  2. Von Willebrand Factor Abnormalities Studied in the Mouse Model: What We Learned about VWF Functions

    OpenAIRE

    Casari, Caterina; Lenting, Peter J.; Christophe, Olivier D.; Denis, Cécile V.

    2013-01-01

    Up until recently, von Willebrand Factor (VWF) structure-function relationships have only been studied through in vitro approaches. A powerful technique known as hydrodynamic gene transfer, which allows transient expression of a transgene by mouse hepatocytes, has led to an important shift in VWF research. Indeed this approach has now enabled us to transiently express a number of VWF mutants in VWF-deficient mice in order to test the relative importance of specific residues in different aspec...

  3. A factor VIII-derived peptide enables von Willebrand factor (VWF)-binding of artificial platelet nanoconstructs without interfering with VWF-adhesion of natural platelets.

    Science.gov (United States)

    Haji-Valizadeh, Hassan; Modery-Pawlowski, Christa L; Sen Gupta, Anirban

    2014-05-01

    There is substantial clinical interest in synthetic platelet analogs for potential application in transfusion medicine. To this end, our research is focused on self-assembled peptide-lipid nanoconstructs that can undergo injury site-selective adhesion and subsequently promote site-directed active platelet aggregation, thus mimicking platelet's primary hemostatic actions. For injury site-selective adhesion, we have utilized a coagulation factor FVIII-derived VWF-binding peptide (VBP). FVIII binds to VWF's D'-D3 domain while natural platelet GPIbα binds to VWF's A1 domain. Therefore, we hypothesized that the VBP-decorated nanoconstructs will adhere to VWF without mutual competition with natural platelets. We further hypothesized that the adherent VBP-decorated constructs can enhance platelet aggregation when co-decorated with a fibrinogen-mimetic peptide (FMP). To test these hypotheses, we used glycocalicin to selectively block VWF's A1 domain and, using fluorescence microscopy, studied the binding of fluorescently labeled VBP-decorated nanoconstructs versus platelets to ristocetin-treated VWF. Subsequently, we co-decorated the nanoconstructs with VBP and FMP and incubated them with human platelets to study construct-mediated enhancement of platelet aggregation. Decoration with VBP resulted in substantial construct adhesion to ristocetin-treated VWF even if the A1-domain was blocked by glycocalicin. In comparison, such A1-blocking resulted in significant reduction of platelet adhesion. Without A1-blocking, the VBP-decorated constructs and natural platelets could adhere to VWF concomitantly. Furthermore, the constructs co-decorated with VBP and FMP enhanced active platelet aggregation. The results indicate significant promise in utilizing the FVIII-derived VBP in developing synthetic platelet analogs that do not interfere with VWF-binding of natural platelets but allow site-directed enhancement of platelet aggregation when combined with FMP.

  4. Nitric oxide level and von Willebrand factor (vWF) secretion are not ...

    African Journals Online (AJOL)

    Jane

    2011-08-15

    Aug 15, 2011 ... monoclonal anti-human antibodies (eBiosciences, San Diego, CA, U.S.A.). All experiments were carried out in .... DISCUSSION. In our experiment, vWF factor was slightly decreased ... cell dysfunction should be sought in vitro based on design ... depletion associated with impaired NO production. Besides ...

  5. [Determination of von Willebrand factor multimers in Mexican population].

    Science.gov (United States)

    Hernández-Zamora, Edgar; Zavala-Hernández, Cesar; Viveros-Sandoval, Martha Eva; Ochoa-Rico, Angeles; Martínez-Murillo, Carlos; Reyes-Maldonado, Elba

    2014-01-01

    Antecedentes: la enfermedad de von Willebrand es un padecimiento hereditario en el que la estructura, función y concentración del factor de von Willebrand están alteradas y, en consecuencia, también la interacción plaqueta-factor de von Willebrand-endotelio. En México no hay registros epidemiológicos de la enfermedad, sólo se han efectuado algunos estudios aislados desde el punto de vista clínico y hematológico. Material y métodos: estudio retrospectivo efectuado en 155 mexicanos mestizos, 75 de ellos con diagnóstico presuntivo de enfermedad de von Willebrand, 15 con sospecha de hemofilia A y 65 donadores sanos (testigos). Se realizaron pruebas: básicas de coagulación, especiales y de clasificación: análisis de la composición multimérica. Resultados: 15 pacientes se diagnosticaron con hemofilia A; de los 75 sujetos con sospecha de enfermedad de von Willebrand se diagnosticaron 50 de la manera siguiente: tipo 1 (62%), tipo 2 (22%) [subtipos: 2A (14%), 2B (2%) y 2N (6%)] y tipo 3 (16%). Conclusión: el análisis de los multímeros del factor de von Willebrand es un método que cumple con las características adecuadas para el diagnóstico de la enfermedad de von Willebrand, por lo que es necesario implementar esta metodología para su estudio y mejorar su diagnóstico específico.

  6. Role of fluid shear stress in regulating VWF structure, function and related blood disorders.

    Science.gov (United States)

    Gogia, Shobhit; Neelamegham, Sriram

    2015-01-01

    Von Willebrand factor (VWF) is the largest glycoprotein in blood. It plays a crucial role in primary hemostasis via its binding interaction with platelet and endothelial cell surface receptors, other blood proteins and extra-cellular matrix components. This protein is found as a series of repeat units that are disulfide bonded to form multimeric structures. Once in blood, the protein multimer distribution is dynamically regulated by fluid shear stress which has two opposing effects: it promotes the aggregation or self-association of multiple VWF units, and it simultaneously reduces multimer size by facilitating the force-dependent cleavage of the protein by various proteases, most notably ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type repeats, motif 1 type 13). In addition to these effects, fluid shear also controls the solution and substrate-immobilized structure of VWF, the nature of contact between blood platelets and substrates, and the biomechanics of the GpIbα-VWF bond. These features together regulate different physiological and pathological processes including normal hemostasis, arterial and venous thrombosis, von Willebrand disease, thrombotic thrombocytopenic purpura and acquired von Willebrand syndrome. This article discusses current knowledge of VWF structure-function relationships with emphasis on the effects of hydrodynamic shear, including rapid methods to estimate the nature and magnitude of these forces in selected conditions. It shows that observations made by many investigators using solution and substrate-based shearing devices can be reconciled upon considering the physical size of VWF and the applied mechanical force in these different geometries.

  7. Binding of factor VIII to von willebrand factor is enabled by cleavage of the von Willebrand factor propeptide and enhanced by formation of disulfide-linked multimers.

    Science.gov (United States)

    Bendetowicz, A V; Morris, J A; Wise, R J; Gilbert, G E; Kaufman, R J

    1998-07-15

    von Willebrand factor (vWF) is a multimeric adhesive glycoprotein with one factor VIII binding site/subunit. Prior reports suggest that posttranslational modifications of vWF, including formation of N-terminal intersubunit disulfide bonds and subsequent cleavage of the propeptide, influence availability and/or affinity of factor VIII binding sites. We found that deletion of the vWF propeptide produced a dimeric vWF molecule lacking N-terminal intersubunit disulfide bonds. This molecule bound fluorescein-labeled factor VIII with sixfold lower affinity than multimeric vWF in an equilibrium flow cytometry assay (approximate KDs, 5 nmol/L v 0.9 nmol/L). Coexpression of propeptide-deleted vWF with the vWF propeptide in trans yielded multimeric vWF that displayed increased affinity for factor VIII. Insertion of an alanine residue at the N-terminus of the mature vWF subunit destroyed binding to factor VIII, indicating that the native mature N-terminus is required for factor VIII binding. The requirement for vWF propeptide cleavage was shown by (1) a point mutation of the vWF propeptide cleavage site yielding pro-vWF that was defective in factor VIII binding and (2) correlation between efficiency of intracellular propeptide cleavage and factor VIII binding. Furthermore, in a cell-free system, addition of the propeptide-cleaving enzyme PACE/furin enabled factor VIII binding in parallel with propeptide cleavage. Our results indicate that high-affinity factor VIII binding sites are located on N-terminal disulfide-linked vWF subunits from which the propeptide has been cleaved.

  8. Severe Plasmodium falciparum malaria is associated with circulating ultra-large von Willebrand multimers and ADAMTS13 inhibition.

    LENUS (Irish Health Repository)

    Larkin, Deirdre

    2009-03-01

    Plasmodium falciparum infection results in adhesion of infected erythrocytes to blood vessel endothelium, and acute endothelial cell activation, together with sequestration of platelets and leucocytes. We have previously shown that patients with severe infection or fulminant cerebral malaria have significantly increased circulatory levels of the adhesive glycoprotein von Willebrand factor (VWF) and its propeptide, both of which are indices of endothelial cell activation. In this prospective study of patients from Ghana with severe (n = 20) and cerebral (n = 13) P. falciparum malaria, we demonstrate that increased plasma VWF antigen (VWF:Ag) level is associated with disproportionately increased VWF function. VWF collagen binding (VWF:CB) was significantly increased in patients with cerebral malaria and severe malaria (medians 7.6 and 7.0 IU\\/ml versus 1.9 IU\\/ml; p<0.005). This increased VWF:CB correlated with the presence of abnormal ultra-large VWF multimers in patient rather than control plasmas. Concomitant with the increase in VWF:Ag and VWF:CB was a significant persistent reduction in the activity of the VWF-specific cleaving protease ADAMTS13 (approximately 55% of normal; p<0.005). Mixing studies were performed using P. falciparum patient plasma and normal pooled plasma, in the presence or absence of exogenous recombinant ADAMTS13. These studies demonstrated that in malarial plasma, ADAMTS13 function was persistently inhibited in a time-dependent manner. Furthermore, this inhibitory effect was not associated with the presence of known inhibitors of ADAMTS13 enzymatic function (interleukin-6, free haemoglobin, factor VIII or thrombospondin-1). These novel findings suggest that severe P. falciparum infection is associated with acute endothelial cell activation, abnormal circulating ULVWF multimers, and a significant reduction in plasma ADAMTS13 function which is mediated at least in part by an unidentified inhibitor.

  9. Severe Plasmodium falciparum malaria is associated with circulating ultra-large von Willebrand multimers and ADAMTS13 inhibition.

    Directory of Open Access Journals (Sweden)

    Deirdre Larkin

    2009-03-01

    Full Text Available Plasmodium falciparum infection results in adhesion of infected erythrocytes to blood vessel endothelium, and acute endothelial cell activation, together with sequestration of platelets and leucocytes. We have previously shown that patients with severe infection or fulminant cerebral malaria have significantly increased circulatory levels of the adhesive glycoprotein von Willebrand factor (VWF and its propeptide, both of which are indices of endothelial cell activation. In this prospective study of patients from Ghana with severe (n = 20 and cerebral (n = 13 P. falciparum malaria, we demonstrate that increased plasma VWF antigen (VWF:Ag level is associated with disproportionately increased VWF function. VWF collagen binding (VWF:CB was significantly increased in patients with cerebral malaria and severe malaria (medians 7.6 and 7.0 IU/ml versus 1.9 IU/ml; p<0.005. This increased VWF:CB correlated with the presence of abnormal ultra-large VWF multimers in patient rather than control plasmas. Concomitant with the increase in VWF:Ag and VWF:CB was a significant persistent reduction in the activity of the VWF-specific cleaving protease ADAMTS13 (approximately 55% of normal; p<0.005. Mixing studies were performed using P. falciparum patient plasma and normal pooled plasma, in the presence or absence of exogenous recombinant ADAMTS13. These studies demonstrated that in malarial plasma, ADAMTS13 function was persistently inhibited in a time-dependent manner. Furthermore, this inhibitory effect was not associated with the presence of known inhibitors of ADAMTS13 enzymatic function (interleukin-6, free haemoglobin, factor VIII or thrombospondin-1. These novel findings suggest that severe P. falciparum infection is associated with acute endothelial cell activation, abnormal circulating ULVWF multimers, and a significant reduction in plasma ADAMTS13 function which is mediated at least in part by an unidentified inhibitor.

  10. Characterization of a novel mutation in the von Willebrand factor propeptide in a distinct subtype of recessive von Willebrand disease

    DEFF Research Database (Denmark)

    Lanke, Elsa; Kristoffersson, Ann-Charlotte; Philips, Malou

    2008-01-01

    von Willebrand factor (VWF) is a plasma protein that consists of a series of multimers of which the high-molecular-weight VWF multimers are the most potent in platelet adhesion and aggregation. The propeptide of the VWF (VWFpp) is known to be essential in the process of multimer assembly. Genetic......, caused by a 1709G>C transition in exon 14 of the VWF gene coding for the propeptide. Three asymptomatic relatives were found to be heterozygous. In-vitro mutagenesis and expression in COS-7 cells confirmed the detrimental effect of the mutation on VWF multimerization. Our findings show that the C570S...... mutation in the VWFpp abolishes multimerization of VWF. The mutation probably disrupts the normal configuration of the VWFpp, which is essential for correct orientation of the protomers and ultimately multimerization. The mutant amino acid is located in a region that is highly conserved across several...

  11. Severe dengue is associated with consumption of von Willebrand factor and its cleaving enzyme ADAMTS-13.

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    Kis Djamiatun

    Full Text Available BACKGROUND: Thrombocytopenia, bleeding and plasma leakage are cardinal features of severe dengue. Endothelial cell activation with exocytosis of Weibel-Palade bodies (WPBs may play an etiological role in this condition. METHODS AND PRINCIPAL FINDINGS: In a cohort of 73 Indonesian children with dengue hemorrhagic fever (DHF, of which 30 with dengue shock syndrome (DSS, we measured plasma levels of the WPB constituents von Willebrand factor antigen (VWF:Ag, VWF propeptide and osteoprotegerin (OPG, together with activity levels of the VWF-cleaving enzyme ADAMTS-13 and the amount of VWF in a platelet binding conformation (VWF activation factor. Compared with healthy controls (n = 17, children with DHF/DSS had significantly higher levels of VWF:Ag, VWF propeptide and OPG and decreased ADAMTS-13 activity. The VWF activation factor was also significantly higher in DHF/DSS and highest in children who died. There were significant differences in the kinetics of the various WPB constituents: VWF propeptide and OPG levels decreased toward discharge, while VWF:Ag levels were lower than expected at enrollment with plasma levels increasing toward discharge. Moreover, VWF propeptide levels correlated better with markers of disease severity (platelet count, liver enzymes, serum albumin and pleural effusion index than corresponding VWF levels. Together, these findings suggest that there is consumption of VWF in DHF/DSS. In 4 out of 15 selected children with low ADAMTS-13 levels on admission, we found a remarkable reduction in the large and intermediate VWF multimers in the discharge blood samples, consistent with an acquired von Willebrand disease. CONCLUSION: These findings suggest that severe dengue is associated with exocytosis of WPBs with increased circulating levels of VWF:Ag, VWF propeptide and OPG. High circulating levels of VWF in its active conformation, together with low ADAMTS-13 activity levels, are likely to contribute to the thrombocytopenia

  12. Diagnosis and classification of von Willebrand disease: a review of the differential utility of various functional von Willebrand factor assays.

    Science.gov (United States)

    Favaloro, Emmanuel J

    2011-10-01

    von Willebrand disease (VWD) is considered to be the most common inherited bleeding disorder. VWD is diagnosed following a clinical and physical review, with personal and familial evidence of (primarily mucocutaneous) bleeding, and confirmed by laboratory testing. The latter typically entails initial plasma testing of factor VIII coagulant, von Willebrand factor (VWF) protein ('antigen') and VWF function which has classically been assessed using the ristocetin cofactor (VWF:RCo) assay. More recent attention has focussed on other functional VWF assays, such as collagen binding and so-called 'VWF activity' assays, as possible replacements to the VWF:RCo, or as supplementary tests of VWF 'function'. Additional laboratory testing can comprise a battery of confirmatory and VWD-type assisting assays, including VWF:multimer and von Willebrand factor VIII binding. This review aims to update knowledge of current VWD diagnostics with a particular emphasis on 'functional' VWF assays.

  13. An update on the von Willebrand factor collagen binding assay: 21 years of age and beyond adolescence but not yet a mature adult.

    Science.gov (United States)

    Favaloro, Emmanuel J

    2007-11-01

    von Willebrand disease (VWD) is considered to be the most common inherited bleeding disorder. It is diagnosed after a clinical and physical review, with personal and familial evidence of (primarily mucocutaneous) bleeding, and confirmed by laboratory testing. The latter typically entails initial plasma testing of factor VIII coagulant (FVIII:C), von Willebrand factor (VWF) protein (antigen; VWF:Ag), and VWF function, which has classically been assessed using the ristocetin cofactor (VWF:RCo) assay. More recent attention has focused on another functional VWF assay, the collagen binding (VWF:CB) assay, as a possible replacement for the VWF:RCo assay or as a supplementary test of VWF adhesive "activity." Additional laboratory testing can comprise a battery of confirmatory and VWD subtype assisting assays, including assessment of VWF:multimers. This review updates our knowledge of VWD diagnostics with a particular emphasis on the VWF:CB assay. There is good evidence now in place that an optimized VWF:CB assay can significantly reduce the diagnostic error rate otherwise arising from the use of a test panel restricted to including the VWF:RCo assay as the sole functional VWF assay. Nevertheless, the VWF:CB assay should not be used to wholly replace the VWF:RCo assay in phenotypic testing but rather as a supplementary assay. However, with some thought and justification, the VWF:CB assay can be used to partly replace the VWF:RCo assay in some "screening" applications and can also be used to abrogate the need to perform routine VWF:multimers in most test cases.

  14. Factor VIII alters tubular organization and functional properties of von Willebrand factor stored in Weibel-Palade bodies.

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    Bouwens, Eveline A M; Mourik, Marjon J; van den Biggelaar, Maartje; Eikenboom, Jeroen C J; Voorberg, Jan; Valentijn, Karine M; Mertens, Koen

    2011-11-24

    In endothelial cells, von Willebrand factor (VWF) multimers are packaged into tubules that direct biogenesis of elongated Weibel-Palade bodies (WPBs). WPB release results in unfurling of VWF tubules and assembly into strings that serve to recruit platelets. By confocal microscopy, we have previously observed a rounded morphology of WPBs in blood outgrowth endothelial cells transduced to express factor VIII (FVIII). Using correlative light-electron microscopy and tomography, we now demonstrate that FVIII-containing WPBs have disorganized, short VWF tubules. Whereas normal FVIII and FVIII Y1680F interfered with formation of ultra-large VWF multimers, release of the WPBs resulted in VWF strings of equal length as those from nontransduced blood outgrowth endothelial cells. After release, both WPB-derived FVIII and FVIII Y1680F remained bound to VWF strings, which however had largely lost their ability to recruit platelets. Strings from nontransduced cells, however, were capable of simultaneously recruiting exogenous FVIII and platelets. These findings suggest that the interaction of FVIII with VWF during WPB formation is independent of Y1680, is maintained after WPB release in FVIII-covered VWF strings, and impairs recruitment of platelets. Apparently, intra-cellular and extracellular assembly of FVIII-VWF complex involves distinct mechanisms, which differ with regard to their implications for platelet binding to released VWF strings.

  15. ATZ11 recognizes not only Z-α1-antitrypsin-polymers and complexed forms of non-Z-α1-antitrypsin but also the von Willebrand factor.

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    Diane Goltz

    Full Text Available AIMS: The ATZ11 antibody has been well established for the identification of α1-anti-trypsin (AAT molecule type PiZ (Z-AAT in blood samples and liver tissue. In this study, we systematically analyzed the antibody for additional binding sites in human tissue. METHODS AND RESULTS: Ultrastructural ATZ11 binding was investigated immunoelectron microscopically in human umbilical vein endothelial cells (HUVECs and in platelets of a healthy individual. Human embryonic kidney (HEK293 cells were transiently transfected with Von Willebrand factor (VWF and analyzed immunocytochemically using confocal microscopy and SDS-PAGE electrophoresis followed by western blotting (WB. Platelets and serum samples of VWF-competent and VWF-deficient patients were investigated using native PAGE and SDS-PAGE electrophoresis followed by WB. The specificity of the ATZ11 reaction was tested immunohistochemically by extensive antibody-mediated blocking of AAT- and VWF-antigens. ATZ11-positive epitopes could be detected in Weibel-Palade bodies (WPBs of HUVECs and α-granules of platelets. ATZ11 stains pseudo-WBP containing recombinant wild-type VWF (rVWF-WT in HEK293 cells. In SDS-PAGE electrophoresis followed by WB, anti-VWF and ATZ11 both identified rVWF-WT. However, neither rVWF-WT-multimers, human VWF-multimers, nor serum proteins of VWF-deficient patients were detected using ATZ11 by WB, whereas anti-VWF antibody (anti-VWF detected rVWF-WT-multimers as well as human VWF-multimers. In human tissue specimens, AAT-antigen blockade using anti-AAT antibody abolished ATZ11 staining of Z-AAT in a heterozygous AAT-deficient patient, whereas VWF-antigen blockade using anti-VWF abolished ATZ11 staining of endothelial cells and megakaryocytes. CONCLUSIONS: ATZ11 reacts with cellular bound and denatured rVWF-WT and human VWF as shown using immunocytochemistry and subsequent confocal imaging, immunoelectron microscopy, SDS-PAGE and WB, and immunohistology. These immunoreactions are

  16. Characterization of Zebrafish von Willebrand Factor Reveals Conservation of Domain Structure, Multimerization, and Intracellular Storage

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    Arunima Ghosh

    2012-01-01

    Full Text Available von Willebrand disease (VWD is the most common inherited human bleeding disorder and is caused by quantitative or qualitative defects in von Willebrand factor (VWF. VWF is a secreted glycoprotein that circulates as large multimers. While reduced VWF is associated with bleeding, elevations in overall level or multimer size are implicated in thrombosis. The zebrafish is a powerful genetic model in which the hemostatic system is well conserved with mammals. The ability of this organism to generate thousands of offspring and its optical transparency make it unique and complementary to mammalian models of hemostasis. Previously, partial clones of zebrafish vwf have been identified, and some functional conservation has been demonstrated. In this paper we clone the complete zebrafish vwf cDNA and show that there is conservation of domain structure. Recombinant zebrafish Vwf forms large multimers and pseudo-Weibel-Palade bodies (WPBs in cell culture. Larval expression is in the pharyngeal arches, yolk sac, and intestinal epithelium. These results provide a foundation for continued study of zebrafish Vwf that may further our understanding of the mechanisms of VWD.

  17. Cryopreservation of MHC multimers

    DEFF Research Database (Denmark)

    Hadrup, Sine Reker; Maurer, Dominik; Laske, Karoline;

    2015-01-01

    and long-term storage is generally not recommended. We investigated here the possibility of cryopreserving MHC multimers, both in-house produced and commercially available, using a wide range of peptide-MHC class I multimers comprising virus and cancer-associated epitopes of different affinities presented...

  18. Plasmatic ADAMTS-13 metalloprotease and von Willebrand factor in children with cyanotic congenital heart disease

    Energy Technology Data Exchange (ETDEWEB)

    Soares, R.P.S. [Fundação Pró-Sangue Hemocentro de São Paulo, São Paulo, SP (Brazil); Bydlowski, S.P.; Nascimento, N.M. [Laboratório de Investigação Médica-31, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Thomaz, A.M.; Bastos, E.N.M.; Lopes, A.A. [Faculdade de Medicina, Instituto do Coração, Universidade de São Paulo, São Paulo, SP (Brazil)

    2013-04-05

    Changes in plasma von Willebrand factor concentration (VWF:Ag) and ADAMTS-13 activity (the metalloprotease that cleaves VWF physiologically) have been reported in several cardiovascular disorders with prognostic implications. We therefore determined the level of these proteins in the plasma of children with cyanotic congenital heart disease (CCHD) undergoing surgical treatment. Forty-eight children were enrolled (age 0.83 to 7.58 years). Measurements were performed at baseline and 48 h after surgery. ELISA, collagen-binding assays and Western blotting were used to estimate antigenic and biological activities, and proteolysis of VWF multimers. Preoperatively, VWF:Ag and ADAMTS-13 activity were decreased (65 and 71% of normal levels considered as 113 (105-129) U/dL and 91 ± 24% respectively, P < 0.003) and correlated (r = 0.39, P = 0.0064). High molecular weight VWF multimers were not related, suggesting an interaction of VWF with cell membranes, followed by proteolytic cleavage. A low preoperative ADAMTS-13 activity, a longer activated partial thromboplastin time and the need for cardiopulmonary bypass correlated with postoperative bleeding (P < 0.05). Postoperatively, ADAMTS-13 activity increased but less extensively than VWF:Ag (respectively, 2.23 and 2.83 times baseline, P < 0.0001), resulting in an increased VWF:Ag/ADAMTS-13 activity ratio (1.20 to 1.54, respectively, pre- and postoperative median values, P = 0.0029). ADAMTS-13 consumption was further confirmed by decreased ADAMTS-13 antigenic concentration (0.91 ± 0.30 to 0.70 ± 0.25 µg/mL, P < 0.0001) and persistent proteolysis of VWF multimers. We conclude that, in pediatric CCHD, changes in circulating ADAMTS-13 suggest enzyme consumption, associated with abnormal structure and function of VWF.

  19. Neutrophil Protease Cleavage of Von Willebrand Factor in Glomeruli - An Anti-thrombotic Mechanism in the Kidney.

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    Tati, Ramesh; Kristoffersson, Ann-Charlotte; Manea Hedström, Minola; Mörgelin, Matthias; Wieslander, Jörgen; van Kooten, Cees; Karpman, Diana

    2017-02-01

    Adequate cleavage of von Willebrand factor (VWF) prevents formation of thrombi. ADAMTS13 is the main VWF-cleaving protease and its deficiency results in development of thrombotic microangiopathy. Besides ADAMTS13 other proteases may also possess VWF-cleaving activity, but their physiological importance in preventing thrombus formation is unknown. This study investigated if, and which, proteases could cleave VWF in the glomerulus. The content of the glomerular basement membrane (GBM) was studied as a reflection of processes occurring in the subendothelial glomerular space. VWF was incubated with human GBMs and VWF cleavage was assessed by multimer structure analysis, immunoblotting and mass spectrometry. VWF was cleaved into the smallest multimers by the GBM, which contained ADAMTS13 as well as neutrophil proteases, elastase, proteinase 3 (PR3), cathepsin-G and matrix-metalloproteinase 9. The most potent components of the GBM capable of VWF cleavage were in the serine protease or metalloprotease category, but not ADAMTS13. Neutralization of neutrophil serine proteases inhibited GBM-mediated VWF-cleaving activity, demonstrating a marked contribution of elastase and/or PR3. VWF-platelet strings formed on the surface of primary glomerular endothelial cells, in a perfusion system, were cleaved by both elastase and the GBM, a process blocked by elastase inhibitor. Ultramorphological studies of the human kidney demonstrated neutrophils releasing elastase into the GBM. Neutrophil proteases may contribute to VWF cleavage within the subendothelium, adjacent to the GBM, and thus regulate thrombus size. This anti-thrombotic mechanism would protect the normal kidney during inflammation and could also explain why most patients with ADAMTS13 deficiency do not develop severe kidney failure.

  20. Expression of a structurally constrained von Willebrand factor variant triggers acute thrombotic thrombocytopenic purpura in mice.

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    Morioka, Yoko; Casari, Caterina; Wohner, Nikolett; Cho, Sungyun; Kurata, Sachiko; Kitano, Ayumi; Christophe, Olivier D; Lenting, Peter J; Li, Renhao; Denis, Cécile V; Prévost, Nicolas

    2014-05-22

    Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease that presents with thrombocytopenia, disseminated thrombosis, hemolytic anemia, and organ dysfunction. The etiology of TTP has revealed that patients share a deficiency in plasma protease a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13), the enzyme responsible for cleaving ultra-large von Willebrand factor (VWF) multimers into nonthrombogenic fragments. Therefore, existing TTP mouse models were developed by targeted disruption of the ADAMTS13 gene. ADAMTS13(-/-) mice are mostly asymptomatic in the absence of a trigger, as redundant proteases appear to take on VWF processing. As an alternative approach to creating one such model, we devised a strategy based on the expression of a cleavage-resistant VWF mutant in mice. The creation of a disulfide bond within the A2 domain of VWF was found to render VWF multimers resistant to proteolysis by plasma proteases under flow. Furthermore, mice expressing the murine VWF/p.S1494C-p.A1534C mutant present with symptoms characteristics of acute TTP such as thrombocytopenia, red cell shredding, accumulation of VWF-rich thrombi in the microvasculature, and advanced TTP symptoms such as renal dysfunction and splenomegaly. Because this model appears to faithfully emulate the pathophysiology of TTP, it should prove most useful in the study of microangiopathic diseases and their treatment. © 2014 by The American Society of Hematology.

  1. A systematic overview of the first pasteurised VWF/FVIII medicinal product, Haemate P/ Humate -P: history and clinical performance

    DEFF Research Database (Denmark)

    Berntorp, E.; Archey, W.; Auerswald, G.

    2008-01-01

    , plasma-derived VWF/FVIII medicinal product, which was first licensed in Germany in 1981 for the treatment of HA-associated bleeding. It has since then come to be accepted as the gold standard for both the treatment and prophylaxis of bleeding in VWD, especially in cases where desmopressin [1-deamino-8-D...... to have a VWF multimer profile remarkably close to that of normal plasma. This bibliographic review presents previously unpublished clinical data of Haemate P, based upon internal clinical study reports of the proprietor, CSL Behring, in addition to data already presented in other publications. The data...

  2. Functional display of platelet-binding VWF fragments on filamentous bacteriophage.

    Directory of Open Access Journals (Sweden)

    Andrew Yee

    Full Text Available von Willebrand factor (VWF tethers platelets to sites of vascular injury via interaction with the platelet surface receptor, GPIb. To further define the VWF sequences required for VWF-platelet interaction, a phage library displaying random VWF protein fragments was screened against formalin-fixed platelets. After 3 rounds of affinity selection, DNA sequencing of platelet-bound clones identified VWF peptides mapping exclusively to the A1 domain. Aligning these sequences defined a minimal, overlapping segment spanning P1254-A1461, which encompasses the C1272-C1458 cystine loop. Analysis of phage carrying a mutated A1 segment (C1272/1458A confirmed the requirement of the cystine loop for optimal binding. Four rounds of affinity maturation of a randomly mutagenized A1 phage library identified 10 and 14 unique mutants associated with enhanced platelet binding in the presence and absence of botrocetin, respectively, with 2 mutants (S1370G and I1372V common to both conditions. These results demonstrate the utility of filamentous phage for studying VWF protein structure-function and identify a minimal, contiguous peptide that bind to formalin-fixed platelets, confirming the importance of the VWF A1 domain with no evidence for another independently platelet-binding segment within VWF. These findings also point to key structural elements within the A1 domain that regulate VWF-platelet adhesion.

  3. von Willebrand factor A1 domain can adequately substitute for A3 domain in recruitment of flowing platelets to collagen

    NARCIS (Netherlands)

    Bonnefoy, A.; Romijn, R. A.; Vandervoort, P. A. H.; Van Rompaey, I.; Vermylen, J.; Hoylaerts, M. F.

    2006-01-01

    Background: Binding of von Willebrand factor (VWF) to platelet GPIb alpha and to collagen is attributed to VWF A1 and A3 domains, respectively. Objectives: Using VWF, VWF lacking A1 (Delta A1-VWF) or A3 (Delta A3-VWF) and VWF with defective A3 (H1786A-VWF), in combination with recombinant A1 (residu

  4. PROTEOLYTIC PROCESSING OF VON WILLEBRAND FACTOR BY ADAMTS13 AND LEUKOCYTE PROTEASES

    Directory of Open Access Journals (Sweden)

    Stefano Lancellotti

    2013-09-01

    Full Text Available ADAMTS13 is a 190 kDa zinc protease encoded by a gene located on chromosome 9q34.   This protease specifically hydrolyzes von Willebrand factor (VWF multimers, thus causing VWF size reduction. ADAMTS13 belongs to the A Disintegrin And Metalloprotease with ThromboSpondin type 1 repeats (ADAMTS family, involved in proteolytic processing of many matrix proteins. ADAMTS13 consists of numerous domains including a metalloprotease domain, a disintegrin domain, several thrombospondin type 1 (TSP1 repeats, a cysteine-rich domain, a spacer domain and 2 CUB (Complement c1r/c1s, sea Urchin epidermal growth factor, and Bone morphogenetic protein domains. ADAMTS13 cleaves a single peptide bond (Tyr1605-Met1606 in the central A2 domain of the VWF molecule. This proteolytic cleavage is essential to reduce the size of ultra-large VWF polymers, which, when exposed to high shear stress in the microcirculation, are prone to form with platelets clumps, which cause severe syndromes called thrombotic microangiopathies (TMAs. In this review, we a discuss the current knowledge of structure-function aspects of ADAMTS13 and its involvement in the pathogenesis of TMAs, b address the recent findings concerning proteolytic processing of VWF multimers by different proteases, such as the leukocyte-derived serine and metallo-proteases and c indicate the direction of future investigations

  5. Re-establishment of VWF-dependent Weibel-Palade bodies in VWD endothelial cells.

    Science.gov (United States)

    Haberichter, Sandra L; Merricks, Elizabeth P; Fahs, Scot A; Christopherson, Pamela A; Nichols, Timothy C; Montgomery, Robert R

    2005-01-01

    Type 3 von Willebrand disease (VWD) is a severe hemorrhagic defect in humans. We now identify the homozygous mutation in the Chapel Hill strain of canine type 3 VWD that results in premature termination of von Willebrand factor (VWF) protein synthesis. We cultured endothelium from VWD and normal dogs to study intracellular VWF trafficking and Weibel-Palade body formation. Weibel-Palade bodies could not be identified in the canine VWD aortic endothelial cells (VWD-AECs) by P-selectin, VWFpp, or VWF immunostaining and confocal microscopy. We demonstrate the reestablishment of Weibel-Palade bodies that recruit endogenous P-selectin by expressing wild-type VWF in VWD-AECs. Expression of mutant VWF proteins confirmed that VWF multimerization is not necessary for Weibel-Palade body creation. Although the VWF propeptide is required for the formation of Weibel-Palade bodies, it cannot independently induce the formation of the granule. These VWF-null endothelial cells provide a unique opportunity to examine the biogenesis of Weibel-Palade bodies in endothelium from a canine model of type 3 VWD.

  6. Bombay phenotype is associated with reduced plasma-VWF levels and an increased susceptibility to ADAMTS13 proteolysis.

    Science.gov (United States)

    O'Donnell, James S; McKinnon, Thomas A J; Crawley, James T B; Lane, David A; Laffan, Michael A

    2005-09-15

    ABO blood group is an important determinant of plasma von Willebrand factor antigen (VWF:Ag) levels, with lower levels in group O. Previous reports have suggested that ABO(H) sugars affect the susceptibility of VWF to ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type-1 repeats-13) cleavage. To further test this hypothesis, we collected plasma from individuals with the rare Bombay blood group. VWF:Ag levels were significantly lower in Bombay patients (median, 0.69 IU/mL) than in groups AB, A, or B (P Bombays compared with either group O or AB. Increasing urea concentration (0.5 to 2 M) increased the cleavage rate for each blood group but eliminated the differences between groups. We conclude that reduction in the number of terminal sugars on N-linked glycan increases susceptibility of globular VWF to ADAMTS13 proteolysis and is associated with reduced plasma VWF:Ag and VWF:CB levels.

  7. Understanding FVIII/VWF complex--report from a symposium of XXIX WFH meeting 2010.

    Science.gov (United States)

    Gringeri, A; Ofosu, F A; Grancha, S; Oldenburg, J; Ewing, N P; Federici, A B

    2012-05-01

    von Willebrand factor (VWF) has the capacity to form a complex with factor VIII (FVIII) which may modulate the immunogenicity of FVIII. It has been proposed that a significant fraction of recombinant FVIII (rFVIII) is unable to bind VWF. In an experimental model studied at the McMaster University in Canada, this VWF-unbound rFVIII fraction showed no coagulant function. Sulphation of FVIII tyrosine (Tyr) 1680 has been reported as essential for the interaction with VWF. In a study performed at the Grifols and CNS-CSIC in Spain, Tyr1680 sulphation was observed to be incomplete in rFVIII and complete in plasma-derived FVIII (pdFVIII). This could explain the incapability of some rFVIII molecules to bind VWF. Experience with immune tolerance induction (ITI) at the Bonn Haemophilia Centre indicates that only eradication of FVIII inhibitors allows safe haemostasis control and the option of prophylactic treatment. Various clinical trials were planned to evaluate the clinical role VWF-containing FVIII concentrates (FVIII/VWF). RES.I.ST (an acronym for REScue Immunotolerance STudy) is an international, prospective study aimed at assessing whether FVIII/VWF can induce ITI in high-risk haemophilia patients (RES.I.ST naïve) and whether patients who previously failed ITI with FVIII alone can be rescued with FVIII/VWF (RES.I.ST experienced). Enrolment started in November 2009. In the FAIReSt.Will (Fanhdi and Alphanate Italian Retrospective Study in Willebrand disease) study, 120 von Willebrand disease (VWD) patients treated with Fanhdi(®) or Alphanate(®) were retrospectively analysed. Efficacy was excellent and no side effects were reported. The ongoing PRO.Will study is a prospective, multicenter trial aimed at assessing the efficacy, safety and pharmacoeconomics of secondary long-term prophylaxis in patients with severe inherited VWD.

  8. Escultura Multimédia

    OpenAIRE

    2009-01-01

    Mestrado em Arte Multimédia A presente investigação realizou-se a partir da consciência da importância das novas ferramentas de modelação digitais, associadas a um alargamento da construção e percepção da experiência da tridimensionalidade, como atesta a quantidade de exemplos que remetem para novas possibilidades de tradução da matéria para a escultura. Intentou-se abordar as tendências estéticas e as potencialidades interactivas, implementadas no território da escultura...

  9. ADAMTS13 activity as a novel risk factor for incident type 2 diabetes mellitus: a population-based cohort study.

    Science.gov (United States)

    de Vries, Paul S; van Herpt, Thijs T W; Ligthart, Symen; Hofman, Albert; Ikram, M Arfan; van Hoek, Mandy; Sijbrands, Eric J G; Franco, Oscar H; de Maat, Moniek P M; Leebeek, Frank W G; Dehghan, Abbas

    2017-02-01

    ADAMTS13 is a protease that breaks down von Willebrand factor (VWF) multimers into smaller, less active particles. VWF has been associated with an increased risk of incident type 2 diabetes mellitus. Here, we determine whether ADAMTS13 activity and VWF antigen are associated with incident diabetes. This study included 5176 participants from the Rotterdam Study, a prospective population-based cohort study. Participants were free of diabetes at baseline and followed up for more than 20 years. Cox proportional hazards models were used to examine the association of ADAMTS13 activity and VWF antigen with incident diabetes. ADAMTS13 activity was associated with an increased risk of incident diabetes (HR 1.17 [95% CI 1.08, 1.27]) after adjustment for known risk factors and VWF antigen levels. Although ADAMTS13 activity was positively associated with fasting glucose and insulin, the association with incident diabetes did not change when we adjusted for these covariates. ADAMTS13 activity was also associated with incident prediabetes (defined on the basis of both fasting and non-fasting blood glucose) after adjustment for known risk factors (HR 1.11 [95% CI 1.03, 1.19]), while the VWF antigen level was not. VWF antigen was associated with incident diabetes, but this association was attenuated after adjustment for known risk factors. ADAMTS13 activity appears to be an independent risk factor for incident prediabetes and type 2 diabetes. As the association between ADAMTS13 and diabetes did not appear to be explained by its cleavage of VWF, ADAMTS13 may have an independent role in the development of diabetes.

  10. Platelet-collagen adhesion enhances platelet aggregation induced by binding of VWF to platelets

    Energy Technology Data Exchange (ETDEWEB)

    Laduca, F.M.; Bell, W.R.; Bettigole, R.E. (Johns Hopkins Univ. School of Medicine, Baltimore, MD (USA) State Univ. of New York, Buffalo (USA))

    1987-11-01

    Ristocetin-induced platelet aggregation (RIPA) was evaluated in the presence of platelet-collagen adhesion. RIPA of normal donor platelet-rich plasma (PRP) demonstrated a primary wave of aggregation mediated by the binding of von Willebrand factor (VWF) to platelets and a secondary aggregation wave, due to a platelet-release reaction, initiated by VWF-platelet binding and inhibitable by acetylsalicylic acid (ASA). An enhanced RIPA was observed in PRP samples to which collagen had been previously added. These subthreshold concentrations of collagen, which by themselves were insufficient to induce aggregation, caused measurable platelet-collagen adhesion. Subthreshold collagen did not cause microplatelet aggregation, platelet release of ({sup 3}H)serotonin, or alter the dose-responsive binding of {sup 125}I-labeled VWF to platelets, which occurred with increasing ristocetin concentrations. However, ASA inhibition of the platelet release reaction prevented collagen-enhanced RIPA. These results demonstrate that platelet-collagen adhesion altered the platelet-release reaction induced by the binding of VWF to platelets causing a platelet-release reaction at a level of VWF-platelet binding not normally initiating a secondary aggregation. These findings suggest that platelet-collagen adhesion enhances platelet function mediated by VWF.

  11. Function of von Willebrand factor in children with diarrhea-associated hemolytic-uremic syndrome (D+ HUS).

    Science.gov (United States)

    Sutor, A H; Thomas, K B; Prüfer, F H; Grohmann, A; Brandis, M; Zimmerhackl, L B

    2001-06-01

    Reports on von Willebrand factor (vWF) in hemolytic-uremic syndrome (HUS) are not unequivocal. Because of potential pathogenic implications, we examined the ability of vWF to bind to collagen in vitro, which reflects its function. Plasma vWF antigen (vWF:Ag) and collagen-binding activity (vWF:CBA) were measured by enzyme-linked immunosorbent assay in children with (1) diarrhea-associated (D+) HUS (n = 27), (2) chronic renal insufficiency (CRI) (n = 8), (3) gastroenteritis (GE) not associated with HUS (n = 15), (4) immune thrombocytopenia (ITP) (n = 40) and from controls (n = 35). Structural vWF was evaluated by multimer analysis. Children with D+ HUS had vWF:Ag of 2.53 and vWF:CBA of 1.98 U/mL. The corresponding values for patients with ITP were 1.35 and 1.82 U/mL, with CRI 1.55 and 1.55 U/mL, and with GE 1.68 and 2.10 U/mL; all values were higher than in controls (1.04 and 1.16 U/mL). The mean ratio of vWF:CBA to vWF:Ag ratio in controls was 1.13; only children with HUS had a dysfunctional vWF, as indicated by a low ratio of 0.78; the ratio was elevated in children with ITP (1.36) and GE (1.27) and was normal in those with CRI (1.06). No ultralarge molecular multimers of vWF were detected in any group, including HUS. The very high concentration of plasma vWF:Ag in HUS probably reflects endothelial cell damage or irritation. In contrast to all other groups, only children with HUS had a dysfunctional vWF, caused either by a primary (due to enterohemorrhagic Escherichia coli) or secondary (due to consumption of functionally active vWF) process. This abnormality was not obvious as structural anomaly by multimer analysis.

  12. [vWF improves secretion and activity of intein spliced BDD-FVIII].

    Science.gov (United States)

    Zhu, Fu-Xiang; Yang, Shu-De; Liu, Ze-Long; Miao, Jing; Qu, Hui-Ge; Chi, Xiao-Yan

    2010-05-01

    As synthesized by vascular endothelial cells and megakaryocytes, the von Willebrand factor (vWF) plays an important hemostatic role in the binding to and stabilizing blood coagulation factor VIII (FVIII) and preventing its enzymatic degradation. Our recent work demonstrated intein can efficiently ligate BDD-FVIII (B-domaim deleted FVIII) posttranslationally by protein trans-splicing after transfer of split BDD-FVIII gene by a dual-vector system. In this study we investigated the effect of vWF on secretion and activity of intein-ligated BDD-FVIII. We observed the levels of full-length BDD-FVIII antigen secreted into culture supernatant by ELISA and their activity by Coatest assay after transfection of cultured 293 cells with intein-fused BDD-FVIII heavy- and light-chain genes simultaneously with the vWF gene co-transfected. The data showed that the amount of full-length BDD-FVIII protein and their bioactivity in vWF gene co-transfected cell supernatant were 235 +/- 21 ng x mL(-1) and 1.98 +/- 0.2 u x mL(-1), respectively, greater than that of non-vWF co-transfected cell (110 +/- 18) ng x mL(-1) and 1.10 +/- 0.15 u x nL(-1)) or just BDD-FVIII gene transfected control cell (131 +/- 25 ng x mL(-1) and 1.22 +/- 0.18 u x mL(-1)) indicating the benefit of vWF gene co-transfection in the secretion and activity of intein-spliced BDD-FVIII protein. It provided evidence that vWF gene co-transfer may be useful to improve efficacy of gene therapy for hemophilia A in protein splicing-based split FVIII gene transfer.

  13. More than a decade of international experience with a pdFVIII/VWF concentrate in immune tolerance.

    Science.gov (United States)

    Santagostino, E

    2013-01-01

    Approximately 20-30% of patients with severe haemophilia A develop alloantibodies ('inhibitors') to infused FVIII rendering use of such replacement therapy ineffective. Once an inhibitor emerges, immune tolerance induction (ITI) is the standard treatment. ITI involves giving regular doses of FVIII concentrate to eradicate the inhibitor and achieve immunogenic acceptance of administered FVIII. In the early 2000s, a retrospective analysis of inhibitor patients treated at a single centre in Germany indicated that success rates were higher when patients were treated with von Willebrand factor (VWF)-containing plasma-derived FVIII (pdFVIII/VWF) concentrate compared with recombinant or non-VWF-containing pdFVIII products. Importantly, pdFVIII/VWF as rescue therapy was able to convert 8 of 10 patients who had failed primary ITI with recombinant or non-VWF-containing pdFVIII product. A subsequent study from Italy in patients with poor prognostic factors for ITI success also reported good success rates with pdFVIII/VWF as rescue therapy (53% success; 41% partial success). The Grifols-Immune Tolerance Induction (G-ITI) Study represents the largest group of haemophilia A inhibitor patients treated with a single pdFVIII/VWF concentrate (Alphanate(®)/Fanhdi(®)) to be reported to date. Data have been collected for 95 patients who underwent primary or rescue ITI at 46 centres in Europe and the US. Currently, published data are available for 33 patients in the US cohort (11 centres), and data from the European cohort are being analysed. Both groups contained patients with poor prognostic factors and most patients received a high-dose regimen (≥ 100 IU pdFVIII/VWF kg(-1) daily). As expected, the success rate was better for primary vs. rescue ITI and for patients with good vs. poor prognostic factors. However, more than half the patients in the US cohort receiving rescue ITI achieved success (33% complete success; 20% partial success). These results should encourage clinicians

  14. Effect of unfractionated heparin, enoxaparin and sulodexide on the relations between secretion and expression of OPG, RANKL and vWF in HUVEC.

    Science.gov (United States)

    Lekesiz, Katarzyna; Naumnik, Beata; Borysewicz-Sanczyk, Hanna; Koc-Zurawska, Ewa; Mysliwiec, Michal

    2013-01-01

    Heparin modulates function of vascular endothelium. We studied the effects of unfractionated heparin (UFH) vs. enoxaparin vs. sulodexide on the levels and gene expression of osteoprotegerin (OPG), Receptor Activator of Nuclear Factor kB Ligand (RANKL) and von Willebrand factor (vWF) in Human Umbilical Vein Endothelial Cells (HUVEC) culture. HUVEC were isolated from human umbilical vein by a standard method. The supernatant concentrations (ELISA) and gene expression (Real Time-PCR) of OPG, RANKL and vWF in HUVEC were determined after incubation with various concentrations of UFH, enoxaparin and sulodexide for up to 16 hours. In control HUVEC strong positive correlation between OPG and vWF levels was observed, whereas sRANKL negatively correlated with OPG and vWF levels. Only in control HUVEC a negative correlation between the supernatant level of vWF and its gene expression was found. Already the lowest concentration of UFH caused 2.5-fold increase in OPG gene expression while higher UFH concentrations substantially increased RANKL mRNA level. A negative correlation between the OPG and sRANKL concentration was noticed in supernatant HUVEC which were incubated with enoxaparine. In conclusion, the observed interrelationships between OPG, RANKL and vWF levels in unstimulated HUVEC support the presumption of the pathophysiological links between these proteins. Of the tested heparin formulas UFH seems to be the most potent in altering the OPG, RANKL and vWF axis.

  15. A comparison of nano-electrospray gas-phase electrophoretic mobility macromolecular analysis and matrix-assisted laser desorption/ionization linear time-of-flight mass spectrometry for the characterization of the recombinant coagulation glycoprotein von Willebrand factor.

    Science.gov (United States)

    Kemptner, Jasmin; Marchetti-Deschmann, Martina; Müller, Roland; Ivens, Andreas; Turecek, Peter; Schwarz, Hans Peter; Allmaier, Günter

    2010-03-01

    Von Willebrand factor (VWF), an adhesive glycoprotein with an approximate molecular weight (MW) of the monomer of 260 kDa, circulates in human blood plasma as a series of multimers ranging in size up to 20.000 kDa; thus the determination of the accurate MW of the monomer is of great importance and due to its high MW quite challenging. In this study accurate MW determination of intact recombinant VWF monomer (rVWF) was performed with GEMMA (gas-phase electrophoretic mobility macromolecular analysis) and MALDI TOF MS (matrix-assisted laser desorption/ionization linear time-of-flight mass spectrometry). Three rVWF preparations with differing buffer systems and glycoprotein concentrations were analyzed. First investigations directed towards heterogeneity determination by means of capillary gel electrophoresis (CGE)-on-the-chip with a laser-induced fluorescence detector revealed two compounds (MW of 277 kDa (migration time 44.3 s) and 341 kDa (migration time 49.5 s)) present in each sample to varying extents, namely mature and pro-rVWF. MALDI MS analysis in the linear positive ion mode allowed the detection of mature rVWF with an exact MW of 256.1 kDa (+/-0.8%) and pro-rVWF with a MW of 349.8 kDa (+/-0.8%). Two samples containing pro-rVWF in very minor concentration resulted in GEMMA detection of the mature rVWF with a MW of 227.4 kDa (+/-2.5%), derived from the measured globular size of 10.9 nm. For one sample containing both rVWF species in almost equal concentrations no differentiation of the two species was possible with GEMMA. Due to its lower resolution only a peak representing a mixture of both species at 11.8 nm could be observed, yielding a MW of 298.8 kDa (+/-1.6%).

  16. Adiponectin multimer distribution in patients with familial combined hyperlipidemia.

    NARCIS (Netherlands)

    Koenen, T.B.; Tits, L.J.H. van; Holewijn, S.; Lemmers, H.L.M.; Heijer, M. den; Stalenhoef, A.F.H.; Graaf, J. de

    2008-01-01

    Adiponectin is secreted from adipocytes in different multimers, of which the high molecular weight (HMW) form is supposed to mediate favorable metabolic and anti-atherogenic effects. We determined adiponectin multimers in 29 female and 22 male patients with familial combined hyperlipidemia (FCH) and

  17. Mechanical Activation of a Multimeric Adhesive Protein through Domain Conformational Change

    Science.gov (United States)

    Wijeratne, Sithara S.; Botello, Eric; Yeh, Hui-Chun; Zhou, Zhou; Bergeron, Angela; Frey, Eric W.; Patel, Jay M.; Moake, Joel; Dong, Jing-fei; Kiang, Ching-Hwa

    2013-01-01

    The mechanical force-induced activation of the adhesive protein von Willebrand Factor (VWF), which experiences high hydrodynamic forces, is essential in initiating platelet adhesion. The importance of the mechanical force-induced functional change is manifested in the multimeric VWF’s crucial role in blood coagulation, when high fluid shear stress activates plasma VWF (pVWF) multimers to bind platelets. Here we showed that a pathological level of high shear stress exposure of pVWF multimers results in domain conformational changes, and the subsequent shifts in the unfolding force allow us to use force as a marker to track the dynamic states of multimeric VWF. We found that shear-activated pVWF multimers (spVWF) are more resistant to mechanical unfolding than non-sheared pVWF multimers, as indicated in the higher peak unfolding force. These results provide insight into the mechanism of shear-induced activation of pVWF multimers. PMID:23521301

  18. Combined analysis of three genome-wide association studies on vWF and FVIII plasma levels

    Directory of Open Access Journals (Sweden)

    Cohen William

    2011-08-01

    Full Text Available Abstract Background Elevated levels of factor VIII (FVIII and von Willebrand Factor (vWF are well-established risk factors for cardiovascular diseases, in particular venous thrombosis. Although high, the heritability of these traits is poorly explained by the genetic factors known so far. The aim of this work was to identify novel single nucleotide polymorphisms (SNPs that could influence the variability of these traits. Methods Three independent genome-wide association studies for vWF plasma levels and FVIII activity were conducted and their results were combined into a meta-analysis totalling 1,624 subjects. Results No single nucleotide polymorphism (SNP reached the study-wide significance level of 1.12 × 10-7 that corresponds to the Bonferroni correction for the number of tested SNPs. Nevertheless, the recently discovered association of STXBP5, STX2, TC2N and CLEC4M genes with vWF levels and that of SCARA5 and STAB2 genes with FVIII levels were confirmed in this meta-analysis. Besides, among the fifteen novel SNPs showing promising association at p -5 with either vWF or FVIII levels in the meta-analysis, one located in ACCN1 gene also showed weak association (P = 0.0056 with venous thrombosis in a sample of 1,946 cases and 1,228 controls. Conclusions This study has generated new knowledge on genomic regions deserving further investigations in the search for genetic factors influencing vWF and FVIII plasma levels, some potentially implicated in VT, as well as providing some supporting evidence of previously identified genes.

  19. Clumping factor A, von Willebrand factor-binding protein and von Willebrand factor anchor Staphylococcus aureus to the vessel wall.

    Science.gov (United States)

    Claes, J; Liesenborghs, L; Peetermans, M; Veloso, T R; Missiakas, D; Schneewind, O; Mancini, S; Entenza, J M; Hoylaerts, M F; Heying, R; Verhamme, P; Vanassche, T

    2017-02-09

    Essentials Staphylococcus aureus (S. aureus) binds to endothelium via von Willebrand factor (VWF). Secreted VWF-binding protein (vWbp) mediates S. aureus adhesion to VWF under shear stress. vWbp interacts with VWF and the Sortase A-dependent surface protein Clumping factor A (ClfA). VWF-vWbp-ClfA anchor S. aureus to vascular endothelium under shear stress.

  20. Evaluation of von Willebrand factor-cleaving protease activity in patients with thrombotic thrombocytopenic purpura

    Institute of Scientific and Technical Information of China (English)

    高维强; 苏健; 白霞; 王兆钺; 阮长耿

    2004-01-01

    Background Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy. In this study we investigated the von Willebrand factor-cleaving protease (vWF-cp) activity deficiency in patients with TTP.Methods The plasma or serum vWF-cp activity was measured using a sensitive enzyme-linked immunosorbent assay (ELISA) by detecting the residual collagen binding activity (R-CBA) of von Willebrand factor (vWF) before and after digestion by vWF-cp. Multimers of vWF in plasma of patients with TTP were also analyzed by SDS-agarose electrophoresis. Moreover, the serum vWF-cp activities were compared between the patients with TTP and those with tumors.Results The coefficient of variation for intra-batch and inter-batch of the assay were 3.60% and 8.35%. The plasma and serum vWF-cp activity in healthy individuals were (78.79±9.17)% (n=30) and (79.47±10.78)% (n=53), respectively, while the plasma vWF-cp activity in 5 patients with TTP was markedly decreased [(21.83±19.98)%, P<0.001]. The unusually large vWF multimers were observed in two plasma samples of the patients with TTP. Although the vWF-cp activities in patients with benign and malignant tumors were also decreased (P<0.03 and P<0.001, respectively), they were relatively high in comparison with that of TTP patients (P<0.001).Conclusion Measurement of the vWF-cp activity using R-CBA is a simple and rapid method for diagnosing TTP. The vWF-cp activity in patients with TTP was markedly lower than those of patients with tumors.

  1. Adaptive evolution of the venom-targeted vWF protein in opossums that eat pitvipers.

    Directory of Open Access Journals (Sweden)

    Sharon A Jansa

    Full Text Available The rapid evolution of venom toxin genes is often explained as the result of a biochemical arms race between venomous animals and their prey. However, it is not clear that an arms race analogy is appropriate in this context because there is no published evidence for rapid evolution in genes that might confer toxin resistance among routinely envenomed species. Here we report such evidence from an unusual predator-prey relationship between opossums (Marsupialia: Didelphidae and pitvipers (Serpentes: Crotalinae. In particular, we found high ratios of replacement to silent substitutions in the gene encoding von Willebrand Factor (vWF, a venom-targeted hemostatic blood protein, in a clade of opossums known to eat pitvipers and to be resistant to their hemorrhagic venom. Observed amino-acid substitutions in venom-resistant opossums include changes in net charge and hydrophobicity that are hypothesized to weaken the bond between vWF and one of its toxic snake-venom ligands, the C-type lectin-like protein botrocetin. Our results provide the first example of rapid adaptive evolution in any venom-targeted molecule, and they support the notion that an evolutionary arms race might be driving the rapid evolution of snake venoms. However, in the arms race implied by our results, venomous snakes are prey, and their venom has a correspondingly defensive function in addition to its usual trophic role.

  2. Storage and secretion of naturally occurring von Willebrand factor A domain variants

    NARCIS (Netherlands)

    Groeneveld, Dafna J; Wang, Jiong-Wei; Mourik, Marjon J; Dirven, Richard J; Valentijn, Karine M; Voorberg, Jan; Reitsma, Pieter H; Eikenboom, Jeroen

    2014-01-01

    Von Willebrand disease (VWD) is a bleeding disorder characterized by reduced plasma von Willebrand factor (VWF) levels or functionally abnormal VWF. Low VWF plasma levels in VWD patients are the result of mutations in the VWF gene that lead to decreased synthesis, impaired secretion, increased clear

  3. Expression of von Willebrand factor Normandy: An autosomal mutation that mimics hemophilia A

    Energy Technology Data Exchange (ETDEWEB)

    Tuley, E.A.; Worrall, N.K.; Sadler, J.E. (Washington Univ. School of Medicine, St. Louis, MO (United States)); Gaucher, C.; Jorieux, S.; Mazurier, C. (Centre Regional de Transfusion Sanguine, Lille (France))

    1991-07-15

    von Willebrand disease Normandy (vWD Normandy) is a recently described phenotype in which a mutant von Willebrand factor (VWF) appears structurally and functionally normal except that is does not bind to blood coagulation factor VIII. This interaction is required for normal survival of factor VIII in the circulation; consequently, vWD Normandy can present as apparent hemophilia A but with autosomal recessive rather than X chromosome-linked inheritance. AvWF missense mutation, Thr{sup 28} {r arrow} Met, was identified in the propositus in or near the factor VIII binding site. The corresponding mutant recombinant vWF(T28M) formed normal multimers and had normal ristocetin cofactor activity. However, vWF(T28M) exhibited the same defect in factor VIII binding as natural vWF Normandy, confirming that this mutation causes the vWD Normandy phenotype. The distinction between hemophilia A and vWD Normandy is clinically important and should be considered in families affected by apparent mild hemophilia A that fail to show strict X chromosome-linked inheritance and, particularly, in potential female carriers with low factor VIII levels attributed to extreme lyonization.

  4. Ensino online e aprendizagem multimédia

    OpenAIRE

    Miranda, Guilhermina Lobato

    2009-01-01

    Este livro está dividido em duas partes: Ensino online e Aprendizaem multimédia, contando com a colaboração de vários autores nacionais e internacionais, que redigiram os 12 capítulos que o compõem. Por exemplo, o capítulo sobre a "Teoria cognitiva da aprendizagem multimédia" foi redigido por Richard Mayer, psicólogio norte-americano que concebeu e desenvolveu esta teoria. Este livro centra-se na concepção de cursos ministrados em regime de eLearning e a distância, interessando também às pess...

  5. Active Von Willebrand Factor, thrombocytopenia and thrombosis

    NARCIS (Netherlands)

    Hulstein, J.J.J.

    2006-01-01

    Platelets and von Willebrand factor (VWF) are unable to interact in circulation. To induce an interaction, a conversion of VWF to a platelet-binding conformation is required. At higher shear stresses, the first step in thrombus formation is binding of VWF to the subendothelium. This results in expos

  6. El context multimèdia, setembre 2010

    OpenAIRE

    2010-01-01

    Ja no es pot pensar un mitjà de comunicació en clau tradicional. Les noves tecnologies fan possible productes multimèdia i multiplataforma que van guanyant terreny dins del mercat informatiu. En primer lloc, perquè responen millor a les necessitats i gustos dels consumidors actuals i, en segon lloc, perquè economitzen recursos i esforços. En aquesta assignatura veurem nous models de producció periodística, quina tendència segueixen les redaccions i quin és el perfil dels professionals que hi ...

  7. On the miscellaneous aspects of von Willebrand factor

    NARCIS (Netherlands)

    Groeneveld, Dafna Jordana

    2015-01-01

    Von Willebrand disease is the most common inherited bleeding disorder and is characterized by reduced plasma von Willebrand factor (VWF) levels or functionally abnormal VWF. VWF is best known for its three classical hemostatic functions: (i) as a carrier protein for coagulation factor VIII, (ii)

  8. Du laboratoire audio au laboratoire multimédia

    Directory of Open Access Journals (Sweden)

    Béatrice Vautherin

    2000-01-01

    Full Text Available Les évolutions technologiques récentes amènent les enseignants de langues à faire des choix pour intégrer les outils multimédias dans leur pratique. Les investissements qu'implique cette modernisation, tant en termes de budgets qu'en termes de formation des utilisateurs, nécessitent que ces choix soient éclairés. La complexité du domaine appelle la fédération des compétences et la circulation de l'information pour surmonter les obstacles les plus fréquents. On trouvera ci-dessous une contribution à ce débat sous la forme d'un état des lieux dans une université spécialisée dans les langues et de l'examen détaillé d'un aspect particulier assez épineux, mais incontournable, la création de cours multimédias à partir de matériau pédagogique existant.

  9. Parallel detection of antigen-specific T-cell responses by multidimensional encoding of MHC multimers

    DEFF Research Database (Denmark)

    Hadrup, Sine Reker; Bakker, Arnold H; Shu, Chengyi J

    2009-01-01

    The use of fluorescently labeled major histocompatibility complex multimers has become an essential technique for analyzing disease- and therapy-induced T-cell immunity. Whereas classical major histocompatibility complex multimer analyses are well-suited for the detection of immune responses to a...

  10. Collagen-bound von Willebrand factor has reduced affinity for factor VIII.

    Science.gov (United States)

    Bendetowicz, A V; Wise, R J; Gilbert, G E

    1999-04-30

    von Willebrand factor (vWf) is a multimeric adhesive glycoprotein that serves as a carrier for factor VIII in plasma. Although each vWf subunit displays a high affinity binding site for factor VIII in vitro, in plasma, only 2% of the vWf sites for factor VIII are occupied. We investigated whether interaction of plasma proteins with vWf or adhesion of vWf to collagen may alter the affinity or availability of factor VIII-binding sites on vWf. When vWf was immobilized on agarose-linked monoclonal antibody, factor VIII bound to vWf with high affinity, and neither the affinity nor binding site availability was influenced by the presence of 50% plasma. Therefore, plasma proteins do not alter the affinity or availability of factor VIII-binding sites. In contrast, when vWf was immobilized on agarose-linked collagen, its affinity for factor VIII was reduced 4-fold, with KD increasing from 0.9 to 3.8 nM. However, one factor VIII-binding site remained available on each vWf subunit. A comparable reduction in affinity for factor VIII was observed when vWf was a constituent of the subendothelial cell matrix and when it was bound to purified type VI collagen. In parallel with the decreased affinity for factor VIII, collagen-bound vWf displayed a 6-fold lower affinity for monoclonal antibody W5-6A, with an epitope composed of residues 78-96 within the factor VIII-binding motif of vWf. We conclude that collagen induces a conformational change within the factor VIII-binding motif of vWf that lowers the affinity for factor VIII.

  11. Native plasma-derived FVIII/VWF complex has lower sensitivity to FVIII inhibitors than the combination of isolated FVIII and VWF proteins. Impact on Bethesda assay titration of FVIII inhibitors.

    Science.gov (United States)

    Bravo, M I; Da Rocha-Souto, B; Grancha, S; Jorquera, J I

    2014-11-01

    Sensitivity to FVIII inhibitors of the native plasma-derived (pd) FVIII/VWF complex vs. the complexes formed after exogenous FVIII infusion in the haemophilic patient has not been thoroughly studied. The role of VWF in the interaction of FVIII with inhibitors was studied in vitro using different combinations of VWF and FVIII concentrates. Normal plasma, pdFVIII/VWF and isolated FVIII (recombinant FVIII, B-domain deleted and pdFVIII) were used. Titre (BU) was kinetically determined (up to 2 h) in serial dilutions of inhibitor IgG (purified from a pool of plasmas with inhibitors) mixed with VWF and then incubated with the different FVIII. Inhibitor was also added to previously mixed VWF+FVIII. Residual FVIII:C was determined. TGA assays were performed with FVIII-deficient plasma spiked with the FVIII-VWF mixtures with/without an ESH-8 antibody. Inhibitor titres for plasma and pdFVIII/VWF were comparable at all time points. Titres for all concentrates of isolated FVIII were significantly higher than those for plasma or pdFVIII/VWF (1.4-1.9 fold) even after preincubation with VWF. At t = 0 h, titres for plasma or pdFVIII/VWF were unquantifiable, but were detectable for isolated FVIII (0.6-1.6 BU). In contrast to pdFVIII/VWF, the decrease in thrombin generation parameters by isolated FVIII in the presence of ESH-8 was significant (P isolated proteins. Bethesda assay titration using different FVIII concentrates would be advisable to guide the treatment of inhibitor patients.

  12. Fator von Willebrand e disfunção endotelial pulmonar. Implicações prognósticas von Willebrand factor and pulmonary vascular endothelial cell dysfunction. Prognostic implications

    Directory of Open Access Journals (Sweden)

    Antonio Augusto B. Lopes

    1998-03-01

    Full Text Available OBJETIVO: Avaliar alterações quantitativas e estruturais do fator von Willebrand (fvW circulante em 40 pacientes com hipertensão pulmonar pré-capilar e verificar possíveis implicações prognósticas dos resultados iniciais, em um ano de seguimento. MÉTODOS: A atividade antigênica plasmática do fator von Willebrand (vWF:Ag foi analisada por imunoeletroforese. A concentração de multímeros de baixo peso molecular em relação ao total de multímeros do fvW (MBPM% e o grau de fragmentação de sua subunidade principal foram analisados por Western immunoblotting. RESULTADOS: Em 40 pacientes, observamos aumento significativo de vWF:Ag em relação aos controles (pPURPOSE: To analyze quantitative and structural changes in circulating von Willebrand factor (vWF in 40 precapillary pulmonary hypertensive patients, as an attempt to identify possible correlations between endothelial cell dysfunction and patient short-term (one year survival. METHODS: Plasma antigenic activity of vWF (vWF:Ag was analyzed by immunoelectrophoresis. The relative concentration of vWF low molecular weight multimers (LMWM% and the composition of vWF subunit were determined by densitometric analysis of Western blots. RESULTS: vWF:Ag was importantly increased in patients in comparison with normals (p<0.001. Patients also had increased LMWM% (p<0.001 and increased degradation of vWF main subunit (p<0.05. At the beginning of the study, nonsurvivors (N=11 had higher vWF:Ag (p<0.001 and LMWM% (p<0.005 values in comparison with survivors. LMWM% was selected by logistic regression analysis as a predictor of death during the first year of follow-up (p<0.05. CONCLUSION: Marked changes in circulating vWF likely reflect extensive pulmonary vascular endothelial cell dysfunction and are associated with poor short-term prognosis in pulmonary hypertension.

  13. Diurnal variation of von Willebrand factor in plasma

    DEFF Research Database (Denmark)

    Timm, Annette; Fahrenkrug, Jan; Jørgensen, Henrik L;

    2014-01-01

    BACKGROUND: Quantitation of von Willebrand factor (VWF) in plasma is a central element in assessing von Willebrand disease (VWD). VWF activity is known to vary, which has partly been ascribed to biological and preanalytical variation. However, a possible diurnal expression of VWF has not been tho...

  14. Weibel-Palade bodies: a window to von Willebrand disease.

    Science.gov (United States)

    Valentijn, K M; Eikenboom, J

    2013-04-01

    Weibel-Palade bodies (WPBs) are the storage organelles for von Willebrand factor (VWF) in endothelial cells. VWF forms multimers that assemble into tubular structures in WPBs. Upon demand, VWF is secreted into the blood circulation, where it unfolds into strings that capture platelets during the onset of primary hemostasis. Numerous mutations affecting VWF lead to the bleeding disorder von Willebrand disease. This review reports the recent findings on the effects of VWF mutations on the biosynthetic pathway of VWF and its storage in WPBs. These new findings have deepened our understanding of VWF synthesis, storage, secretion, and function.

  15. IL1B and VWF variants are associated with fibrinolytic early recanalization in patients with ischemic stroke.

    Science.gov (United States)

    Fernández-Cadenas, Israel; Del Río-Espínola, Alberto; Giralt, Dolors; Domingues-Montanari, Sophie; Quiroga, Adoracion; Mendióroz, Maite; Ruíz, Agustin; Ribó, Marc; Serena, Joaquin; Obach, Victor; Freijo, Mari Mar; Martí-Fábregas, Joan; Delgado, Pilar; Montaner, Joan

    2012-10-01

    There is a great interindividual variability among patients with acute ischemic stroke regarding the response to intravenous tissue-type plasminogen activator treatment. The aim of this study was to identify genetic variants associated with recanalization, and thus treatment efficacy, after tissue-type plasminogen activator administration. A total of 140 single nucleotide polymorphisms from 97 candidate genes were successfully genotyped by SNPlex in 2 cohorts, accounting for 497 prospectively recruited tissue-type plasminogen activator-treated patients, of whom 33% recanalized during tissue-type plasminogen activator infusion. Functional studies were then performed, including assessment of interleukin 1B mRNA levels and von Willebrand factor, FIII, FVII, FVIII, and FX protein activity. After replication, the following single nucleotide polymorphisms were associated with early recanalization: rs1143627 in IL1B gene (CC: 53.1% of recanalization, A-carriers: 32.7%; P=0.022; replication cohort: P=0.046), rs16944 in IL1B gene (AA: 50% of recanalization, G-carriers: 32%; P=0.038; replication cohort: P=0.049), and rs1063856 in the vWF gene (GG: 53.8% of recanalization, A-carriers: 31.5%; P=0.006; replication cohort: P=0.046). The functional studies revealed an association between the rs1063856 single nucleotide polymorphisms in vWF and FVIII activity (AA: 115.93%, AG: 156.07%, GG: 83.42%; P=0.005). Three single nucleotide polymorphisms were associated with tissue-type plasminogen activator efficacy in the Spanish population, and their mechanism of action might be associated with the activity of coagulation factors.

  16. Structural studies on the von Willebrand factor A1 and A3 domains

    NARCIS (Netherlands)

    Romijn, R.A.P.

    2003-01-01

    Von Willebrand factor (VWF), a multimeric plasma glycoprotein, mediates platelet adhesion to sites of vascular damage. In this proces, the VWF-A3 domain binds to collagen in the vessel wall. This is followed by binding of the VWF-A1 domain to platelet receptor glycoprotein (Gp) Ibalpha. The investig

  17. Ammoniated electron as a solvent stabilized multimer radical anion

    CERN Document Server

    Shkrob, I A

    2005-01-01

    The excess electron in liquid ammonia ("ammoniated electron") is commonly viewed as a cavity electron in which the s-type wave function fills the interstitial void between 6-9 ammonia molecules. Herewith an alternative model is examined in which the ammoniated electron is regarded as a solvent stabilized multimer radical anion, as was originally suggested by Symons [Chem. Soc. Rev. 1976, 5, 337]. In this model, most of the excess electron density resides in the frontier orbitals of N atoms in the ammonia molecules forming the solvation cavity; a fraction of this spin density is transferred to the molecules in the second solvation shell. The cavity is formed due to the repulsion between negatively charged solvent molecules. Using density functional theory calculations for small ammonia cluster anions in the gas phase, it is demonstrated that such core anions would quantitatively account for the observed pattern of Knight shifts for 1H and 14N nuclei as observed by NMR spectroscopy and the downshifted stretchin...

  18. An ELISA for the quantitation of von Willebrand Factor

    DEFF Research Database (Denmark)

    Vinholt, Pernille Just; Overgaard, Martin; Diederichsen, Axel Cosmus Pyndt;

    2013-01-01

    with and without documented coronary calcification (total n=118). RESULTS AND CONCLUSIONS: The assay detected VWF:OPG complexes in human plasma, while no significant signal was observed when testing solutions containing VWF or recombinant OPG alone. Importantly, the ELISA assay was able to detect in vitro formed...... for measurement of von Willebrand factor-osteoprotegerin complex (VWF:OPG) in human plasma. Furthermore, the significance of VWF:OPG complex as a marker of cardiovascular disease (CVD) was evaluated. PATIENTS/METHODS: A sandwich ELISA for quantification of VWF:OPG was developed using a polyclonal rabbit anti...

  19. Children with dyslexia lack multiple specializations along the visual word-form (VWF) system.

    Science.gov (United States)

    van der Mark, Sanne; Bucher, Kerstin; Maurer, Urs; Schulz, Enrico; Brem, Silvia; Buckelmüller, Jsabelle; Kronbichler, Martin; Loenneker, Thomas; Klaver, Peter; Martin, Ernst; Brandeis, Daniel

    2009-10-01

    Developmental dyslexia has been associated with a dysfunction of a brain region in the left inferior occipitotemporal cortex, called the "visual word-form area" (VWFA). In adult normal readers, the VWFA is specialized for print processing and sensitive to the orthographic familiarity of letter strings. However, it is still unclear whether these two levels of occipitotemporal specialization are affected in developmental dyslexia. Specifically, we investigated whether (a) these two levels of specialization are impaired in dyslexic children with only a few years of reading experience and (b) whether this impairment is confined to the left inferior occipitotemporal VWFA, or extends to adjacent regions of the "VWF-system" with its posterior-anterior gradient of print specialization. Using fMRI, we measured brain activity in 18 dyslexic and 24 age-matched control children (age 9.7-12.5 years) while they indicated if visual stimuli (real words, pseudohomophones, pseudowords and false-fonts) sounded like a real word. Five adjacent regions of interest (ROIs) in the bilateral occipitotemporal cortex covered the full anterior-posterior extent of the VWF-system. We found that control and dyslexic children activated the same main areas within the reading network. However, a gradient of print specificity (higher anterior activity to letter strings but higher posterior activity to false-fonts) as well as a constant sensitivity to orthographic familiarity (higher activity for unfamiliar than familiar word-forms) along the VWF-system could only be detected in controls. In conclusion, analyzing responses and specialization profiles along the left VWF-system reveals that children with dyslexia show impaired specialization for both print and orthography.

  20. Genetic Drivers of von Willebrand Factor Levels in an Ischemic Stroke Population and Association With Risk for Recurrent Stroke.

    Science.gov (United States)

    Williams, Stephen R; Hsu, Fang-Chi; Keene, Keith L; Chen, Wei-Min; Dzhivhuho, Godfrey; Rowles, Joe L; Southerland, Andrew M; Furie, Karen L; Rich, Stephen S; Worrall, Bradford B; Sale, Michèle M

    2017-06-01

    von Willebrand factor (vWF) plays an important role in thrombus formation during cerebrovascular damage. We sought to investigate the potential role of circulating vWF in recurrent cerebrovascular events and identify genetic contributors to variation in vWF level in an ischemic stroke population. We analyzed the effect of circulating vWF on risk of recurrent stroke using survival models in the VISP trial (Vitamin Intervention for Stroke Prevention) and the use of vWF in reclassification over traditional factors. We conducted a genome-wide association study) with imputation, based on 1000 Genomes Project data, for circulating vWF levels and then interrogated loci previously associated with vWF levels. We performed expression quantitative trait locus analysis for vWF across different tissues. Elevated vWF levels were associated with increased risk for recurrent stroke in VISP. Adding vWF to traditional clinical parameters also improved recurrent stroke risk prediction. We identified single-nucleotide polymorphisms significantly associated with circulating vWF at the ABO locus (Pgenetic associations of vWF levels in humans. Expression quantitative trait locus analyses demonstrate that most associated ABO single-nucleotide polymorphisms were also associated with vWF gene expression. Elevated vWF levels are associated with recurrent stroke in VISP. In the VISP population, genetic determinants of vWF levels that impact vWF gene expression were identified. These data add to our knowledge of the pathophysiologic and genetic basis for recurrent stroke risk and may have implications for clinical care decision making. © 2017 American Heart Association, Inc.

  1. The important role of von Willebrand factor in platelet-derived FVIII gene therapy for murine hemophilia A in the presence of inhibitory antibodies.

    Science.gov (United States)

    Shi, Q; Schroeder, J A; Kuether, E L; Montgomery, R R

    2015-07-01

    Our previous studies have demonstrated that targeting FVIII expression to platelets results in FVIII storage together with von Willebrand factor (VWF) in platelet α-granules and that platelet-derived FVIII (2bF8) corrects the murine hemophilia A phenotype even in the presence of high-titer anti-FVIII inhibitory antibodies (inhibitors). To explore how VWF has an impact on platelet gene therapy for hemophilia A with inhibitors. 2bF8 transgenic mice in the FVIII(-/-) background (2bF8(tg+/-) F8(-/-) ) with varying VWF phenotypes were used in this study. Animals were analyzed by VWF ELISA, FVIII activity assay, Bethesda assay and tail clip survival test. Only 18% of 2bF8(tg+/-) F8(-/-) VWF(-/-) animals, in which VWF was deficient, survived the tail clip challenge with inhibitor titers of 3-8000 BU mL(-1) . In contrast, 82% of 2bF8(tg+/-) F8(-/-) VWF(+/+) mice, which had normal VWF levels, survived tail clipping with inhibitor titers of 10-50,000 BU mL(-1) . All 2bF8(tg+/-) F8(-/-) VWF(-/-) mice without inhibitors survived tail clipping and no VWF(-/-) F8(-/-) mice survived this challenge. Because VWF is synthesized by endothelial cells and megakaryocytes and is distributed in both plasma and platelets in peripheral blood, we further investigated the effect of each compartment of VWF on platelet-FVIII gene therapy for hemophilia A with inhibitors. In the presence of inhibitors, 42% of animals survived tail clipping in the group with plasma-VWF and 50% survived in the platelet-VWF group. VWF is essential for platelet gene therapy for hemophilia A with inhibitors. Both platelet-VWF and plasma-VWF are required for optimal platelet-derived FVIII gene therapy for hemophilia A in the presence of inhibitors. © 2015 International Society on Thrombosis and Haemostasis.

  2. Arachidonic acid mediates the formation of abundant alpha-helical multimers of alpha-synuclein

    Science.gov (United States)

    Iljina, Marija; Tosatto, Laura; Choi, Minee L.; Sang, Jason C.; Ye, Yu; Hughes, Craig D.; Bryant, Clare E.; Gandhi, Sonia; Klenerman, David

    2016-09-01

    The protein alpha-synuclein (αS) self-assembles into toxic beta-sheet aggregates in Parkinson’s disease, while it is proposed that αS forms soluble alpha-helical multimers in healthy neurons. Here, we have made αS multimers in vitro using arachidonic acid (ARA), one of the most abundant fatty acids in the brain, and characterized them by a combination of bulk experiments and single-molecule Fӧrster resonance energy transfer (sm-FRET) measurements. The data suggest that ARA-induced oligomers are alpha-helical, resistant to fibril formation, more prone to disaggregation, enzymatic digestion and degradation by the 26S proteasome, and lead to lower neuronal damage and reduced activation of microglia compared to the oligomers formed in the absence of ARA. These multimers can be formed at physiologically-relevant concentrations, and pathological mutants of αS form less multimers than wild-type αS. Our work provides strong biophysical evidence for the formation of alpha-helical multimers of αS in the presence of a biologically relevant fatty acid, which may have a protective role with respect to the generation of beta-sheet toxic structures during αS fibrillation.

  3. The Levels of vWF in the Plasma of Voluntary Blood Donors and its Clinical Significance%无偿献血者血管性血友病因子的含量及临床意义

    Institute of Scientific and Technical Information of China (English)

    姚根宏; 吴永政; 栾建凤; 朱培元; 叶东; 严京梅; 雷千

    2012-01-01

    Objective The von Willebrand Factor (vWF) in the plasma of voluntary blood donors was detected, for the purpose to provide evidence for its clinical application and producing of cryoprecipitate. Methods The concentrations of vWF in fresh plasma and cryoprecipitate reduced plasma were determined by enzyme linked-immuno-sorbent assay. Results The levels of vWF in the fresh and ordinary frozen plasma were (125. 81±48. 71)% and (25. 52±9. 29) % respectively. Conclusion The vWF in the donated blood is stable within 6 hours. The plasma is qualified for vWF supplement and producing cryoprecipitate.%目的 通过检测献血者血浆中血管性血友病因子(vWF),为其制备冷沉淀和临床应用提供依据.方法 应用酶联免疫吸附法检测无偿献血者血浆和普通冰冻血浆中vWF含量.结果 无偿献血者血浆中vWF含量为(125.81±48.71)%,去冷沉淀血浆中含量为(25.52±9.29)%.结论 无偿献血者血液采集后6h内分离的血浆,其vWF含量稳定,可用于冷沉淀制备和临床应用.

  4. Performance related factors are the main determinants of the von Willebrand factor response to exhaustive physical exercise.

    Directory of Open Access Journals (Sweden)

    Janine E van Loon

    Full Text Available Physical stress triggers the endothelium to release von Willebrand Factor (VWF from the Weibel Palade bodies. Since VWF is a risk factor for arterial thrombosis, it is of great interest to discover determinants of VWF response to physical stress. We aimed to determine the main mediators of the VWF increase by exhaustive physical exercise.105 healthy individuals (18-35 years were included in this study. Each participant performed an incremental exhaustive exercise test on a cycle ergometer. Respiratory gas exchange measurements were obtained while cardiac function was continuously monitored. Blood was collected at baseline and directly after exhaustion. VWF antigen (VWF:Ag levels, VWF collagen binding (VWF:CB levels, ADAMTS13 activity and common variations in Syntaxin Binding Protein-5 (STXBP5, rs1039084 and rs9399599, Syntaxin-2 (STX2, rs7978987 and VWF (promoter, rs7965413 were determined.The median VWF:Ag level at baseline was 0.94 IU/mL [IQR 0.8-1.1] and increased with 47% [IQR 25-73] after exhaustive exercise to a median maximum VWF:Ag of 1.38 IU/mL [IQR 1.1-1.8] (p<0.0001. VWF:CB levels and ADAMTS13 activity both also increased after exhaustive exercise (median increase 43% and 12%, both p<0.0001. The strongest determinants of the VWF:Ag level increase are performance related (p<0.0001. We observed a gender difference in VWF:Ag response to exercise (females 1.2 IU/mL; males 1.7 IU/mL, p = 0.001, which was associated by a difference in performance. Genetic variations in STXBP5, STX2 and the VWF promoter were not associated with VWF:Ag levels at baseline nor with the VWF:Ag increase.VWF:Ag levels strongly increase upon exhaustive exercise and this increase is strongly determined by physical fitness level and the intensity of the exercise, while there is no clear effect of genetic variation in STXBP5, STX2 and the VWF promoter.

  5. Antibody Stabilization of Peptide–MHC Multimers Reveals Functional T Cells Bearing Extremely Low-Affinity TCRs

    DEFF Research Database (Denmark)

    Tungatt, Katie; Bianchi, Valentina; Crowther, Michael D;

    2015-01-01

    Fluorochrome-conjugated peptide-MHC (pMHC) multimers are commonly used in combination with flow cytometry for direct ex vivo visualization and characterization of Ag-specific T cells, but these reagents can fail to stain cells when TCR affinity and/or TCR cell-surface density are low. pMHC multim...

  6. Screening for von Willebrand disease: contribution of an automated assay for von Willebrand factor activity.

    Science.gov (United States)

    Lasne, D; Dey, C; Dautzenberg, M-D; Cherqaoui, Z; Monge, F; Aouba, A; Torchet, M-F; Geloen, D; Landais, P; Rothschild, C

    2012-05-01

    Measuring von Willebrand factor (VWF) activity is essential to the diagnosis of von Willebrand disease (VWD). The VWF activity is usually assessed based on measurement of the ristocetin cofactor (VWF:RCo). However, that test is technically challenging and has high intra- and inter-assay variabilities. The HemosIL VWF activity (VWF:AC) is a fully automated assay, recently proposed as a good alternative to VWF:RCo for VWD diagnosis. This study was undertaken to assess this new method. First, the analytical performance of VWF:AC on an automated coagulo-meter (ACLTop) was determined, and then this new method was compared with VWF:RCo and the platelet function analyzer (PFA100) for 160 patients referred for VWD screening. The VWF:AC achieved acceptable precision with within-run and between-run coefficients of variation ranging from 2.3% to 14.1%, and linearity from 10% to 100%. Despite some marked differences between VWF:AC and VWF:RCo for 10 plasmas tested, their agreement for VWD diagnosis was good. The VWF:AC had sensitivity similar to that of PFA100 (close to 100%), but better specificity (97.7% vs. 66% or 60%, depending on the cartridge used). The good analytical performance, and the sensitivity and specificity of VWF:AC to detect VWF deficiency renders it a suitable method for VWD screening. Our findings support VWF:AC use for the diagnostic work-up of VWD, paying close attention to concomitant clinical signs and bleeding score, as recommended for VWD. © 2011 Blackwell Publishing Ltd.

  7. Microsatellite (GT)(n) repeats and SNPs in the von Willebrand factor gene promoter do not influence circulating von Willebrand factor levels under normal conditions.

    Science.gov (United States)

    Daidone, Viviana; Cattini, Maria Grazia; Pontara, Elena; Sartorello, Francesca; Gallinaro, Lisa; Marotti, Alberto; Scaroni, Carla; Pagnan, Antonio; Casonato, Alessandra

    2009-02-01

    Von Willebrand factor (VWF) levels vary considerably in normal individuals, influenced by inherited and acquired modulators. ABO blood group is the major inherited determinant of VWF levels, but a role has also been attributed to the VWF gene promoter, haplotype 1 (-3268G/-2709C/-2661A/-2527G) being associated with higher VWF levels than haplotype 2 (-3268C/-2709T/-2661G/-2527A), and the polymorphic locus (GT)(n) modulating the shear stress-induced activation of the VWF promoter. We characterized the (GT)(n) of the VWF promoter in 394 healthy individuals and assessed whether its variable length influenced VWF levels in normal conditions. (GT)(n) proved highly polymorphic, with alleles from 15 to 24 repeats long. (GT)(21) and (GT)(19) were the most common variants (37.4% and 34.4%, respectively). Short GT repeats (15-19) segregated mainly with haplotype 1, long GT repeats (20-24) with haplotype 2 (p < 0.0001). The number of GT repeats did not correlate with VWF levels, nor did such levels correlate with haplotypes 1 and 2, considered alone or in association with the (GT)(n) locus. We conclude that (GT)(n) and -3268/-2709/-2661/-2527 loci are in strong linkage disequilibrium. This polymorphic region of the VWF promoter does not affect VWF levels under normal conditions, though it might represent an environmentally activable VWF regulation site.

  8. Evaluation of von Willebrand factor phenotypes and genotypes in Hemophilia A patients with and without identified F8 mutations

    Science.gov (United States)

    Boylan, Brian; Rice, Anne S.; De Staercke, Christine; Eyster, M. Elaine; Yaish, Hassan M.; Knoll, Christine M.; Bean, Christopher J.; Miller, Connie H.

    2015-01-01

    Summary Background Hemophilia A (HA) is an X-linked bleeding disorder caused by a deficiency in factor VIII (FVIII). von Willebrand disease (VWD) is characterized by a quantitative or qualitative defect in von Willebrand Factor (VWF). Patients with VWD with severely low VWF or VWD Type 2N (VWD2N), a VWD subtype distinguished by defective VWF binding to FVIII, may have reduced FVIII levels secondary to their VWD. These patients superficially resemble patients with HA, and pose a potential for misdiagnosis. Objectives Investigate the unexplained cause of bleeding in HA patients without known FVIII mutations by assessing plasma VWF antigen (VWF:Ag), FVIII binding capacities, and VWF genotypes. Patients/Methods Thirty-seven of 1027 patients with HA studied as part of the Hemophilia Inhibitor Research Study lacked identifiable F8 mutations. These patients (cases) and 73 patients with identified F8 mutations (controls) were evaluated for VWF:Ag, patient's VWF capacity to bind FVIII (VWF:FVIIIB), and VWF sequence. Results Four cases had VWF:Ag <3 IU/dL and VWF mutations consistent with Type3 VWD. Six cases and one control were heterozygous for mutations previously reported to cause Type1 VWD (VWD1) (n=5 cases and 1 control) or predicted to be deleterious by Polyphen2 and SIFT prediction tools (n=1 case). One control had VWF:Ag <30 IU/dl, and seven patients (4 cases and 3 controls), including two cases who were heterozygous for a known VWD2N mutation, had reduced VWF:FVIIIB. Conclusions These data emphasize that some patients diagnosed with HA require VWF assessments in order to achieve a comprehensive diagnosis and an optimal treatment strategy. PMID:25780857

  9. Von Willebrand factor inhibits mature smooth muscle gene expression through impairment of Notch signaling.

    Directory of Open Access Journals (Sweden)

    He Meng

    Full Text Available Von Willebrand factor (vWF, a hemostatic protein normally synthesized and stored by endothelial cells and platelets, has been localized beyond the endothelium in vascular disease states. Previous studies have implicated potential non-hemostatic functions of vWF, but signaling mechanisms underlying its effects are currently undefined. We present evidence that vWF breaches the endothelium and is expressed in a transmural distribution pattern in cerebral small vessel disease (SVD. To determine the potential molecular consequences of vWF permeation into the vessel wall, we also tested whether vWF impairs Notch regulation of key smooth muscle marker genes. In a co-culture system using Notch ligand expressing cells to stimulate Notch in A7R5 cells, vWF strongly inhibited both the Notch pathway and the activation of mature smooth muscle gene promoters. Similar repressive effects were observed in primary human cerebral vascular smooth muscle cells. Expression of the intracellular domain of NOTCH3 allowed cells to bypass the inhibitory effects of vWF. Moreover, vWF forms molecular complexes with all four mammalian Notch ectodomains, suggesting a novel function of vWF as an extracellular inhibitor of Notch signaling. In sum, these studies demonstrate vWF in the vessel wall as a common feature of cerebral SVD; furthermore, we provide a plausible mechanism by which non-hemostatic vWF may play a novel role in the promotion of vascular disease.

  10. Multiple functions of the von Willebrand Factor A domain in matrilins: secretion, assembly, and proteolysis

    Directory of Open Access Journals (Sweden)

    Kanbe Katsuaki

    2008-06-01

    Full Text Available Abstract The von Willebrand Factor A (vWF A domain is one of the most widely distributed structural modules in cell-matrix adhesive molecules such as intergrins and extracellular matrix proteins. Mutations in the vWF A domain of matrilin-3 cause multiple epiphyseal dysplasia (MED, however the pathological mechanism remains to be determined. Previously we showed that the vWF A domain in matrilin-1 mediates formation of a filamentous matrix network through metal-ion dependent adhesion sites in the domain. Here we show two new functions of the vWF A domain in cartilage-specific matrilins (1 and 3. First, vWF A domain regulates oligomerization of matrilins. Insertion of a vWF A domain into matrilin-3 converts the formation of a mixture of matrilin-3 tetramer, trimer, and dimer into a tetramer only, while deletion of a vWF A domain from matrilin-1 converts the formation of the native matrilin-1 trimer into a mixture of trimer and dimer. Second, the vWF A domain protects matrilin-1 from proteolysis. We identified a latent proteolytic site next to the vWF A2 domain in matrilin-1, which is sensitive to the inhibitors of matrix proteases. Deletion of the abutting vWF A domain results in degradation of matrilin-1, presumably by exposing the adjacent proteolytic site. In addition, we also confirmed the vWF A domain is vital for the secretion of matrilin-3. Secretion of the mutant matrilin-3 harbouring a point mutation within the vWF A domain, as occurred in MED patients, is markedly reduced and delayed, resulting from intracellular retention of the mutant matrilin-3. Taken together, our data suggest that different mutations/deletions of the vWF A domain in matrilins may lead to distinct pathological mechanisms due to the multiple functions of the vWF A domain.

  11. Distinct roles of Ser-764 and Lys-773 at the N terminus of von Willebrand factor in complex assembly with coagulation factor VIII.

    Science.gov (United States)

    Castro-Núñez, Lydia; Bloem, Esther; Boon-Spijker, Mariëtte G; van der Zwaan, Carmen; van den Biggelaar, Maartje; Mertens, Koen; Meijer, Alexander B

    2013-01-04

    Complex formation between coagulation factor VIII (FVIII) and von Willebrand factor (VWF) is of critical importance to protect FVIII from rapid in vivo clearance and degradation. We have now employed a chemical footprinting approach to identify regions on VWF involved in FVIII binding. To this end, lysine amino acid residues of VWF were chemically modified in the presence of FVIII or activated FVIII, which does not bind VWF. Nano-LC-MS analysis showed that the lysine residues of almost all identified VWF peptides were not differentially modified upon incubation of VWF with FVIII or activated FVIII. However, Lys-773 of peptide Ser-766-Leu-774 was protected from chemical modification in the presence of FVIII. In addition, peptide Ser-764-Arg-782, which comprises the first 19 amino acid residues of mature VWF, showed a differential modification of both Lys-773 and the α-amino group of Ser-764. To verify the role of Lys-773 and the N-terminal Ser-764 in FVIII binding, we employed VWF variants in which either Lys-773 or Ser-764 was replaced with Ala. Surface plasmon resonance analysis and competition studies revealed that VWF(K773A) exhibited reduced binding to FVIII and the FVIII light chain, which harbors the VWF-binding site. In contrast, VWF(S764A) revealed more effective binding to FVIII and the FVIII light chain compared with WT VWF. The results of our study show that the N terminus of VWF is critical for the interaction with FVIII and that Ser-764 and Lys-773 have opposite roles in the binding mechanism.

  12. Storage of factor VIII variants with impaired von Willebrand factor binding in Weibel-Palade bodies in endothelial cells.

    Directory of Open Access Journals (Sweden)

    Maartje van den Biggelaar

    Full Text Available BACKGROUND: Point mutations resulting in reduced factor VIII (FVIII binding to von Willebrand factor (VWF are an important cause of mild/moderate hemophilia A. Treatment includes desmopressin infusion, which concomitantly increases VWF and FVIII plasma levels, apparently from storage pools containing both proteins. The source of these VWF/FVIII co-storage pools and the mechanism of granule biogenesis are not fully understood. METHODOLOGY/PRINCIPAL FINDINGS: We studied intracellular trafficking of FVIII variants implicated in mild/moderate hemophilia A together with VWF in HEK293 cells and primary endothelial cells. The role of VWF binding was addressed using FVIII variants displaying reduced VWF interaction. Binding studies using purified FVIII proteins revealed moderate (Arg2150His, Del2201, Pro2300Ser to severe (Tyr1680Phe, Ser2119Tyr VWF binding defects. Expression studies in HEK293 cells and primary endothelial cells revealed that all FVIII variants were present within VWF-containing organelles. Quantitative studies showed that the relative amount of FVIII storage was independent of various mutations. Substantial amounts of FVIII variants are co-stored in VWF-containing storage organelles, presumably by virtue of their ability to interact with VWF at low pH. CONCLUSIONS: Our data suggest that the potential of FVIII co-storage with VWF is not affected in mild/moderate hemophilia A caused by reduced FVIII/VWF interaction in the circulation. These data support the hypothesis that Weibel-Palade bodies comprise the desmopressin-releasable FVIII storage pool in vivo.

  13. Study on multimers and their structures in molecular association mixture

    Institute of Scientific and Technical Information of China (English)

    NI Yi; DOU XiaoMing; ZHAO HaiYing; YIN GuangZhong; YAMAGUCHI Yoshinori; OZAKI Yukihiro

    2007-01-01

    Self-association system of (R)-1,3-butanediol in dilute carbon tetrachloride (CCl4) solution is studied as a model of molecular association mixture. Analysis methods including FSMWEFA (fixed-size moving window evolving factor analysis) combined with PCA (principal component analysis), SIMPLISMA (simple-to-use interactive self-modeling mixture analysis), and ITTFA (iterative target transformation factor analysis) are adopted to resolve infrared spectra of (R)-1,3-butanediol solution. Association number and equilibrium constant are computed. (R)-1,3-butanediol in dilute inert solution is determined as a monomer-trimer equilibrium system. Theoretical investigation of trimer structures is carried out with DFT (density functional theory), and structural factors are analyzed.

  14. Study on multimers and their structures in molecular association mixture

    Institute of Scientific and Technical Information of China (English)

    YAMAGUCHI; Yoshinori; OZAKI; Yukihiro

    2007-01-01

    Self-association system of(R)-1,3-butanediol in dilute carbon tetrachloride(CCl4)solution is studied as a model of molecular association mixture.Analysis methods including FSMWEFA(fixed-size moving window evolving factor analysis)combined with PCA(principal component analysis),SIMPLISMA (simple-to-use interactive self-modeling mixture analysis),and ITTFA(iterative target transformation factor analysis)are adopted to resolve infrared spectra of(R)-1,3-butanediol solution.Association number and equilibrium constant are computed.(R)-1,3-butanediol in dilute inert solution is determined as a monomer-trimer equilibrium system.Theoretical investigation of trimer structures is carried out with DFT(density functional theory),and structural factors are analyzed.

  15. Correlation between HIF-1αprotein level in the placenta and concentration of vWF in peripheral blood of aged puerpera in pre-eclampsia%子痫前期高龄产妇胎盘 HIF-1α蛋白与外周血 vWF 的相关性

    Institute of Scientific and Technical Information of China (English)

    谭小平; 宁景春; 向兰花; 王芬; 张汉英

    2014-01-01

    目的:探究子痫前期高龄产妇胎盘低氧诱导因子-1α( HIF-1α)蛋白水平与外周血血管性假血友病性因子( vWF )浓度的相关性,为及时有效预防子痫的发生提供实验室依据。方法对30例正常分娩高龄产妇( A组)、35例子痫前期轻度高龄产妇( B组)、41例子痫前期重度高龄产妇( C组)的HIF-1α蛋白水平与外周血vWF浓度进行测定,并分析HIF-1α蛋白水平与vWF浓度的相关性。结果 B组、C组的HIF-1α蛋白水平、vWF浓度显著高于A组,( B组:t1=13.194,P1=0.000;t2=4.856, P2=0.000。 C组:t1=17.441,P1=0.000;t2=9.156,P2=0.000);C组的HIF-1α蛋白水平、vWF浓度显著高于B组,差异均有统计学意义(t1=9.681,P1=0.000;t2=4.899,P2=0.000)。 Spearman 相关性分析显示,vWF 浓度与子痫前期的病情程度(r=0.288,P=0.000)、HIF-1α蛋白水平(r=0.410,P=0.000)均呈显著正相关关系。结论子痫前期高龄产妇的胎盘HIF-1α蛋白水平与外周血vWF浓度明显升高,二者可能共同参与子痫前期的发生和发展。%Objective To investigate the correlation between hypoxia induced factor-1α( HIF-1α) protein level in the placenta and concentration of von Willbrand Factor ( vWF) in peripheral blood of aged puerpera in pre-eclampsia, so as to provide laboratory basis for preventing the happening of eclampsia timely and effectively .Methods The HIF-1αprotein level and concentration of vWF of peripheral blood in 30 cases of aged normal delivery (group A), 35 cases of aged puerpera with mild pre-eclampsia (group B) and 41 cases of aged puerpera with severe pre-eclampsia (group C) were measureed, and the correlation between HIF-1αprotein level and the concentration of vWF was analyzed .Results The HIF-1αprotein level and the concentration of vWF of group B and group C were significantly higher than those of

  16. In vivo gene transfer strategies to achieve partial correction of von Willebrand disease.

    Science.gov (United States)

    Wang, Lan; Rosenberg, Jonathan B; De, Bishnu P; Ferris, Barbara; Wang, Rui; Rivella, Stefano; Kaminsky, Stephen M; Crystal, Ronald G

    2012-06-01

    von Willebrand disease (VWD), the most common hereditary coagulation disorder, results from mutations in the 52-exon gene for von Willebrand factor (VWF), which encodes an 8.4-kB cDNA. Studies with VWF cDNA plasmids have demonstrated that in vivo gene transfer to the liver will correct the coagulation dysfunction in VWF(-/-) mice, but the correction is transient. To develop gene therapy for VWF that would mediate long-term expression of the VWF cDNA in liver, we first evaluated segmental pre-mRNA trans-splicing (SPTS) with two adeno-associated virus (AAV) serotype 8 vectors, each delivering one-half of the VWF cDNA. However, although the two vectors functioned well to generate VWF multimers after infection of cells in vitro, the efficiency of SPTS was insufficient to correct the VWF(-/-) mouse in vivo. As an alternative, we assessed the ability of a lentiviral vector to transfer the intact murine VWF cDNA in vivo directly to the neonatal liver of VWF(-/-) mice, using generation of VWF multimers, bleeding time, and bleeding volume as efficacy parameters. The VWF lentivirus generated VWF multimers and partially or completely corrected the coagulation defect on a persistent basis in 33% of the treated VWF-deficient mice. On the basis of the concept that partial persistent correction with gene transfer could be beneficial in VWD patients, these observations suggest that lentiviral delivery of VWF cDNA should be explored as a candidate for gene therapy in patients with a severe form of VWD.

  17. Von Willebrand factor deficiency reduces liver fibrosis in mice

    NARCIS (Netherlands)

    Joshi, Nikita; Kopec, Anna K.; Ray, Jessica L.; Cline-Fedewa, Holly; Groeneveld, Dafna J.; Lisman, Ton; Luyendyk, James P.

    2017-01-01

    Liver diseases are associated with complex changes in the hemostatic system and elevated levels of the platelet adhesive protein Von Willebrand factor (VWF) are reported in patients with acute and chronic liver damage. Although elevated levels of VWF are associated with fibrosis in the general popul

  18. N-linked glycans within the A2 domain of von Willebrand factor modulate macrophage-mediated clearance.

    Science.gov (United States)

    Chion, Alain; O'Sullivan, Jamie M; Drakeford, Clive; Bergsson, Gudmundur; Dalton, Niall; Aguila, Sonia; Ward, Soracha; Fallon, Padraic G; Brophy, Teresa M; Preston, Roger J S; Brady, Lauren; Sheils, Orla; Laffan, Michael; McKinnon, Thomas A J; O'Donnell, James S

    2016-10-13

    Enhanced von Willebrand factor (VWF) clearance is important in the etiology of von Willebrand disease. However, the molecular mechanisms underlying VWF clearance remain poorly understood. In this study, we investigated the role of VWF domains and specific glycan moieties in regulating in vivo clearance. Our findings demonstrate that the A1 domain of VWF contains a receptor-recognition site that plays a key role in regulating the interaction of VWF with macrophages. In A1-A2-A3 and full-length VWF, this macrophage-binding site is cryptic but becomes exposed following exposure to shear or ristocetin. Previous studies have demonstrated that the N-linked glycans within the A2 domain play an important role in modulating susceptibility to ADAMTS13 proteolysis. We further demonstrate that these glycans presented at N1515 and N1574 also play a critical role in protecting VWF against macrophage binding and clearance. Indeed, loss of the N-glycan at N1515 resulted in markedly enhanced VWF clearance that was significantly faster than that observed with any previously described VWF mutations. In addition, A1-A2-A3 fragments containing the N1515Q or N1574Q substitutions also demonstrated significantly enhanced clearance. Importantly, clodronate-induced macrophage depletion significantly attenuated the increased clearance observed with N1515Q and N1574Q in both full-length VWF and A1-A2-A3. Finally, we further demonstrate that loss of these N-linked glycans does not enhance clearance in VWF in the presence of a structurally constrained A2 domain. Collectively, these novel findings support the hypothesis that conformation of the VWF A domains plays a critical role in modulating macrophage-mediated clearance of VWF in vivo.

  19. Nicolas Guichon, Langues et TICE. Méthodologie de conception multimédia

    OpenAIRE

    Dan Frost

    2014-01-01

    Nicolas Guichon est enseignant-chercheur en anglais et en didactique des langues au centre de langues de l’université Lumière (Lyon 2). Il est concepteur du logiciel Virtual Cabinet, responsable de l’enseignement TICE du master « Didactique des langues et TICE » et membre de l’équipe Plurilinguisme et multimédia (ENS de Lyon). Cet ouvrage est le fruit de son expérience dans le domaine des recherches, du développement et de l’enseignement dans l’univers des TICE et de l’apprentissage des langu...

  20. Estudio Clásico de Estabilidad Transitoria para Sistemas Multimáquina

    Directory of Open Access Journals (Sweden)

    José Alejandro Morones Alba

    2000-01-01

    Full Text Available En este artículo se muestra una descripción del modelo matemático en el que se basa el diseño de un simulador para el estudio clásico de estabilidad transitoria en Sistemas Eléctricos de Potencia. El simulador determina el comportamiento transitorio de primera oscilación para sistemas multimáquina ante disturbios como fallas trifásicas, cambios de configuración, pérdida de carga y pérdida de generación.

  1. Enhancing antisense efficacy with multimers and multi-targeting oligonucleotides (MTOs) using cleavable linkers.

    Science.gov (United States)

    Subramanian, Romesh R; Wysk, Mark A; Ogilvie, Kathleen M; Bhat, Abhijit; Kuang, Bing; Rockel, Thomas D; Weber, Markus; Uhlmann, Eugen; Krieg, Arthur M

    2015-10-30

    The in vivo potency of antisense oligonucleotides (ASO) has been significantly increased by reducing their length to 8-15 nucleotides and by the incorporation of high affinity RNA binders such as 2', 4'-bridged nucleic acids (also known as locked nucleic acid or LNA, and 2',4'-constrained ethyl [cET]). We now report the development of a novel ASO design in which such short ASO monomers to one or more targets are co-synthesized as homo- or heterodimers or multimers via phosphodiester linkers that are stable in plasma, but cleaved inside cells, releasing the active ASO monomers. Compared to current ASOs, these multimers and multi-targeting oligonucleotides (MTOs) provide increased plasma protein binding and biodistribution to liver, and increased in vivo efficacy against single or multiple targets with a single construct. In vivo, MTOs synthesized in both RNase H-activating and steric-blocking oligonucleotide designs provide ≈4-5-fold increased potency and ≈2-fold increased efficacy, suggesting broad therapeutic applications. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  2. HTML5 e as possibilidades narrativas jornalísticas na infografia multimídia

    Directory of Open Access Journals (Sweden)

    Walter Teixeira Lima Junior

    2015-12-01

    Full Text Available O artigo propõe o estudo comparativo dos infográficos multimídia produzidos pelos sites Clarín.com, da Argentina e Folha.com, do Brasil. A pesquisa tem como objetivo verificar e analisar como esses dois importantes veículos de comunicação online da América Latina têm utilizado a tecnologia HTML5 e suas possibilidades interativas na narrativa jornalística. Para tanto, a análise vai se ater à infografia multimídia, que tem passado por profundas mudanças tecnológicas, alterando o formato e o conteúdo da notícia. Para abordar as possibilidades narrativas das tecnologias Flash e HTLM5 na produção de infográficos interativos, o trabalho compara as seções Infográficos, veiculada pela Folha.com, e Especiales Multimedia, do Clarín.com. O estudo, quantitativo e qualitativo, verificou quais recursos narrativos e informativos, ferramentas e tecnologias de linguagem de programação para Internet foram utilizados pelos dois meios de comunicação, com base no modelo de análise proposto por Alberto Cairo no livro Infografia 2.0.

  3. Rearrangement of MICU1 multimers for activation of MCU is solely controlled by cytosolic Ca(2.).

    Science.gov (United States)

    Waldeck-Weiermair, Markus; Malli, Roland; Parichatikanond, Warisara; Gottschalk, Benjamin; Madreiter-Sokolowski, Corina T; Klec, Christiane; Rost, Rene; Graier, Wolfgang F

    2015-10-22

    Mitochondrial Ca(2+) uptake is a vital process that controls distinct cell and organelle functions. Mitochondrial calcium uptake 1 (MICU1) was identified as key regulator of the mitochondrial Ca(2+) uniporter (MCU) that together with the essential MCU regulator (EMRE) forms the mitochondrial Ca(2+) channel. However, mechanisms by which MICU1 controls MCU/EMRE activity to tune mitochondrial Ca(2+) signals remain ambiguous. Here we established a live-cell FRET approach and demonstrate that elevations of cytosolic Ca(2+) rearranges MICU1 multimers with an EC50 of 4.4 μM, resulting in activation of mitochondrial Ca(2+) uptake. MICU1 rearrangement essentially requires the EF-hand motifs and strictly correlates with the shape of cytosolic Ca(2+) rises. We further show that rearrangements of MICU1 multimers were independent of matrix Ca(2+) concentration, mitochondrial membrane potential, and expression levels of MCU and EMRE. Our experiments provide novel details about how MCU/EMRE is regulated by MICU1 and an original approach to investigate MCU/EMRE activation in intact cells.

  4. The impact of von Willebrand factor on factor VIII memory immune responses.

    Science.gov (United States)

    Chen, Juan; Schroeder, Jocelyn A; Luo, Xiaofeng; Shi, Qizhen

    2017-08-22

    Immune tolerance induction (ITI) with aggressive infusion of factor VIII (FVIII) is the current strategy used to eradicate FVIII inhibitors and restore normal FVIII pharmacokinetics in inhibitor patients. Whether the use of FVIII products containing von Willebrand factor (VWF) will affect the efficacy of ITI is still controversial. In this study, we explored the impact of VWF on FVIII memory immune responses in hemophilia A (HA) mice. A T-cell proliferation assay and cytokine profile analysis were used to study FVIII-primed CD4(+) T cells. When CD4(+) T cells from primed FVIII(null) mice were restimulated with recombinant human FVIII (rhF8) plus recombinant human VWF (rhVWF) in vitro, the percentages of daughter CD4(+) T cells were significantly decreased compared with the groups cultured with rhF8 only. Levels of interferon-γ and interleukin 10 were significantly lower in the rhF8 plus rhVWF groups than in the rhF8 groups. When memory B-cell pools from primed FVIII(null) mice were cultured with rhF8 with or without rhVWF to induce differentiation of memory B cells into antibody-secreting cells (ASCs), the number of ASCs was significantly lower in the rhF8 plus VWF group than in the rhF8 group. When memory B-cell pools were transferred into NSGF8KO mice followed by rhF8 immunization with or without rhVWF, the titers of anti-F8 inhibitors and total immunoglobulin G were significantly higher in the rhF8 group than in the rhF8 plus rhVWF group, with an average difference of 2.23- and 2.04-fold. Together, our data demonstrate that VWF attenuates FVIII memory immune responses in HA mice.

  5. Expression and Significance of VEGF and vWF in Metabolic Syndrome in Young Rats%代谢综合征幼鼠血管VEGF和vWF的表达及意义

    Institute of Scientific and Technical Information of China (English)

    李亚璞; 刘戈力; 魏莹; 陈维彬; 高芳芳

    2012-01-01

    目的:探讨血管内皮生长因子(VEGF)和血管性假血友病因子(vWF)在代谢综合征(MS)幼鼠血管壁和血清中的表达及意义.方法:3周龄SD大鼠随机分为普通饮食组(NC组)、高脂组(FC组)和高脂+高盐组(FSC组).实验4周末测体质量、腹围、血压、内脏脂肪质量、血脂,行口服葡萄糖耐量试验,计算胰岛素抵抗指数.取腹主动脉免疫组化法检测血管壁VEGF和vWF表达,ELISA方法检测血清VEGF和vWF表达.结果:FSC组体质量、腹围、血压、内脏脂肪、血糖、胰岛素水平均较NC组增加,血脂紊乱加重,并出现胰岛素抵抗.FC组仅体质量、内脏脂肪质量高于NC 组,其他上述指标差异无统计学意义.FSC组血管壁及血清中VEGF和vWF较NC组和FC组均升高.FC组较NC组血管VEGF及血清中VEGF和vWF均升高.结论:VEGF和vWF参与了血管壁的功能紊乱或损伤的病生理改变.%Objective: To investigate the expression of vascular endothelial growth factor (VEGF) and Von Wille-brand factor (vWF) in vascular wall and serum of metabolic syndrome in young rats. Methods: Three-week-old SD rats (50 g body weight) were randomly divided into 3 groups, routine diet group (NC), high fat diet group (FC) and high fat + high salt diet group (FSC). The values of body weight, abdominal circumference, blood pressure, visceral fat weight and plasma lipids were measured in rats 4 weeks after experiments. The oral glucose tolerance test (OGTDwas performed and the insulin resistance index was calculated. The expressions of VEGF and vWF in the abdominal aorta were detected by immunohistochemis-try method. The serum levels of VEGF and vWF were detected by ELISA method. Results: The values of body weight, abdominal circumference, blood pressure, visceral fat, plasma glucose and insulin level were significantly higher in FSC group than those of NC group. There were increased dyslipidemia and insulin resistance in FSC group compared with those of NC group. The

  6. Pràctica final de l'assignatura "Disseny Gràfic" (Grau de Multimèdia)

    OpenAIRE

    2010-01-01

    Pràctica final de l'assignatura "Disseny Gràfic" (Grau de Multimèdia). Final practice of the "Graphic Design" course (Degree of Multimedia). Práctica final de la asignatura "Diseño Gráfico" (Grado de Multimedia).

  7. Magnetic microparticle-based multimer detection system for the detection of prion oligomers in sheep

    Directory of Open Access Journals (Sweden)

    Lim K

    2015-09-01

    Full Text Available Kuntaek Lim,1 Su Yeon Kim,2 Byoungsub Lee,1 Christiane Segarra,3 Sungmin Kang,1 Youngran Ju,2 Mary Jo Schmerr,4 Joliette Coste,3 Sang Yun Kim,5 Takashi Yokoyama,6 Seong Soo A An7 1Department of Research and Development, PeopleBio Inc., 2Department of Arborbiology, Korean Center for Diseases and Control (KCDC, Seoul, Republic of Korea; 3Department of Blood Screening, Etablissement Français Du Sang (EFS, Montpellier, France; 4Ames Laboratories, US Department of Energy (USDOE, Iowa State University, Ames, IA, USA; 5Department of Neurology, Seoul National University Bundang Hospital, Sungnam-si, Republic of Korea; 6Department of Prion Research, National Institute of Animal Health, Tsukuba, Japan; 7Department of Bionano Technology, Gachon University, Sungnam-si, Republic of Korea Abstract: Transmissible spongiform encephalopathies (TSEs are zoonotic fatal neurodegenerative diseases in animals and humans. TSEs are commonly known as bovine spongiform encephalopathy in cattle, scrapie in sheep and goats, chronic wasting disease in cervids, and Creutzfeldt–Jakob disease in humans. The putative transmissible agents are infectious prion proteins (PrPSc, which are formed by the conversion of the normal prion protein on the glycoprotein cell surface in the presence of other PrPSc. Reports of the transmission of TSEs through blood raised considerable concern about the safety of blood and blood products. To address this issue, many laboratories attempted to develop a sensitive and accurate blood diagnostic test to detect PrPSc. Previously, we reported that, compared to normal controls, the multimer detection system (MDS was more efficient in detecting PrPSc in infected hamster brain homogenate, mouse plasma spiked with purified PrPSc from scrapie mouse brain, and scrapie-infected hamster plasmas. MDS differentiates prion multimers from the cellular monomer through the multimeric expression of epitopes on prion multimers, in contrast to the monomeric form

  8. Hypercortisolism and pregnancy upregulate von Willebrand factor through different mechanisms: report on a pregnant patient with Cushing's syndrome.

    Science.gov (United States)

    Casonato, Alessandra; Daidone, Viviana; Pontara, Elena; Albiger, Nora; Cattini, Maria G; Scaroni, Carla

    2010-07-01

    Von Willebrand factor (VWF) is reportedly increased in pregnancy and Cushing's syndrome, inducing a hypercoagulable state. In Cushing's syndrome, VWF gene promoter polymorphisms modulate cortisol-dependent VWF upregulation, haplotype 1 (GCAG) and short GT-repeats (GT)(S) being the susceptible, and haplotype 2 (CTGA) and long GT-repeats (GT)(L) the protective pattern. We report on a Cushing's syndrome patient who became pregnant under hypercortisolism, in whom we monitored the evolution of her hypercoagulable state. During the active phase of Cushing's syndrome, the patient's VWF and factor VIII concentrations were normal, despite high urinary-free cortisol levels consistent with the presence of haplotype 2 and (GT)(L) alleles in the VWF gene promoter. VWF and factor VIII increased significantly and progressively after she became pregnant and peaked just before delivery, returning to normal 5 months later, while her hypercortisolism persisted. Our data indicate that two different mechanisms upregulate VWF under hypercortisolism and pregnancy, the latter being independent of the VWF promoter haplotypes sensitive to cortisol excess.

  9. HLA micropolymorphisms strongly affect peptide-MHC multimer-based monitoring of antigen-specific CD8+ T cell responses.

    Science.gov (United States)

    van Buuren, Marit M; Dijkgraaf, Feline E; Linnemann, Carsten; Toebes, Mireille; Chang, Cynthia X L; Mok, Juk Yee; Nguyen, Melanie; van Esch, Wim J E; Kvistborg, Pia; Grotenbreg, Gijsbert M; Schumacher, Ton N M

    2014-01-15

    Peptide-MHC (pMHC) multimers have become one of the most widely used tools to measure Ag-specific T cell responses in humans. With the aim of understanding the requirements for pMHC-based personalized immunomonitoring, in which individuals expressing subtypes of the commonly studied HLA alleles are encountered, we assessed how the ability to detect Ag-specific T cells for a given peptide is affected by micropolymorphic differences between HLA subtypes. First, analysis of a set of 10 HLA-A*02:01-restricted T cell clones demonstrated that staining with pMHC multimers of seven distinct subtypes of the HLA-A*02 allele group was highly variable and not predicted by sequence homology. Second, to analyze the effect of minor sequence variation in a clinical setting, we screened tumor-infiltrating lymphocytes of an HLA-A*02:06 melanoma patient with either subtype-matched or HLA-A*02:01 multimers loaded with 145 different melanoma-associated Ags. This revealed that of the four HLA-A*02:06-restricted melanoma-associated T cell responses observed in this patient, two responses were underestimated and one was overlooked when using subtype-mismatched pMHC multimer collections. To our knowledge, these data provide the first demonstration of the strong effect of minor sequence variation on pMHC-based personalized immunomonitoring, and they provide tools to prevent this issue for common variants within the HLA-A*02 allele group.

  10. Significance of VWF, ADAMTS13 level in the serum of patients with sepsis%脓毒症患者血清假血友病因子血管性血友病因子裂解酶水平变化的临床意义

    Institute of Scientific and Technical Information of China (English)

    徐俊; 杨静; 孟令毅; 程立顺; 于海洋; 俞凤; 张泓

    2013-01-01

    Objective To investigate the clinical significance of Von Willebrand Factors (VWF) and a distintegrin-like and metalloprotease with thrombospondin type 1 domain 13 (ADAMTS13) level in the serum of patients with sepsis.Methods Serum and clinical data of 66 septic patients were collected,and the serum of 20 volunteers were chosen at random.ELISA was performed to detect VWF and ADAMTS13 level in serum.Septic patients were randomly divided into sepsis group,severe sepsis group and multiple organ dysfunction syndrome (MODS) group.Comparedwith control group,the relationship of VWF,ADAMTS13 level change in serum with sepsis severity degree was observed.Results There was a statistically significant difference in VWF,ADAMTS13 level between control group and each group (sepsis group,severe sepsis group,MODS group).The serum VWF level was significantly higher in sepsis group and severe sepsis group than in control group,and was significantly higher in MODS group than in sepsis group and severe sepsis group.Serum ADAMTS13 level was significantly lower in each model group than in control group.Conclusion At the early stage of sepsis,VWF and ADAMTS13 has participated in.The change of serum VWF level is more sensitive than ADAMTS13 in predicting the outcome of sepsis.%目的 探讨脓毒症患者血清假血友病因子(VWF)、血管性血友病因子裂解酶(ADAMTS13)水平变化的临床意义.方法 收集66例脓毒症患者的血清及临床资料,并从正常人群中随机抽取20例志愿者的血清,采用ELISA法分别定量检测血清VWF和ADAMTS13水平.把脓毒症患者分为脓毒症(sepsis,S)组、严重脓毒症(severe sepsis,SS)组及多器官功能障碍综合征(multiple organ dysfunction syndrome,MODS)组,与正常对照(C)组比较,观察血清VWF、ADAMTS13水平变化与脓毒症严重程度之间的关系.结果 S组、SS组和MODS组血清VWF、ADAMTS13水平与C组比较差异有统计学意义(P<0.05).S组和SS组血清VWF水平显著高于C

  11. Seed-specific expression of spider silk protein multimers causes long-term stability

    Directory of Open Access Journals (Sweden)

    Nicola eWeichert

    2016-01-01

    Full Text Available Seeds enable plants to germinate and to grow in situations of limited availability of nutrients. The stable storage of different seed proteins is a remarkable presumption for successful germination and growth. These strategies have been adapted and used in several molecular farming projects. In this study, we explore the benefits of seed-based expression to produce the high molecular weight spider silk protein FLAG using intein-based trans-splicing. Multimers larger than 460 kDa in size are routinely produced, which is above the native size of the FLAG protein. The storage of seeds for eight weeks and one year at an ambient temperature of 15°C does not influence the accumulation level. Even the extended storage time does not influence the typical pattern of multimerized bands. These results show that seeds are the method of choice for stable accumulation of products of complex transgenes and have the capability for long-term storage at moderate conditions, an important feature for the development of suitable downstream processes.

  12. Aquisição e complexidade em narrativas multimídia de aprendizagem

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    Vera Lúcia Menezes de Oliveira e Paiva

    2008-01-01

    Full Text Available Este artigo apresenta reflexões sobre a aquisição de língua inglesa, entendida como sistema complexo em uma perspectiva êmica. Para tanto, discute aspectos da pesquisa narrativa, da multimodalidade e da complexidade da aquisição de segunda língua. Como evidências empíricas da aquisição, esta pesquisa utiliza excertos de narrativas multimídia de aprendizagem de língua inglesa, em que os narradores revelam aspectos de seus processos de aprendizagem por meio de textos, hipertextos, imagens e sons. Essas narrativas mostram que o processo de aquisição é um sistema complexo e que a segunda língua emerge da interação entre as diferentes experiências de aprendizagem dentro e fora do ambiente escolar.This paper reflects upon the acquisition of English language, understood as a complex system, in the light of an emic approach. In order to do that, it discusses aspects of narrative research, of multimodality, and of the complexity of second language acquisition. As empirical evidences of acquisition, the article presents excerpts of multimedia language learning narratives through wich the authors reveal aspects of their learning processes by means of texts, hypertexts, images and sounds. Those narratives show that the acquisition process is a complex system and that the second language emerges from the interaction among the different learning experiences lived inside and outside the classroom.

  13. A critical assessment for the value of markers to gate-out undesired events in HLA-peptide multimer staining protocols

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    Odunsi Kunle

    2011-07-01

    Full Text Available Abstract Background The introduction of antibody markers to identify undesired cell populations in flow-cytometry based assays, so called DUMP channel markers, has become a practice in an increasing number of labs performing HLA-peptide multimer assays. However, the impact of the introduction of a DUMP channel in multimer assays has so far not been systematically investigated across a broad variety of protocols. Methods The Cancer Research Institute's Cancer Immunotherapy Consortium (CRI-CIC conducted a multimer proficiency panel with a specific focus on the impact of DUMP channel use. The panel design allowed individual laboratories to use their own protocol for thawing, staining, gating, and data analysis. Each experiment was performed twice and in parallel, with and without the application of a dump channel strategy. Results The introduction of a DUMP channel is an effective measure to reduce the amount of non-specific MULTIMER binding to T cells. Beneficial effects for the use of a DUMP channel were observed across a wide range of individual laboratories and for all tested donor-antigen combinations. In 48% of experiments we observed a reduction of the background MULTIMER-binding. In this subgroup of experiments the median background reduction observed after introduction of a DUMP channel was 0.053%. Conclusions We conclude that appropriate use of a DUMP channel can significantly reduce background staining across a large fraction of protocols and improve the ability to accurately detect and quantify the frequency of antigen-specific T cells by multimer reagents. Thus, use of a DUMP channel may become crucial for detecting low frequency antigen-specific immune responses. Further recommendations on assay performance and data presentation guidelines for publication of MULTIMER experimental data are provided.

  14. [Deposition of von Willebrand factor in human endothelial cells HUVEC in the endoplasmic reticulum stress induced by an excess of homocysteine in vitro].

    Science.gov (United States)

    Ignashkova, T I; Mesitov, M V; Rybakov, A S; Moskovtsev, A A; Sokolovskaia, A A; Kubatiev, A A

    2012-01-01

    Von Willebrand factor (vWF) is an adhesive glycoprotein synthesized and secreted by endothelial cells and megakaryocytes. Violation of vWF secretion by endothelial cells is a characteristic feature of endothelial dysfunction in hyperhomocysteinemia. In our study we examined to clarify the concentration-dependent effect of homocysteine (Hcy) on the expression of vWF. Our studies have shown that homocysteine excess induces changes in the intracellular deposition of von Willebrand factor in cultured human endothelial cells in vitro. Primary cultures of human umbilical vein endothelial cells (HUVEC) were incubated with the various concentrations of D,L-homocysteine (0.025 - 5 mM). Homocysteine at a concentration of 0.025 and 0.25 mM after 18 h incubation caused an increase in the intracellular fraction of vWF in HUVEC cells. High concentrations of homocysteine induced a dose-dependent decrease in the intracellular fraction of vWF. These dose-dependent variations may indicate the modulation by homocysteine of different mechanisms of the deposition, the constitutive secretion and the degradation of vWF in human endothelial cells. We proposed that Endoplasmic reticulum stress, in HUVEC cells by the action of an excess of homocysteine associated with increased intracellular levels of vWF at a relatively low concentration of the inducer. We found decline in intracellular vWF at the same duration but higher concentrations of inducer, which may be due to the ER-associated protein degradation.

  15. Functional significance of a hepta nucleotide motif present at the junction of Cucumber mosaic virus satellite RNA multimers in helper-virus dependent replication.

    Science.gov (United States)

    Seo, Jang-Kyun; Kwon, Sun-Jung; Chaturvedi, Sonali; Choi, Soon Ho; Rao, A L N

    2013-01-20

    Satellite RNAs (satRNA) associated with Cucumber mosaic virus (CMV) have been shown to generate multimers during replication. We have discovered that multimers of a CMV satRNA generated in the absence of its helper virus (HV) are characterized by the addition of a hepta nucleotide motif (HNM) at the monomer junctions. Here, we evaluated the functional significance of HNM in HV-dependent replication by ectopically expressing wild type and mutant forms of satRNA multimers in planta either in (+) or (-)-strand polarity. Comparative replication profiles revealed that (-)-strand multimers with complementary HNM (cHNM) are the preferred initial templates for HV-dependent replication than (-)-strand monomers and multimers lacking the cHNM. Further mutational analyses of the HNM accentuate that preservation of the sequence and native length of HNM is obligatory for efficient replication of satRNA. A model implicating the significance of HNM in HV-dependent production of monomeric and multimeric forms of satRNA is presented.

  16. IDEVI – informática básica para deficientes visuais: um software em multimídia

    OpenAIRE

    2000-01-01

    Este trabalho apresenta o desenvolvimento de um software educacional em multimídia, abordando a informática básica para portadores de deficiência visual. O software educacional IDEVI é uma ferramenta de aprendizagem dos conceitos básicos em computação. Divide-se em duas etapas. A primeira trata de um levantamento bibliográfico das alternativas tecnológicas, que oportunizam o conhecimento para o desenvolvimento profissional do portador de deficiência visual. A segunda etapa é a definição...

  17. Dispositifs de formation en anglais à l'Espace Multimédia (Montpellier-III. Description et approche critique Learning Modes in English at the Espace Multimédia (Montpellier-III. Description and Critical Approach.

    Directory of Open Access Journals (Sweden)

    Cécile Poussard

    1998-06-01

    Full Text Available Cet article présente l’Espace Multimédia de l’Université Paul-Valéry (Montpellier-III ; après une description du lieu, du public et des langues proposées, les auteurs proposent une description, assortie d’une évaluation critique des dispositifs mis en ouvre pour la formation en anglais des étudiants non-spécialistes. Pour le premier cycle, il s’agit d’un dispositif mixte, faisant alterner le travail autonome et les séances de groupe. Pour le second cycle, il s’agit d’un dispositif d’autoformation guidée, incluant des séances de tutorat, de travail autonome et de pratique orale.This article presents the Espace Multimédia (Université Paul-Valéry, Montpellier-III; after a short description of the site, its public and the languages concerned, the authors give a description, along with a critical evaluation of the learning modes at work for non-specialist students of English. For first and second year students, autonomous work and group work alternate. For third year students, a guided self-learning mode is provided, which includes tutorials, autonomous work and oral practice.

  18. Polymorphisms in von Willebrand factor gene promoter influence the glucocorticoid-induced increase in von Willebrand factor: the lesson learned from Cushing syndrome.

    Science.gov (United States)

    Casonato, Alessandra; Daidone, Viviana; Sartorello, Francesca; Albiger, Nora; Romualdi, Chiara; Mantero, Franco; Pagnan, Antonio; Scaroni, Carla

    2008-01-01

    Cushing syndrome (CS) features high-glucocorticoid secretion and an associated hypercoagulable state often involving an increase in von Willebrand factor (VWF). To identify any influence of VWF promoter on glucocorticoid haemostatic effects, four polymorphic positions (-3267, -2708, -2659 and -2525) segregating as haplotypes 1 (GCAG) or 2 (CTGA) were analysed in 50 CS patients with high VWF (group I) and normal VWF (group II) levels, divided by ABO group. Genotype distribution differed significantly between the two groups: in group I, 25.8% had genotype 1/1, 22.6% had 2/2 and 38.7% had 1/2; in group II, 0% had genotype 1/1, 57.9% had 2/2 and 31.6% had 1/2 (P = 0.03). Patients' genotypes also differed from those of controls (P = 0.003 for group I, P = 0.03 for group II). Haplotype 1 was prevalent in group I, haplotype 2 in group II (P = 0.002), both with frequencies differing from controls (P < 0.001 and P = 0.009). By odds ratio analysis, genotype 1/1 carried a 12 times greater risk of high-VWF levels than genotype 2/2, and haplotype 1 carried a five times greater risk than haplotype 2. Our findings suggest that VWF promoter haplotypes influence the corticosteroid-mediated increase in VWF.

  19. Expression of vWF in Kidney of diabetic rats and effeet of danhong%糖尿病大鼠肾脏中vWF的表达及丹红注射液的干预研究

    Institute of Scientific and Technical Information of China (English)

    高倩; 栗娜; 王战建

    2014-01-01

    observe the level of serum yon Willebrand factor(vWF) and expression of vWF in Kidney of Diabetic Rats to study the change of vWF before and after the interventionof Danhong.The pathogenesis of diabetic nephropathy and renoprotective effects of Danhong are specially studied.Methods 36 SD rats were randomly divided into three groups as follows:10 normol rats,14 diabetic rats,11 Danhong intervention ratsand 11 Metformin intervention rats. (Two died in diabetic group,one died in Danhong intervention group) . Except the normal control group,all the rats in the other groups were established an animal model of diabetes by a single intraperitoneal injection of streptozotocin (55mg/kg).After72 hours,get blood from caudal vein to test blood sugar,those higher than 16.7mmol/L regard as succeed in diabetic models.Then Danhong (2ml/kg.d) was given by intraperitoneal injection to Danhong intervention group.The same amount of water was given by intraperitoneal injection to normal control group and diabetic group.The experiment lasted for eight weeks.At the end of eight weeks,blood,urine and renal tissue samples were collected in four groups of rats.Then blood sugar,cholesterol (TC),triglycerides (TG),Low density lipoprotein cholesterol (LDL-C),Serum creatinine (Scr),Urea nitrogen (BUN) were tested.24h Urinary albuminwere measured by radioimmunoassay.Serum vWF was determined by Enzyme-linked immunoassay (ELISA).We used HE staining to observe the renal pathological changes under optical microscope. Expression of vWF in renal tissue was measured by immunohistochemistry.Renal vWFmRNA expression was measured by Real-time fluorescent quantitative PCR.Results After eight weeks,Compared with normal control group,blood sugar,TC,TG,LDL-C,Scr,BUN,Kidney hypertrophy index,24h Urinary albumin,Serum vWF were all inereased significantlyin diabetic group(P <0.01).Kidneys of Diabetic rats have obvious pathological changes.The expression of vWF in Diabetic rat kidneywas obviously increased compared

  20. Automated Analysis of Flow Cytometry Data to Reduce Inter-Lab Variation in the Detection of Major Histocompatibility Complex Multimer-Binding T Cells

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    Natasja Wulff Pedersen

    2017-07-01

    Full Text Available Manual analysis of flow cytometry data and subjective gate-border decisions taken by individuals continue to be a source of variation in the assessment of antigen-specific T cells when comparing data across laboratories, and also over time in individual labs. Therefore, strategies to provide automated analysis of major histocompatibility complex (MHC multimer-binding T cells represent an attractive solution to decrease subjectivity and technical variation. The challenge of using an automated analysis approach is that MHC multimer-binding T cell populations are often rare and therefore difficult to detect. We used a highly heterogeneous dataset from a recent MHC multimer proficiency panel to assess if MHC multimer-binding CD8+ T cells could be analyzed with computational solutions currently available, and if such analyses would reduce the technical variation across different laboratories. We used three different methods, FLOw Clustering without K (FLOCK, Scalable Weighted Iterative Flow-clustering Technique (SWIFT, and ReFlow to analyze flow cytometry data files from 28 laboratories. Each laboratory screened for antigen-responsive T cell populations with frequency ranging from 0.01 to 1.5% of lymphocytes within samples from two donors. Experience from this analysis shows that all three programs can be used for the identification of high to intermediate frequency of MHC multimer-binding T cell populations, with results very similar to that of manual gating. For the less frequent populations (<0.1% of live, single lymphocytes, SWIFT outperformed the other tools. As used in this study, none of the algorithms offered a completely automated pipeline for identification of MHC multimer populations, as varying degrees of human interventions were needed to complete the analysis. In this study, we demonstrate the feasibility of using automated analysis pipelines for assessing and identifying even rare populations of antigen-responsive T cells and discuss

  1. Biografia e Autobiografia Universal (Para um Modelo de Análise dos Rituais de Produção e Consumo na Arte Multimédia)

    OpenAIRE

    2011-01-01

    Mestrado em Arte Multimédia Biografia e Autobiografia Universal: para um modelo de análise dos rituais de produção e consumo na arte multimédia trata do estudo e análise de formas alternativas que questionam o modo como criamos a nossa memória cultural colectiva por meio de objectos e rituais. O campo de investigação aqui exposto permanece distinto da História ou Crítica da arte. A abordagem aos rituais é realizada pelo do ponto de vista sócio-cultural, ambicionando reco...

  2. Interference from lupus anticoagulant on von Willebrand factor measurement in splenic marginal zone lymphoma

    DEFF Research Database (Denmark)

    Vinholt, Pernille J; Nybo, Mads

    2015-01-01

    We present a case concerning a patient with splenic marginal zone lymphoma (SMZL) and isolated prolonged activated partial thromboplastin time (aPTT) caused by lupus anticoagulant. Von Willebrand factor (VWF) activity and antigen were immeasurable by latex particle immunoturbidimetric assays......, and several coagulation factor levels were decreased. However, VWF activity and antigen were normal when analyzed by other methods. Also, coagulation factor levels were normal if an aPTT reagent with low lupus anticoagulant sensitivity or a chromogenic method was applied. Altogether, the initial findings were...... because of lupus anticoagulant interference and in fact, the patient had normal VWF activity and coagulation status. Interference of lupus anticoagulant in clot-based assays is well known but has not previously been described in VWF assays. This is furthermore the first report in which lupus anticoagulant...

  3. Tissue factor: A potent stimulator of Von Willebrand factor synthesis by human umbilical vein endothelial cells

    Science.gov (United States)

    Meiring, Muriel; Allers, W.; Le Roux, E.

    2016-01-01

    Inflammation and dysfunction of endothelial cells are thought to be triggers for the secretion of Von Willebrand factor. The aim of this study was to examine the effects of the inflammatory cytokines interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor-alpha (TNF-α) and the coagulation factors, tissue factor and thrombin on the release and cleavage potential of ultra-large von Willebrand factor (ULVWF) and its cleavage protease by cultured human umbilical vein endothelial cells (HUVEC). HUVEC were treated with IL-6, IL-8, and TNF-α, tissue factor (TF) and thrombin, and combinations thereof for 24 hours under static conditions. The cells were then exposed to shear stress after which the VWF-propeptide levels and the VWF cleavage protease, ADAMTS13 content were measured. All treatments and their combinations, excluding IL-6, significantly stimulated the secretion of VWF from HUVEC. The VWF secretion from the HUVEC was stimulated most by the combination of TF with TNF-α. Slightly lower levels of ADAMTS13 secretion were found with all treatments. This may explain the thrombogenicity of patients with inflammation where extremely high VWF levels and slightly lower ADAMTS13 levels are present.

  4. A +220 GATA motif mediates basal but not endotoxin-repressible expression of the von Willebrand factor promoter in Hprt-targeted transgenic mice

    Science.gov (United States)

    LIU, J.; KANKI, Y.; OKADA, Y.; JIN, E.; YANO, K.; SHIH, S.-C.; MINAMI, T.; AIRD, W. C.

    2012-01-01

    Summary Background The von Willebrand factor (VWF) gene is a marker for spatial and temporal heterogeneity of the endothelium. A GATA motif at +220 has been implicated in basal VWF expression in vitro. Other studies have shown that GATA3 and VWF are transcriptionally downregulated in response to inflammatory mediators. Objectives Our goal was to determine the importance of the +220 GATA motif in mediating expression of VWF promoter in vivo, and to elucidate whether the GATA element plays a role in spatial and/or temporal regulation of VWF expression. Methods ChIP and electrophoretic mobility shift assays were carried out in human umbilical vein endothelial cells (HUVEC). Reporter gene constructs containing 3.6 kb of the human VWF promoter with and without amutation of the +220 GATA element were transfected into cultured endothelial cells or targeted to the Hprt locus of mice. The Hprt-targeted mice were subjected to endotoxemia. Results In protein-DNA binding assays, the +220 GATA motif bound GATA-2, -3 and -6. Mutation of the GATA site resulted in reduced basal promoter activity in HUVEC. When targeted to the Hprt locus of mice, the GATA mutation resulted in a significant, proportionate reduction of promoter activity in LacZ expressing vascular beds. Systemic administration of lipopolysaccharide (LPS) resulted in a widespread reduction in VWF mRNA expression and promoter activity. LPS-mediated repression of the VWF promoter was unaffected by the GATA mutation. Conclusions A region of the VWF promoter between −2182 and the end of the first intron contains information for LPS-mediated gene repression. The +220 GATA motif is important for basal, but not LPS-repressible expression of the VWF gene. PMID:19496923

  5. Evaluation of von Willebrand factor in COPD patients

    Directory of Open Access Journals (Sweden)

    Thiago Prudente Bártholo

    2014-08-01

    Full Text Available OBJECTIVE: To compare the absolute serum von Willebrand factor (vWF levels and relative serum vWF activity in patients with clinically stable COPD, smokers without airway obstruction, and healthy never-smokers. METHODS: The study included 57 subjects, in three groups: COPD (n = 36; smoker (n = 12; and control (n = 9. During the selection phase, all participants underwent chest X-rays, spirometry, and blood testing. Absolute serum vWF levels and relative serum vWF activity were obtained by turbidimetry and ELISA, respectively. The modified Medical Research Council scale (cut-off score = 2 was used in order to classify COPD patients as symptomatic or mildly symptomatic/asymptomatic. RESULTS: Absolute vWF levels were significantly lower in the control group than in the smoker and COPD groups: 989 ± 436 pg/mL vs. 2,220 ± 746 pg/mL (p < 0.001 and 1,865 ± 592 pg/mL (p < 0.01. Relative serum vWF activity was significantly higher in the COPD group than in the smoker group (136.7 ± 46.0% vs. 92.8 ± 34.0%; p < 0.05, as well as being significantly higher in the symptomatic COPD subgroup than in the mildly symptomatic/asymptomatic COPD subgroup (154 ± 48% vs. 119 ± 8%; p < 0.05. In all three groups, there was a negative correlation between FEV1 (% of predicted and relative serum vWF activity (r2 = −0.13; p = 0.009. CONCLUSIONS: Our results suggest that increases in vWF levels and activity contribute to the persistence of systemic inflammation, as well as increasing cardiovascular risk, in COPD patients.

  6. Site-specific deletions of chromosomally located DNA segments with the multimer resolution system of broad-host-range plasmid RP4

    DEFF Research Database (Denmark)

    Sternberg, Claus; Eberl, Leo; Sanchezromero, Juan M.

    1995-01-01

    The multimer resolution system (mrs) of the broad-host-range plasmid RP4 has been exploited to develop a general method that permits the precise excision of chromosomal segments in a variety of gram-negative bacteria. The procedure is based on the site-specific recombination between two directly ...

  7. Aplicativo multimídia em plataforma móvel para o ensino da mensuração da pressão venosa central

    Directory of Open Access Journals (Sweden)

    Elizabeth Correia Ferreira Galvão

    2012-10-01

    Full Text Available O objetivo do estudo foi desenvolver e avaliar um aplicativo multimídia em plataforma móvel para o ensino da Mensuração da Pressão Venosa Central (PVC. A pesquisa foi desenvolvida em três fases (Levantamento das necessidades; Metodologia de desenvolvimento do aplicativo multimídia e Avaliação do aplicativo multimídia. A multimídia foi o método escolhido por favorecer um ambiente motivador e dinâmico, integrar imagens e textos num aplicativo disponível para celulares, constituindo-se um meio móvel e autônomo de aprendizagem. Os resultados permitem demonstrar a viabilidade do desenvolvimento da ferramenta para subsidiar a prática pedagógica e abrem perspectivas para acreditar que, na educação em Enfermagem, a tecnologia disponível pode descortinar novos modos de aprender significativamente.

  8. A BENCHMARKING ANALYSIS FOR FIVE RADIONUCLIDE VADOSE ZONE MODELS (CHAIN, MULTIMED_DP, FECTUZ, HYDRUS, AND CHAIN 2D) IN SOIL SCREENING LEVEL CALCULATIONS

    Science.gov (United States)

    Five radionuclide vadose zone models with different degrees of complexity (CHAIN, MULTIMED_DP, FECTUZ, HYDRUS, and CHAIN 2D) were selected for use in soil screening level (SSL) calculations. A benchmarking analysis between the models was conducted for a radionuclide (99Tc) rele...

  9. Insulin resistance is accompanied by increased von Willebrand factor levels in nondiabetic women: a study of offspring of type 2 diabetic subjects compared to offspring of nondiabetic subjects

    DEFF Research Database (Denmark)

    Foss, Anne-Catherine; Vestbo, Else; Frøland, Anders

    2002-01-01

    OBJECTIVES: To examine whether levels of von Willebrand factor (vWF), fibrinogen and fibronectin are related to a parental history of type 2 diabetes and to determine possible explanatory factors for high versus low vWF and fibrinogen. DESIGN: Cross-sectional study. SUBJECTS, MAIN OUTCOME MEASURES......: We compared vWF, fibrinogen and fibronectin in 88 nondiabetic offspring of type 2 diabetic subjects (relatives) and 103 offspring of nondiabetic subjects (controls). Other measurements included urinary albumin excretion rate, blood pressure, lipid profile and insulin resistance using homeostasis....... Odds ratio for high versus low insulin resistance was 18.39 (P index (BMI) (P

  10. Weibel-Palade body size modulates the adhesive activity of its von Willebrand Factor cargo in cultured endothelial cells

    Science.gov (United States)

    Ferraro, Francesco; Mafalda Lopes da, Silva; Grimes, William; Lee, Hwee Kuan; Ketteler, Robin; Kriston-Vizi, Janos; Cutler, Daniel F.

    2016-01-01

    Changes in the size of cellular organelles are often linked to modifications in their function. Endothelial cells store von Willebrand Factor (vWF), a glycoprotein essential to haemostasis in Weibel-Palade bodies (WPBs), cigar-shaped secretory granules that are generated in a wide range of sizes. We recently showed that forcing changes in the size of WPBs modifies the activity of this cargo. We now find that endothelial cells treated with statins produce shorter WPBs and that the vWF they release at exocytosis displays a reduced capability to recruit platelets to the endothelial cell surface. Investigating other functional consequences of size changes of WPBs, we also report that the endothelial surface-associated vWF formed at exocytosis recruits soluble plasma vWF and that this process is reduced by treatments that shorten WPBs, statins included. These results indicate that the post-exocytic adhesive activity of vWF towards platelets and plasma vWF at the endothelial surface reflects the size of their storage organelle. Our findings therefore show that changes in WPB size, by influencing the adhesive activity of its vWF cargo, may represent a novel mode of regulation of platelet aggregation at the vascular wall. PMID:27576551

  11. Weibel-Palade body size modulates the adhesive activity of its von Willebrand Factor cargo in cultured endothelial cells.

    Science.gov (United States)

    Ferraro, Francesco; Mafalda Lopes da, Silva; Grimes, William; Lee, Hwee Kuan; Ketteler, Robin; Kriston-Vizi, Janos; Cutler, Daniel F

    2016-08-31

    Changes in the size of cellular organelles are often linked to modifications in their function. Endothelial cells store von Willebrand Factor (vWF), a glycoprotein essential to haemostasis in Weibel-Palade bodies (WPBs), cigar-shaped secretory granules that are generated in a wide range of sizes. We recently showed that forcing changes in the size of WPBs modifies the activity of this cargo. We now find that endothelial cells treated with statins produce shorter WPBs and that the vWF they release at exocytosis displays a reduced capability to recruit platelets to the endothelial cell surface. Investigating other functional consequences of size changes of WPBs, we also report that the endothelial surface-associated vWF formed at exocytosis recruits soluble plasma vWF and that this process is reduced by treatments that shorten WPBs, statins included. These results indicate that the post-exocytic adhesive activity of vWF towards platelets and plasma vWF at the endothelial surface reflects the size of their storage organelle. Our findings therefore show that changes in WPB size, by influencing the adhesive activity of its vWF cargo, may represent a novel mode of regulation of platelet aggregation at the vascular wall.

  12. Selective Protein Extraction from Chlorobium tepidum Chlorosomes Using Detergents. Evidence That CsmA Forms Multimers and Binds Bacteriochlorophyll a

    DEFF Research Database (Denmark)

    Bryant, Donald A; Vassilieva, Elena V; Frigaard, Niels-Ulrik

    2002-01-01

    and location of this BChl a are not yet clearly understood. Chlorosomes were treated with sodium dodecyl sulfate (SDS), Lubrol PX, or Triton X-100, separately or in combination with 1-hexanol, and the extracted components were separated from the residual chlorosomes by ultrafiltration on centrifugal filters....... When chlorosomes were treated with low concentrations of SDS, all proteins except CsmA were extracted. However, this treatment did not significantly alter the size and shape of the chlorosomes, did not extract the BChl a, and caused only minor changes in the absorption spectrum of the chlorosomes....... Cross-linking studies with SDS-treated chlorosomes revealed the presence of multimers of the major chlorosome protein, CsmA, up to homooctamers. Extraction of chlorosomes with SDS and 1-hexanol solubilized all ten chlorosome envelope proteins as well as BChl a. Although the size and shape...

  13. The application value of changes in four items of coagulation routine and vWF in severe preeclampsia patients%重度子痫前期患者凝血功能及vWF含量的变化和意义

    Institute of Scientific and Technical Information of China (English)

    熊贤海; 郑丹

    2016-01-01

    目的:观察重度子痫前期患者凝血四项、血管性假血友病因子(vWF)的变化,探讨其临床检测意义。方法选择2014年1月-2015年12月在我院门诊就诊单胎妊娠无合并症的孕妇30例作为对照组,同期发生子痫前期患者30例作为实验组,用酶联免疫吸附(ELESA)法进行血清vWF水平检测,我院中心实验室进行凝血四项检测。结果实验组PT、APTT低于对照组,Fig、vWF水平高于对照组,有统计学差异。结论重度子痫前期孕妇血液呈高凝状态,vWF水平可作为初步判断其病情严重程度的指标之一。%Objective To observe the application value of prothrombin time (PT),activated partial thromboplastin time(APTT), thrombin time (TT) and fibrinogen (FIB),also with the von Willebrand factor (vWF) on the change characteristics of plasma in se-vere preeclampsia women and its significance. Methods Detect both 30 case in severe preeclampsia and normal pregnant women in coagulation routine and vWF levels. Results The time of PT and APTT in observation group were lower than those in control group(P<0.05). The level of FIB and vWF of severe preeclampsia were higher than those of normal pregnant women(P<0.05). Con-clusion The blood of pregnant women with severe preeclampsia is in a high coagulation state ,and the vWF level can be used as one of the indicators to judge the severity of preeclampsia.

  14. Ion Mobility Measurements of Nondenatured 12-150 kDa Proteins and Protein Multimers by Tandem Differential Mobility Analysis-Mass Spectrometry (DMA-MS)

    Science.gov (United States)

    Hogan, Christopher J.; de la Mora, Juan Fernández

    2011-01-01

    The mobilities of electrosprayed proteins and protein multimers with molecular weights ranging from 12.4 kDa (cytochrome C monomers) to 154 kDa (nonspecific concanavalin A hexamers) were measured in dry air by a planar differential mobility analyzer (DMA) coupled to a time-of-flight mass spectrometer (TOF-MS). The DMA determines true mobility at atmospheric pressure, without perturbing ion structure from that delivered by the electrospray. A nondenaturing aqueous 20 mM triethylammonium formate buffer yields compact ions with low charge states, moderating polarization effects on ion mobility. Conversion of mobilities into cross-sections involves a reduction factor ξ for the actual mobility relative to that associated with elastic specular collisions with smooth surfaces. ξ is known to be 1.36 in air from Millikan's oil drop experiments. A similar enhancement effect ascribed to atomic-scale surface roughness has been found in numerical simulations. Adopting Millikan's value ξ = 1.36 and assuming a spherical geometry yields a gas-phase protein density ρ p = 0.949 ± 0.053 g cm-3 for all our protein data. This is substantially higher than the 0.67 g cm-3 found in recent low-resolution DMA measurements of singly charged proteins. DMA-MS can distinguish nonspecific protein aggregates formed during the electrospray process from those formed preferentially in solution. The observed charge versus diameter relation is compatible with a protein charge reduction mechanism based on the evaporation of triethylammonium ions from electrosprayed drops.

  15. Technological advances in diagnostic testing for von Willebrand disease: new approaches and challenges.

    Science.gov (United States)

    Hayward, C P M; Moffat, K A; Graf, L

    2014-06-01

    Diagnostic tests for von Willebrand disease (VWD) are important for the assessment of VWD, which is a commonly encountered bleeding disorder worldwide. Technical innovations have been applied to improve the precision and lower limit of detection of von Willebrand factor (VWF) assays, including the ristocetin cofactor activity assay (VWF:RCo) that uses the antibiotic ristocetin to induce plasma VWF binding to glycoprotein (GP) IbIXV on target platelets. VWF-collagen-binding assays, depending on the type of collagen used, can improve the detection of forms of VWD with high molecular weight VWF multimer loss, although the best method is debatable. A number of innovations have been applied to VWF:RCo (which is commonly performed on an aggregometer), including replacing the target platelets with immobilized GPIbα, and quantification by an enzyme-linked immunosorbent assay (ELISA), immunoturbidimetric, or chemiluminescent end-point. Some common polymorphisms in the VWF gene that do not cause bleeding are associated with falsely low VWF activity by ristocetin-dependent methods. To overcome the need for ristocetin, some new VWF activity assays use gain-of-function GPIbα mutants that bind VWF without the need for ristocetin, with an improved precision and lower limit of detection than measuring VWF:RCo by aggregometry. ELISA of VWF binding to mutated GPIbα shows promise as a method to identify gain-of-function defects from type 2B VWD. The performance characteristics of many new VWF activity assays suggest that the detection of VWD, and monitoring of VWD therapy, by clinical laboratories could be improved through adopting newer generation VWF assays.

  16. Activation of pathways involved in HUVEC apoptosis and proliferation. Sex hormones agonist related. Effect of hormones on von Willebrand factor and ADAMTS 13 release

    OpenAIRE

    Powazniak, Yanina

    2008-01-01

    El VWF es una glicoproteína adhesiva, sintetizada en las CE y megacariocitos. Se sintetiza en forma monomérica, luego se organiza en dímeros y se multimeriza. El VWF media la adhesión de plaquetas al subendotelio vascular dañado y lel transporte del factor FVIII. La ADAMTS13, proteasa que cliva al VWF, pertenece a la familia de metaloproteasas ADAMTS, llamadas así por la combinación característica de una desintegrina y una metaloproteasa con motivos trombospondina tipo 1. La ADAMTS13 es sinte...

  17. Von Willebrand Factor Antigen Predicts Response to Double Dose of Aspirin and Clopidogrel by PFA-100 in Patients Undergoing Primary Angioplasty for St Elevation Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Jacopo Gianetti

    2013-01-01

    Full Text Available Von Willebrand factor (VWF is an emerging risk factor in acute coronary syndromes. Platelet Function Analyzer (PFA-100 with Collagen/Epinephrine (CEPI is sensitive to functional alterations of VWF and also identifies patients with high on-treatment platelet reactivity (HPR. The objective of this study was to verify the effect of double dose (DD of aspirin and clopidogrel on HPR detected by PFA-100 and its relation to VWF and to its regulatory metalloprotease ADAMTS-13. Between 2009 and 2011 we enrolled 116 consecutive patients with ST elevation myocardial infarction undergoing primary PCI with HPR at day 5 after PCI. Patients recruited were then randomized between a standard dose (SD, n=58 or DD of aspirin and clopidogrel (DD, n=58, maintained for 6 months follow-up. Blood samples for PFA-100, light transmittance aggregometry, and VWF/ADAMTS-13 analysis were collected after 5, 30, and 180 days (Times 0, 1, and 2. At Times 1 and 2 we observed a significantly higher CEPI closure times (CT in DD as compared to SD (P<0.001. Delta of CEPI-CT (T1-T0 was significantly related to VWF (P<0.001 and inversely related to ADAMTS-13 (0.01. Responders had a significantly higher level of VWF at T0. Finally, in a multivariate model analysis, VWF and ADAMTS-13 in resulted significant predictors of CEPI-CT response (P=0.02. HRP detected by PFA-100 in acute myocardial infarction is reversible by DD of aspirin and clopidogrel; the response is predicted by basal levels of VWF and ADAMTS-13. PFA-100 may be a useful tool to risk stratification in acute coronary syndromes given its sensitivity to VWF.

  18. Adhesive Forces between A1 Domain of von Willebrand Factor and N-terminus Domain of Glycoprotein Ibα Measured by Atomic Force Microscopy.

    Science.gov (United States)

    Tobimatsu, Hiroaki; Nishibuchi, Yuichiro; Sudo, Ryo; Goto, Shinya; Tanishita, Kazuo

    2015-01-01

    von Willebrand factor (VWF) plays an important role in the regulation of hemostasis and thrombosis formation, particularly under a high shear rate. However, the adhesive force due to the molecular interaction between VWF and glycoprotein Ibα (GPIbα) has not been fully explored. Thus, we employed atomic force microscopy to directly measure the adhesive force between VWF and GPIbα. We measured the adhesive force between VWF and GPIbα at the molecular level using an atomic force microscope (AFM). An AFM cantilever was coated with recombinant N-terminus VWF binding site of GPIbα, whereas a cover glass was coated with native VWF. The adhesive force at the molecular level was measured using an AFM. In the presence of 1 μg/mL VWF, the adhesion force was nearly 200 pN. As per the Gaussian fit analysis, the adhesive force of a single bond could have been 54 or 107 pN. Our consideration with the Gaussian fit analysis proposed that the adhesive force of a single bond could be 54 pN, which is very close to that obtained by optical tweezers (50 pN).

  19. P-selectin can promote thrombus propagation independently of both von Willebrand factor and thrombospondin-1 in mice.

    Science.gov (United States)

    Prakash, P; Nayak, M K; Chauhan, A K

    2017-02-01

    Essentials The main receptor for platelet glycoprotein (GP) Ibα is von Willebrand factor (VWF). P-selectin and thrombospondin-1 (TSP1) have been suggested as counter receptors for GPIbα. In a laser injury model, P-selectin promotes thrombus propagation independently of VWF and TSP1. In a laser injury model, thrombus persists in interleukin-4 receptor α/GPIbα-transgenic mice.

  20. Jornalismo e educomunicação: a produção de narrativas multimídia no ensino-aprendizagem

    Directory of Open Access Journals (Sweden)

    Adriana Alves Rodrigues

    2014-01-01

    Full Text Available A proposta principal do artigo é discutir a pertinência das reportagens multimídias desenvolvidas em sala de aula para a formação dos futuros jornalistas, produzida no primeiro semestre de 2013, por estudantes de graduação do quinto semestre do curso de Comunicação Social: habilitação em Jornalismo, da Universidade Estadual da Paraíba (UEPB. A ideia foi produzir um produto jornalístico multimídia, colocando em prática as discussões teóricas estudadas no decorrer das aulas. Tais produções visavam inserir os alunos nas práticas do jornalismo convergente contemporâneo, visualizando os diversos modos de produção jornalística no contexto da convergência midiática, mídias digitais e cibercultura.

  1. Is there an effect of folic acid supplementation on the coagulation factors and C-reactive protein concentrations in subjects with atherosclerosis risk factors

    Directory of Open Access Journals (Sweden)

    Artur Mierzecki

    2012-10-01

    Full Text Available Introduction:Folic acid (FA may delay the formation of atherosclerotic lesions. Increased plasma levels of von Willebrand factor (VWF are observed in cardiovascular disease, which leads to higher risk of thrombosis. Fibrinogen (Fb is a well-documented risk factor of cardiovascular disease. The aim of this study was to analyze the effect of FA supplementation on the Fb, VWF and C-reactive protein (CRP plasma concentrations in subjects with atherosclerosis risk factors.Material/Methods:The study enrolled 124 Caucasian individuals (60 M, 64 F with atherosclerosis risk factors – family history of premature ischaemic stroke, arterial hypertension, dyslipidaemia, overweight and obesity, cigarette smoking and low physical activity. The participants were asked to take FA in the low dose of 0.4 mg/24 h for three months.Results:After FA supplementation a significant reduction of the VWF concentrations in females (76.6 vs 72.3�20p=0.028 and in males (75.5 vs 66.9�20p=0.001 was observed. Among women and men with dyslipidaemia concentrations of VWF decreased after FA supplementation (76.8�0vs 69.6�20p=0.003 and 76.7�0vs 67.8�20p=0.001 respectively. Among females and males with BMI ≥25 kg/m2 concentrations of VWF decreased only in men (77.6�0vs 66.5�20p=0.001. In female and male smokers supplementation of FA decreased VWF concentrations (82.5�0vs 74.4�20p=0.012 and 76.6�0vs 69.5�20p=0.036 respectively.Discussion:The results of our study suggest that there is an effect of FA supplementation on VWF concentrations in subjects with atherosclerosis risk factors

  2. Establishment of reference intervals for von Willebrand factor antigen and eight coagulation factors in a Korean population following the Clinical and Laboratory Standards Institute guidelines.

    Science.gov (United States)

    Jang, Ja-Hyun; Seo, Ja-Young; Bang, Sung-Hwan; Park, In-Ae; Kim, Hee-Jin; Kim, Sun-Hee

    2010-04-01

    Establishment of reference intervals for coagulation molecules is important but is costly and sometimes not feasible. Since reference intervals from manufacturers or the literature are mostly out of date or involved Western populations, the authors determined reference intervals for VWF: Ag and eight factors in a Korean population. VWF: Ag, factor VIII (FVIII), FII, FV, FVII, FIX, FX, FXI, and FXII were determined in Korean individuals visiting for routine checkup following the CLSI (Clinical and Laboratory Standards Institute) guidelines. Reagents by Diagnostica Stago were used on the STA Compact Analyzer (Diagnostica Stago). Exclusion criteria were medical history or laboratory findings that could affect the factor levels. Influence of demographic factors was analyzed. Mean +/- 2 x SD or central 95 percentile was used, as appropriate. We obtained data from 266 adults for VWF: Ag, 371 adults for FVIII, and minimum 136 adults for the rest. Reference interval for VWF was 51-176% (52-155% in blood group O and 71-186% for non-O). Reference interval for FVIII was 64-197% (55-150% in O and 77-205% in non-O). Reference interval for FII was 77-121%, FV 81-160%, FVII 68-149%, FIX 67-154%, FX 69-126%, FXI 59-138%, and FXII 48-177%. The medians of VWF: Ag, FVIII, and FIX were significantly higher in the elderly group (> or =60 years). We established local reference intervals for VWF: Ag and eight coagulation factors in a Korean population according to the CLSI guidelines. Significantly, different reference intervals were obtained in blood group O vs. non-O for VWF: Ag and FVIII. The reference intervals obtained in this study could be adopted in other clinical laboratories after appropriate validation.

  3. Lei da gravitação universal e os satélites: uma abordagem histórico-temática usando multimídia

    Directory of Open Access Journals (Sweden)

    Elvis Vilela Rodrigues

    2012-01-01

    Full Text Available Examina-se, neste artigo, o desenvolvimento de aulas de Física em que, usando-se uma multimídia, a Lei da Gravitação Universal é abordada de forma contextualizada a partir da História da Ciência e de um tema atual (os satélites. O objetivo foi examinar como estudantes de Ensino Médio aceitam e se envolvem nesse estudo. Usando uma abordagem metodológica qualitativa, a multimídia apresenta o que são e como funcionam os satélites artificiais, trazendo uma narrativa histórica desde as ideias de movimento do sistema planetário de Ptolomeu até as de Isaac Newton sobre o movimento dos corpos, culminando na Lei da Gravitação Universal. Entrevistas, observações de sala de aula e documentos produzidos pelos estudantes mostram que as imagens, os filmes e os textos contidos na multimídia enriquecem, de modo significativo, o conteúdo, facilitando o entendimento de conceitos da Física. A contextualização histórico-temática, por sua vez, produz maior envolvimento dos alunos no estudo da Física.

  4. Role of RNA splicing in mediating lineage-specific expression of the von Willebrand factor gene in the endothelium.

    Science.gov (United States)

    Yuan, Lei; Janes, Lauren; Beeler, David; Spokes, Katherine C; Smith, Joshua; Li, Dan; Jaminet, Shou-Ching; Oettgen, Peter; Aird, William C

    2013-05-23

    We previously demonstrated that the first intron of the human von Willebrand factor (vWF) is required for gene expression in the endothelium of transgenic mice. Based on this finding, we hypothesized that RNA splicing plays a role in mediating vWF expression in the vasculature. To address this question, we used transient transfection assays in human endothelial cells and megakaryocytes with intron-containing and intronless human vWF promoter-luciferase constructs. Next, we generated knockin mice in which LacZ was targeted to the endogenous mouse vWF locus in the absence or presence of the native first intron or heterologous introns from the human β-globin, mouse Down syndrome critical region 1, or hagfish coagulation factor X genes. In both the in vitro assays and the knockin mice, the loss of the first intron of vWF resulted in a significant reduction of reporter gene expression in endothelial cells but not megakaryocytes. This effect was rescued to varying degrees by the introduction of a heterologous intron. Intron-mediated enhancement of expression was mediated at a posttranscriptional level. Together, these findings implicate a role for intronic splicing in mediating lineage-specific expression of vWF in the endothelium.

  5. Does von Willebrand factor improve the predictive ability of current risk stratification scores in patients with atrial fibrillation?

    Science.gov (United States)

    García-Fernández, Amaya; Roldán, Vanessa; Rivera-Caravaca, José Miguel; Hernández-Romero, Diana; Valdés, Mariano; Vicente, Vicente; Lip, Gregory Y. H.; Marín, Francisco

    2017-01-01

    Von Willebrand factor (vWF) is a biomarker of endothelial dysfunction. We investigated its role on prognosis in anticoagulated atrial fibrillation (AF) patients and determined whether its addition to clinical risk stratification schemes improved event-risk prediction. Consecutive outpatients with non-valvular AF were recruited and rates of thrombotic/cardiovascular events, major bleeding and mortality were recorded. The effect of vWF on prognosis was calculated using a Cox regression model. Improvements in predictive accuracy over current scores were determined by calculating the integrated discrimination improvement (IDI), net reclassification improvement (NRI), comparison of receiver-operator characteristic (ROC) curves and Decision Curve Analysis (DCA). 1215 patients (49% males, age 76 (71–81) years) were included. Follow-up was almost 7 years. Significant associations were found between vWF and cardiovascular events, stroke, mortality and bleeding. Based on IDI and NRI, addition of vWF to CHA2DS2-VASc statistically improved its predictive value, but c-indexes were not significantly different. For major bleeding, the addition of vWF to HAS-BLED improved the c-index but not IDI or NRI. DCA showed minimal net benefit. vWF acts as a simple prognostic biomarker in AF and, whilst its addition to current scores statistically improves prediction for some endpoints, absolute changes and impact on clinical decision-making are marginal. PMID:28134282

  6. Type II PI4-kinases control Weibel-Palade body biogenesis and von Willebrand factor structure in human endothelial cells.

    Science.gov (United States)

    Lopes da Silva, Mafalda; O'Connor, Marie N; Kriston-Vizi, Janos; White, Ian J; Al-Shawi, Raya; Simons, J Paul; Mössinger, Julia; Haucke, Volker; Cutler, Daniel F

    2016-05-15

    Weibel-Palade bodies (WPBs) are endothelial storage organelles that mediate the release of molecules involved in thrombosis, inflammation and angiogenesis, including the pro-thrombotic glycoprotein von Willebrand factor (VWF). Although many protein components required for WPB formation and function have been identified, the role of lipids is almost unknown. We examined two key phosphatidylinositol kinases that control phosphatidylinositol 4-phosphate levels at the trans-Golgi network, the site of WPB biogenesis. RNA interference of the type II phosphatidylinositol 4-kinases PI4KIIα and PI4KIIβ in primary human endothelial cells leads to formation of an increased proportion of short WPB with perturbed packing of VWF, as exemplified by increased exposure of antibody-binding sites. When stimulated with histamine, these cells release normal levels of VWF yet, under flow, form very few platelet-catching VWF strings. In PI4KIIα-deficient mice, immuno-microscopy revealed that VWF packaging is also perturbed and these mice exhibit increased blood loss after tail cut compared to controls. This is the first demonstration that lipid kinases can control the biosynthesis of VWF and the formation of WPBs that are capable of full haemostatic function.

  7. Desenvolvimento de um recurso didático multimídia para o ensino de higiene brônquica Development of a multimedia tool for teaching bronchial hygiene

    Directory of Open Access Journals (Sweden)

    Cibele Cristine Berto Marques da Silva

    2009-03-01

    Full Text Available As novas tecnologias da informação têm sido amplamente utilizadas no ensino em saúde. No entanto, não há descrição na literatura do desenvolvimento de recurso multimídia para o ensino de fisioterapia respiratória. O objetivo deste trabalho foi desenvolver material didático multimídia para o ensino de manobras de higiene brônquica (MHB disponibilizado na internet. O material elaborado foi dividido em três módulos: Princípios fisiológicos, Fisiopatologia e MHB. O material foi disponibilizado em diversos formatos (páginas on-line, apostila e recursos audiovisuais e inserido no sítio da internet Ambiente Colaborativo de Aprendizagem. A página on-line de introdução contém links para acesso aleatório aos módulos e um link para acesso à apostila. No módulo Princípios fisiológicos há links para informações sobre o aparelho mucociliar, produção do muco e fatores prejudiciais à defesa pulmonar. No módulo Fisiopatologia há links para informações sobre as principais doenças ou condições causadoras de hipersecreção pulmonar. No módulo MHB há links para informações sobre as manobras e para vídeos. Este recurso didático multimídia para o ensino de MHB, disponibilizado na internet, pode facilitar o aprendizado em fisioterapia respiratória. Entretanto, há necessidade de se avaliar sua efetividade.Advances in information technology have been widely used in teaching health care providers. However, no reports were found on its use in the instruction on respiratory therapy. The purpose here was to develop audiovisual supporting material for teaching bronchial hygiene techniques (BHT available through the internet. The material was organized into three modules: Physiological principles, Physiopathology, and BHT. Each module is available in several formats (online page, booklet and audiovisual resources and is inserted in a collaborative learning environment at the internet. The opening online page has links for

  8. Discovery of low-affinity preproinsulin epitopes and detection of autoreactive CD8 T-cells using combinatorial MHC multimers.

    Science.gov (United States)

    Unger, Wendy W; Velthuis, Jurjen; Abreu, Joana R F; Laban, Sandra; Quinten, Edwin; Kester, Michel G D; Reker-Hadrup, Sine; Bakker, Arnold H; Duinkerken, Gaby; Mulder, Arend; Franken, Kees L M C; Hilbrands, Robert; Keymeulen, Bart; Peakman, Mark; Ossendorp, Ferry; Drijfhout, Jan Wouter; Schumacher, Ton N; Roep, Bart O

    2011-11-01

    Autoreactive cytotoxic CD8 T-cells (CTLs) play a key pathogenic role in the destruction of insulin-producing beta-cells resulting in type 1 diabetes. However, knowledge regarding their targets is limited, restricting the ability to monitor the course of the disease and immune interventions. In a multi-step discovery process to identify novel CTL epitopes in human preproinsulin (PPI), PPI was digested with purified human proteasomes, and resulting COOH-fragments aligned with algorithm-predicted HLA-binding peptides to yield nine potential HLA-A1, -A2, -A3 or -B7-restricted candidates. An UV-exchange method allowed the generation of a repertoire of multimers including low-affinity HLA-binding peptides. These were labeled with quantum dot-fluorochromes and encoded in a combinatorial fashion, allowing parallel and sensitive detection of specific, low-avidity T-cells. Significantly increased frequencies of T-cells against four novel PPI epitopes (PPI(4-13)/B7, PPI(29-38)/A2, PPI(76-84)/A3 and PPI(79-88)/A3) were detected in stored blood of patients with recent onset diabetes but not in controls. Changes in frequencies of circulating CD8 T-cells against these novel epitopes were detected in blood of islet graft recipients at different time points after transplantation, which correlated with clinical outcome. In conclusion, our novel strategy involving a sensitive multiplex detection technology and requiring minimal volumes of stored blood represents a major improvement in the direct ex-vivo characterization and enumeration of immune cells in the pathogenesis of type 1 diabetes. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Selective protein extraction from Chlorobium tepidum chlorosomes using detergents. Evidence that CsmA forms multimers and binds bacteriochlorophyll a.

    Science.gov (United States)

    Bryant, Donald A; Vassilieva, Elena V; Frigaard, Niels-Ulrik; Li, Hui

    2002-12-03

    Chlorosomes of the photosynthetic green sulfur bacterium Chlorobium tepidum consist of bacteriochlorophyll (BChl) c aggregates that are surrounded by a lipid-protein monolayer envelope that contains ten different proteins. Chlorosomes also contain a small amount of BChl a, but the organization and location of this BChl a are not yet clearly understood. Chlorosomes were treated with sodium dodecyl sulfate (SDS), Lubrol PX, or Triton X-100, separately or in combination with 1-hexanol, and the extracted components were separated from the residual chlorosomes by ultrafiltration on centrifugal filters. When chlorosomes were treated with low concentrations of SDS, all proteins except CsmA were extracted. However, this treatment did not significantly alter the size and shape of the chlorosomes, did not extract the BChl a, and caused only minor changes in the absorption spectrum of the chlorosomes. Cross-linking studies with SDS-treated chlorosomes revealed the presence of multimers of the major chlorosome protein, CsmA, up to homooctamers. Extraction of chlorosomes with SDS and 1-hexanol solubilized all ten chlorosome envelope proteins as well as BChl a. Although the size and shape of these extracted chlorosomes did not initially differ significantly from untreated chlorosomes, the extracted chlorosomes gradually disintegrated, and rod-shaped BChl c aggregates were sometimes observed. These results strongly suggest that CsmA binds the BChl a in Chlorobium-type chlorosomes and further indicate that none of the nine other chlorosome envelope proteins are absolutely required for maintaining the shape and integrity of chlorosomes. Quantitative estimates suggest that chlorosomes contain approximately equimolar amounts of CsmA and BChl a and that roughly one-third of the surface of the chlorosome is covered by CsmA.

  10. Factors Associated with Early Platelet Activation in Obese Children

    Science.gov (United States)

    García, Anel Gómez; Núñez, Guillermina García; Sandoval, Martha Eva Viveros; Castellanos, Sergio Gutierrez; Aguilar, Cleto Alvarez

    2014-01-01

    Objective To investigate the factors associated with platelet activation in obese children. Design Cross-sectional study. Setting Department of Pediatrics of Regional Hospital N∘ 1 of Mexican Institute of Social Security in Morelia, Michoacán, Mexico. Participants 79 obese and 64 non-obese children between the ages of 5 and 10 years. Main Outcomes Measures Obese children (body mass index [BMI] >85 in growth curves for Centers for Disease Control/National Center for Health Statistics), and the control group of 64 non-obese children (percentile <85), % body fat, platelet activation was assessed by sP-selectin. Other measures were leptin, uric acid (UA), von Willebrand Factor (vWF), plasminogen activator inhibitor (PAI-1), lipid profile, and glucose. Results Obese children displayed higher plasma sP-selectin, leptin, PAI-1, and vWF than non-obese children. In the univariate logistic regression analysis, leptin, vWF, UA, and high density lipoprotein (HDL), but not with PAI-1, were factors associated with platelet activation. By stepwise linear regression analysis adjusted by sex and age, the best predictor variables for platelet activation were leptin (β:0.381; t:4.665; P=0.0001), vWF (β:0.211; t:2.926; P=0.004), UA (β:0.166; t:2.146; P=0.034), and HDL (β:−0.215; t:−2.819; P=0.006). Conclusions Obese children have a higher risk of developing early platelet activation. Factors associated with platelet activation were Leptin, vWF, UA, and HDL. Further studies involving larger numbers of patients over a longer duration are needed to understand the possible molecular mechanism underlying the association between leptin, vWF, and UA and endothelial activation and/or endothelial damage/dysfunction in obese children and its influence in cardiovascular disease in adults. PMID:24415745

  11. Laboratory testing for von Willebrand's disease: an assessment of current diagnostic practice and efficacy by means of a multi-laboratory survey. RCPA Quality Assurance Program (QAP) in Haematology Haemostasis Scientific Advisory Panel.

    Science.gov (United States)

    Favaloro, E J; Smith, J; Petinos, P; Hertzberg, M; Koutts, J

    1999-10-01

    We report an evaluation of current laboratory practice for the diagnosis of von Willebrand's disease (VWD) by means of a multilaboratory survey. This assessment was undertaken with the RCPA Quality Assurance Program (QAP) in Haematology, which covers a wide geographic area encompassing Australia, New Zealand and Asia. A total of 25 laboratories actively involved in testing for VWD were selected to participate in a sample testing assessment exercise. Samples comprised 10 plasmas: (i) a normal plasma pool (in duplicate), (ii) this pool diluted to 50% (in duplicate), (iii) a normal individual (X1), (iv) severe Type 1 VWD (X1), (v) Type 2B VWD (x2 unrelated donors), (vi) Type 3 VWD (x1), (vii) Type 2A VWD (x1). Laboratories were asked to perform all tests available to them in order to establish a laboratory diagnosis of VWD, and then to comment on the possibility or otherwise of VWD. Overall findings indicated a wide variation in test practice, in the effectiveness of various test procedures in detecting VWD, and in the ability of various composite test panels to identify type 2 VWD subtypes. Firstly, while all laboratories (n = 25) performed tests for FVIII:C activity, von Willebrand factor 'antigen' (VWF:Ag) and a functional VWF assay [using the ristocetin cofactor assay (VWF:RCo; n = 23) and/or the collagen binding assay (VWF:CBA; n = 12)], only three laboratories carried out VWF:Multimer analysis. Secondly, for the three quantitative VWF assays, 10/25 (40%) laboratories performed all three, whereas 15/25 (60%) performed only two [VWF:Ag and VWF:RCo (n = 13); VWF:Ag and VWF:CBA (n = 2)]. Thirdly, a variety of assay methodologies were evident for VWF:Ag [ELISA, electro-immuno diffusion (EID), latex immuno-assay (LIA), and VIDAS assay] and VWF:RCo (platelet agglutination/'aggregometry' and a 'functional VWF:RCo-alternative' ELISA assay). Between method analysis for the quantitative VWF assays showed that the VWF:RCo yielded the greatest degree of inter

  12. Evaluación de la satisfacción del paciente hospitalizado: empleo de una matriz multirrasgo-multimétodo reducida

    OpenAIRE

    Cabrero García, Julio; Richart Martínez, Miguel; Reig Ferrer, Abilio

    1993-01-01

    En esta investigación sobre la satisfacción del paciente con la hospitalización y los cuidados de enfermería se hace uso de la estrategia "matriz multirrasgo-multimétodo". Los sujetos (n=116) fueron personas ingresadas en los hospitales del Servicio Valenciano de Salud de Alicante y Elche. Se midieron dos rasgos: satisfacción con los cuidados de enfermería y satisfacción con la hospitalización. Los métodos fueron: escalas con formato de respuesta "acuerdo-desacuerdo" con clave positiva (AD+),...

  13. Rethinking the diagnosis of von Willebrand disease.

    Science.gov (United States)

    Favaloro, Emmanuel J

    2011-01-01

    von Willebrand disease (VWD) is the most common inherited bleeding disorder and arises from deficiencies and/or defects in the plasma protein von Willebrand factor (VWF). VWD is classified into 6 different types, with type 1 identified as a (partial) quantitative deficiency of VWF, type 3 defined by a (virtual) total deficiency of VWF, and type 2 identifying four separate types (2A, 2B, 2M, 2N) characterised by qualitative defects. The classification is based on phenotypic assays including FVIII, VWF:Ag and VWF activity, typically by ristocetin cofactor (VWF:RCo), but also increasingly by collagen binding (VWF:CB). Phenotypic testing may be supplemented by multimer analysis, RIPA, and VWF:FVIII binding. Although genetic analysis is not required to diagnose VWD or to define a classification type, it may be useful in discrete situations. The current review briefly covers this diagnostic process, with a focus on newer approaches, including extended test panels and the use of data from desmopressin challenges as a diagnostic tool. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Comparison of automated von Willebrand factor activity assays

    DEFF Research Database (Denmark)

    Timm, Annette; Hillarp, Andreas; Philips, Malou

    2015-01-01

    activity/antigen ratios in samples classified as having VWD (activity classification power might interfere with the interpretation......INTRODUCTION: Von Willebrand Disease (VWD) is the most common inherited bleeding disorder. Measurement of von Willebrand factor (VWF) activity in plasma is often based on platelet agglutination stimulated by the ristocetin cofactor activity. Novel assays, based on latex beads with recombinant...... glycoprotein Ib instead of platelets, have recently been developed but it is unclear whether these can improve the diagnostic capability for VWD. AIM: To compare four automated VWF activity methods in a mixed population of patients referred for evaluation of bleeding tendency. METHODS: The analytical...

  15. Effects of increased von Willebrand factor levels on primary hemostasis in thrombocytopenic patients with liver cirrhosis.

    Science.gov (United States)

    Wannhoff, Andreas; Müller, Oliver J; Friedrich, Kilian; Rupp, Christian; Klöters-Plachky, Petra; Leopold, Yvonne; Brune, Maik; Senner, Mirja; Weiss, Karl-Heinz; Stremmel, Wolfgang; Schemmer, Peter; Katus, Hugo A; Gotthardt, Daniel N

    2014-01-01

    In patients with liver cirrhosis procoagulant and anticoagulant changes occur simultaneously. During primary hemostasis, platelets adhere to subendothelial structures, via von Willebrand factor (vWF). We aimed to investigate the influence of vWF on primary hemostasis in patients with liver cirrhosis. Therefore we assessed in-vitro bleeding time as marker of primary hemostasis in cirrhotic patients, measuring the Platelet Function Analyzer (PFA-100) closure times with collagen and epinephrine (Col-Epi, upper limit of normal ≤ 165 s) or collagen and ADP (Col-ADP, upper limit of normal ≤ 118 s). If Col-Epi and Col-ADP were prolonged, the PFA-100 was considered to be pathological. Effects of vWF on primary hemostasis in thrombocytopenic patients were analyzed and plasma vWF levels were modified by adding recombinant vWF or anti-vWF antibody. Of the 72 included cirrhotic patients, 32 (44.4%) showed a pathological result for the PFA-100. They had mean closure times (± SD) of 180 ± 62 s with Col-Epi and 160 ± 70 s with Col-ADP. Multivariate analysis revealed that hematocrit (P = 0.027) and vWF-antigen levels (P = 0.010) are the predictors of a pathological PFA-100 test in cirrhotic patients. In 21.4% of cirrhotic patients with platelet count ≥ 150/nL and hematocrit ≥ 27.0%, pathological PFA-100 results were found. In thrombocytopenic (hemostasis is impaired in cirrhotic patients. The effect of reduced platelet count in cirrhotic patients can at least be partly compensated by increased vWF levels. Recombinant vWF could be an alternative to platelet transfusions in the future.

  16. MHC multimer-guided and cell culture-independent isolation of functional T cell receptors from single cells facilitates TCR identification for immunotherapy.

    Directory of Open Access Journals (Sweden)

    Georg Dössinger

    Full Text Available Adoptive therapy using T cells redirected to target tumor- or infection-associated antigens is a promising strategy that has curative potential and broad applicability. In order to accelerate the screening process for suitable antigen-specific T cell receptors (TCRs, we developed a new approach circumventing conventional in vitro expansion-based strategies. Direct isolation of paired full-length TCR sequences from non-expanded antigen-specific T cells was achieved by the establishment of a highly sensitive PCR-based T cell receptor single cell analysis method (TCR-SCAN. Using MHC multimer-labeled and single cell-sorted HCMV-specific T cells we demonstrate a high efficacy (approximately 25% and target specificity of TCR-SCAN receptor identification. In combination with MHC-multimer based pre-enrichment steps, we were able to isolate TCRs specific for the oncogenes Her2/neu and WT1 even from very small populations (original precursor frequencies of down to 0.00005% of CD3(+ T cells without any cell culture step involved. Genetic re-expression of isolated receptors demonstrates their functionality and target specificity. We believe that this new strategy of TCR identification may provide broad access to specific TCRs for therapeutically relevant T cell epitopes.

  17. Significance of plasma von Willebrand factor level and von Willebrand factor-cleaving protease activity in patients with chronic renal diseases

    Institute of Scientific and Technical Information of China (English)

    LU Guo-yuan; SHEN Lei; WANG Zhao-yue; GUO Xiao-fang; BAI Xia; SU Jian; RUAN Chang-geng

    2008-01-01

    Background yon Willebrand factor(vWF)mediates the initial capture of platelets to vascular subendothelium and is essential for platelet aggregation under high fluid shear stress as in arteriaI stenosis.On release frOm endothelial cells,vWF is rapidly cleaved by ADAMTSl 3/vWF-cleaving protease (vWF-CP).We investigated the clinical significance of changes in plasma vWF and vWF-CP activities in chronic renal disease.Methods Plasma vWF and vWF-CP activities were measured using enzyme-linked immunosorbent assay(ELISA)and residual collagen binding assay respectively in patients with lupus nephritis(n=31),primary nephritic syndrome(n=25),diabetic nephropathy(n=45),chronic glomerulonephritis(n=38)and 40 normal controls.The reIation of their levels with pathological and renal status was analyzed.Results In all diseased patients the levels of vWF were significantly higher and vWF-CP activity significantly lower than the controls(both P<0.01).vWF in the four subgroups did not correlate with the stage of disease but correlated negatively with vWF-CP activity.vWF-CP activity was not changed two weeks after renal transplantation.Renal biopsy demonstrated that the vWF level in stage Ⅳ was higher than in stages Ⅱ and Ⅲ while vWF-CP activity was lower in patients with lupus nephritis.After eight-week treatment,the vWF level significantly decreased and the vWF-CP activity significantly increased in systemic lupus erythema,disease activity index<9,but not with index≥9.Even though the vWF-CP activity was significantly lower in membranous nephropathy than in minimal change disease,mesangial proliferative glomerulonephritis or IgA glomerulonephritis,the vWF level was not significantly different.Conclusions The alterations of plasma vWF and vWF-CP activities were associated with different renal pathologies.Injury to endothelial cells and autoantibodies against vWF-CP activity may result in higher vWF Ievel and Iower vWF-CP activity in chronic renaI disease and thus a

  18. Active von Willebrand factor in thrombotic thrombocytopenic purpura and malaria

    NARCIS (Netherlands)

    Groot, E.

    2009-01-01

    Thrombotic thrombocytopenic purpura (TTP) and malaria are two diseases of distinct origin. TTP is a rare disorder caused by a deficiency of the von Willebrand factor (VWF) cleaving protease ADAMTS13. Malaria is a poverty-related disease caused by protozoan parasites from the genus Plasmodium. TTP an

  19. Tutorial multimèdia per a guiar la preparació i defensa del Treball de Fi de Grau

    Directory of Open Access Journals (Sweden)

    Gregorio González Alcaide

    2013-12-01

    Full Text Available La preparació i defensa d’un Treball de Fi de Grau constitueix una de les principals novetats derivades del procés de construcció de l’Espai Europeu d’Educació Superior. En aquest treball queden reflectides totes les habilitats adquirides pels estudiants en els anys previs a la finalització del Grau, ja que els estudiants han d’enfrontar-se en el mateix al procés de generació autònoma de coneixement i a les dificultats del treball pràctic. El present estudi recull l’experiència de desenvolupament d’un tutorial multimèdia per a guiar el procés de realització del Treball de Fi de Grau, adaptats als objectius d’aprenentatge i a l’adquisició de competències dels alumnes destinataris. El treball s’ha desenvolupat en les següents fases: a determinació dels continguts que havien d’esser inclosos en el tutorial i disseny dels objectes d’aprenentatge; b desenvolupament tècnic e implementació dels materials en un tutorial accessible a través de la web; i c avaluació dels materials desenvolupats i dels processos d’aprenentatge. S’han desenvolupat els següents objectes d’aprenentatge: unitats didàctiques que descriuen les característiques, estructura i continguts que s’han d’incloure en cadascuna de les seccions que conformen el Treball de Fi de Grau; llistat de recursos que poden resultar d’interès per a realitzar una aproximació a “l’estat del art” i que poden resultar d’utilitat per a la creació del text escrit (com ara bases de dades i programes gestors de bibliografia; tests per a que els alumnes puguen verificar l’adequació dels textos que han preparat en relació amb la normativa i les característiques dels Treballs de Fi de Grau; i finalment, un video que recrea l’exposició oral i defensa d’un Treball de Fi de Grau. El programa eXeLearning fou utilitzat per al desenvolupament dels materials i del tutorial. Per a l’avaluació dels materials elaborats es combinaren t

  20. No evidence for a direct effect of von Willebrand factor's ABH blood group antigens on von Willebrand factor clearance

    NARCIS (Netherlands)

    Groeneveld, D J; van Bekkum, T; Cheung, K L; Dirven, R J; Castaman, G; Reitsma, P H; van Vlijmen, B; Eikenboom, J

    2015-01-01

    BACKGROUND: One of the major determinants of von Willebrand factor (VWF) plasma levels is ABO blood group status, and individuals with blood group O have ~ 25% lower plasma levels. The exact mechanism behind this relationship remains unknown, although effects on clearance have been postulated. OBJEC

  1. von Willebrand Factor and Oxidative Stress Parameters in Acute Coronary Syndromes

    Directory of Open Access Journals (Sweden)

    Zoran Koprivica

    2011-01-01

    Full Text Available Considering the role of von Willebrand factor (vWf in hemostasis, and the role of oxidative stress in the development of endothelial dysfunction and atherosclerotic disease, the aim of our study was to investigate the relationship between vWf, parameters of oxidative stress and different types of acute coronary syndromes (ACS. Levels of vWf activity (vWfAct, vWf antigen (vWfAg, nitric oxide (estimated through nitrites–NO2 −, superoxide anion radical (O2 −, hydrogen peroxide (H2O2, index of lipid peroxidation (estimated through thiobarbituric acid reactive substances–TBARS, superoxide dismutase (SOD and catalase (CAT activity of 115 patients were compared with those of 40 healthy controls. ACS patients had significantly higher vWfAct and vWfAg levels, as well as TBARS levels, while their levels of NO2 −, H2O2, SOD and CAT activities were lower than controls'. vWfAg showed high specificity and sensitivity as a test to reveal healthy or diseased subjects. Multivariant logistic regression marked only vWfAg and TBARS as parameters that were under independent effect of ACS type. The results of our study support the implementation of vWf in clinical rutine and into therapeutic targets, and suggest that ACS patients are in need of antioxidant supplementation to improve their impaired antioxidant defence.

  2. Von Willebrand factor and oxidative stress parameters in acute coronary syndromes.

    Science.gov (United States)

    Koprivica, Zoran; Djordjevic, Dusica; Vuletic, Milena; Zivkovic, Vladimir; Barudzic, Nevena; Andjelkovic, Nebojsa; Djuric, Dragan; Iric-Cupic, Violeta; Krkeljic, Jelena; Jakovljevic, Vladimir

    2011-01-01

    Considering the role of von Willebrand factor (vWf) in hemostasis, and the role of oxidative stress in the development of endothelial dysfunction and atherosclerotic disease, the aim of our study was to investigate the relationship between vWf, parameters of oxidative stress and different types of acute coronary syndromes (ACS). Levels of vWf activity (vWfAct), vWf antigen (vWfAg), nitric oxide (estimated through nitrites-NO(2)-), superoxide anion radical (O(2)-), hydrogen peroxide (H2O2), index of lipid peroxidation (estimated through thiobarbituric acid reactive substances-TBARS), superoxide dismutase (SOD) and catalase (CAT) activity of 115 patients were compared with those of 40 healthy controls. ACS patients had significantly higher vWfAct and vWfAg levels, as well as TBARS levels, while their levels of NO(2)-, H2O2, SOD and CAT activities were lower than controls'. vWfAg showed high specificity and sensitivity as a test to reveal healthy or diseased subjects. Multivariant logistic regression marked only vWfAg and TBARS as parameters that were under independent effect of ACS type. The results of our study support the implementation of vWf in clinical rutine and into therapeutic targets, and suggest that ACS patients are in need of antioxidant supplementation to improve their impaired antioxidant defence.

  3. Regulatory components of the alternative complement pathway in endothelial cell cytoplasm, factor H and factor I, are not packaged in Weibel-Palade bodies.

    Directory of Open Access Journals (Sweden)

    Nancy A Turner

    Full Text Available It was recently reported that factor H, a regulatory component of the alternative complement pathway, is stored with von Willebrand factor (VWF in the Weibel-Palade bodies of endothelial cells. If this were to be the case, it would have therapeutic importance for patients with the atypical hemolytic-uremic syndrome that can be caused either by a heterozygous defect in the factor H gene or by the presence of an autoantibody against factor H. The in vivo Weibel-Palade body secretagogue, des-amino-D-arginine vasopressin (DDAVP, would be expected to increase transiently the circulating factor H levels, in addition to increasing the circulating levels of VWF. We describe experiments demonstrating that factor H is released from endothelial cell cytoplasm without a secondary storage site. These experiments showed that factor H is not stored with VWF in endothelial cell Weibel-Palade bodies, and is not secreted in response in vitro in response to the Weibel-Palade body secretagogue, histamine. Furthermore, the in vivo Weibel-Palade body secretagogue, DDAVP does not increase the circulating factor H levels concomitantly with DDAVP-induced increased VWF. Factor I, a regulatory component of the alternative complement pathway that is functionally related to factor H, is also located in endothelial cell cytoplasm, and is also not present in endothelial cell Weibel-Palade bodies. Our data demonstrate that the factor H and factor I regulatory proteins of the alternative complement pathway are not stored in Weibel-Palade bodies. DDAVP induces the secretion into human plasma of VWF--but not factor H.

  4. Regulatory components of the alternative complement pathway in endothelial cell cytoplasm, factor H and factor I, are not packaged in Weibel-Palade bodies.

    Science.gov (United States)

    Turner, Nancy A; Sartain, Sarah E; Hui, Shiu-Ki; Moake, Joel L

    2015-01-01

    It was recently reported that factor H, a regulatory component of the alternative complement pathway, is stored with von Willebrand factor (VWF) in the Weibel-Palade bodies of endothelial cells. If this were to be the case, it would have therapeutic importance for patients with the atypical hemolytic-uremic syndrome that can be caused either by a heterozygous defect in the factor H gene or by the presence of an autoantibody against factor H. The in vivo Weibel-Palade body secretagogue, des-amino-D-arginine vasopressin (DDAVP), would be expected to increase transiently the circulating factor H levels, in addition to increasing the circulating levels of VWF. We describe experiments demonstrating that factor H is released from endothelial cell cytoplasm without a secondary storage site. These experiments showed that factor H is not stored with VWF in endothelial cell Weibel-Palade bodies, and is not secreted in response in vitro in response to the Weibel-Palade body secretagogue, histamine. Furthermore, the in vivo Weibel-Palade body secretagogue, DDAVP does not increase the circulating factor H levels concomitantly with DDAVP-induced increased VWF. Factor I, a regulatory component of the alternative complement pathway that is functionally related to factor H, is also located in endothelial cell cytoplasm, and is also not present in endothelial cell Weibel-Palade bodies. Our data demonstrate that the factor H and factor I regulatory proteins of the alternative complement pathway are not stored in Weibel-Palade bodies. DDAVP induces the secretion into human plasma of VWF--but not factor H.

  5. Magnetic-Activated Cell Sorting of TCR-engineered T cells using tCD34 as a gene marker, but not peptide-MHC multimers, results in significant numbers of functional CD4 and CD8 T cells

    NARCIS (Netherlands)

    Govers, C.; Berrevoets, C.; Treffers-Westerlaken, E.; Broertjes, M.; Debets, R.

    2012-01-01

    T cell sorting technologies with peptide-MHC multimers or antibodies against gene markers enable enrichment of antigen-specific T cells and are expected to enhance therapeutic efficacy of clinical T cell therapy. However, a direct comparison between sorting reagents for their ability to enrich T cel

  6. Magnetic-activated cell sorting of TCR-engineered T cells, using tCD34 as a gene marker, but not peptide-MHC multimers, results in significant numbers of functional CD4+ and CD8+ T cells

    NARCIS (Netherlands)

    C.C.F.M. Govers (Coen); C.A. Berrevoets (Cor); E. Treffers-Westerlaken (Elike); M. Broertjes (Marieke); J.E.M.A. Debets (Reno)

    2012-01-01

    textabstractT cell-sorting technologies with peptide-MHC multimers or antibodies against gene markers enable enrichment of antigen-specific T cells and are expected to enhance the therapeutic efficacy of clinical T cell therapy. However, a direct comparison between sorting reagents for their ability

  7. Storage and regulated secretion of factor VIII in blood outgrowth endothelial cells

    NARCIS (Netherlands)

    van den Biggelaar, M.; Bouwens, E.A.M.; Kootstra, N.A.; Hebbel, R.P.; Voorberg, J.; Mertens, K.

    2009-01-01

    Background Gene therapy provides an attractive alternative for protein replacement therapy in hemophilia A patients. Recent studies have shown the potential benefit of directing factor (F)VIII gene delivery to cells that also express its natural carrier protein von Willebrand factor (VWF). In this

  8. Storage and regulated secretion of factor VIII in blood outgrowth endothelial cells

    NARCIS (Netherlands)

    van den Biggelaar, M.; Bouwens, E.A.M.; Kootstra, N.A.; Hebbel, R.P.; Voorberg, J.; Mertens, K.

    2009-01-01

    Background Gene therapy provides an attractive alternative for protein replacement therapy in hemophilia A patients. Recent studies have shown the potential benefit of directing factor (F)VIII gene delivery to cells that also express its natural carrier protein von Willebrand factor (VWF). In this s

  9. Storage and regulated secretion of factor VIII in blood outgrowth endothelial cells

    NARCIS (Netherlands)

    van den Biggelaar, M.; Bouwens, E.A.M.; Kootstra, N.A.; Hebbel, R.P.; Voorberg, J.; Mertens, K.

    2009-01-01

    Background Gene therapy provides an attractive alternative for protein replacement therapy in hemophilia A patients. Recent studies have shown the potential benefit of directing factor (F)VIII gene delivery to cells that also express its natural carrier protein von Willebrand factor (VWF). In this s

  10. Characterisation of adiponectin multimers and the IGF axis in humans with a heterozygote mutation in the tyrosine kinase domain of the insulin receptor gene

    DEFF Research Database (Denmark)

    Højlund, Kurt; Beck-Nielsen, Henning; Flyvbjerg, Allan

    2012-01-01

    Objective: Low levels of adiponectin, IGF-binding protein (IGFBP)-1, and IGFBP-2, and high levels of leptin correlate with several indices of insulin resistance and risk of type 2 diabetes. However, in insulin receptoropathies plasma adiponectin is paradoxically increased despite severe insulin...... an euglycemic-hyperinsulinemic clamp were examined for plasma adiponectin multimers, leptin, total IGF-I, IGF-II, free IGF-I, IGFBP-1 and IGFBP-2.Results: Despite 10-fold elevated fasting insulin and marked insulin resistance in Arg1174Gln-carriers, the levels of total adiponectin, leptin, IGFBP-1 and IGFBP-2......1174Gln-carriers. Interestingly, exogenous insulin failed to suppress total adiponectin in Arg1174Gln-carriers, but reduced IGFBP-1 and increased IGFBP-2 as in controls.Conclusion: The normal levels of adiponectin, IGFBP-1 and IGFBP-2 in the face of highly elevated insulin levels suggest an impaired...

  11. La eficiencia teórica y metodológica de los diseños multimétodo

    Directory of Open Access Journals (Sweden)

    JOAN M. VERD

    2008-01-01

    Full Text Available En los últimos años, el ya viejo debate en torno a la articulación metodológica se ha centrado con fuerza en las implicaciones de las investigaciones multimétodo o basadas en la mezcla de métodos (métodos mixtos. En este contexto se ha reflexionado con cierta profundidad, especialmente en el ámbito anglosajón, respecto a las ventajas metodológicas que aportan este tipo de diseños, aunque bastante menos respecto a los beneficios que se aportan a la reflexión teórica. Partiendo de la premisa de que este tipo de diseño no debe entenderse como una vía de escape a la realidad multiparadigmática de la investigación sociológica, el artículo defiende que el diseño multimétodo es más eficiente teórica y metodológicamente que los diseños exclusivamente cuantitativos o cualitativos. Utilizando la terminología de Creswell, se argumenta que la eficiencia metodológica se consigue especialmente con los diseños de carácter secuencial, mientras que la eficiencia teórica se consigue especialmente con los diseños de carácter concurrente, sobre todo en su vertiente anidada. Estos argumentos se refuerzan con ejemplos de una investigación que los dos autores han terminado recientemente, centrada en la realidad juvenil catalana.

  12. Usos e apropriações de multimídias na educação para a biodiversidade em escolas de Belém/PA

    Directory of Open Access Journals (Sweden)

    Mayara Santos Maciel

    2016-01-01

    Full Text Available Esta pesquisa, realizada no âmbito do Programa de Capacitação Institucional através do Museu Paraense Emilio Goeldi/MCTI, identificou as percepções sobre o conceito de biodiversidade em duas comunidades escolares de Ensino Fundamental e Médio da cidade de Belém do Pará - Brasil, vinculadas aos sistemas municipal e estadual de ensino, a saber: Fundação Centro de Referência em Educação Ambiental Professor Eidorfe Moreira e Escola Estadual de Ensino Fundamental e Médio Vilhena Alves. Também identificou como as Tecnologias da Informação e da Comunicação e multimídias atuam como mediadoras dos processos de ensino e aprendizado sobre biodiversidade nestas comunidades. Como metodologia foi utilizada a pesquisa-ação com observação participante (PERUZZO, 2003 e entrevistas em profundidade do tipo semi-abertas com questões semi-estruturadas (Duarte, 2009. Concluiu-se que o conceito de biodiversidade deve ser melhor trabalhado em âmbito escolar, de uma forma estruturada e com o auxílio pedagógico das TICs, cujo uso educativo deve ser favorecido com melhores investimentos na educação pública, principalmente na formação e sensibilização de professores para o uso pedagógico das TICs e multimídias.

  13. A separate pool of cardiac phospholemman that does not regulate or associate with the sodium pump: multimers of phospholemman in ventricular muscle.

    Science.gov (United States)

    Wypijewski, Krzysztof J; Howie, Jacqueline; Reilly, Louise; Tulloch, Lindsay B; Aughton, Karen L; McLatchie, Linda M; Shattock, Michael J; Calaghan, Sarah C; Fuller, William

    2013-05-10

    Phospholemman regulates the plasmalemmal sodium pump in excitable tissues. In cardiac muscle, a subpopulation of phospholemman with a unique phosphorylation signature associates with other phospholemman molecules but not with the pump. Phospholemman oligomers exist in cardiac muscle. Much like phospholamban regulation of SERCA, phospholemman exists as both a sodium pump inhibiting monomer and an unassociated oligomer. Phospholemman (PLM), the principal quantitative sarcolemmal substrate for protein kinases A and C in the heart, regulates the cardiac sodium pump. Much like phospholamban, which regulates the related ATPase SERCA, PLM is reported to oligomerize. We investigated subpopulations of PLM in adult rat ventricular myocytes based on phosphorylation status. Co-immunoprecipitation identified two pools of PLM: one not associated with the sodium pump phosphorylated at Ser(63) and one associated with the pump, both phosphorylated at Ser(68) and unphosphorylated. Phosphorylation of PLM at Ser(63) following activation of PKC did not abrogate association of PLM with the pump, so its failure to associate with the pump was not due to phosphorylation at this site. All pools of PLM co-localized to cell surface caveolin-enriched microdomains with sodium pump α subunits, despite the lack of caveolin-binding motif in PLM. Mass spectrometry analysis of phosphospecific immunoprecipitation reactions revealed no unique protein interactions for Ser(63)-phosphorylated PLM, and cross-linking reagents also failed to identify any partner proteins for this pool. In lysates from hearts of heterozygous transgenic animals expressing wild type and unphosphorylatable PLM, Ser(63)-phosphorylated PLM co-immunoprecipitated unphosphorylatable PLM, confirming the existence of PLM multimers. Dephosphorylation of the PLM multimer does not change sodium pump activity. Hence like phospholamban, PLM exists as a pump-inhibiting monomer and an unassociated oligomer. The distribution of different PLM

  14. Data analysis as a source of variability of the HLA-peptide multimer assay: from manual gating to automated recognition of cell clusters.

    Science.gov (United States)

    Gouttefangeas, Cécile; Chan, Cliburn; Attig, Sebastian; Køllgaard, Tania T; Rammensee, Hans-Georg; Stevanović, Stefan; Wernet, Dorothee; thor Straten, Per; Welters, Marij J P; Ottensmeier, Christian; van der Burg, Sjoerd H; Britten, Cedrik M

    2015-05-01

    Multiparameter flow cytometry is an indispensable method for assessing antigen-specific T cells in basic research and cancer immunotherapy. Proficiency panels have shown that cell sample processing, test protocols and data analysis may all contribute to the variability of the results obtained by laboratories performing ex vivo T cell immune monitoring. In particular, analysis currently relies on a manual, step-by-step strategy employing serial gating decisions based on visual inspection of one- or two-dimensional plots. It is therefore operator dependent and subjective. In the context of continuing efforts to support inter-laboratory T cell assay harmonization, the CIMT Immunoguiding Program organized its third proficiency panel dedicated to the detection of antigen-specific CD8(+) T cells by HLA-peptide multimer staining. We first assessed the contribution of manual data analysis to the variability of reported T cell frequencies within a group of laboratories staining and analyzing the same cell samples with their own reagents and protocols. The results show that data analysis is a source of variation in the multimer assay outcome. To evaluate whether an automated analysis approach can reduce variability of proficiency panel data, we used a hierarchical statistical mixture model to identify cell clusters. Challenges for automated analysis were the need to process non-standardized data sets from multiple centers, and the fact that the antigen-specific cell frequencies were very low in most samples. We show that this automated method can circumvent difficulties inherent to manual gating strategies and is broadly applicable for experiments performed with heterogeneous protocols and reagents.

  15. New developments in lung endothelial heterogeneity: Von Willebrand factor, P-selectin, and the Weibel-Palade body.

    Science.gov (United States)

    Ochoa, Cristhiaan D; Wu, Songwei; Stevens, Troy

    2010-04-01

    Quiescent pulmonary endothelium establishes an antithrombotic, anti-inflammatory surface that promotes blood flow. However, the endothelium rapidly responds to injury and inflammation by promoting thrombosis and enabling the directed transmigration of inflammatory cells, such as neutrophils, into the alveolar airspace. Although the endothelial cell signals responsible for establishing a prothrombotic surface are distinct from those responsible for recognizing circulating neutrophils, these processes are highly interrelated. Von Willebrand factor (VWF)-stimulated secretion plays an important role in thrombus formation, and P-selectin surface expression plays a key role in neutrophil binding necessary for transmigration. Both VWF and P-selectin are located within Weibel-Palade bodies in pulmonary arteries and arterioles, yet Weibel-Palade bodies are absent in capillaries. Despite the absence of the Weibel-Palade bodies, pulmonary capillaries express both VWF and P-selectin. The physiological and pathophysiological significance of these observations is unclear. In this review, we address some anatomical and physiological features that distinguish pulmonary artery, capillary, and vein endothelium. In addition, we review our current understanding regarding the stimulated secretion of VWF and P-selectin in pulmonary artery and capillary endothelium. This information is considered in the context of vasculitis and pneumonia, two pathophysiological processes to which the stimulated secretion of VWF and P-selectin contribute.

  16. Flow-induced elongation of von Willebrand factor precedes tension-dependent activation.

    Science.gov (United States)

    Fu, Hongxia; Jiang, Yan; Yang, Darren; Scheiflinger, Friedrich; Wong, Wesley P; Springer, Timothy A

    2017-08-23

    Von Willebrand factor, an ultralarge concatemeric blood protein, must bind to platelet GPIbα during bleeding to mediate hemostasis, but not in the normal circulation to avoid thrombosis. Von Willebrand factor is proposed to be mechanically activated by flow, but the mechanism remains unclear. Using microfluidics with single-molecule imaging, we simultaneously monitored reversible Von Willebrand factor extension and binding to GPIbα under flow. We show that Von Willebrand factor is activated through a two-step conformational transition: first, elongation from compact to linear form, and subsequently, a tension-dependent local transition to a state with high affinity for GPIbα. High-affinity sites develop only in upstream regions of VWF where tension exceeds ~21 pN and depend upon electrostatic interactions. Re-compaction of Von Willebrand factor is accelerated by intramolecular interactions and increases GPIbα dissociation rate. This mechanism enables VWF to be locally activated by hydrodynamic force in hemorrhage and rapidly deactivated downstream, providing a paradigm for hierarchical mechano-regulation of receptor-ligand binding.Von Willebrand factor (VWF) is a blood protein involved in clotting and is proposed to be activated by flow, but the mechanism is unknown. Here the authors show that VWF is first converted from a compact to linear form by flow, and is subsequently activated to bind GPIbα in a tension-dependent manner.

  17. Temperature-dependence of Weibel-Palade body exocytosis and cell surface dispersal of von Willebrand factor and its propolypeptide.

    Directory of Open Access Journals (Sweden)

    Lindsay Hewlett

    Full Text Available BACKGROUND: Weibel-Palade bodies (WPB are endothelial cell (EC specific secretory organelles containing Von Willebrand factor (VWF. The temperature-dependence of Ca(2+-driven WPB exocytosis is not known, although indirect evidence suggests that WPB exocytosis may occur at very low temperatures. Here we quantitatively analyse the temperature-dependence of Ca(2+-driven WPB exocytosis and release of secreted VWF from the cell surface of ECs using fluorescence microscopy of cultured human ECs containing fluorescent WPBs. PRINCIPAL FINDINGS: Ca(2+-driven WPB exocytosis occurred at all temperatures studied (7-37°C. The kinetics and extent of WPB exocytosis were strongly temperature-dependent: Delays in exocytosis increased from 0.92 s at 37°C to 134.2 s at 7°C, the maximum rate of WPB fusion decreased from 10.0±2.2 s(-1 (37°C to 0.80±0.14 s(-1 (7°C and the fractional extent of degranulation of WPBs in each cell from 67±3% (37°C to 3.6±1.3% (7°C. A discrepancy was found between the reduction in Ca(2+-driven VWF secretion and WPB exocytosis at reduced temperature; at 17°C VWF secretion was reduced by 95% but WPB exocytosis by 75-80%. This discrepancy arises because VWF dispersal from sites of WPB exocytosis is largely prevented at low temperature. In contrast VWF-propolypeptide (proregion dispersal from WPBs, although slowed, was complete within 60-120 s. Novel antibodies to the cleaved and processed proregion were characterised and used to show that secreted proregion more accurately reports the secretion of WPBs at sub-physiological temperatures than assay of VWF itself. CONCLUSIONS: We report the first quantitative analysis of the temperature-dependence of WPB exocytosis. We provide evidence; by comparison of biochemical data for VWF or proregion secretion with direct analysis of WPB exocytosis at reduced temperature, that proregion is a more reliable marker for WPB exocytosis at reduced temperature, where VWF-EC adhesion is increased.

  18. Factor VIII Is Synthesized in Human Endothelial Cells, Packaged in Weibel-Palade Bodies and Secreted Bound to ULVWF Strings.

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    Nancy A Turner

    Full Text Available The cellular synthesis site and ensuing storage location for human factor VIII (FVIII, the coagulation protein deficient in hemophilia A, has been elusive. FVIII stability and half-life is dependent on non-covalent complex formation with von Willebrand factor (VWF to avoid proteolysis and clearance. VWF is synthesized in megakaryocytes and endothelial cells, and is stored and secreted from platelet alpha granules and Weibel-Palade bodies of endothelial cells. In this paper we provide direct evidence for FVIII synthesis in 2 types of primary human endothelial cells: glomerular microvascular endothelial cells (GMVECs and umbilical vein endothelial cells (HUVECs. Gene expression quantified by real time PCR revealed that levels of F8 and VWF are similar in GMVECs and HUVECs. Previous clinical studies have shown that stimulation of vasopressin V2 receptors causes parallel secretion of both proteins. In this study, we found that both endothelial cell types express AVPR2 (vasopressin V2 receptor gene and that AVPR2 mRNA levels are 5-fold higher in GMVECs than HUVECs. FVIII and VWF proteins were detected by fluorescent microscopy in Weibel-Palade bodies within GMVECs and HUVECs using antibodies proven to be target specific. Visual presence of FVIII and VWF in Weibel-Palade bodies was confirmed by correlation measurements. The high extent of correlation was compared with negative correlation values obtained from FVIII detection with cytoplasmic proteins, β-actin and Factor H. FVIII activity was positive in GMVEC and HUVEC cell lysates. Stimulated GMVECs and HUVECs were found to secrete cell-anchored ultra-large VWF strings covered with bound FVIII.

  19. Factor VIII Is Synthesized in Human Endothelial Cells, Packaged in Weibel-Palade Bodies and Secreted Bound to ULVWF Strings.

    Science.gov (United States)

    Turner, Nancy A; Moake, Joel L

    2015-01-01

    The cellular synthesis site and ensuing storage location for human factor VIII (FVIII), the coagulation protein deficient in hemophilia A, has been elusive. FVIII stability and half-life is dependent on non-covalent complex formation with von Willebrand factor (VWF) to avoid proteolysis and clearance. VWF is synthesized in megakaryocytes and endothelial cells, and is stored and secreted from platelet alpha granules and Weibel-Palade bodies of endothelial cells. In this paper we provide direct evidence for FVIII synthesis in 2 types of primary human endothelial cells: glomerular microvascular endothelial cells (GMVECs) and umbilical vein endothelial cells (HUVECs). Gene expression quantified by real time PCR revealed that levels of F8 and VWF are similar in GMVECs and HUVECs. Previous clinical studies have shown that stimulation of vasopressin V2 receptors causes parallel secretion of both proteins. In this study, we found that both endothelial cell types express AVPR2 (vasopressin V2 receptor gene) and that AVPR2 mRNA levels are 5-fold higher in GMVECs than HUVECs. FVIII and VWF proteins were detected by fluorescent microscopy in Weibel-Palade bodies within GMVECs and HUVECs using antibodies proven to be target specific. Visual presence of FVIII and VWF in Weibel-Palade bodies was confirmed by correlation measurements. The high extent of correlation was compared with negative correlation values obtained from FVIII detection with cytoplasmic proteins, β-actin and Factor H. FVIII activity was positive in GMVEC and HUVEC cell lysates. Stimulated GMVECs and HUVECs were found to secrete cell-anchored ultra-large VWF strings covered with bound FVIII.

  20. The Change of The Plasma TXB2, 6-KETO-PGF1 Alpha and vWF in Cirrhosis with Upper Gastrointestinal Bleeding%肝硬化上消化道出血患者血浆TXB2、6-酮-PGF1α及vWF的变化

    Institute of Scientific and Technical Information of China (English)

    黄智铭; 韩清锡; 林秀英; 胡滨

    2001-01-01

    To explore mechanism and pathophysiologic significance of the upper gastrointestinal bleeding in cirrhotic patients, the plasma thromboxane B2(TXB2),6-Keto-prostaglandin F1 alpha(6-Keto-PGF1 alpha) and von Willebrand factor (vWF) were detected in 40 patients with liver cirrhosis and 10 controls using enzyme-linked immunosorbent assay(ELISA). The results showed that the levels of TXB2 and TXB2/6-Keto-PGF1 alpha ratio in cirrhosis without upper gastrointestinal bleeding were significantly decreased in comparison with controls(P<0.05), but were markedly increased than that with bleeding (P<0.05-0.01). The levels of 6-Keto-PGF1 alpha and vWF in cirrhosis without bleeding were much higher than that of controls (P<0.05-0.01), and were significantly decreased in comparison with bleeding (P<0.05). The results indicated that there were a strong correlation between the upper gastrointestinal bleeding in cirrhosis and the decrement of TXB2,TXB2/6-Keto-PGF1 alpha ratio and elevation of 6-Keto-PGF1 alpha. The elevation of vWF may reflect the degree of injury in hepatic vascular endothelium and the tendency of upper gastrointestinal bleeding.%进一步探讨肝硬化患者上消化道出血的发生机制及病理生理意义,采用ELISA方法分别定量测定40例肝硬化患者与10例对照组患者血浆血栓素B2(TXB2)、6-酮-前列腺素F1α(6-酮-PGF1α)及血管性假血友病因子(vWF)的水平。结果显示:肝硬化患者无上消化道出血组血浆TXB2水平、TXB2/6-酮-PGF1α比值较对照组明显降低(P<0.05),较出血组显著增高(P<0.05或0.01);而血浆6-酮-PGF1α与vWF水平较对照组明显增高(P<0.05或0.01),较出血组显著降低(P<0.05)。结果表明,肝硬化患者上消化道出血与血浆TXB2下降、6-酮-PGF1α升高及其比例失衡有密切关系,vWF水平升高能反映肝硬化血管内皮损伤及上消化道出血倾向。

  1. 模拟大深度快速上浮脱险兔血浆血管性血友病因子和一氧化氮水平变化%Experimental Study on the Changes of vWF and NO in Rabbits with Decompression Injury induced by Simulated Deep Fast Buoyancy Ascent Escape

    Institute of Scientific and Technical Information of China (English)

    许骥; 何佳; 陈锐勇; 顾靖华; 刘晓波; 陈新; 向导

    2015-01-01

    Objective:To investigate the changes of von Willebrand Factor(vWF)and Nitric oxide(NO)in rabbits with decompression injury induced by simulated deep fast buoyancy ascent escape and to evaluate their role in the pathogenesis of decompression sickness.Method:Sixteen male SD rabbits were compressed to a pressure of 1.5 MPa at an exponential rate of 2 t/4 with compressed air,after staying for 80s at the above pressure,the animals were decompressed to atmospheric pressure at linear speed (30KPa/s).Morbidity and symptoms of decompression sick-ness in animal model was monitored.The blood samples were collected before compression and after decompression respectively.vWF and NO were measured immediately.Results:The Morbidity of decompression sickness in animal model was 68.8%.Compared with those before compression,vWF levels[(2.65 ± 0.26 )μg/L]and NO levels[ (64.5 ± 26.6)μmol/L]in the of rabbits were increased significantly after decompression [(3.59 ± 0.31 )μg/L, (1 1 7.0±36.0)μmol/L](P <0.01).Conclusion:The changes of vWF and NO in the could be used as indicators for the occurrence of decompression injury induced by simulated deep fast buoyancy ascent escape.%目的::研究大深度快速上浮脱险兔血浆血管性血友病因子(vWF)和一氧化氮(NO)浓度变化及在减压损伤中的意义。方法:成年雄性新西兰兔16只,以2 t/4指数速率加压至1.5MPa(表压),稳压停留80s,以30kPa/s 匀速减压至常压。出舱后观察动物行为并统计减压病发病率。实验前及出舱后各采血2ml,4℃离心分离血浆,分别采用酶联免疫吸附法及硝酸还原酶法检测实验兔血浆 vWF 和 NO 浓度。结果:实验兔减压病发病率68.75%(11/16);实验后兔血浆 vWF 和 NO 浓度分别为3.59±0.31μg/L 和117.00±36.00μmol/L,较实验前(2.65±0.26μg/L 和64.50±26.60μmol/L)显著升高,差异有统计学意义(P <0.01)。结论:血浆 vWF、NO 浓度升高可以作为大深度快速上浮脱险机体减压

  2. Desenvolvimento de um Sistema Multimídia Educacional sobre a Paleontologia da Bacia de Pirabas, Mioceno do Norte do Brasil.

    Directory of Open Access Journals (Sweden)

    Márcia Aparecida Fernandes dos Reis

    2007-07-01

    Full Text Available O conhecimento paleontológico é umaferramenta importante para a compreensão dabiologia e das geociências, por isso, a divulgaçãodesta ciência necessita ser ampliada, em especialno ensino fundamental e no ensino médio. Afalta de recursos didáticos que estimulem ointeresse dos alunos no ensino de paleontologiaé uma das principais dificuldades no processo deensino-aprendizagem nesta disciplina. Um outroproblema observado é a falta de conhecimento e/ou atualização dos professores nesta área. Com oobjetivo de fornecer uma estratégia didática para oconhecimento e a divulgação da paleontologia noensino fundamental e médio, foi elaborado um CDROMsobre a Bacia de Pirabas, localizada no Estadodo Pará, Norte do Brasil. Este trabalho faz parte deum projeto maior que visa o desenvolvimento deum sistema multimídia educacional relacionado àpaleontologia e às principais bacias sedimentaresbrasileiras. O software desenvolvido fornece aosalunos e professores de ensino fundamental e médiouma ferramenta dinâmica e interativa que auxilia oprocesso ensino-aprendizagem em paleontologia,permitindo a divulgação científica e cultural dos sítiosfossilíferos destacando a importância da preservaçãodestes locais. O Sistema Multimídia utilizado paraeste trabalho foi desenvolvido no software de autoriaDirector 8.5 em conjunto com o software de apoiopara manipulação de imagens, textos e sons e parao cenário paleoambiental foi utilizado o programa“Vue 5 Infinite versão 2004”. O sistema multimídiaapresenta um histórico da Bacia de Pirabas, suaimportância, além da reconstituição paleoambientale dos seguintes conteúdos: micropalentologia,paleobotânica, paleontologia de invertebrados epaleontologia de vertebrados. Em relação à geologiaforam destacados os conteúdos: localização,extensão, origem e evolução, idade e estratigrafiada bacia. Todo o conteúdo foi baseado em livros,revistas, sites e trabalhos publicados em peri

  3. Endothelial haemostatic factors are associated with progression of urinary albumin excretion in clinically healthy subjects

    DEFF Research Database (Denmark)

    Clausen, P; Feldt-Rasmussen, B; Jensen, G;

    1999-01-01

    ), whereas no changes in UAER were seen in subjects with vWF and tPA below the medians. Subjects with high tPA were also characterized by an excess of other cardiovascular risk factors at baseline. No significant differences in these risk factors were present between subjects with high or low vWF. High...... of endothelial dysfunction, predicts a subsequent increase of UAER in patients with diabetes. The aim of this study is to test the hypothesis that high concentrations of vWF as well as other haemostatic factors predict progression of UAER in clinically healthy subjects. UAER was measured together with selected...... markers of haemostatic function-vWF, tissue plasminogen activator (tPA), plasminogen activator inhibitor, factor VII and fibrinogen-in healthy volunteers aged 40-65 years. After a mean follow-up of 4.1 years, 64 of 74 agreed to a re-examination including re-measurement of UAER. Baseline vWF and tPA were...

  4. Um caso multimédia na formação inicial: contributos para o conhecimento sobre o ensino exploratório da Matemática

    OpenAIRE

    Canavarro, Ana Paula

    2013-01-01

    Este artigo tem como foco o uso de casos multimédia na formação inicial de professores e procura analisar o seu contributo para o desenvolvimento do conhecimento didático de futuras professoras acerca do ensino exploratório da Matemática, bem como apreciar as suas perspetivas sobre as mais-valias do caso multimédia utilizado como recurso formativo. Analisam-se questionários e relatórios de treze alunas do Mestrado em Educação Pré-Escolar e Ensino do 1.º Ciclo da Universidade de Évora, que tra...

  5. Common carotid intima-media thickness and von Willebrand factor serum levels in rheumatoid arthritis female patients without cardiovascular risk factors.

    Science.gov (United States)

    Daza, Leonel; Aguirre, Martin; Jimenez, Martin; Herrera, Rafael; Bollain, J J

    2007-04-01

    High atherosclerosis prevalence was found in rheumatoid arthritis (RA), and the von Willebrand factor (vWF) was shown to be a marker for endothelial damage. The aim of this study was to evaluate the association of intima-media thickness of the left common carotid artery with vWF serum levels in rheumatoid arthritis patients without cardiovascular risk factors. We included 55 RA female patients, each with at least 5 years of duration of the disease, and 20 healthy female subjects as members of the control group. The vWF, cholesterol, triglycerides, and the immune variables-rheumatoid factor and reactive C protein-were evaluated. The media thickness and intima-media thickness (IMT) in patients and in the control subjects were assessed by Doppler ultrasound of the left common carotid artery. Although the ages for RA patients and healthy female controls were not different, the IMT of the left common carotid artery (IMT CCA) in rheumatoid arthritis patients was increased in comparison with healthy control measurements, the mean being 0.67 mm (SD 0.18) vs 0.58 mm (SD 0.10) with a p value 0.01. The vWF serum levels showed differences in RA patients from those in control patients, 145.6 (SD 30.08) vs 121.8 (SD 37.17), respectively, with p=0.007. A correlation was also found between vWF with IMT CCA in the RA patients: r=0.390 and p<0.05. We concluded that the measurements of the left common carotid artery intima-media thickness together with the von Willebrand factor serum levels could give valuable information about the artery status and the atherosclerosis process in early stages in patients with rheumatoid arthritis without cardiovascular risk factors.

  6. Effects of increased von Willebrand factor levels on primary hemostasis in thrombocytopenic patients with liver cirrhosis.

    Directory of Open Access Journals (Sweden)

    Andreas Wannhoff

    Full Text Available In patients with liver cirrhosis procoagulant and anticoagulant changes occur simultaneously. During primary hemostasis, platelets adhere to subendothelial structures, via von Willebrand factor (vWF. We aimed to investigate the influence of vWF on primary hemostasis in patients with liver cirrhosis. Therefore we assessed in-vitro bleeding time as marker of primary hemostasis in cirrhotic patients, measuring the Platelet Function Analyzer (PFA-100 closure times with collagen and epinephrine (Col-Epi, upper limit of normal ≤ 165 s or collagen and ADP (Col-ADP, upper limit of normal ≤ 118 s. If Col-Epi and Col-ADP were prolonged, the PFA-100 was considered to be pathological. Effects of vWF on primary hemostasis in thrombocytopenic patients were analyzed and plasma vWF levels were modified by adding recombinant vWF or anti-vWF antibody. Of the 72 included cirrhotic patients, 32 (44.4% showed a pathological result for the PFA-100. They had mean closure times (± SD of 180 ± 62 s with Col-Epi and 160 ± 70 s with Col-ADP. Multivariate analysis revealed that hematocrit (P = 0.027 and vWF-antigen levels (P = 0.010 are the predictors of a pathological PFA-100 test in cirrhotic patients. In 21.4% of cirrhotic patients with platelet count ≥ 150/nL and hematocrit ≥ 27.0%, pathological PFA-100 results were found. In thrombocytopenic (< 150/nL patients with cirrhosis, normal PFA-100 results were associated with higher vWF-antigen levels (462.3 ± 235.9% vs. 338.7 ± 151.6%, P = 0.021. These results were confirmed by multivariate analysis in these patients as well as by adding recombinant vWF or polyclonal anti-vWF antibody that significantly shortened or prolonged closure times, respectively. In conclusion, primary hemostasis is impaired in cirrhotic patients. The effect of reduced platelet count in cirrhotic patients can at least be partly compensated by increased vWF levels. Recombinant vWF could be an alternative to platelet transfusions in the

  7. Surface-secreted von Willebrand factor mediates aggregation of ADP-activated platelets at moderate shear stress: facilitated by GPIb but controlled by GPIIb-IIIa.

    Science.gov (United States)

    Frojmovic, M M; Kasirer-Friede, A; Goldsmith, H L; Brown, E A

    1997-03-01

    We previously showed that ADP activation of washed human platelets in plasma-free suspensions supports aggregation at moderate shear stress (0.4-1.6 Nm-2) in Poiseuille flow. Although most activated platelets expressed maximal fibrinogen-occupied GPIIb-IIIa receptors, aggregation appeared to be independent of bound fibrinogen, but blocked by the hexapeptide GRGDSP. Here, we tested the hypothesis that von Willebrand factor (vWF) secreted and expressed on activated platelets mediates aggregation at moderate shear rates from 300 to 1000 s-1 corresponding to shear stresses from 0.3 to 1.1 Nm-2. Relatively unactivated platelets (Flow cytometric measurements with monoclonal antibody (mAb) 2.2.9 reporting on surface-bound vWF, and with mAb S12 reporting on alpha-granule secreted P-selectin, showed that 65% and 80%, respectively, of all platelets were maximally activated with respect to maximal secretion and surface expression of these proteins. "Resting" washed platelets exhibited both surface-bound vWF and significant P-selectin secretion. We showed that mAbs 6D1 and NMC4, respectively blocking the adhesive domains on the GPIb receptor recognizing vWF, and on the vWF molecule recognizing the GPIb receptor, partially inhibited ADP-induced aggregation under shear in Couette flow, the degree of inhibition increasing with increasing shear stress. In contrast, mAb 10E5, blocking the vWF binding domain on GPIIb-IIIa, essentially blocked all aggregation at the shear rates tested. We conclude that vWF, expressed on ADP-activated platelets, is at least the predominant cross-bridging molecule mediating aggregation at moderate shear stress. There is an absolute requirement for free activated GPIIb-IIIa receptors, postulated to interact with platelet-secreted, surface bound vWF. The GPIb-vWF cross-bridging reaction plays a facilitative role becoming increasingly important with increasing shear stress. Since aurin tricarboxylic acid, which blocks the GPIb binding domain on vWF, was

  8. Réflexions linguistiques et sémiologiques pour une écriture didactique du multimédia de langues Linguistic and "semiologic" reflections to set out a multimedia approach for foreign languages teaching and learning

    Directory of Open Access Journals (Sweden)

    Anne-Laure Foucher

    1998-06-01

    Full Text Available Dans une combinaison originale de domaines souvent envisagés de manière fermée que sont la didactique des langues, la linguistique, la sémiologie et l'ALAO (Apprentissage des Langues Assisté par Ordinateur, nous mettons en avant la nécessité de concevoir l'image multimédia comme un objet composite, lieu véritable d'interactions entre modes iconique, auditif et linguistique. De cette option théorique découle, selon nous, une philosophie qui préside à la conception d'un multimédia pour l'apprentissage des langues. Nous en donnons les grandes lignes sous forme de jalons méthodologiques destinés à une écriture du multimédia en langues.Assuming CALL to need language didactics, assuming didactics to need linguistics and CALL to need minimal " semiologic " reflections, we show how is profitable to adopt a didactic point of view linking linguistic and semiologic aspects in order to examine the contributions to learning of a multimedia approach for foreign languages. To complete these theorical considerations, we propose to set out methodological advice to design a multimedia approach for language learning and teaching.

  9. Confusão do Consumidor no Cenário Multimídia e Multicanal: Definição do Construto e Agenda de Pesquisa

    Directory of Open Access Journals (Sweden)

    Patricia Liebesny Broilo

    2016-03-01

    Full Text Available A crescente oferta de escolha no universo de consumo pode implicar em confusão do consumidor. Frente à falta de uma definição consolidada desse construto, investigou-se a compreensão e conhecimentos acumulados sobre o fenômeno. Utilizou-se o método de teoria fundamentada aplicado a uma revisão sistematizada da literatura, em seleção de 93 artigos publicados na última década. Como resultado, foram identificadas seis compreensões distintas e achados empíricos associados a cada uma delas. Concluiu-se existir uma tendência de compreensão abrangente à trajetória de consumo como um todo, faltando, porém, maior enfoque na confusão relacionada à conectividade do consumidor no cenário multimídia e multicanal. O presente artigo propõe, portanto, uma nova definição do construto e questões a serem exploradas em estudos futuros.

  10. Painel de especialistas e estratégia multimétodos: reflexões, exemplos, perspectivas = Expert panel and multimethods strategy: reflections, examples and perspectives

    Directory of Open Access Journals (Sweden)

    Pinheiro, José Q. (Queiroz

    2013-01-01

    Full Text Available Utilizamos a expressão painel de especialistas para identificar uma técnica de pesquisa empregada em psicologia, administração e ciências sociais em geral. Mostramos sua utilização tradicional em pesquisa, contextos científicos em que tem sido empregada, enfatizando sua aplicação em pesquisas que adotem a estratégia multimétodos, seja na modalidade de técnicas concomitantes ou sequenciais. Para maior clareza, acrescentamos dois exemplos extraídos de nossos estudos na área das relações pessoa-ambiente. O sentido clássico do termo é redefinido para o contexto desta apresentação, na medida em que apresentamos o painel de especialistas como uma das técnicas de coleta de dados propriamente dita, assegurando maior fidedignidade na representação do fenômeno investigado e redução do viés metodológico

  11. Subclinical Atherosclerosis in Patients with Rheumatoid Arthritis and Low Cardiovascular Risk: The Role of von Willebrand Factor Activity.

    Directory of Open Access Journals (Sweden)

    Gorica G Ristić

    Full Text Available To evaluate association between von Willebrand factor (vWF activity, inflammation markers, disease activity, and subclinical atherosclerosis in patients with rheumatoid arthritis (RA and low cardiovascular risk.Above mentioned parameters were determined in blood samples of 74 non-diabetic, normotensive, female subjects, with no dyslipidemia(42 patients, 32 matched healthy controls, age 45.3±10.0 vs. 45.2±9.8 years. Intima-media thickness (IMT was measured bilaterally, at common carotid, bifurcation, and internal carotid arteries. Subclinical atherosclerosis was defined as IMT>IMTmean+2SD in controlsat each carotid level and atherosclerotic plaque as IMT>1.5 mm. Majority of RA patients were on methotrexate (83.3%, none on steroids >10 mg/day or biologic drugs. All findings were analysed in the entire study population and in RA group separately.RA patients with subclinical atherosclerosis had higher vWF activity than those without (133.5±69.3% vs. 95.3±36.8%, p<0.05. Predictive value of vWF activity for subclinical atherosclerosis was confirmed by logistic regression. vWF activity correlated significantly with erythrocyte sedimentation rate, fibrinogen, modified disease activity scores (mDAS28-ESR, mDAS28-CRP, modified Health Assessment Questionnaire (p<0.01 for all, duration of smoking, number of cigarettes/day, rheumatoid factor concentration (p<0.05 for all, and anti-CCP antibodies (p<0.01. In the entire study population, vWF activity was higher in participants with subclinical atherosclerosis (130±68% vs. 97±38%, p<0.05 or atherosclerotic plaques (123±57% vs. 99±45%, p<0.05 than in those without. Duration of smoking was significantly associated with vWF activity (β 0.026, p = 0.039.We demonstrated association of vWF activity and subclinical atherosclerosis in low-risk RA patients as well as its correlation with inflammation markers, all parameters of disease activity, and seropositivity. Therefore, vWF might be a valuable marker of

  12. Implications for collagen I chain registry from the structure of the collagen von Willebrand factor A3 domain complex

    NARCIS (Netherlands)

    Brondijk, T.H.C.; Bihan, D.; Farndale, R.W.; Huizinga, E.G.

    2012-01-01

    Fibrillar collagens, the most abundant proteins in the vertebrate body, are involved in a plethora of biological interactions. Plasma protein von Willebrand factor (VWF) mediates adhesion of blood platelets to fibrillar collagen types I, II, and III, which is essential for normal haemostasis. High a

  13. 冠心病患者vWF基因A1381T多态性分析%Analysis of vWF Gene A1381T Polymorphism in Patients with Coronary Heart Disease

    Institute of Scientific and Technical Information of China (English)

    袁忠海; 侯毅鞠; 李艳; 张慧; 李中言; 李欣; 于东汇

    2011-01-01

    性,冠心病组血浆vWF水平随ABO血型和vWF基因A1381T多态性不同而有明显的不同,尤其AG基因型血浆v岍增高最明显,冠心病组O血型A1381T多态性的AG基因型血浆vWF水平明显高于GG基因型.这些结果对于进一步研究A1381T多态性是否影响vWF基因表达及vWF活性具有一定的参考意义.%This study was purposed to investigate the vWF gene A1381T polymorphism in patients with coronary heart disease (CHD).A case-control study was designed, including 104 continuously hospitalized patients with CHD, aging from 40 to 75 years (average 59 ) and 96 persons underwent physical examination in outpatient department as controls, aging from 39 to 70 years ( average 56).The plasma vWF: Ag level of CHD patients and control persons was detected by ILISA.vWF gene A1381T polymorphism was analyzed by the polymerase chain reaction-restriction fragment length polymorphism and sequencing when it is necessary.The data were grouped by gender, blood group and/or genotype in CHD group and control groups.The difference of plasma vWF level between male and female was analyzed by independent sample t test; one way ANOVA was used to analyze the difference of vWF level between different blood group genotypes, while the factorial design ANOVA was used to test the difference of vWF level in plasma between A1381T genotype and/or ABO blood groups.x2 Crosstabs were used to test the CHD susceptibility.The results showed that the frequencies of GG genotype ( wild type) of vWF gene A1381T polymorphism were 62.5% in CHD group and 67.7% in control group, and the frequencies of AG genotype ( heterozygous variant) were 37.5% in CHD group and 32.3% in control group.x2 Crosstabs showed no significant correlation between vWF gene A1381T polymorphism (AG) and CHD ( OR = 1.258, 95% CI = 0.702 - 2.255, x2 = 0.595,p = 0.440).The plasma vWF level in CHD group was statistically very higher than that in control group(p < 0.001 ), even though the

  14. Functional architecture of Weibel-Palade bodies.

    Science.gov (United States)

    Valentijn, Karine M; Sadler, J Evan; Valentijn, Jack A; Voorberg, Jan; Eikenboom, Jeroen

    2011-05-12

    Weibel-Palade bodies (WPBs) are elongated secretory organelles specific to endothelial cells that contain von Willebrand factor (VWF) and a variety of other proteins that contribute to inflammation, angiogenesis, and tissue repair. The remarkable architecture of WPBs is because of the unique properties of their major constituent VWF. VWF is stored inside WPBs as tubules, but on its release, forms strikingly long strings that arrest bleeding by recruiting blood platelets to sites of vascular injury. In recent years considerable progress has been made regarding the molecular events that underlie the packaging of VWF multimers into tubules and the processes leading to the formation of elongated WPBs. Mechanisms directing the conversion of tightly packaged VWF tubules into VWF strings on the surface of endothelial cells are starting to be unraveled. Several modes of exocytosis have now been described for WPBs, emphasizing the plasticity of these organelles. WPB exocytosis plays a role in the pathophysiology and treatment of von Willebrand disease and may have impact on common hematologic and cardiovascular disorders. This review summarizes the major advances made on the biogenesis and exocytosis of WPBs and places these recent discoveries in the context of von Willebrand disease.

  15. Von Willebrand factor in patients on mechanical circulatory support – a double-edged sword between bleeding and thrombosis

    Science.gov (United States)

    Kaczmarski, Jacek; Pacholewicz, Jerzy; Zakliczynski, Michal; Gasior, Mariusz; Zembala, Marian

    2015-01-01

    Mechanical circulatory support (MCS) is an umbrella term describing the various technologies used in both short- and long-term management of patients with either end-stage chronic heart failure (HF) or acute HF. Most often, MCS has emerged as a bridge to transplantation, but more recently it is also used as a destination therapy. Mechanical circulatory support includes left ventricular assist device (LVAD) or bi-ventricular assist device (Bi-VAD). Currently, 2- to 3-year survival in carefully selected patients is much better than with medical therapy. However, MCS therapy is hampered by sometimes life-threatening complications including bleeding and device thrombosis. Von Willebrand factor (vWF) has two major functions in haemostasis. First, it plays a crucial role in platelet-subendothelium adhesion and platelet-platelet interactions (aggregation). Second, it is the carrier of factor VIII (FVIII) in plasma. Von Willebrand factor prolongs FVIII half-time by protecting it from proteolytic degradation. It delivers FVIII to the site of vascular injury thus enhancing haemostatic process. On one hand, high plasma levels of vWF have been associated with an increased risk of thrombosis. On the other, defects or deficiencies of vWF underlie the inherited von Willebrand disease or acquired von Willebrand syndrome. Here we review the pathophysiology of thrombosis and bleeding associated with vWF. PMID:26702279

  16. Von Willebrand factor in patients on mechanical circulatory support - a double-edged sword between bleeding and thrombosis.

    Science.gov (United States)

    Hudzik, Bartosz; Kaczmarski, Jacek; Pacholewicz, Jerzy; Zakliczynski, Michal; Gasior, Mariusz; Zembala, Marian

    2015-09-01

    Mechanical circulatory support (MCS) is an umbrella term describing the various technologies used in both short- and long-term management of patients with either end-stage chronic heart failure (HF) or acute HF. Most often, MCS has emerged as a bridge to transplantation, but more recently it is also used as a destination therapy. Mechanical circulatory support includes left ventricular assist device (LVAD) or bi-ventricular assist device (Bi-VAD). Currently, 2- to 3-year survival in carefully selected patients is much better than with medical therapy. However, MCS therapy is hampered by sometimes life-threatening complications including bleeding and device thrombosis. Von Willebrand factor (vWF) has two major functions in haemostasis. First, it plays a crucial role in platelet-subendothelium adhesion and platelet-platelet interactions (aggregation). Second, it is the carrier of factor VIII (FVIII) in plasma. Von Willebrand factor prolongs FVIII half-time by protecting it from proteolytic degradation. It delivers FVIII to the site of vascular injury thus enhancing haemostatic process. On one hand, high plasma levels of vWF have been associated with an increased risk of thrombosis. On the other, defects or deficiencies of vWF underlie the inherited von Willebrand disease or acquired von Willebrand syndrome. Here we review the pathophysiology of thrombosis and bleeding associated with vWF.

  17. Animal study of thrombosis detaining needle and changes of vWF and DD%静脉留置针致血栓形成与vWF、DD浓度关系的动物实验研究

    Institute of Scientific and Technical Information of China (English)

    卢孟密; 张丽凤; 廖海涛; 韦义萍

    2014-01-01

    Objective To observe the relations ot vWF,DD concentration and venous thrombosis caused by detaining needle of different time.Sensitive indicators for early prediction of venous thrombosis would be seeked so as to provide theoretical and experimental basis for the selection of intervention time.Methods The detaining needle were placed in the vein of rabbit ears with transfusion.The changes of vWF and DD concentration for the mannitol group and the saline group were measured in different retention time,while the venous thrombosis caused by detaining needle was observed pathologically.Results The results of serological test:(1)vWF concentration:when the needle was detained for 1 day,the vWF concentration of two groups peaked.(2)DD concentration:after the needler was set,the DD concentration of both groups was higher than those before detaining needler.When the needle was detained for 1 day and 3 days,the DD concentration was significantly different from those before using detaining needle.Result of pathological observation:When the needle was detained for 1 day,the venous throm-bosis rate was 100% for both groups with a moderate degree of thrombosis.Conclusions Detection of the concentration of vWF and DD has certain reference value for predicting detaining needle-induced venous thrombosis.In order to prevent venous thrombosis,intervention should be carried out as soon as possible after detaining needle was set.%目的 探讨静脉留置针不同留置时间静脉血栓形成与vWF、DD浓度变化的关系,寻找早期预测静脉血栓形成的敏感指标,为选择干预时机提供理论和实验依据.方法 选择36只实验兔随机分为甘露醇组和生理盐水组各18只,在兔耳缘静脉置入留置针并留置输液,分别测定甘露醇组和生理盐水组不同留置时间vWF和DD的浓度变化,同时病理学观察置针血管静脉血栓形成情况.结果 血清学检测结果:(1)vWF浓度:置针1d时,2组vWF浓度达到高峰.(2)DD

  18. Expression, purification, and characterization of protective MPT64 antigen protein and identification of its multimers isolated from nontoxic Mycobacterium tuberculosis H37Ra.

    Science.gov (United States)

    Chu, Teng-Ping J; Yuann, Jeu-Ming P

    2011-05-01

    MPT64, a secreted protein of Mycobacterium tuberculosis (MTB), stimulates the immune reactions within cells and is a protective antigen that is lost by the bacilli Calmette-Guérin (BCG) vaccine during propagation. To minimize the toxicity caused by MTB, we used the MPT64 gene encoded by nontoxic H37Ra MTB to carry out genetic expansion via polymerase chain reaction and gene clone MPT64. The plasmid DNA encoded MPT64 was expressed at 20°C for 22 H, and a large quantity of MPT64 was obtained. In the absence of urea, MPT64 multimers with subunits being covalently connected via disulfide bonds were detected by Western blot showing strong protein-protein interactions, as evidenced by the formation of MPT64 tetramers. Finally, with urea of decreasing concentrations, we refolded MPT64 purified in the presence of urea and determined its secondary structures using circular dichroism. MPT64 was found to contain 2.2% α-helix, 50.9% β-sheet, 19.5% turn, and 27.4% random coil. The molecular weight of MPT64 was determined by a matrix-assisted laser desorption ionization-time of flight mass spectrometer and found to be 23,497 Da, very close to the theoretical molecular weight of MPT64. The results presented here provide a sound basis for future biochemical and biophysical studies of MPT64 or any other proteins encoded by nontoxic H37Ra MTB. Copyright © 2011 International Union of Biochemistry and Molecular Biology, Inc.

  19. The vitamin K oxidoreductase is a multimer that efficiently reduces vitamin K epoxide to hydroquinone to allow vitamin K-dependent protein carboxylation.

    Science.gov (United States)

    Rishavy, Mark A; Hallgren, Kevin W; Wilson, Lee A; Usubalieva, Aisulu; Runge, Kurt W; Berkner, Kathleen L

    2013-11-01

    The vitamin K oxidoreductase (VKORC1) recycles vitamin K to support the activation of vitamin K-dependent (VKD) proteins, which have diverse functions that include hemostasis and calcification. VKD proteins are activated by Glu carboxylation, which depends upon the oxygenation of vitamin K hydroquinone (KH2). The vitamin K epoxide (KO) product is recycled by two reactions, i.e. KO reduction to vitamin K quinone (K) and then to KH2, and recent studies have called into question whether VKORC1 reduces K to KH2. Analysis in insect cells lacking endogenous carboxylation components showed that r-VKORC1 reduces KO to efficiently drive carboxylation, indicating KH2 production. Direct detection of the vitamin K reaction products is confounded by KH2 oxidation, and we therefore developed a new assay that stabilized KH2 and allowed quantitation. Purified VKORC1 analyzed in this assay showed efficient KO to KH2 reduction. Studies in 293 cells expressing tagged r-VKORC1 revealed that VKORC1 is a multimer, most likely a dimer. A monomer can only perform one reaction, and a dimer is therefore interesting in explaining how VKORC1 accomplishes both reactions. An inactive mutant (VKORC1(C132A/C135A)) was dominant negative in heterodimers with wild type VKORC1, resulting in decreased KO reduction in cells and carboxylation in vitro. The results are significant regarding human VKORC1 mutations, as warfarin-resistant patients have mutant and wild type VKORC1 alleles. A VKORC1 dimer indicates a mixed population of homodimers and heterodimers that may have different functional properties, and VKORC1 reduction may therefore be more complex in these patients than appreciated previously.

  20. ADAMTS13 content in plasma-derived factor VIII/von Willebrand factor concentrates.

    Science.gov (United States)

    Peyvandi, Flora; Mannucci, Pier M; Valsecchi, Carla; Pontiggia, Silvia; Farina, Claudio; Retzios, Anastassios D

    2013-10-01

    Thrombotic thrombocytopenic purpura (TTP) is a microangiopathy syndrome caused by a congenital or acquired deficiency of ADAMTS13, a plasma metalloprotease that cleaves von Willebrand factor (VWF) and thus prevents the formation of platelet-rich thrombi in the microcirculation. TTP can be fatal if not appropriately and timely treated with the infusion of fresh frozen plasma (FFP) or exchange plasmapheresis, that reverse the process of microangiopathy by removing anti-ADAMTS13 autoantibodies and replacing functional ADAMTS13. The treatment of TTP with FFP is not free from risks and must be administered in hospitals or clinics, owing to the substantial amount of plasma volume infused or exchanged and the frequent need of catheter application. Moreover, most FFPs are not subjected to treatments to remove or inactivate blood-borne infectious agents. A number of recent reports indicate that certain plasma-derived VWF-factor VIII (FVIII) concentrates are clinically effective in the treatment of congenital TTP. In this study, we measured ADAMTS13 levels in various plasma-derived VWF-FVIII concentrates, showing that Koate(®) -DVI (Grifols), contained relatively high amounts of ADAMTS13 and that Alphanate(®) (Grifols) was the closest other product in terms of protease content. Koate(®) -DVI contains, on average (five lots tested), 0.091 ± 0.007 Units of ADAMTS13 activity per IU of FVIII. On the basis of this analysis and other reports of VWF-FVIII concentrate utilization in congenital TTP, potential dosing, and future clinical developments are discussed.

  1. von Willebrand factor antigen levels in plasma of patients with malignant breast disease

    Directory of Open Access Journals (Sweden)

    L.M. Röhsig

    2001-09-01

    Full Text Available von Willebrand factor (vWF is a protein that mediates platelet adherence to the subendothelium during primary hemostasis. High plasma vWF concentrations have been reported in patients with various types of cancer, such as head and neck, laryngeal and prostatic cancer, probably representing an acute phase reactant. In the present study we determined the plasma levels of vWF antigen (vWF:Ag by quantitative immunoelectrophoresis in 128 female patients with breast cancer as well as in 47 women with benign breast disease and in 27 healthy female controls. The levels of vWF:Ag were 170.7 ± 78 U/dl in patients with cancer, 148.4 ± 59 U/dl in patients with benign disease and 130.6 ± 45 U/dl in controls (P<0.005. We also detected a significant increase in the levels of vWF:Ag (P<0.0001 in patients with advanced stages of the disease (stage IV = 263.3 ± 113 U/dl, stage IIIB = 194.0 ± 44 U/dl as compared to those with earlier stages of the disease (stage I = 155.3 ± 65 U/dl, stage IIA = 146.9 ± 75 U/dl. In conclusion, vWF levels were increased in plasma of patients with malignant breast disease, and these levels correlated with tumor progression.

  2. Venous thromboembolism in patients with Cushing's syndrome: need of a careful investigation of the prothrombotic risk profile.

    Science.gov (United States)

    Koutroumpi, S; Daidone, V; Sartori, M T; Cattini, M G; Albiger, N M; Occhi, G; Ferasin, S; Frigo, A; Mantero, F; Casonato, A; Scaroni, C

    2013-06-01

    A high incidence of venous thromboembolic (VTE) complications has been reported in Cushing's syndrome (CS), mostly post-operatively and attributable to hypercoagulability. The prevalence of symptomatic VTE was investigated retrospectively in 58 consecutive CS patients in relation to acquired and genetic thrombotic risk factors. Eight CS patients (14 %) developed VTE (group A), 3 of them related and 5 unrelated to surgery. These patients had higher urinary free cortisol (p = 0.01) and VWF levels (p = 0.02) than the 50 patients without VTE (group B), as well an increase in the hemostatically more efficient, high-molecular-weight VWF multimers (p = 0.002). Factor V Leiden and the prothrombin gene 20210A variants (the most common inherited thrombophilic defects) were more represented in group A than in group B, as was the genotype GCAG/GCAG of the VWF gene promoter, known to hyperinduce VWF upregulation under cortisol excess. All but one of the patients with VTE unrelated to surgery had at least four acquired and at least one inherited risk factor. Severe hypercortisolism and VWF levels with increased haemostatic activity are strongly associated with VTE in CS. VTE episodes unrelated to surgery are attributable to the synergistic action of acquired and inherited thrombotic risk factors. Based on these observations, we believe that severely affected CS patients should be screened for coagulation disorders and receive antithrombotic prophylaxis whenever they have concomitant prothrombotic risk factors.

  3. The effect of exercise on von Willebrand factor and ADAMTS-13 in individuals with type 1 and type 2B von Willebrand disease

    NARCIS (Netherlands)

    Stakiw, J.; Bowman, M.; Hegadorn, C.; Pruss, C.; Notley, C.; Groot, E.; Lenting, P. J.; Rapson, D.; Lillicrap, D.; James, P.

    2008-01-01

    Background: The effect of exercise on von Willebrand factor (VWF) and ADAMTS-13 levels in individuals with von Willebrand disease (VWD) has never been reported. Objectives: The aim was to quantify the effect of a standardized exercise protocol on individuals with type 1 and type 2B VWD. Patients/met

  4. Magnetic-activated cell sorting of TCR-engineered T cells, using tCD34 as a gene marker, but not peptide-MHC multimers, results in significant numbers of functional CD4+ and CD8+ T cells.

    Science.gov (United States)

    Govers, Coen; Berrevoets, Cor; Treffers-Westerlaken, Elike; Broertjes, Marieke; Debets, Reno

    2012-06-01

    T cell-sorting technologies with peptide-MHC multimers or antibodies against gene markers enable enrichment of antigen-specific T cells and are expected to enhance the therapeutic efficacy of clinical T cell therapy. However, a direct comparison between sorting reagents for their ability to enrich T cells is lacking. Here, we compared the in vitro properties of primary human T cells gene-engineered with gp100(280-288)/HLA-A2-specific T cell receptor-αβ (TCRαβ) on magnetic-activated cell sorting (MACS) with various peptide-MHC multimers or an antibody against truncated CD34 (tCD34). With respect to peptide-MHC multimers, we observed that Streptamer(®), when compared with pentamers and tetramers, improved T cell yield as well as level and stability of enrichment, of TCR-engineered T cells (>65% of peptide-MHC-binding T cells, stable for at least 6 weeks). In agreement with these findings, Streptamer, the only detachable reagent, revealed significant T cell expansion in the first week after MACS. Sorting TCR and tCD34 gene-engineered T cells with CD34 monoclonal antibody (mAb) resulted in the most significant T cell yield and enrichment of T cells (>95% of tCD34 T cells, stable for at least 6 weeks). Notably, T cells sorted with CD34 mAb, when compared with Streptamer, bound about 2- to 3-fold less peptide-MHC but showed superior antigen-specific upregulated expression of CD107a and production of interferon (IFN)-γ. Multiparametric flow cytometry revealed that CD4(+) T cells, uniquely present in CD34 mAb-sorted T cells, contributed to enhanced IFN-γ production. Taken together, we postulate that CD34 mAb-based sorting of gene-marked T cells has benefits toward applications of T cell therapy, especially those that require CD4(+) T cells.

  5. Dogs with hearth diseases causing turbulent high-velocity blood flow have changes in patelet function and von Willebrand factor multimer distribution

    DEFF Research Database (Denmark)

    Tarnow, Inge; Kristensen, Annemarie Thuri; Olsen, Lisbeth Høier

    2005-01-01

    and echocardiography were performed in all dogs. PFA100 closure times (the ability of platelets to occlude a hole in a membrane at high shear rates), platelet activation markers (plasma thromboxane B2 concentration, platelet surface P-selectin expression), platelet aggregation (in whole blood and platelet-rich plasma...

  6. Effect of captopril on vWF in radiation renal injury%卡托普利对放射性肾损伤中血管性血友病因子的影响

    Institute of Scientific and Technical Information of China (English)

    张银铃; 曹永珍; 张文学; 耿凯; 王克强; 周琰; 毛羽; 魏健; 李素芬

    2013-01-01

    .05).且卡托普利+照射组的大鼠肾脏未出现明显的病理变化.结论 卡托普利能够降低放射性肾损伤大鼠血浆和肾小球中的vWF,并有效地保护了肾脏.%Objective To explore the effect of captopril on plasma and glomerular vWF in radiation renal injury.Methods A total of 96 male SD rats weighing 280-300 g were randomly divided into three groups:control group (n =20),radiation alone group (n =38),captopril + radiation group (n =38).The latter two groups were subjected to a single-dose of 12 Gy 5 MeV electron rays to the kidneys.The captopril + radiation group began to receive captopril at the concentration of 0.38-0.50 mg/ml at 24 h before irradiation.The blood and urine samples were collected in the radiation alone and captopril +radiation groups at 48 h,1,2,4,8,16,24 weeks after irradiation (six rats per time in each group).Except for the 2 weeks after irradiation,kidneys were removed in the two groups at other point in time(six rats per time in each group).The kidneys,blood and urine samples were collected in the control group at 48 h,4,24 weeks after irradiation (six rats per time in each group).The glomerular vWF was detected by immunohistochemistry,collagen deposition in glomeruli by Sirius Red F3B in saturated carbazotic acid stain and plasma vWF and cystatin C levels by ELISA.Roche biochemical automatic analyzer and roche specific reagent were used to examine urine protein and urine creatinine,and urine protein clearance by urine protein and urine creatinine were calculated.The renal morphological feature was observed under light microscope after HE staining.Results In radiation alone group,glomerulus vWF increased gradually at 16 and 24 weeks after irradiation (t =3.53-6.95,5.71-12.66,P < 0.05),collagen deposition in glomerular also gradually increased at 8,16 and 24 weeks after irradiation(t =3.03-5.13,3.48-4.68,4.68-9.03,P < 0.05),and there was an obvious positive correlation between collagen and vWF (r =0.819,P <0

  7. Human von Willebrand factor/factor VIII concentrates in the management of pediatric patients with von Willebrand disease/hemophilia A

    OpenAIRE

    Castaman G; Linari S

    2016-01-01

    Giancarlo Castaman, Silvia Linari Department of Oncology, Center for Bleeding Disorders, Careggi University Hospital, Florence, ItalyAbstract: Several plasma-derived intermediate and high-purity concentrates containing von Willebrand factor (VWF) and factor VIII (FVIII) are currently available. The main role of these products in the management of pediatric the population is represented by the replacement therapy in patients with severe or intermediate forms of von Willebrand disease, in whom ...

  8. Consumo sostenible en organizaciones: enfoques multimétodo para estudiar la conducta proambiental en lugares de trabajo = Consumo sustentável nas organizações: abordagens multimétodo de estudo do comportamento pró-ambiental no local de trabalho = Sustainable consumption in organizations: multi-method approaches to the study of pro-environmental behavior in the workplace

    Directory of Open Access Journals (Sweden)

    Garcia-Mira, Ricardo

    2014-01-01

    Full Text Available Este artigo tem como objetivo apresentar brevemente o projeto LOCAW (Low Carbon at Work, um projecto financiado pelo 7º Programa Cadro da União Europeia que visa promover a compreensão das barreiras e melhorar estilos de vida sustentáveis através da investigação sobre os determinantes do comportamento nas práticas cotidianas e no local de trabalho. Este projecto centra-se em seis grandes organizações que ocupam diferentes posições no debate sobre a abordagem da sustentabilidade. Um enfoque multimétodo é apresentado, com ênfase especial sobre o uso de cenários de back-casting como metodologia inovadora que pode ajudar a projetar padrões sustentáveis de mudança nas organizações. Finalmente, este trabalho apresenta os resultados preliminares da primeira parte do projeto, que incide sobre o diagnóstico das práticas cotidianas no ambiente de trabalho. Tanto a metodologia de cenários de back-casting e os resultados preliminares serão apresentados exclusivamente relacionados com o estudo de caso espanhol, ou seja, uma universidade

  9. Von Willebrand factor and coagulation factor VIII in Moyamoya disease associated with Graves' disease: A case report

    Science.gov (United States)

    Ren, Shou-Chen; Gao, Bao-Qin; Yang, Wei-Li; Feng, Wei-Xin; Xu, Jian; Li, Shao-Wu; Wang, Yong-Jun

    2016-01-01

    The present study reported the case of a Chinese boy who was diagnosed with Moyamoya disease (MMD) associated with Graves' disease (GD). An overactivation of von Willebrand factor (vWF) and coagulation factor VIII (FVIII) was identified in the plasma of the patient. Thiamazole and metoprolol treatment was thus administrated. After 2 months of treatment, the patient's thyroid function returned to normal and the neurological symptoms improved gradually. At the same time, the activities of vWF and FVIII were depressed. During the 20-month follow-up, information regarding the neurological symptoms, cerebrovascular imaging, thyroid function, thyroid autoantibodies and coagulation parameters was collected. High levels of thyroid autoantibodies persisted throughout the follow-up period, while other coagulation parameters remained in the normal range. In conclusion, considering the vital role of vWF and FVIII in vascular diseases, it is hypothesized that these two factors may serve an important role in the occurrence of GD associated with MMD. PMID:27882137

  10. Allelic associations of two polymorphic microsatellites in intron 40 of the human von Willebrand factor gene

    Energy Technology Data Exchange (ETDEWEB)

    Pena, S.D.J.; De Souza, K.T. (Nucleo de Genetica Medica de Minas Gerais, Belo Horizonte (Brazil)); De Andrade, M.; Chakraborty, R. (Univ. of Texas Graduate School of Biomedical Sciences, Houston, TX (United States))

    1994-01-18

    At intron 40 of the von Willebrand factor (vWF) gene, two GATA-repeat polymorphic sites exist that are physically separated by 212 bp. At the first site (vWF1 locus), seven segregating repeat alleles were observed in a Brazilian Caucasian population, and at the second (vWF2 locus) there were eight alleles, detected through PCR amplifications of this DNA region. Haplotype analysis of individuals revealed 36 different haplotypes in a sample of 338 chromosomes examined. Allele frequencies between generations and gender at each locus were not significantly different, and the genotype frequencies were consistent with their Hardy-Weinberg expectations. Linkage disequilibrium between loci is highly significant with positive allele size association; that is, large alleles at the loci tend to occur together, and so do the same alleles. Variability at each locus appeared to have arisen in a stepwise fashion, suggesting replication slippage as a possible mechanism of production of new alleles. However, the authors observed an increased number of haplotypes, in contrast with the predictions of a stepwise production of variation in the entire region, suggesting some form of cooperative changes between loci that could be due to either gene conversion, or a common control mechanism of production of new variation at these repeat polymorphism sites. The high degree of polymorphism (gene diversity values of 72% and 78% at vWF1 and vWF2, respectively, and of 93% at the haplotype level) makes these markers informative for paternity testing, genetic counseling, and individual-identification purposes.

  11. Évaluer l'impact des stéréotypes dans les supports multimédia Evaluating the impact of stereotypes in multimedia tools

    Directory of Open Access Journals (Sweden)

    Joëlle Aden

    2006-12-01

    Full Text Available La navigation sur Internet offre aux enseignants de langues vivantes un kaléidoscope de supports authentiques variés, qui reflète des points de vues multi perspectivistes sur les réalités socioculturelles des groupes qui utilisent la langue apprise. La navigation est probablement un des usages du multimédia les plus développés dans l'enseignement de masse en langues. Il suffit, pour s'en convaincre, de parcourir les méthodes éditées ces cinq dernières années pour voir que l'outil multimédia est surtout sollicité pour faire des recherches sur des thèmes étudiés en classe et de nombreux travaux ont mis en avant le potentiel de cet outil. Dans les classes, l'idée selon laquelle il est indispensable de laisser les élèves naviguer sans guidage dans l'hypertexte a très vite cédé la place à la nécessité de réduire l'accès aux ressources Internet à l'intérieur de cadres contraints, en général à partir de sites présélectionnés à cet effet en vue de réaliser des tâches dans la langue d'étude. Aujourd'hui, dans la formation en langue des enseignants, deux types de dispositifs Tice (technologies de l'information et de la communication pour l'éducation occupent la première place : les cyberenquêtes (webquests et les échanges par courrier électronique, mais à nouveau, les limites des cyberenquêtes sont perceptibles, elles recréent des contraintes formelles dans lesquelles on force les repérages. Dans cet article, nous nous intéresserons à un dispositif[1] intégrant des activités plus libres de navigation et de choix de supports vidéo que nous avons réintégré dans une démarche culturelle en classe. Nous considérerons la façon dont la variété de ces supports, libres et contraints, influe sur la construction des repères identitaires des élèves. Nous étudierons ce phénomène en lien avec les mécanismes cognitifs et socio discursifs que les apprenants mettent en œuvre lorsqu'ils sont exposés

  12. Endothelial cell processing and alternatively spliced transcripts of factor VIII: potential implications for coagulation cascades and pulmonary hypertension.

    Directory of Open Access Journals (Sweden)

    Claire L Shovlin

    Full Text Available BACKGROUND: Coagulation factor VIII (FVIII deficiency leads to haemophilia A. Conversely, elevated plasma levels are a strong predictor of recurrent venous thromboemboli and pulmonary hypertension phenotypes in which in situ thromboses are implicated. Extrahepatic sources of plasma FVIII are implicated, but have remained elusive. METHODOLOGY/PRINCIPAL FINDINGS: Immunohistochemistry of normal human lung tissue, and confocal microscopy, flow cytometry, and ELISA quantification of conditioned media from normal primary endothelial cells were used to examine endothelial expression of FVIII and coexpression with von Willebrand Factor (vWF, which protects secreted FVIII heavy chain from rapid proteloysis. FVIII transcripts predicted from database mining were identified by RT-PCR and sequencing. FVIII mAb-reactive material was demonstrated in CD31+ endothelial cells in normal human lung tissue, and in primary pulmonary artery, pulmonary microvascular, and dermal microvascular endothelial cells. In pulmonary endothelial cells, this protein occasionally colocalized with vWF, centered on Weibel Palade bodies. Pulmonary artery and pulmonary microvascular endothelial cells secreted low levels of FVIII and vWF to conditioned media, and demonstrated cell surface expression of FVIII and vWF Ab-reacting proteins compared to an isotype control. Four endothelial splice isoforms were identified. Two utilize transcription start sites in alternate 5' exons within the int22h-1 repeat responsible for intron 22 inversions in 40% of severe haemophiliacs. A reciprocal relationship between the presence of short isoforms and full-length FVIII transcript suggested potential splice-switching mechanisms. CONCLUSIONS/SIGNIFICANCE: The pulmonary endothelium is confirmed as a site of FVIII secretion, with evidence of synthesis, cell surface expression, and coexpression with vWF. There is complex alternate transcription initiation from the FVIII gene. These findings provide a

  13. Evaluation of a multimedia online tool for teaching bronchial hygiene to physical therapy students Avaliação de um recurso multimídia para ensino de higiene brônquica para estudantes de fisioterapia

    Directory of Open Access Journals (Sweden)

    Cibele C. B. Marques da Silva

    2012-02-01

    Full Text Available BACKGROUND: Advances in information technology have been widely used in teaching health care professionals. The use of multimedia resources may be important for clinical learning and we are not aware of previous reports using such technology in respiratory physical therapy education. Objectives: Our approach was to evaluate a conventional bronchial hygiene techniques (BHTs course with an interactive online environment, including multimedia resources. METHODS: Previous developed audiovisual support material comprised: physiology, physiopathology and BHTs, accessible to students through the Internet in conjunction with BHTs classes. Two groups of students were compared and both attended regular classes: the on-line group (n=8 received access to online resources, while the control group (n=8 received conventional written material. Student's performance was evaluated before and after the course. RESULTS: A preliminary test (score 0 to 10 was applied before the beginning of the course, showing that the initial knowledge of both groups was comparable [online, 6.75 (SD=0.88 vs. control, 6.125 (SD=1.35; p>0.05]. Two weeks after the end of the course, a second test showed that the online group performed significantly better than the control group [respectively, 7.75 (SD=1.28 vs. 5.93 (SD=0.72; p>0.05]. CONCLUSIONS: The use of a multimedia online resource had a positive impact on student's learning in respiratory therapy field in which instrumental and manual resources are often used and can be explored using this technology.CONTEXTUALIZAÇÃO: As novas tecnologias da informação têm sido amplamente utilizadas no ensino em saúde. O uso de recursos multimídia pode ser importante para o aprendizado clínico, no entanto não há descrição na literatura da aplicação e relevância desses recursos para o ensino de fisioterapia respiratória. OBJETIVOS: Avaliar o impacto de um recurso didático multimídia no ensino de manobras de higiene brônquica (MHB

  14. Characterization of bitiscetin-2, a second form of bitiscetin from the venom of Bitis arietans : comparison of its binding site with the collagen-binding site on the von Willebrand factor A3-domain

    NARCIS (Netherlands)

    Obert, B.; Romijn, R. A.; Houllier, A.; Huizinga, E. G.; Girma, J. P.

    2006-01-01

    Background: Bitiscetin, a heterodimeric snake venom protein purified from Bitis arietans, binds to the A1 domain of von Willebrand factor (VWF) and induces binding of this domain to platelet glycoprotein (GP) Ib. We previously purified a distinct form of dimeric bitiscetin (herein called bitiscetin-

  15. Characterization of bitiscetin-2, a second form of bitiscetin from the venom of Bitis arietans : comparison of its binding site with the collagen-binding site on the von Willebrand factor A3-domain

    NARCIS (Netherlands)

    Obert, B.; Romijn, R. A.; Houllier, A.; Huizinga, E. G.; Girma, J. P.

    2006-01-01

    Background: Bitiscetin, a heterodimeric snake venom protein purified from Bitis arietans, binds to the A1 domain of von Willebrand factor (VWF) and induces binding of this domain to platelet glycoprotein (GP) Ib. We previously purified a distinct form of dimeric bitiscetin (herein called bitiscetin-

  16. Analyse d’applications multimédias pour un usage pédagogique. À la recherche de l’intentionnalité partagée Analyse d’applications multimédias pour un usage pédagogique. À la recherche de l’intentionnalité partagée

    Directory of Open Access Journals (Sweden)

    Didier Paquelin

    2002-03-01

    Full Text Available Développer des usages pédagogiques d’applications multimédias interactives nécessite que l’on s’approprie ces objets technologiques conçus par d’autres. Ressources pédagogiques porteuses d’intentionnalité d’apprentissage, elles requièrent de nouveaux modes d’approche, de lecture, d’appropriation. Là où les repères habituels du livre, du manuel, du vidéogramme ne suffisent plus à établir un choix, l’enseignant, le formateur est amené à se construire un nouveau cadre de référence pour interpréter ces oeuvres. Cet article propose une démarche d’analyse structuraliste et intentionnelle, qui vise à identifier et comprendre l’activité d’apprentissage proposée par le ou les concepteurs.Pedagogical uses of interactive multimedia applications cannot be developed as long as we have not managed to make ours such technological objects designed by others. They are pedagogical resources that carry an intention to trigger learning and request new ways of approaching, reading and mastering the material. Teachers and trainers are led to build new reference frameworks up in order to make sense of them. The markers they are used to with books or video works turn out to be inadequate and cannot be relied upon when selecting materials. The article suggests a structuralist and intentional analytical process that aims at identifying and understanding the learning activity the designers put forward.

  17. Plasma-derived versus recombinant factor concentrates in PUPs: a never ending debate?

    Science.gov (United States)

    Berntorp, Erik

    2017-01-31

    Inhibitor development in haemophilia is a serious complication to treatment with factor concentrates. Since the advent of more pure products, especially developed using recombinant DNA technology, some studies have shown an increased incidence of inhibitors in previously untreated patients (PUPs) receiving recombinant products whereas plasma-derived concentrates sometimes have been claimed to have a protective role, probably due to the content of von Willebrand factor (VWF). In fact, experiments indicate that the VWF may block uptake of factor VIII into macrophages for further processing to the immune system. Also, a competition between VWF and inhibitor binding to the C2 domain of factor VIII has been suggested. Recently, large cohort and surveillance studies have created a vigorous debate about the role of product class for inhibitor development as results have been conflicting. The only randomised prospective study, the SIPPET study, was published in 2016, and substantiated previous reports claiming that plasma derived concentrates give less inhibitors in patients with severe haemophilia A, previously not exposed to factor VIII. The debate will continue.

  18. Produção de multimídia e acessibilidade em cursos de aprendizagem a distância/Multimedia production and accessibility on distance learning courses

    Directory of Open Access Journals (Sweden)

    Joni A. Amorim

    2009-06-01

    Full Text Available Estudantes online que são surdos podem encontrar diferentes barreiras em cursos baseados na Web incluindo falta de imagens relacionadas ao conteúdo em páginas tomadas por texto. As diferentes barreiras podem diminuir a compreensão para pessoas cuja primeira língua seja a linguagem de sinais ao invés da linguagem escrita, um desafio para pesquisadores e professores interessados em desenvolver conteúdo multimídia. A combinação de texto, imagem, áudio e vídeo foi potencializada devido à convergência digital e passa a caracterizar os textos virtuais. O uso de multimídia agora permite diferentes efeitos na elaboração de significados. Nesta perspectiva de mudanças constantes, este artigo busca discutir alguns dos muitos desafios para o oferecimento de Cursos de Graduação em larga escala, apresentando algumas das características dos Cursos de Graduação em Letras-Libras. Também se discute a acessibilidade de conteúdo educacional digital multimídia no contexto de um projeto em andamento na UNICAMP.Online students who are deaf may encounter different barriers on Web based courses including lack of content-related images in pages full of text. The different barriers can slow comprehension for people whose first language may be a sign language instead of a written language, a challenge for researchers and teachers interested in developing multimedia content. The intermix of text, image, audio, and video has been increased due to the digital convergence and characterize the virtual texts. Multimedia usage now brings different effects on meaning making. In this perspective, this paper intends to discuss some of the many challenges in the offer of large scale undergraduate courses presenting some characteristics of a course on the Brazilian Sign Language. The paper discusses educational digital multimedia content accessibility in the context of an ongoing project at UNICAMP.

  19. "Amor e sexo: mitos, verdades e fantasias": jovens avaliam potencial de material multimídia educativo em saúde "Love and sex: myths, truths and fantasies": youth evaluation of the multimedia resource as educational health material

    Directory of Open Access Journals (Sweden)

    Sonia Maria Figueira Mano

    2009-01-01

    Full Text Available A educação sexual na escola é prática defendida e prescrita pelo Ministério da Educação nos Parâmetros Curriculares Nacionais como eixo transversal ao currículo. O tema é complexo e a proposta expressa demandas específicas, como a formação dos professores e materiais educativos adequados. O Museu da Vida, COC/Fiocruz, desenvolveu o multimídia «Amor e sexo: mitos, verdades e fantasias» e, neste artigo, apresenta a avaliação efetuada por 36 alunos do Ensino Médio de escolas públicas do Rio de Janeiro sobre o produto. A avaliação permitiu identificar o multimídia como recurso educativo capaz de promover o tema sexualidade em situações de aprendizagem. Um recurso do multimídia, denominado Caderno de Perguntas, mostrou-se como espaço de interlocução entre os jovens, permitindo troca anônima de dúvidas e ideias, e alimentando um banco de dados que permite aos professores e pesquisadores conhecerem melhor o pensamento dos adolescentes.Sex education in schools is advised and agreed as a universal theme in the National Curriculum of the Brazilian Education Ministry. This subject is complex and the proposal expresses specific needs, such as teacher training and the support of educational materials. The Museum of Life, COC/Fiocruz, developed the multimedia resource, "Love and Sex: myths, truths and fantasies" and this study presents the results of the evaluation made by 36 high school students from public schools, in Rio de Janeiro about the multimedia resource. The evaluation identified it as an educational resource, able to promote dialogue and support the the theme sexuality in teaching situations. A multimedia resource, called Answers Notebook, gives a dialogue space between adolescents, allowing anonymity in the exchange of doubts and ideas, and feeding into a database that allow teachers and professionals to know better how adolescents think.

  20. Representação da Estruturação de Segmentos de Objetos de Aprendizagem Multimídia: Uma Abordagem Baseada em Meta-modelos de Conteúdo

    Directory of Open Access Journals (Sweden)

    Edmar Welington Oliveira

    2009-06-01

    Full Text Available No contexto de e-learning, o desenvolvimento de materiais de aprendizagem, principalmente os que incorporam multimídia, é visto como um processo caro e demorado. Assim, há um enfoque na reutilização, que é obtida através da abordagem de orientação a objetos, resultando nos Objetos de Aprendizagem (OAs. Entretanto, atualmente, OAs são estruturados como arquivos multimídia e, portanto, seu reuso se dá como um todo, limitando seu aproveitamento e o retorno de investimento sobre seu desenvolvimento. Por outro lado, observa-se que vários OAs multimídia já foram desenvolvidos e um esforço em refazê-los seria inviável. Além disso, OAs são agrupados no intuito de formar aulas e/ou cursos e a semântica aplicada a este agrupamento, bem como a semântica aplicada na construção dos próprios OAs se perde, dificultando o compartilhamento de materiais instrucionais entre diferentes desenvolvedores de conteúdo, grupos de pesquisa ou instituições. Neste sentido, o trabalho apresentado neste artigo propõe uma representação da estrutura de segmentação do conteúdo presente nos OAs existentes. De modo a permitir o compartilhamento destes OAs e o reuso dos segmentos segundo a estruturação de seu conteúdo, meta-modelos de conteúdos guiam a segmentação e são representados em OWL, a linguagem para ontologias definida como padrão pelo W3C. Entretanto, como diferentes meta-modelos podem ser definidos por diferentes grupos de usuário, mapeamentos entre os próprios meta-modelos e entre conteúdos e outros meta-modelos devem ser considerados. A arquitetura de representação desta segmentação de OAs baseada em meta-modelos de conteúdo é apresentada neste artigo e um protótipo e um estudo de caso apresentam a funcionalidade da arquitetura proposta.

  1. A perspective on the measurement of ADAMTS13 in thrombotic thrombocytopaenic purpura.

    Science.gov (United States)

    Pimanda, John E; Chesterman, Colin N; Hogg, Philip J

    2003-04-01

    The recent discovery of the von Willebrand Factor (vWF) cleaving protease (ADAMTS13) and the association of its deficiency with thrombotic thrombocytopaenic purpura (TTP) has generated both enormous interest and considerable confusion. Ultra large von Willebrand Factor (UL vWF) multimers are present in the plasmas of patients with chronic relapsing TTP in remission but disappear during an attack. This observation led to the recognition that UL vWF multimers precipitate the thrombotic occlusion of arterioles, a feature that characterizes TTP. Multiple mutations in ADAMTS13 are associated with congenital TTP and neutralizing autoantibodies have been demonstrated in the acquired TTP syndrome. Although a number of functional assays for this enzyme have been described, the more rigorously evaluated assays are difficult to perform outside a research laboratory. There is also an enduring uncertainty about the specificity of ADAMTS13 deficiency for the diagnosis of acquired TTP and a perception that the result does not alter patient management. The cloning of the ADAMTS13 gene has also raised the prospect of recombinant enzyme therapy for the treatment of TTP, and this has heightened the need for a simple assay. In this review, we evaluate the value of measuring this enzyme in the management of TTP.

  2. von Willebrand Factor Test

    Science.gov (United States)

    ... in women Blood in urine or stool Prolonged bleeding after surgery VWF tests may be repeated when they are initially normal but suspicions of VWD remain high. When VWF testing suggests VWD, ... in bleeding disorders , such as a hematologist or coagulation specialist, ...

  3. Association analysis between endothelial function related factors and coronary artery stenosis degree in coronary heart disease patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Li, Quanmin; Zhang, Zhifang; Du, Ruiqin; Hu, Xiaoqiang; Yan, Yan; Gao, Qing; Fan, Yanting

    2012-01-01

    To investigate the relationship between soluble intercellular adhesion molecule (sICAM-1), vascular endothelial cell adhesion molecule (VCAM-1), monocytes chemotactic protein (MCP-1), von Willebrand factor (vWF), and coronary artery stenoses degree in coronary heart disease (CHD) within type 2 diabetes mellitus (T2DM) patients. A total of 92 subjects were treated with coronary angiography (CAG), including 62 subjects with CHD. The individuals were divided into three groups, group A (32 patients with CHD and T2DM), group B (30 patients with CHD but no T2DM) and group C (30 patients with no CHD and T2DM). All patients were treated with a Gensini coronary angiography check. The correlations between sICAM-1, VCAM-1, MCP-1 and vWF in peripheral blood and coronary artery stenosis degree were analyzed. The average score of coronary artery stenosis degree was 30.75 +/-12.67 in group A, which was significantly higher than group B (11.20 +/-7.51) and group C (2.40 +/- 1.23) (p coronary artery stenosis and the mean level of sICAM-1, VCAM-1, MCP-1, vWF in group A (p 0.05). Association analysis shown that the level of sICAM-1, VCAM-1, MCP-1 and vWF elevated in CHD with T2DM patients. Vascular endothelial dysfunction could be caused to the coronary artery stenosis pathophysiological process. Results from this study suggested that sICAM-1, VCAM-1, MCP-1 and vWF may contribute to the occurrence and development of vascular lesions in T2DM. These endothelial function related factors could be acceptable as a prediction and testing index of vascular complications in T2DM.

  4. A single chain variant of factor VIII Fc fusion protein retains normal in vivo efficacy but exhibits altered in vitro activity.

    Directory of Open Access Journals (Sweden)

    Yang Buyue

    Full Text Available Recombinant factor VIII Fc (rFVIIIFc is a fusion protein consisting of a single B-domain-deleted (BDD FVIII linked recombinantly to the Fc domain of human IgG1 to extend half-life. To determine if rFVIIIFc could be further improved by maintaining the heavy and light chains within a contiguous single chain (SC, we evaluated the activity and function of SC rFVIIIFc, an isoform that is not processed at residue R1648. SC rFVIIIFc showed equivalent activity in a chromogenic assay compared to rFVIIIFc, but approximately 40% activity by the one-stage clotting assay in the presence of von Willebrand Factor (VWF, with full activity in the absence of VWF. Moreover, SC rFVIIIFc demonstrated markedly delayed thrombin-mediated release from VWF, but an activity similar to that of rFVIIIFc upon activation in FXa generation assays. Therefore, the apparent reduction in specific activity in the aPTT assay appears to be primarily due to delayed release of FVIII from VWF. To assess whether stability and activity of SC rFVIIIFc were affected in vivo, a tail vein transection model in Hemophilia A mice was utilized. The results demonstrated similar pharmacokinetic profiles and comparable efficacy for SC rFVIIIFc and rFVIIIFc. Thus, while the single chain configuration did not promote enhanced half-life, it reduced the rate of release of FVIII from VWF required for activation. This impaired release may underlie the observed reduction in the one-stage clotting assay, but does not appear to affect the physiological activity of SC rFVIIIFc.

  5. "Amor e sexo: mitos, verdades e fantasias": jovens avaliam potencial de material multimídia educativo em saúde "Love and sex: myths, truths and fantasies": youth evaluation of the multimedia resource as educational health material

    OpenAIRE

    Sonia Maria Figueira Mano; Fabio Castro Gouveia; Virgínia Torres Schall

    2009-01-01

    A educação sexual na escola é prática defendida e prescrita pelo Ministério da Educação nos Parâmetros Curriculares Nacionais como eixo transversal ao currículo. O tema é complexo e a proposta expressa demandas específicas, como a formação dos professores e materiais educativos adequados. O Museu da Vida, COC/Fiocruz, desenvolveu o multimídia «Amor e sexo: mitos, verdades e fantasias» e, neste artigo, apresenta a avaliação efetuada por 36 alunos do Ensino Médio de escolas públicas do Rio de J...

  6. The CentriMag centrifugal blood pump as a benchmark for in vitro testing of hemocompatibility in implantable ventricular assist devices.

    Science.gov (United States)

    Chan, Chris H H; Pieper, Ina Laura; Hambly, Rebecca; Radley, Gemma; Jones, Alyssa; Friedmann, Yasmin; Hawkins, Karl M; Westaby, Stephen; Foster, Graham; Thornton, Catherine A

    2015-02-01

    Implantable ventricular assist devices (VADs) have proven efficient in advanced heart failure patients as a bridge-to-transplant or destination therapy. However, VAD usage often leads to infection, bleeding, and thrombosis, side effects attributable to the damage to blood cells and plasma proteins. Measuring hemolysis alone does not provide sufficient information to understand total blood damage, and research exploring the impact of currently available pumps on a wider range of blood cell types and plasma proteins such as von Willebrand factor (vWF) is required to further our understanding of safer pump design. The extracorporeal CentriMag (Thoratec Corporation, Pleasanton, CA, USA) has a hemolysis profile within published standards of normalized index of hemolysis levels of less than 0.01 g/100 L at 100 mm Hg but the effect on leukocytes, vWF multimers, and platelets is unknown. Here, the CentriMag was tested using bovine blood (n = 15) under constant hemodynamic conditions in comparison with a static control for total blood cell counts, hemolysis, leukocyte death, vWF multimers, microparticles, platelet activation, and apoptosis. The CentriMag decreased the levels of healthy leukocytes (P pump which could be used as a standard in blood damage assays to inform the design of new implantable blood pumps.

  7. Functional variation in the arginine vasopressin 2 receptor as a modifier of human plasma von Willebrand factor levels

    DEFF Research Database (Denmark)

    Nossent, Anne Yaël; Robben, J H; Deen, P M T

    2010-01-01

    SUMMARY OBJECTIVES: Stimulation of arginine vasopressin 2 receptor (V2R) with arginine vasopressin (AVP) results in a rise in von Willebrand factor (VWF) and factor VIII plasma levels. We hypothesized that gain-of-function variations in the V2R gene (AVPR2) would lead to higher plasma levels of VWF....... The functionality of the G12E variant was studied in stably transfected MDCKII cells, expressing constructs of either 12G-V2R or 12E-V2R. Both V2R variants were fully glycosylated and expressed on the basolateral membrane. The binding affinity of V2R for AVP was increased three-fold in 12E-V2R-green fluorescent...

  8. 用心率变异性谱分析法研究振动性白指患者自主神经系统对冷刺激的反应%Autonomic Nervous Response to Cold Provocation in Vibration-Induced White Finger(VWF) Patients with HRV Analysis

    Institute of Scientific and Technical Information of China (English)

    罗进; 神原久孝; 朱善宽

    1999-01-01

    目的研究振动性白指患者的自主神经系统对冷刺激的反应.方法 22名振动性白指患者(VWF组)及19名正常对照(对照组)进行了局部冷水刺激实验,记录受试者的心电信号,实验后将记录的心电信号通过处理转化为R-R间期信号,然后对这些R-R间期信号进行功率谱分析,计算标准化的LF(0.02~0.15 Hz)功量(LF%),标准化的HF(0.15~0.40Hz)功量(HF%),以及LF/HF比率.结果冷暴露开始后,VWF组及对照组的HF%与暴露前的水平相比都有显著下降,VWF组的LF/HF比率与暴露前的水平相比有显著增大,而且冷暴露中VWF组的LF/HF比率显著高于对照组的相应的LF/HF比率.结论冷刺激导致VWF组和对照组的副交感神经活动减弱,但对照组还能保持交感与副交感的平衡,而VWF组却不能保持两者平衡,交感神经活动明显占优,冷刺激中VWF组LF/HF比率明显高于对照组的LF/HF比率说明振动性白指患者的交感神经系统对冷刺激可能存在过敏反应.%Objective To evaluate the autonomic nervous response of Vibration-induced white finger(VWF) patients to cold provocation test by power spectral analysis of heart rate variability(HRV).Methods The cold provocation test was conducted in 22 VWF patients and 19 healthy volunteers.ECG was recorded during the experiment,and converted to R-R interval signals after the experiment.The normalized LF[(0.02~0.15) Hz]component power,normalized HF[(0.15~0.40) Hz] component power and the ratio of LF to HF power(LF/HF ratio) were calculated.Results At the beginning of cold exposure,there were a significant decrease of HF% in both groups,and a significant increase of LF/HF ratio in VWF group as compared with pre-exposure value.The LF/HF ratio in VWF group during cold exposure was significantly higher than that in the control group.Conclusion Cold stimuli induced depression of parasympathetic nervous system in both groups,and the sympatho-vagal balance was maintained in the

  9. Specific inhibiting effects of Ilexonin A on von Willebrand factor-dependent platelet aggregation under high shear rate

    Institute of Scientific and Technical Information of China (English)

    李敏; 吴伟康; 刘良; 廖福龙; 篠原幸人; 半田俊之介; 後藤信哉

    2004-01-01

    Background Ilexonin A (IA), purified from the Chinese herbal medicine Maodongqing (Ilex pubescens Hook, et Am) has been commonly used in south China to treat thrombotic disorders. In this study, we aimed to study the inhibiting effects and mechanism of lA on von Willebrand factor (vWF)-dependent high shear-induced platelet aggregation. Methods vWF-dependent high shear (10 800 s-1) induced aggregation of platelets obtained from normal donors in the presence or absence of lA was measured by a modified cone-plate viscometer and shear-induced vWF binding was measured by quantitative flowcytometry with monoclonal antibody known to bind exclusively to the C-terminal domain of vWF (LJ-C3) directly labeled with fluorescein isothiocyanate (FITC). P-selectin surface expression was also measured by a similar method with FITC conjugated anti-P-selectin monoclonal antibody (WGA1).Results Shear-induced platelet aggregation was inhibited by IA in a dose-dependent manner. The extent of aggregation decreased from (78.6±4.6)% in the absence of lA to (36.5±2.1 )% in the presence of lA (3.3 mmol/L) (P<0.0001, n=9) with a high shear rate of 10800 s-1. vWF binding and P-selectin expression were also inhibited by lA in a dose dependent manner. The number of binding FITC-LJ-C3 molecules increased after exposure of platelet-rich plasma to a high shear rate of 10 800 s-1 for 6 minutes, but this shear-induced increased binding platelet surface vWF molecules and P-selectin expression can be decreased in the presence of IA.Conclusion vWF binding and vWF mediated platelet activation, aggregation occurring under high shear rate were inhibited by IA. lA may be a unique antithrombotic drug inhibiting the vWF-GP Ib α interaction, and may thus facilitate drug design targeting arterial thrombosis.

  10. [Hemostatic coronary risk factors in a healthy population of Maracaibo, Venezuela].

    Science.gov (United States)

    Diez-Ewald, María; Campos, Gilberto; Rivero, Francisco; Alvarez, Luis; Torres, Enrique; Arocha-Piñango, Carmen L; Ryder, Elena; Arteaga-Vizcaíno, Melvis; Vizcaíno, Gilberto; Fernández, Nelson

    2003-03-01

    The purpose of the present work was to determine the plasma concentrations of fibrinogen and Von Willebrand Factor (VWF) as well as platelet aggregation, in an apparently healthy population of 306 men and 41 women, 33 to 65 years of age, workers of the national oil industry (PDVSA, Maracaibo), as a base investigation in a 5-year prospective national collaborative study. The participants were previously subjected to a thorough clinical examination with cardiovascular evaluation and laboratory tests. Clottable fibrinogen and VWF concentrations were determined in platelet poor plasma, the last one by immunoclectrophoresis, and a multimeric analysis of VWF was performed on those plasmas with concentrations higher than 150 U/dL by SDS agarose electrophoresis, followed by cellulose membrane transference. Platelet aggregation was studied in platelet rich plasma with no addition of stimulants and after collagen and ristocetin were added. Forty per cent of men and 65.8% of women, showed fibrinogen concentrations above 300 mg/dL (p < 0.01) and 12.2% of men and 15.4% of women had VWF values higher than 150 U/dL, with normal multimeric distribution. Fourteen individuals presented spontancous platelet aggregation and increased aggregation in 12 and 13 of them, after induction with collagen and ristocetin respectively. Comparing these findings with those of previous collaborative studies from other countries, the present results could mean that an important proportion of the population here studied, could be at risk for a future coronary event; however, as these are the base findings in Maracaibo, the significance of our results will be better evaluated at the end of the five year study.

  11. Zyxin regulates endothelial von Willebrand factor secretion by reorganizing actin filaments around exocytic granules

    Science.gov (United States)

    Han, Xiaofan; Li, Pin; Yang, Zhenghao; Huang, Xiaoshuai; Wei, Guoqin; Sun, Yujie; Kang, Xuya; Hu, Xueting; Deng, Qiuping; Chen, Liangyi; He, Aibin; Huo, Yingqing; Li, Dong; Betzig, Eric; Luo, Jincai

    2017-01-01

    Endothelial exocytosis of Weibel–Palade body (WPB) is one of the first lines of defence against vascular injury. However, the mechanisms that control WPB exocytosis in the final stages (including the docking, priming and fusion of granules) are poorly understood. Here we show that the focal adhesion protein zyxin is crucial in this process. Zyxin downregulation inhibits the secretion of von Willebrand factor (VWF), the most abundant cargo in WPBs, from human primary endothelial cells (ECs) induced by cAMP agonists. Zyxin-deficient mice exhibit impaired epinephrine-stimulated VWF release, prolonged bleeding time and thrombosis, largely due to defective endothelial secretion of VWF. Using live-cell super-resolution microscopy, we visualize previously unappreciated reorganization of pre-existing actin filaments around WPBs before fusion, dependent on zyxin and an interaction with the actin crosslinker α-actinin. Our findings identify zyxin as a physiological regulator of endothelial exocytosis through reorganizing local actin network in the final stage of exocytosis. PMID:28256511

  12. Reduced ADAMTS13 activity is associated with thrombotic risk in systemic lupus erythematosus.

    Science.gov (United States)

    Martin-Rodriguez, S; Reverter, J C; Tàssies, D; Espinosa, G; Heras, M; Pino, M; Escolar, G; Diaz-Ricart, M

    2015-10-01

    Severe deficiency of ADAMTS13 activity leads to von Willebrand factor (VWF) ultralarge multimers with high affinity for platelets, causing thrombotic thrombocytopenic purpura. Other pathological conditions with moderate ADAMTS13 activity exhibit a thrombotic risk. We examined the ADAMTS13 activity in systemic lupus erythematosus (SLE) and its value as a thrombotic biomarker. ADAMTS13 activity, VWF antigen and multimeric structure, and vascular cell adhesion molecule 1 (VCAM-1) were measured in plasma samples from 50 SLE patients and 50 healthy donors. Disease activity (systemic lupus erythematosus disease activity index; SLEDAI) and organ damage (systemic lupus international collaborating clinics) scores, thrombotic events, antiphospholipid syndrome (APS) and antiphospholipid antibodies (aPLs) were registered. SLE patients showed decreased ADAMTS13 activity and high VWF levels compared with controls (66 ± 27% vs. 101 ± 8%, P 60%, 60-40% and <40%), comparative analysis showed significant association between ADAMTS13 activity and SLEDAI (P < 0.05), presence of aPLs (P < 0.001), APS (P < 0.01) and thrombotic events (P < 0.01). Reduced ADAMTS13 activity together with increased VWF levels were especially notable in patients with active disease and with aPLs. ADAMTS13 activity, in combination with other laboratory parameters, could constitute a potential prognostic biomarker of thrombotic risk in SLE. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  13. Von Willebrand Factor Gene Variants Associate with Herpes simplex Encephalitis.

    Science.gov (United States)

    Abdelmagid, Nada; Bereczky-Veress, Biborka; Atanur, Santosh; Musilová, Alena; Zídek, Václav; Saba, Laura; Warnecke, Andreas; Khademi, Mohsen; Studahl, Marie; Aurelius, Elisabeth; Hjalmarsson, Anders; Garcia-Diaz, Ana; Denis, Cécile V; Bergström, Tomas; Sköldenberg, Birgit; Kockum, Ingrid; Aitman, Timothy; Hübner, Norbert; Olsson, Tomas; Pravenec, Michal; Diez, Margarita

    2016-01-01

    Herpes simplex encephalitis (HSE) is a rare complication of Herpes simplex virus type-1 infection. It results in severe parenchymal damage in the brain. Although viral latency in neurons is very common in the population, it remains unclear why certain individuals develop HSE. Here we explore potential host genetic variants predisposing to HSE. In order to investigate this we used a rat HSE model comparing the HSE susceptible SHR (Spontaneously Hypertensive Rats) with the asymptomatic infection of BN (Brown Norway). Notably, both strains have HSV-1 spread to the CNS at four days after infection. A genome wide linkage analysis of 29 infected HXB/BXH RILs (recombinant inbred lines-generated from the prior two strains), displayed variable susceptibility to HSE enabling the definition of a significant QTL (quantitative trait locus) named Hse6 towards the end of chromosome 4 (160.89-174Mb) containing the Vwf (von Willebrand factor) gene. This was the only gene in the QTL with both cis-regulation in the brain and included several non-synonymous SNPs (single nucleotide polymorphism). Intriguingly, in human chromosome 12 several SNPs within the intronic region between exon 43 and 44 of the VWF gene were associated with human HSE pathogenesis. In particular, rs917859 is nominally associated with an odds ratio of 1.5 (95% CI 1.11-2.02; p-value = 0.008) after genotyping in 115 HSE cases and 428 controls. Although there are possibly several genetic and environmental factors involved in development of HSE, our study identifies variants of the VWF gene as candidates for susceptibility in experimental and human HSE.

  14. Von Willebrand Factor Gene Variants Associate with Herpes simplex Encephalitis.

    Directory of Open Access Journals (Sweden)

    Nada Abdelmagid

    Full Text Available Herpes simplex encephalitis (HSE is a rare complication of Herpes simplex virus type-1 infection. It results in severe parenchymal damage in the brain. Although viral latency in neurons is very common in the population, it remains unclear why certain individuals develop HSE. Here we explore potential host genetic variants predisposing to HSE. In order to investigate this we used a rat HSE model comparing the HSE susceptible SHR (Spontaneously Hypertensive Rats with the asymptomatic infection of BN (Brown Norway. Notably, both strains have HSV-1 spread to the CNS at four days after infection. A genome wide linkage analysis of 29 infected HXB/BXH RILs (recombinant inbred lines-generated from the prior two strains, displayed variable susceptibility to HSE enabling the definition of a significant QTL (quantitative trait locus named Hse6 towards the end of chromosome 4 (160.89-174Mb containing the Vwf (von Willebrand factor gene. This was the only gene in the QTL with both cis-regulation in the brain and included several non-synonymous SNPs (single nucleotide polymorphism. Intriguingly, in human chromosome 12 several SNPs within the intronic region between exon 43 and 44 of the VWF gene were associated with human HSE pathogenesis. In particular, rs917859 is nominally associated with an odds ratio of 1.5 (95% CI 1.11-2.02; p-value = 0.008 after genotyping in 115 HSE cases and 428 controls. Although there are possibly several genetic and environmental factors involved in development of HSE, our study identifies variants of the VWF gene as candidates for susceptibility in experimental and human HSE.

  15. Les outils multimédia d’aide à l’apprentissage des langues : de l’évaluation à la réflexion prospective Multimedia aid tools for language learning: from evaluation to a prospective reflection

    Directory of Open Access Journals (Sweden)

    Christine Rodrigues

    2000-06-01

    Full Text Available En partant de la conception d´un logiciel multimédia, CAMILLE Travailler en France, et de résultats d´expérimentation, nous avons amorcé une réflexion prospective sur ce que pourrait être un logiciel d´aide à l´apprentissage des langues répondant vraiment aux besoins des utilisateurs. Ayant pointé certains dysfonctionnements, nous nous sommes interrogées sur leurs causes et avons tenté de poser les bonnes questions, avant de nous aventurer vers de nouvelles créations. Un des pré-requis de départ est le suivant : dans la mesure où les TIC (Technologies de l´Information et de la Communication ne peuvent certainement pas réussir partout, dans quel domaine leur apport peut-il être bénéfique, voire irremplaçable ? Dans un premier temps, nous présenterons le fonctionnement de CAMILLE et nous décrirons brièvement la méthodologie d´évaluation adoptée. Nous verrons ensuite à quelles questions précises l´expérimentation a cherché à répondre. En nous basant sur les gains effectifs des apprenants, nous chercherons à comprendre si le logiciel les a fait progresser dans la connaissance générale de la langue, en particulier en compréhension orale et écrite. Nous conclurons sur la détermination de quelques éléments à prendre en compte lors de la conception de nouveaux outils multimédia d´aide à l´apprentissage.In this article, we present the results of the evaluation of a multimedia software CAMILLE Travailler en France that we had designed. We then started a prospective reflection on what could be supportive multimedia language learning environments really meeting learners´ needs. As the experimentation revealed certain lacks in the environment, we tried to find out their causes before going further in the design process. We started from the following statement: since Information and Communication Technologies (ICT cannot succeed everywhere in which area can they be useful or even irreplaceable? We will

  16. Aplicación del algoritmo de optimización metaheurístico BOA en el diseño de PSSs robustos para sistemas de potencia multimáquina.

    Directory of Open Access Journals (Sweden)

    Miguel Ramírez

    2016-01-01

    Full Text Available Se presenta la aplicación del algoritmo de optimización BO A (de las siglas en inglés para Bat Optimization Algorithm en el diseño robusto de estabilizadores de sistemas de potencia (PSSs por sus siglas en inglés en sistemas multimáquina. Con el fin de amortiguar las oscila ciones electromecánicas del sistema, la sintonización de parámetros de los PSSs involucrados se efectúa de manera coordinada mediante la alternativa de optimización propuesta y la min imización de una función objetivo calculada directamente de simulaciones en el dominio del tiempo. La efectividad y robustez de los PSSs propuestos (BOAPSSs es investigada a través de la simulación del sistema de estudio bajo diferentes condiciones de operación y perturba ciones. El desempeño de los BOAPSSs es comparado tanto con la respuesta de PSSs diseña dos conve ncionalmente como con el comportamiento proporcionado por PSSs basados en algoritmos genéticos y en optimización de enjambres de partículas. Los resultados obtenidos de este estudio muestran un desempeño notablemente supe rior de los PSSs propuestos con res pecto a los PSSs diseñados convencionalmente. Así mismo y en comparación con PSSs basados tanto en algoritmos genéticos como en inteligencia de enjambres, se verifica la mej ora en el comportamiento dinámico del sistema al utilizar los PSSs diseñados con la metodol ogía propuesta.

  17. Teoría de la carga cognitiva, diseño multimedia y aprendizaje: un estado del arte (Cognitive Load Theory, Design and Multimedia Learning: A State of the Art (Théorie de la charge cognitive, dessin multimédia et apprentissage: un état de l′art (Teoria da carga cognitiva, desenho multimídia e aprendizagem: um estado da arte

    Directory of Open Access Journals (Sweden)

    Luis Alejandro Andrade Lotero

    2012-12-01

    Full Text Available ResumenEn este artículo de revisión se presenta un resumen de la Teoría de la Carga Cognitiva y la Teoría Cognitiva del Aprendizaje Multimedia. Se dan algunos ejem- plos de investigaciones empíricas y se reflexiona acerca del valor explicativo de estas teorías del aprendizaje. Se exponen diez principios para el diseño de material instruccional. No obstante, otras investigaciones han encontrado limitaciones en el uso y práctica de estas teorías. Se refieren principalmente a la medición de la carga cognitiva, a la experiencia, al conocimiento previo de los aprendices y a la motivación y aspectos afectivos que intervienen en el proceso de aprendizaje.AbstractIn this review article is a summary of the Cognitive Load Theory and Cognitive Theory of Multimedia Lear- ning. Some examples of empirical research and considerations on the explanatory value of these learning theories are given, and ten principles for designing instructional material are shown. However, other research has found limitations in the use and practice of these theories. They mainly concern the measurement of cognitive load, experience and prior knowledge of the learners, as well as motivation and emotional aspects in- volved in the learning process.RésuméDans cet article de révision on pré- sente un résumé de la théorie de la charge cognitive et la théorie cogniti- ve de l'apprentissage multimédia. On fournit des exemples de recherches empiriques et on fait une réflexion par rapport à l'importance explica- tive de ces théories d’apprentissage. On présente dix principes pour le dessin du matériel d'instruction. Mal- gré les recherches qu'ont trouvé des limitations dans l'usage et la pratique de ces théories. Elles font référence, notamment à la mesure de la charge cognitive, à l'expérience et la con- naissance préalable des apprentis et aussi à la motivation et aux aspects affectifs qui intervient dans le pro- cessus de l

  18. [Thrombotic microangiopathies: HUS/TTP. Physiopathological aspects].

    Science.gov (United States)

    Sánchez Avalos, J C

    2000-01-01

    In thrombotic thrombocytopenic purpura (TTP) and in the hemolytic uremic syndrome (HUS) fibrin-platelet thrombi occlude arterioles and capillaries. The mechanism of endothelial cell injury and the mechanism of thrombosis are the most important physiopathological events in this pathology and are largely unknown. In HUS due to the Shiga toxin, the lesion of the endothelial cells is due to penetration of the toxin into the cell via the Gb3 receptor. Endothelial cell death is a consequence of altered protein synthesis at the ribosomal level. Cytokines released during the inflammatory process, possibly enhance the endothelial damage. Genetic and immunologic predisposing factors for the development of HUS have also been postulated. In idiopathic, secondary and familial HUS/TTP the mechanism of endothelial lesion is unknown, but multiple responsible factors have been advocated such as infections, drugs, pregnancy, autoantibodies, apoptosis inducing molecules, etc. and other genetic, hormonal or immunologic predisposing factors may also be involved. Factor H deficiency has been blamed in familiar cases. The most important cause of microcirculation thrombosis is the thrombogenic capacity of endothelial cell "activation" or injury induced by multiple mechanisms. The predominant source of plasma vW factor multimers is apparent in the altered endothelial cell. The unusually large vWF multimers are more effective at binding to platelet glycoprotein Ib-IX and IIb-IIIa complexes and inducing aggregation, as also occurred with the low weight multimers formed with excessive proteolysis, as described in the acute phase of HUS/TTP. The recent report of congenital deficiency of a vWF protease in familial TTP and its functional inhibition by autoantibodies in acquired cases is characteristic of TTP. This protease inhibition has never been described in HUS and might represent pathogenetic differences between TTP and HUS, and contribute to the differential diagnosis, but further

  19. Uma proposta de instrumento de roteirização de videoaulas à luz da teoria instrucional e da aprendizagem multimídia

    Directory of Open Access Journals (Sweden)

    Vinicius Carvalho Pereira

    2017-06-01

    ABSTRACT: The contemporary educational scenario witnesses an exponential growth of distance education, where print materials stand out in terms of research, production and distribution. However, the spread of audiovisual resources in cyberculture, as well as the emergence of new paradigms of teaching and learning, demands researches on didactic materials in other medias. This research aims at identifying guidelines for a scripting tool that empowers teachers as active members throughout the production of audiovisual didactic materials. In terms of methodology, we designed a scripting tool based on instructional theories and theories of multimedia learning. Five teachers were given that instrument to write the script of a simple videoclass about a daily activity. Then, the research subjects were interviewed for a qualitatively assessing of the scripting tool, in order to validate/reformulate it. The results from the interviews and from the analyses of the tools suggest that such an instrument can allow teachers to better understand the videoclass production process. Besides, it was possible to elicit some factors that should be adapted to improve the scripting tool. Besides, we noticed that some multimedia learning principles were not respected by research subjects when they were scripting their videoclasses, which suggests the need to clarify the scripting tool.

  20. The expression and significance of hypertensive disorders in pregnancy,placenta derived vWF and vWF-cp%妊娠期高血压疾病胎盘源性vWF与vWF-cp的表达及意义

    Institute of Scientific and Technical Information of China (English)

    李媛; 张延丽

    2015-01-01

    目的:探讨血管性血友病因子(vWF)与血管性血友病因子裂解酶(vWF-cp)在妊娠期高血压疾病胎盘组织中的表达及意义。方法采用免疫组织化学方法检测妊娠期高血压疾病患者90例(妊娠期高血压组、轻度子痫前期组、重度子痫前期组,各30例)与30名正常妊娠产妇胎盘组织中vWF和vWF-cp的表达。结果妊娠期高血压组、轻度子痫前期组、重度子痫前期组对比正常妊娠组,vWF在胎盘组织的表达强度显著升高,差异有统计学意义(P<0.05);vWF-cp在胎盘组织里的表达强度显著降低,差异有统计学意义(P<0.05)。结论妊娠期高血压疾病中vWF及vWF-cp的表达水平变化最终导致血管内皮细胞脱落产生胎盘源性改变,从而与妊娠期高血压疾病的发病与病情有关。%Objective Study of vWF and vWF-cp expression and significance in placental of hypertensive disorder in pregnancy.Methods Detection of 90 cases of gestational hypertension group by munohistochemical method (30 cases of gestational hypertension; 30 cases of mild preeclampsia; 30 cases of severe preeclampsia) and 30 cases of normal pregnancy the expression of vWF and vWF-cp in the placenta. Results Gestational hypertension;30 cases of mild preeclampsia; 30 cases of severe preeclampsia compared with normal pregnancy group, the expression intensity of vWF in placenta in significantly increased (P<0.05), with a statistically significant difference between the groups; the expression intensity of vWF-cp in placenta tissue was significantly lower (P<0.05), with a statistically significant difference between the groups.Conclusion The expression levels of vWF and vWF-cp in gestational hypertension disease in patients with damaged vascular endothelial cells in the placenta, the placenta is small, resulting in the pathogenesis of vascular endothelial cell loss hypertension induced apoptosis of placenta derived cells and pregnancy

  1. Modelo computacional para o gerenciamento de dados e exames de pacientes para o acompanhamento remoto por meio de conferência multimídia Computational model for data and patients' exams management for remote follow-up by multimedia conferences

    Directory of Open Access Journals (Sweden)

    Huei Diana Lee

    2010-12-01

    Full Text Available OBJETIVO: Desenvolver um modelo computacional para aquisição, gerenciamento e armazenamento de dados e exames de pacientes, e definir uma arquitetura de conferência multimídia para o acompanhamento remoto de exames. MATERIAIS E MÉTODOS: Definiu-se uma arquitetura computacional para a aquisição de exames a partir de equipamentos hospitalares, e para o armazenamento e gerenciamento de dados e exames de pacientes foram utilizados o servidor de aplicações Jboss, o sistema gerenciador de banco de dados MySQL, o servidor de páginas Apache e o framework Jboss-Seam para o desenvolvimento de aplicações. Para a conferência multimídia, foi aplicado um estudo de caso utilizando a arquitetura Openmeetings. RESULTADOS: Foram definidos modelos computacionais para o gerenciamento consistente e seguro de dados e exames de pacientes e estudou-se uma arquitetura para conferência multimídia. CONCLUSÃO: Os modelos computacionais, o protótipo implementado e a arquitetura de conferência multimídia avaliada poderão ser aplicados em situações reais da área médica, contribuindo para o acompanhamento remoto de pacientes.OBJECTIVE: To develop a computational model for acquisition, management and storing data and patients' exams, and to define a multimedia conference architecture to remote patients' follow-up. MATERIALS AND METHODS: A computational architecture was defined to acquire exams' information from hospital equipment and to store and manage patients' data and exams using the JBoss application server, the MySql database manager system, the Apache web page server and the Jboss Seam framework for application development. For multimedia conference, a case study using the Openmeetins architecture was performed. RESULTS: computational models intended to the consistent and safe management of data and patients' exams were defined and a multimedia conference architecture was studied. CONCLUSION: The computational models, the prototype developed and

  2. Avaliação de habilidades sociais de crianças com um inventário multimídia: indicadores sociométricos associados a freqüência versus dificuldade Evaluation of children’s social skills using a multimedia social skills inventoire: psichometric indexes of frequency versus difficulty

    Directory of Open Access Journals (Sweden)

    Zilda Aparecida Pereira Del Prette

    2002-06-01

    Full Text Available A literatura sobre avaliação da competência social e das habilidades sociais é permeada de resultados controvertidos, provavelmente devidos ao uso de diferentes indicadores, informantes e conceitos norteadores. Dada a relevância dessas questões, em particular da auto-avaliação de crianças, e a relativa escassez de estudos a seu respeito, este artigo relata uma pesquisa que teve por objetivo comparar diferenças e semelhanças em algumas propriedades psicométricas, associadas a indicadores de freqüência e dificuldade de desempenhos sociais obtidos com o "Inventário multimídia de habilidades sociais para crianças" (IMHSC-Del-Prette. O IMHSC-Del-Prette foi aplicado inicialmente a 406 escolares de 7 a 13 anos (média =8, de ambos os sexos, com diferentes graus de dificuldade de aprendizagem, e reaplicado um mês depois com 191 (47% estudantes dessa amostra. Os resultados foram mais favoráveis ao indicador de dificuldade que ao de freqüência nos seguintes aspectos: simetria na distribuição dos escores, consistência interna, correlação entre teste e reteste, índices de discriminação entre itens e escores e estrutura fatorial (quatro ao invés de três fatores. São discutidas as implicações metodológicas e práticas desses resultados, indicando-se novas direções de pesquisa.The field of the social competence and social skills evaluation are permeated of contradictory results, largely associated to the use, in many studies, of different indexes, informers and concepts. Given the relevance and relative scarcity of studies on that subject, in particular about children's self-evaluation, the present paper aims to compare differences and similarities, in some psychometric properties associated to two indicators - frequency and difficulty of skilled social reactions - obtained with a Multimedia Social Skills Inventoire for Children (MUSSIC-Del-Prette. MUSSIC-Del-Prette was applied initially to 406 children of 7 a 13 years old

  3. Is ABO blood group truly a risk factor for thrombosis and adverse outcomes?

    Science.gov (United States)

    Zhou, Shan; Welsby, Ian

    2014-01-01

    ABO blood type is one of the most readily available laboratory tests, and serves as a vital determinant in blood transfusion and organ transplantation. The ABO antigens are expressed not only on red blood cell membranes, determining the compatibility of transfusion, but also on the surface of other human cells, including epithelium, platelet and vascular endothelium, therefore extending the research into other involvements of cardiovascular disease and postoperative outcomes. ABO blood group has been recognized as a risk factor of venous thrombosis embolism since the 1960’s, effects now understood to be related to ABO dependent variations are procoagulant factor VIII (FVIII) and von Willebrand factor (vWF) levels. Levels of vWF, mostly genetically determined, are strongly associated with venous thromboembolism (VTE). It mediates platelet adhesion aggregation and stabilizes FVIII in plasma. Moreover, many studies have tried to identify the relationship between ABO blood types and ischemic heart disease. Unlike the clear and convincing associations between VTE and ABO blood type, the link between ABO blood type and ischemic heart disease is less consistent and may be confusing. Other than genetic factors, ischemic heart disease is strongly related to diet, race, lipid metabolism and economic status. In this review, we’ll summarize the data relating race and genetics, including ABO blood type, to VTE, ischemic heart disease and postoperative bleeding after cardiac surgery. PMID:25276299

  4. Distribution of von Willebrand factor levels in young women with and without bleeding symptoms: influence of ABO blood group and promoter haplotypes

    DEFF Research Database (Denmark)

    Lethagen, S.; Hillarp, A.; Ekholm, C.;

    2008-01-01

    . It was the objective of the present study to evaluate the distribution of VWF levels in young females with or without bleeding symptoms in this population, and the influence of ABO blood group and promoter haplotypes on VWF levels and to identify a possible increased prevalence of VWD in females with bleeding symptoms.......4%) (p = 0.017). Blood group O was found in 14/18 girls with low VWF:RCo. There was a highly significant correlation between VWF:RCo and blood group O and non-O genotypes. Two common VWF promoter haplotypes did not contribute to the VWF:RCo variation. VWF levels did not correlate with time during...... menstrual cycle, or the use of oral contraceptives. No case fulfilled the diagnostic criteria for VWD. In conclusion, low VWF:RCo was significantly more frequent in females with bleeding symptoms. However, we found no case fulfilling strict diagnostic criteria for VWD. The ABO blood group was a strong...

  5. Ferramenta de autoria multimídia para ensino de língua estrangeira em ambiente multiagente Multimedia authorship tool for the teaching of foreign languages in a multi-agent environment

    Directory of Open Access Journals (Sweden)

    Adroaldo Guimarães Rossetti

    2009-04-01

    Full Text Available A comunicação é essencial nas atividades do mundo globalizado, onde conhecimento e tecnologia são a chave do progresso. Dominar outros idiomas nesse cenário é vital para a sustentação das pessoas no exercício de suas atividades. O sistema de ensino de línguas estrangeiras no Brasil, tanto nas escolas públicas quanto em parte das escolas particulares, não oferece condições para que as pessoas adquiram conhecimentos sólidos de língua estrangeira, conforme suas potencialidades e disponibilidades de tempo, sem prejuízo de outras atividades que exerçam no seu cotidiano. O objetivo deste artigo é apresentar uma ferramenta de autoria multimídia para ensino de língua estrangeira, disponível continuamente na Internet, que possa ser acessada de qualquer local e a qualquer momento. A ferramenta será construída baseada em arquitetura multiagente, constituindo um ambiente compartilhado semelhante à cooperação entre pessoas, cumprindo eficazmente a tarefa de ensino. Os idiomas, inicialmente inglês e francês, constarão de três módulos: básico, intermediário e avançado. Após ser disponibilizada na Web, a ferramenta será validada com base na crítica dos usuários por cerca de seis a doze meses e será avaliada periodicamente pelos gestores do programa. A ferramenta propiciará o acesso ao aprendizado eficaz de idiomas estrangeiros a quaisquer interessados, de acordo com suas potencialidades, seus interesses e tempo disponível.Communication is essential in the activities of a globalized world in which knowledge and technology are the keys to progress. In this scenario, having command of other languages is a vital support for people in their activities. The system for teaching foreign languages in Brazil, both in public schools and in part of the private institutions, fails to offer the basic conditions for people to acquire solid knowledge of a foreign language, according to their potential and time availability, and without

  6. Nerve growth factor improves ligament healing.

    Science.gov (United States)

    Mammoto, Takeo; Seerattan, Ruth A; Paulson, Kent D; Leonard, Catherine A; Bray, Robert C; Salo, Paul T

    2008-07-01

    Previous work has shown that innervation participates in normal ligament healing. The present study was performed to determine if exogenous nerve growth factor (NGF) would improve the healing of injured ligament by promoting reinnervation, blood flow, and angiogenesis. Two groups of 30 Sprague-Dawley rats underwent unilateral medial collateral ligament transection (MCL). One group was given 10 microg NGF and the other was given PBS via osmotic pump over 7 days after injury. After 7, 14, and 42 days, in vivo blood flow was measured using laser speckle perfusion imaging (LSPI). Morphologic assessments of nerve density, vascularity, and angiogenesis inhibitor production were done in three animals at each time point by immunohistochemical staining for the pan-neuronal marker PGP9.5, the endothelial marker vWF, and the angiogenesis inhibitor thrombospondin-2 (TSP-2). Ligament scar material and structural mechanical properties were assessed in seven rats at each time point. Increased nerve density was promoted by NGF at both 14 and 42 days. Exposure to NGF also led to increased ligament vascularity, as measured by histologic assessment of vWF immunohistochemistry, although LSPI-measured blood flow was not significantly different from controls. NGF treatment also led to decreased expression of TSP-2 at 14 days. Mechanical testing revealed that exposure to NGF increased failure load by 40%, ultimate tensile strength by 55%, and stiffness by 30% at 42 days. There were no detectable differences between groups in creep properties. The results suggest that local application of NGF can improve ligament healing by promoting both reinnervation and angiogenesis, and results in scars with enhanced mechanical properties.

  7. First prospective report on immune tolerance in poor risk haemophilia A inhibitor patients with a single factor VIII/von Willebrand factor concentrate in an observational immune tolerance induction study.

    Science.gov (United States)

    Kreuz, W; Escuriola Ettingshausen, C; Vdovin, V; Zozulya, N; Plyushch, O; Svirin, P; Andreeva, T; Bubanská, E; Campos, M; Benedik-Dolničar, M; Jiménez-Yuste, V; Kitanovski, L; Klukowska, A; Momot, A; Osmulskaya, N; Prieto, M; Šalek, S Z; Velasco, F; Pavlova, A; Oldenburg, J; Knaub, S; Jansen, M; Belyanskaya, L; Walter, O

    2016-01-01

    Development of neutralizing inhibitors against factor VIII (FVIII) is a major complication of haemophilia A treatment. The ongoing, international, open-label, uncontrolled, observational immune tolerance induction (ObsITI) study evaluates ITI, the standard of care in patients with inhibitors. Forty-eight prospective patients in this interim analysis received a single plasma-derived, von Willebrand factor-stabilized, FVIII concentrate (pdFVIII/VWF) for ITI. According to recommended Bonn protocol, 'low responders' at ITI start (2 years since inhibitor diagnosis, inhibitor titre ≥10 BU at the start of ITI, or prior ITI failure). Nonetheless, 34 patients (70.8%) achieved complete success, 3 (6.3%) partial success, 1 (2.1%) partial response; ITI failed in 10 patients (20.8%), all with poor prognosis factors. All six low responders achieved complete success. ITI outcome was significantly associated with inhibitor titre level at ITI start (P = 0.0068), number of poor prognosis factors for ITI success (P = 0.0187), monthly bleeding rate during ITI (P = 0.0005) and peak inhibitor titre during ITI (P = 0.0007). Twenty-two of 35 high responder patients (62.9%) with ≥1 poor prognosis factor achieved complete success. Treatment with a single pdFVIII/VWF concentrate, mainly according to the Bonn protocol, resulted in a high ITI success rate in haemophilia A patients with inhibitors and poor prognosis for ITI success. © 2015 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

  8. 血浆vWF:Ag、蛋白C活性在ALI/ARDS患者诊断和预后中的意义%Evaluation of Plasma vWF : Ag and Protein C Activity in the Diagnosis and Prognosis of Patients at Risk of ALI/ARDS

    Institute of Scientific and Technical Information of China (English)

    夏炎火; 林锡芳; 潘景业; 王丹; 李卓英; 杨梅

    2013-01-01

    Objective To evaluate the value and feasibility of plasma vWF: Ag and protein C activity in the diagnosis and prognosis in ALI/ARDS patients. Methods The clinical data of 49 ALI/ARDS patients and 21 non - ALI / ARDS patients was collected and evaluated with APACHE II score system and lung injury score(LIS). Furthermore, ALI/ARDS patients were divided into two groups by prognosis, etiology, and organ failure number ( nonpulmonary). Mortality of every group was collected. Plasma vWF:Ag and protein C activity of patients were detected and evaluated. The value of plasma vWF:Ag and protein C activity in diagnosis of ALI/ARDS was analyzed by receiver operator characteristic( ROC) curve. Results Compared with non - ALI/ARDS group, the mortality and LIS score of ALI/ARDS group were significantly increased, PaO2/FiO2 was significantly declined. Plasma vWF: Ag (104% -752% ) in ALI / ARDS group was higher (P = 0.026), but PC activity ( 14% -125%) was significantly lower (P =0. 002). In the ALI/ARDS patients, plasma vWF: Ag of dead group, infected group and 3: 2 organ failure group were significantly higher than their control group; while PC activity of the three groups were greatly lower than their control groups. ROC curve analysis showed that PC activity was better in prediction ALI/ARDS (AUC = 0.709,95% CI:0.588 -0. 811 ,P =0. 0016) ,and the sensitivity and specificity were respectively 77. 75% and 57. 14% when PC activity ≤83% ; but vWF: Ag was poor in prediction ALI/ARDS ( AUC =0. 584,95% CI:0. 460-0. 701, P=0.2426). Conclusion Elevated plasma vWF;Ag and declined PC activity are associated with an increased risk of death and worse prognosis in ALI/ARDS patients. The accuracy of plasma PC activity to predict ALI/ARDS was better, but it is a controversial conclusion in prediction ALI/ARDS by plasma vWF:Ag.%目的 探讨血浆血管性血友病因子抗原(vWF:Ag)、蛋白C(PC)活性在急性肺损伤(ALI)/急性呼吸窘迫综合征(ARDS)患者早期诊断

  9. Platelet-type von Willebrand disease: new insights into the molecular pathophysiology of a unique platelet defect.

    Science.gov (United States)

    Othman, Maha; Kaur, Harmanpreet; Emsley, Jonas

    2013-09-01

    Compared with coagulation factor defects, little attention is given to defects of platelet function as causes of rare bleeding disorders. Platelet-type von Willebrand disease (PT-VWD) is an autosomal dominant bleeding disorder and is unique among platelet disorders because it is characterized by platelet hyperresponsiveness rather than decreased function. The disease is caused by gain-of-function mutations in the platelet GP1BA gene, which codes for the platelet von Willebrand factor (VWF) receptor, GPIbα. Only five mutations (four missense and one deletion) have so far been reported. Affected patients suffer from mild to moderate mucocutaneous bleeding, low VWF activity compared with antigen, decreased high-molecular-weight VWF multimers, variable degree of thrombocytopenia and typically platelet aggregation in response to low concentrations of ristocetin. All reported PT-VWD missense mutations occur within the R-loop of GPIbα and it was speculated that the introduction of short branched chain mutations such as Val in PT-VWD stabilized the extended β-hairpin. Examination of this theory by surveying all the available GPIbα structures showed that a distinct conformation predominates for the R-loop when GPIbα is not bound to VWF-A1 and this provides the framework of a new hypothesis for the molecular basis of PT-VWD. Worldwide efforts to improve diagnosis of PT-VWD continue, and international systematic studies are required to further our understanding of the phenotype and the influence of the hyperresponsive GPIbα beyond hemostasis.

  10. Actomyosin II contractility expels von Willebrand factor from Weibel-Palade bodies during exocytosis.

    Science.gov (United States)

    Nightingale, Thomas D; White, Ian J; Doyle, Emily L; Turmaine, Mark; Harrison-Lavoie, Kimberly J; Webb, Kathleen F; Cramer, Louise P; Cutler, Daniel F

    2011-08-22

    The study of actin in regulated exocytosis has a long history with many different results in numerous systems. A major limitation on identifying precise mechanisms has been the paucity of experimental systems in which actin function has been directly assessed alongside granule content release at distinct steps of exocytosis of a single secretory organelle with sufficient spatiotemporal resolution. Using dual-color confocal microscopy and correlative electron microscopy in human endothelial cells, we visually distinguished two sequential steps of secretagogue-stimulated exocytosis: fusion of individual secretory granules (Weibel-Palade bodies [WPBs]) and subsequent expulsion of von Willebrand factor (VWF) content. Based on our observations, we conclude that for fusion, WPBs are released from cellular sites of actin anchorage. However, once fused, a dynamic ring of actin filaments and myosin II forms around the granule, and actomyosin II contractility squeezes VWF content out into the extracellular environment. This study therefore demonstrates how discrete actin cytoskeleton functions within a single cellular system explain actin filament-based prevention and promotion of specific exocytic steps during regulated secretion.

  11. Factores de riesgo relacionados al uso de drogas ilegales: perspectiva crítica de familiares y personas cercanas en un centro de salud público en San Pedro Sula, Honduras

    OpenAIRE

    RODRÍGUEZ FUNES, Gladys Magdalena; Brands,Bruna; Adlaf,Edward; Giesbrecht, Norman; Simich,Laura; Wright,Maria da Gloria Miotto

    2009-01-01

    En este estudio, se presentan datos cuantitativos del estudio multicéntrico, multimétodos, de corte transversal realizado en un centro de salud público en San Pedro Sula, en Honduras. Su objetivo es describir la perspectiva crítica que tienen los familiares o personas, que se consideran afectadas por tener a alguien cercano que usa o ha usado drogas ilegales, con relación a factores de riesgo. Los datos se obtuvieron mediante una encuesta con 100 entrevistados. La mayor parte de las personas ...

  12. Relevance of hemostatic risk factors on coronary morphology in patients with diabetes mellitus type 2

    Directory of Open Access Journals (Sweden)

    Peters Ansgar J

    2009-05-01

    Full Text Available Abstract Objective The influence hemostatitc parameters on the morphological extent and severity of coronary artery disease were studied in patients with and without DM type 2. Background It is known that patients with diabetes (DM have abnormal metabolic and hemostatic parameters Methods Of 150 consecutive patients with angiographically proven coronary artery disease 29 presented with DM. Additionally to parameters of lipid-metabolism fibrinogen, tissue-plasminogenactivator (t-PA, plasminogen-activator-inhibitor (PAI, plasmin-a-antiplasmin (PAP, prothrombin-fragment 1+2 (F1+2, thrombin-antithrombin (TAT, von-willebrand-factor (vWF, platelet factor 4 (PF4, glykomembranproteine 140 (GMP140 and the rheologic parameters plasma viscosity and red blood cell aggregation were evaluated. The extent and severity of CAD was evaluated according to the criteria of the American Heart Association. Results Patients with DM presented with a higher number of conventional risk factors as compared to non-diabetic patients. Additionally there were significant differences for F1+2, red blood cell aggregation and PAI. Diabetic patients showed a more severe extent of coronary arteriosclerosis, which also could be found more distally. A significant relationship between blood-glucose, thrombocyte-activation (vWF, endogenous fibrinolysis (PAI and the severity of CAD and a more distal location of stenoses could be found (r = 0.6, p Conclusion Patients with coronary artery disease and DM type 2 showed marked alterations of metabolic, hemostatic, fibrinolytic and rheologic parameters, which can produce a prothrombogenic state. A direct association of thrombogenic factors on coronary morphology could be shown. This can be the pathophysiologic mechanism of more severe and distal pronounced coronary atherosclerosis in these patients.

  13. Solvent-detergent filtered (S/D-F) fresh frozen plasma and cryoprecipitate minipools prepared in a newly designed integral disposable processing bag system.

    Science.gov (United States)

    El-Ekiaby, M; Sayed, M A; Caron, C; Burnouf, S; El-Sharkawy, N; Goubran, H; Radosevich, M; Goudemand, J; Blum, D; de Melo, L; Soulié, V; Adam, J; Burnouf, T

    2010-02-01

    Solvent-detergent (S/D) viral inactivation was recently adapted to the treatment of single plasma donations and cryoprecipitate minipools. We present here a new process and a new bag system where the S/D reagents are removed by filtration and the final products subjected to bacterial (0.2 microm) filtration. Recovered and apheresis plasma for transfusion (FFP) and cryoprecipitate minipools (400 +/- 20 mL) were subjected to double-stage S/D viral inactivation, followed by one oil extraction and a filtration on a S/D and phthalate [di(2-ethylhexyl) phthalate (DEHP)] adsorption device and a 0.2 microm filter. The initial and the final products were compared for visual appearance, blood cell count and cell markers, proteins functional activity, von Willebrand factor (VWF) multimers and protein profile by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Tri (n-butyl) phosphate (TnBP) was quantified by gas chromatography and Triton X-45 and DEHP by high-performance-liquid chromatography (HPLC). General safety tests were by 6.5 mL/kg intravenous injection in rats. The treated plasmas and cryoprecipitates were very clear and the protein content and functionality, VWF multimers and SDS-PAGE profiles were well preserved. TnBP and Triton X-45 were < 1 and <25 ppm, respectively, and DEHP (about 5 ppm) was less than it was in the starting materials. Blood cell counts and CD45, CD61 and glycophorin A markers were negative. There was no enhanced toxicity in rats. Thus, plasma and cryoprecipitate can be S/D-treated in this new CE-marked disposable integral processing system under conditions preserving protein function and integrity, removing blood cells, S/D agents and DEHP, and ensuring bacterial sterility. This process may offer one additional option to blood establishments for the production of virally inactivated plasma components.

  14. Leukocyte telomere length is inversely correlated with plasma Von Willebrand factor

    DEFF Research Database (Denmark)

    Hjelmborg, Jacob V B; Nzietchueng, Rosine; Kimura, Masayuki;

    2010-01-01

    INTRODUCTION: Leukocyte telomere length (LTL) is short, while the plasma level of Von Willebrand (VWF) is high in persons with atherosclerosis. Moreover, both short LTLs and high VWF levels are observed in individuals who display risks for atherosclerosis, including hypertension, obesity, insulin...

  15. Violation of the vascular platelet hemostasis as a risk factor of primary open-angle glaucoma progression

    Directory of Open Access Journals (Sweden)

    N. I. Kurysheva

    2015-01-01

    Full Text Available Purpose: to study the vascular platelet hemostasis parameters in primary open-angle glaucoma (POAG.Patients and methods: ophthalmic examination, plasma level of spontaneous and induced platelet aggregation and von Willebrand factor (vWF were performed in 67 patients with high pressure glaucoma (HPG, 41 patients had normal tension glaucoma (NTG and 38 were in control group. Period of study was 36 months. The statistical analysis included standard methods of variation statistics. The threshold P value for statistical significance was 0.05.Results: platelet aggregation was increased in glaucoma (adrenalin-induced aggregation in HPG was 63,34 %±20,42 %, р = 0,043, in NTG 62,35 %±11,53 %, р = 0,047, in comparison with control group — 49,71 %±15,96 %; ristocetin-induced aggregation in HPG was 79,45 %±28,63 %, р = 0,015, in NTG 68,98 %±12,42 %, р = 0,022, and in control group 53,56 %±8,80 % accordingly; the mean level of vWF was increased in HPG (113,25 %±24,31 %, р = 0,009 and NTG (106,85 %±21,02 %, р = 0,012 in comparisonwith control group (93,86 %±17,13 %. Patients with normal level of vWF did not have a progression of glaucoma optical neuropathy. Patients with normalized level of vWF under treatment had significant improvement of MD in 6 months (from –4,916±5,121 to –4,103±4,658, р = 0,037 and were stable in the further follow up period. Patients with increased level of vWF had deterioration of MD in 36 months (from –4,616dB±8,426 dB to –5,974dB±8,852 dB, р = 0,042, increase of cup / disk ratio (from 0,59±0,21 to 0,66±0,24, р = 0,041 and thinning of average RNFL according to HRT and OCT (from 0,21±0,09 μm to 0,17±0,08 μm, р = 0,04; from 74,37±15,34 μm to 69,44±15,12 μm, р = 0,04.Conclusion. The obtained results indicate the importance of the vascular platelet hemostasis in POAG pathogenesis and the perspectives of its correction in glaucoma treatment.

  16. Studies of some cancer markers and blood factors in DMBA- induced breast cancer in SD rat strains

    Directory of Open Access Journals (Sweden)

    Ahmad Hamta

    2011-07-01

    Full Text Available Background: Animal suitable models are very useful tools in the studies of complicated diseases. In this way we can study the heterogeneity of human genome and also we can minimize the effect of environmental factors in the incidence of cancers. In this study the expression of VWF and PCNA in tumors was determined by immunohistochemistry and also we measured three cancer markers and two blood factors from affected rats.Methods: We have gavaged 10 mg DMBA dissolved in 0.5 ml sesame oil to the DMBA-treated SD rat strains. After tumor were appeared tumors were used for immunohistochemistry tests. Also we measured three cancer markers and two blood factors according to the manufacturer's protocol and results were analyzed by SPSS software.Results: Interaction of two antibodies PCNA and VWF with their antigen were more robust in tumors samples compared to controls with control samples. From blood factors only in tumors CA13.5 showed significant expression (p<0.05.Conclusion: Histopathology and immunohistochemistry results showed that breast cancer by induced DMBA in rats were similar to human breast cancer. The level of CA15.3 in induced tumors showed significantly increase compared to control blood samples, which is similar to behavior of this cancer marker in human breast cancer. But there was no significant association between treated and control samples related to the other four cancer markers and blood factors These results emphasized that DMBA-induced breast cancer in SD rat strains is a suitable model for biological studies on breast cancers.

  17. Changes in Content of Von Willebrand Factor and Its Catenase in Placental-Abruption Preterm Infants Cord Blood and Maternal Blood%胎盘早剥早产儿脐血与产妇静脉血血管性血友病因子及其裂解酶水平的变化

    Institute of Scientific and Technical Information of China (English)

    许靖; 李秋平; 孔祥永; 孔令凯; 陈冲; 杨璐; 周丽; 马兴娜; 封志纯

    2012-01-01

    目的 观察胎盘早剥新生儿脐血与产妇静脉血血管性血友病因子(VWF)及血管性血友病因子裂解酶(ADAMTS13)水平变化,探讨胎盘早剥新生儿凝血功能异常的病理机制.方法 北京军区总医院、北京妇产医院、北京市海淀医院产科2010年11月-2011年11月产科住院病人中,纳入发生胎盘早剥的产妇及新生儿作为胎盘早剥观察组(早剥组);非胎盘早剥观察组(非早剥组)为上述单位早剥组每例患者后2名产科入院患者,以办理入院登记时间为准.采集产妇的静脉血及新生儿脐静脉血、脐动脉血,并收集胎盘组织,用ELISA法检测其VWF、ADAMTS13水平.结果 早剥组共纳入58例,非早剥组共纳入116例.根据非早剥组检测值计算出单侧95%参考值.产妇静脉血:VWF< 857.80 U·L-1,ADAMTS13> 119.63 U·L-1;脐静脉血:VWF<852.71 U·L-1,ADAMTS13 >28.12 U·L-1;脐动脉血:VWF<1416.96 U·L-1,ADAMTS13> 147.90 U·L-1;胎盘组织VWF<760.66 U·L-1,ADAMTS13 >27.53 U·L-1.早剥组各项VWF高于非早剥组(Pa<0.05);早剥组产妇血及脐血ADAMTS13水平均低于非早剥组(Pa<0.05).结论 胎盘早剥孕妇/产妇及胎儿/新生儿体内ADAMTS13水平随VWF水平的升高而下降,VWF是胎盘早剥发生时母儿高凝状态的因素之一,ADAMTS13具有保护作用.%Objective To observe the changes in content of von willebrand factor( VWF) and its catenase(a disintegrin and metallopro-teinase with a thrombospondin type 1 motif, member 13, ADAMTS13) in the umbilical cord blood and maternal blood after placental abruption happening and to explore the pathophysiological mechanisms of the coagulation abnormalities of placental abruption. Methods The placental abruption group included the cases admitted to the General Hospital of Beijing Military Region, Obstetrics and Gynecology Hospital of Beijing and Haidian Obstetrics and Gynecology Hospital of Beijing from Nov. 2010 to Nov. 2011 ,and the 2 non

  18. Viagem ao País das Letras. Programa de Treino em Suporte Multimédia para Indução do Princípio Alfabético

    OpenAIRE

    Moreira, Maria de Lurdes

    2015-01-01

    As investigações que têm ajudado a perceber as dificuldades que as crianças enfrentam durante a aprendizagem da leitura e da escrita e a forma como o ensino pode ser estruturado no sentido de ajudar a ultrapassar essas dificuldades, têm identificado, fundamentalmente, como factores determinantes, a consciência fonológica, o conhecimento das letras, e as conceptualizaçõs infantis sobre a escrita. Neste sentido, e partindo dos pressupostos que o contacto com a linguagem escrita e a possibilidad...

  19. Therapeutic and routine prophylactic properties of rFactor VIII Fc (efraloctocog alfa, Eloctate®) in hemophilia A

    Science.gov (United States)

    Chowdary, Pratima; Fosbury, Emma; Riddell, Anne; Mathias, Mary

    2016-01-01

    rFVIIIFc (efraloctocog alfa, Eloctate®) is an extended half-life (EHL) factor VIII licensed for use in patients with hemophilia A for prophylaxis and treatment of bleeding and surgical episodes. Pharmacokinetic studies in adults have shown a mean 1.5-fold increase in half-life compared to full-length factor VIII. When compared to adults, the half-life is decreased by 8% in adolescents between 12 and 17 years, by 18% in children 6 to <12 years, and by 33% in children between the ages of 2 and <6 years. There is a considerable interindividual variation in the prolongation of the half-life particularly in children and across the age groups, the range extending from no increase to a 2.5-fold increase. In addition to age, von willebrand factor (VWF) antigen level has demonstrated a significant impact on rFVIIIFc half-life, with higher VWF levels associated with greater prolongation of half-life. The pivotal and pediatric clinical trials have demonstrated the efficacy and safety of rFVIIIFc for use in regular prophylaxis and in management of bleeds and surgery. In these studies, just under half the participants showed a zero annualized bleed rate (ABR), and the median ABR (1.6 in the pivotal study for the individualized prophylaxis arm) showed a further decrease in the extension study. On average, the patients required fewer infusions (reduced by at least a third), and the mean weekly consumption seems to be in keeping with standard recombinant factor VIII. EHL rFVIIIFc has made decreased infusion frequency a possibility. However, the interindividual variability in dose and infusion frequency highlights the need for a personalized approach based on individual patient’s half-life and/or response to treatment. PMID:27695377

  20. Profils d’apprentissage et représentations dans l’apprentissage des langues en environnement multimédia. Résultats d’une enquête en contexte universitaire. Learner profiles and attitudes in foreign language learning in a multimedia environment. Results of a survey conducted in a higher education context.

    Directory of Open Access Journals (Sweden)

    Joseph Rézeau

    1999-06-01

    Full Text Available Dans le domaine de l’apprentissage, les profils d’apprentissage et les représentations des apprenants jouent un rôle fondamental. La recherche exposée dans cet article met en évidence des différences sensibles de profil d’apprentissage des langues chez des étudiants spécialisés en langues d’une part et des étudiants d’autres disciplines d’autre part. Elle montre également que les représentations de l’apprentissage des langues et celles des Technologies de l’Information et de la Communication (TIC chez ces deux populations sont des représentations sociales, qui montrent un recouvrement entre les deux domaines étudiés. Enfin, une étude longitudinale d’un échantillon de la population étudiée montre que les profils d’apprentissage et les représentations sont susceptibles d’évolution. La question reste posée de l’influence de l’environnement multimédia d’apprentissage de la langue sur cette évolution constatée.In the field of learning, the learners’ attitudes and representations play a fundamental role. The research presented in this article shows significant differences in the language learning profiles of university students specialised in languages on the one hand and specialists of other disciplines on the other hand. Our research also shows that the representations of language learning and the representations of the Information and Communication Technologies (ICT held by the subjects in these two populations are social representations, showing overlap between the two domains studied. Finally, a longitudinal study of a sample of the population under review shows that both learners’ profiles and representations are open to evolution. The question remains of the influence exerted by the multimedia language learning environment over the said evolution.

  1. Un environnement multimédia privilégiant l’expression en langage naturel, pour des activités éducatives de type piagétien A multimedia environment favouring natural language expression, for educational piagetian games

    Directory of Open Access Journals (Sweden)

    Élisabeth Godbert

    2000-12-01

    Full Text Available Nous nous intéressons dans cet article au développement de logiciels éducatifs proposant, dans un environnement multimédia, multimodal et réactif privilégiant l’expression en langage naturel, des exercices de type piagétien pour l’aide à l’apprentissage du langage. Dans ce type de système, chaque exercice met en jeu un micro-monde d’objets graphiques sur lesquels l’enfant utilisateur peut agir (modification, déplacement, suppression d’objets, etc., en formulant des requêtes en langage naturel auxquelles le système répond. Nous présentons un logiciel éducatif de cette famille, que nous avons conçu et développé ces dernières années. Nous décrivons en premier lieu les objectifs pédagogiques et les fonctionnalités de notre logiciel, puis le système que nous y utilisons pour le traitement automatique du langage. Nous décrivons ensuite l’ensemble des composants qui structure les connaissances qu’il a été nécessaire de modéliser, articuler et gérer pour la réalisation de ce système.This paper deals with the development of educational software, which proposes, in a multimedia, multimodal and reactive environment favoring natural language expression, piagetian games designed for natural language learning. In such systems, each exercise brings into play a micro-world of graphic objects on which the user can act (for example to modify, move or withdraw the objects, by composing natural language queries to which the system gives an answer. We present a software of this type, that has been designed and implemented these last years. We firstly describe the educational objectives and the functionality of the software, then the natural language processing system which is used in it. Finally we describe the set of components that structures knowledge modeled, articulated and managed in order to carry out this educational system.

  2. Plasma von Willebrand factor as a predictor of survival in pulmonary arterial hypertension associated with congenital heart disease

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    A.A. Lopes

    2011-12-01

    Full Text Available Biomarkers have been identified for pulmonary arterial hypertension, but are less well defined for specific etiologies such as congenital heart disease-associated pulmonary arterial hypertension (CHDPAH. We measured plasma levels of eight microvascular dysfunction markers in CHDPAH, and tested for associations with survival. A cohort of 46 inoperable CHDPAH patients (age 15.0 to 60.2 years, median 33.5 years, female:male 29:17 was prospectively followed for 0.7 to 4.0 years (median 3.6 years. Plasma levels of von Willebrand factor antigen (VWF:Ag, tissue plasminogen activator (t-PA and its inhibitor (PAI-1, P-selectin, reactive C-protein, tumor necrosis factor alpha, and interleukin-6 and -10 were measured at baseline, and at 30, 90, and 180 days in all subjects. Levels of six of the eight proteins were significantly increased in patients versus controls (13 to 106% increase, P < 0.003. Interleukin-10 level was 2.06 times normal (P = 0.0003; Th2 cytokine response. Increased levels of four proteins (t-PA, PAI-1, P-selectin, and interleukin-6 correlated with disease severity indices (P < 0.05. Seven patients died during follow-up. An average VWF:Ag (mean of four determinations above the level corresponding to the 95th percentile of controls (139 U/dL was independently associated with a high risk of death (hazard ratio = 6.56, 95%CI = 1.46 to 29.4, P = 0.014. Thus, in CHDPAH, microvascular dysfunction appears to involve Th2 inflammatory response. Of the biomarkers studied, plasma vWF:Ag was independently associated with survival.

  3. The expression of von Willebrand factor and interleukin-8 in severe pulmonary contusion patients%严重肺挫伤患者冯·维勒布兰德因子,白介素8的动态变化及其意义

    Institute of Scientific and Technical Information of China (English)

    钱进先; 陆骏灏; 陆士奇; 赵益明

    2011-01-01

    Objective To study the clinical changes of von Willebrand factor( vWF) and interleukin-8 (IL-8) in patients with severe pulmonary contusion. Methods Sixty-three patients with severe pulmonary contusion were divided into three different classifications for the sake of comparison in different respects, namely (1) severe pulmonary contusion with ARDS group and severe pulmonary contusion without ARDS group, (2) survival group and non-survival group, and (3) ISS score <20 group and ISS scored 20 group. In addition, the normal control group was set up. The levels of plasma vWF and serum IL-8 were respectively detected by double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) within 24 hours of injury and 1,3,5 and 7days after injury. The regularity of their changes was observed and the correlation factors were analyzed from the data. Results Compared with normal controls, the concentrations of plasma vWF and serum IL-8 were significantly increased in patients with severe pulmonary contusion in all intervals of detection. The concentrations of plasma vWF escalated gradually in severe pulmonary contusion with ARDS, and reached significantly higher levels in 5 days and 7 days after injury compared with those without ARDS group (P <0. 05). The increase in concentrations of serum IL-8 peaked in 5day after injury, and then declined. The levels of serum IL-8 were higher in patients with severe pulmonary contusion with ARDS group than those in this kind of patients without ARDS group. The levels of plasma vWF and serum IL-8 were higher in non - survival group than those in survival group (P < 0.05). The increase in levels of plasma vWF and serum IL-8 peaked and then declined in 5 days in ISS score 3:20 group, whereas it peaked and declined in 3 days after injury in ISS score < 20 group. The level of plasma vWF was positively correlated with platelets and negatively correlated with oxygenation index. The levels of serum IL-8 was positively correlated with white blood

  4. 冠心病患者 PCI 治疗前后内皮素、血管性假血友病因子改变与早期并发症的关系%Correlation between Endothelin and the von Willebrand Factor Changes with the Presence of Complications in Patients with Coronary Heart Disease After the PCI Procedure

    Institute of Scientific and Technical Information of China (English)

    苏布道

    2015-01-01

    Objective]To study the changes of endothelin (ET)and the von Willebrand factor (vWF)before and af-ter interventional therapy in patients with coronary heart disease and the use of the two variables in predicting the presence of postoperative complications.[Methods]Two hundred and seventy-three patients with coronary heart disease in our hos-pital from January 2014 to January 2010 were selected,and the levels of serum ET and vWF were carefully monitored at certain time intervals.Additionally,the presence of postoperative complications after one year were compared with the changes of serum ET and vWF to find any correlation.[Results]Serum ET and vWF levels in the Acute Myocardia Infarc-tion (AMI)group,Unstable Angina Pectoris (UAP)group,and Stable Angina Pectoris (SAP)group before surgery,30 minutes after,and 24 hours after surgery were all significantly higher than those of the control group.The difference was statistically significant (all P <0.05).The serum Et and vWF levels in the AMI,UAP,SAP groups before surgery,30 minutes after,24 hours after,and three days after surgery were presented first as increasing and then decreasing.,The serum ET level reached its peak 30 min after the surgery while the serum vWF level peaks at 24 hours after the surgery. Peak levels of serum ET and vWF in patients with complications were significantly higher than the peak levels in the pa-tients without complications (P <0.05).Logistic regression analysis of hypertension (RR = 1.752,P =0.033),diabe-tes (RR = 1.325,P =0.038),preoperative ET level (RR = 2.896,P =0.041),and preoperative vWF levels (RR =2.336,P =0.035)were statistically significant (P <0.05)in predicting PCI complications.[Conclusion]Endothelin and the von Willebrand factor can reflect the damage of endothelium to provide value for predicting the presence of postopera-tive complications in patients with coronary heart disease..%【目的】研究冠心病患者行经皮冠状动脉介入术(PCI)前后内皮素(ET)、血

  5. Accurate Extraction of Nanometer Distances in Multimers by Pulse EPR

    Science.gov (United States)

    Valera, Silvia; Ackermann, Katrin; Pliotas, Christos; Huang, Hexian; Naismith, James H.

    2016-01-01

    Abstract Pulse electron paramagnetic resonance (EPR) is gaining increasing importance in structural biology. The PELDOR (pulsed electron–electron double resonance) method allows extracting distance information on the nanometer scale. Here, we demonstrate the efficient extraction of distances from multimeric systems such as membrane‐embedded ion channels where data analysis is commonly hindered by multi‐spin effects. PMID:26865468

  6. Formation of highly ordered multimers in G-quadruplexes.

    Science.gov (United States)

    Tóthová, Petra; Krafčíková, Petra; Víglaský, Viktor

    2014-11-18

    G-Rich DNA and RNA have a higher propensity to form G-quadruplex structures, but the presence of G-runs alone is not sufficient to prove that such sequences can form stable G-quadruplexes. While G-rich sequences are essential for G-quadruplex formation, not all G-rich sequences have the propensity to form G-quadruplex structures. In addition, monovalent metal ions, dehydrating agents, and loop sequences connecting the G-runs also play important roles in the topology of G-quadruplex folding. To date, no quantitative analysis of the CD spectra of G-quadruplexes in confrontation with the electrophoretic results has been performed. Therefore, in this study, we use information gained through the analysis of a series of well-known G-quadruplex-forming sequences to evaluate other less-studied sets of aptameric sequences. A simple and cost-effective methodology that can verify the formation of G-quadruplex motifs from oligomeric DNA sequences and a technique to determine the molecularity of these structures are also described. This methodology could be of great use in the prediction of G-quadruplex assembly, and the basic principles of our techniques can be extrapolated for any G-rich DNA sequences. This study also presents a model that can predict the multimerization of G-quadruplexes; the predictions offered by this model are shown to match the results obtained using circular dichroism.

  7. Synthesis and evaluation of radiolabeled peptide multimers for tumor targeting

    NARCIS (Netherlands)

    Yim, C.B.

    2011-01-01

    Many cancer types express specific receptors on their cellular surface onto which regulatory peptides bind with high affinity. This mechanism can be exploited by labeling the peptide with a radionuclide and using the radiolabeled peptide as a vehicle to guide the radioactivity to receptor-rich cells

  8. The role of adiponectin multimers in anorexia nervosa.

    Science.gov (United States)

    Amitani, Haruka; Asakawa, Akihiro; Ogiso, Kazuma; Nakahara, Toshihiro; Ushikai, Miharu; Haruta, Izumi; Koyama, Ken-ichiro; Amitani, Marie; Cheng, Kai-chun; Inui, Akio

    2013-01-01

    Anorexia nervosa (AN) continues to be a refractory disease because of its unknown pathogenesis. The role of adiponectin in AN has not been clarified. Moreover, few reports have described the relations between adiponectin isoforms and AN in the physical and psychological states. Therefore, we measured plasma adiponectin and its isoforms levels in patients with AN to examine their roles in AN. Eighteen women participated in this study: nine patients with AN and nine age-matched healthy controls. We examined plasma adiponectin and its isoforms levels in all subjects and administered three types of psychological test to patients with AN: the Eating Disorders Inventory-2, the Maudsley Obsessional-Compulsive Inventory, and the Beck Depression Inventory-2. We found that the percentage of high-molecular-weight (HMW) to total adiponectin (%HMW) was significantly low and the percentage of low-molecular-weight (LMW) to total adiponectin (%LMW) was significantly high in the AN group compared with the control group. The %HMW positively and the %LMW negatively correlated with body mass index in the entire study population. The %HMW was also positively correlated with psychological symptoms such as social insecurity or cleaning evaluated with the Eating Disorders Inventory-2 or the Maudsley Obsessional-Compulsive Inventory. Our study indicates that all adiponectin isoforms should be evaluated in patients with AN in addition to total adiponectin. The decreased %HMW and the increased %LMW that were correlated with the body mass index and some components of psychopathology in our patients may indicate a complex role of adiponectin isoforms in maintaining energy homeostasis and emotion during extreme malnourishment. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Consumption of nattokinase is associated with reduced blood pressure and von Willebrand factor, a cardiovascular risk marker: results from a randomized, double-blind, placebo-controlled, multicenter North American clinical trial

    Directory of Open Access Journals (Sweden)

    Jensen GS

    2016-10-01

    Full Text Available Gitte S Jensen,1 Miki Lenninger,1 Michael P Ero,2 Kathleen F Benson,1 1NIS Labs, Klamath Falls, OR, 2Machaon Diagnostics, Inc., Oakland, CA, USA Objective: The objective of this study is to evaluate the effects of consumption of nattokinase on hypertension in a North American hypertensive population with associated genetic, dietary, and lifestyle factors. This is in extension of, and contrast to, previous studies on Asian populations.Materials and methods: A randomized, double-blind, placebo-controlled, parallel-arm clinical study was performed to evaluate nattokinase (NSK-SD, a fermented soy extract nattō from which vitamin K2 has been removed. Based on the results from previous studies on Asian populations, 79 subjects were enrolled upon screening for elevated blood pressure (BP; systolic BP ≥130 or diastolic BP ≥90 mmHg who consumed placebo or 100 mg nattokinase/d for the 8-week study duration. Blood collections were performed at baseline and 8 weeks for testing plasma renin activity, von Willebrand factor (vWF, and platelet factor-4. Seventy-four people completed the study with good compliance.Results: Consumption of nattokinase was associated with a reduction in both systolic and diastolic BP. The reduction in systolic BP was seen for both sexes but was more robust in males consuming nattokinase. The average reduction in diastolic BP in the nattokinase group from 87 mmHg to 84 mmHg was statistically significant when compared to that in the group consuming placebo, where the average diastolic BP remained constant at 87 mmHg (P<0.05, and reached a high level of significance for males consuming nattokinase, where the average diastolic BP dropped from 86 mmHg to 81 mmHg (P<0.006. A decrease in vWF was seen in the female population consuming nattokinase (P<0.1. In the subpopulation with low plasma renin activity levels at baseline (<0.29 ng/mL/h, an increase was seen for 66% of the people after 8-week consumption of nattokinase (P

  10. Endothelial markers in malignant vascular tumours of the liver: superiority of QB-END/10 over von Willebrand factor and Ulex europaeus agglutinin 1.

    Science.gov (United States)

    Anthony, P P; Ramani, P

    1991-01-01

    A new monoclonal antibody, QB-END/10, raised against the CD34 antigen in human endothelial cell membranes and haemopoietic progenitor cells, was studied for its usefulness as a marker of neoplastic vascular cells in 21 angiosarcomas and seven malignant haemangioendotheliomas of the liver. QB-END/10 was both more sensitive and more specific than Von Willebrand factor (VWF) and Ulex europaeus 1 agglutinin (UEA-1) in labelling endothelial cells and it did not cross react with epithelia as UEA-1 often does. Staining was uniformly strong and clear in all histological variants of these two tumours. QB-END/10 should prove particularly useful in the differential diagnosis of malignant vascular tumours of the liver. Images PMID:1705261

  11. Six amino acid residues in a 1200 A2 interface mediate binding of factor VIII to an IgG4κ inhibitory antibody.

    Directory of Open Access Journals (Sweden)

    Jasper C Lin

    Full Text Available The development of neutralizing anti-factor VIII (FVIII antibodies complicates the treatment of many hemophilia A patients. The C-terminal C2 domain is a particularly antigenic FVIII region. A crystal structure of recombinant FVIII-C2 bound to an Fab fragment of the patient-derived monoclonal antibody BO2C11, which recognizes an immunodominant inhibitor epitope on FVIII and blocks its ability to bind von Willebrand factor (VWF and phospholipids, revealed that 15 amino acids in FVIII contact this antibody. Forty-three recombinant FVIII-C2 proteins, each with a surface-exposed side chain mutated to alanine or another residue, were generated, and surface plasmon resonance studies were carried out to evaluate effects of these substitutions on BO2C11/FVIII-C2 binding affinity. Thermodynamic analysis of experiments carried out at three temperatures indicated that one beta hairpin turn at the antigen-antibody interface (FVIII-F2196, N2198, M2199 and F2200 plus two non-contiguous arginines (FVIII-R2215 and R2220, contributed appreciably to the affinity. B-domain-deleted (BDD FVIII-F2196A, FVIII-F2196K and FVIII-M2199A were generated and characterized. Their pro-coagulant activities and binding to VWF were similar to those of WT-BDD-FVIII, and FVIII-F2196K avoided neutralization by BO2C11 and murine inhibitory mAb 1B5. This study suggests specific sites for amino acid substitutions to rationally design FVIII variants capable of evading immunodominant neutralizing anti-FVIII antibodies.

  12. Correlation between expressions of hypoxia -inducible factor (HIF-1α, blood vessels density, cell proliferation, and apoptosis intensity in canine fibromas and fibrosarcomas

    Directory of Open Access Journals (Sweden)

    Madej Janusz A.

    2014-03-01

    Full Text Available The study aimed to demonstrate the expression of hypoxia-inducible factor (HIF-1α in soft tissue mesenchymal tumours (fibroma and fibrosarcoma in dogs. An attempt was made to correlate the obtained results with density of blood vessels (expression of von Willebrand Factor, vWF, expression of Ki-67 proliferation antigen, and with intensity of apoptosis in studied tumours. The study was performed on paraffin sections of 15 fibromas and 40 fibrosarcomas sampled from 55 female dogs aged 6 to 16 years. Immunohistochemical staining against HIF-1α, vWF, and Ki-67 was performed. Apoptosis was detected with the use of TUNEL reaction. A significantly higher HIF-1α expression was noted in fibrosarcomas in comparison to fibromas (P < 0.0001. HIF-1α expression in fibromas manifested strong positive correlation with tumour vascularity (r = 0.67, P = 0.007. Moreover, HIF-1α expression in fibrosarcomas manifested a moderate positive correlation with tumour malignancy grade (r = 0.44, P = 0.004, tumour vascularity (r = 0.52, P < 0.001, Ki-67 antigen expression (r = 0.42; P = 0.007, and TUNELpositive cells (r = 0.37, P = 0.017. Expression of HIF-1α was detected in 86.7% of fibroma type tumours and in 100% of fibrosarcomas. In all studied tumours expression of HIF-1α manifested positive correlation with the density of blood vessels, and in fibrosarcomas it correlated also with malignancy grade, intensity of Ki-67 expression, and with intensity of apoptosis in tumour cells.

  13. Histone H1 functions as a stimulatory factor in backup pathways of NHEJ

    Science.gov (United States)

    Rosidi, Bustanur; Wang, Minli; Wu, Wenqi; Sharma, Aparna; Wang, Huichen; Iliakis, George

    2008-01-01

    DNA double-strand breaks (DSBs) induced in the genome of higher eukaryotes by ionizing radiation (IR) are predominantly removed by two pathways of non-homologous end-joining (NHEJ) termed D-NHEJ and B-NHEJ. While D-NHEJ depends on the activities of the DNA-dependent protein kinase (DNA-PK) and DNA ligase IV/XRCC4/XLF, B-NHEJ utilizes, at least partly, DNA ligase III/XRCC1 and PARP-1. Using in vitro end-joining assays and protein fractionation protocols similar to those previously applied for the characterization of DNA ligase III as an end-joining factor, we identify here histone H1 as an additional putative NHEJ factor. H1 strongly enhances DNA-end joining and shifts the product spectrum from circles to multimers. While H1 enhances the DNA-end-joining activities of both DNA Ligase IV and DNA Ligase III, the effect on ligase III is significantly stronger. Histone H1 also enhances the activity of PARP-1. Since histone H1 has been shown to counteract D-NHEJ, these observations and the known functions of the protein identify it as a putative alignment factor operating preferentially within B-NHEJ. PMID:18250087

  14. Crosslinking of eukaryotic initiation factor eIF3 to the 40S ribosomal subunit from rabbit reticulocytes.

    Science.gov (United States)

    Tolan, D R; Hershey, J W; Traut, R T

    1983-07-01

    Complexes of purified 40S ribosomal subunits and initiation factor 3 from rabbit reticulocytes were crosslinked using the reversible protein crosslinking reagent, 2-iminothiolane, under conditions shown previously to lead to the formation of dimers between 40S proteins but not higher multimers. The activity of both the 40S subunits and initiation factor 3 was maintained. Protein crosslinked to the factor was purified by sucrose density gradient centrifugation following nuclease digestion of the ribosomal subunit: alternatively, the total protein was extracted from 40S: factor complexes. The protein obtained by either method was analyzed by two-dimensional diagonal polyacrylamide/sodium dodecyl sulfate gel electrophoresis. Ribosomal proteins were found in multimeric complexes of high molecular weight due to their crosslinking to components of eIF3. Identification of the ribosomal proteins appearing below the diagonal was accomplished by elution, radioiodination, two-dimensional polyacrylamide/urea gel electrophoresis, and radioautography. Proteins S2, S3, S3a, S4, S5, S6, S8, S9, S11, S12, S14, S15, S16, S19, S24, S25, and S26 were identified. Because many of the proteins in this group form crosslinked dimers with each other, it was impossible to distinguish proteins directly crosslinked to eIF3 from those crosslinked indirectly through one bridging protein. The results nonetheless imply that the 40S ribosomal proteins identified are at or near the binding site for initiation factor 3.

  15. Effects of Hirudo (水蛭) extract on release of coagulation factor from cultured human umbilical vein endothelial cells induced by thrombin%水蛭提取液对凝血酶诱导血管内皮细胞释放凝血因子的影响

    Institute of Scientific and Technical Information of China (English)

    黄莺; 张晓青; 李龙; 易小民; 田雪飞

    2011-01-01

    Objective To study the effect of Hirudo (水蛭) extract on the release of von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (t-PA) from cultured human umbilical vein endothelial cells (HUVECs) induced by thrombin, and preliminarily investigate the anti-coagulating mechanism of the extract. Methods The HUVECs were cultured in vitro. The well grown 2 - 3 generation HUVECs were divided into five groups: the control, thrombin challenge, and high,medium, and low concentration Hirudo extract groups. Different concentrations of Hirudo extracts (600, 300,150 mg/L) were given after administration of thrombin (10 kU/L) in the high, medium, and low concentration Hirudo extract groups. The control group was given equal amount of RPMI1640 culture medium. The HUVECs were cultured for 12 hours and the supernatant was then collected in each group. The concentrations of vWF, PAI-1, and t-PA were measured with enzyme linked immunosorbent assay (ELISA).Results Compared with the control group, the concentrations of vWF and PAI-1 (μg/L) were significantly increased [vWF: (11.01±0.54)% vs. (7.05±0.49)%; PAI-1: 72.26±0.85 vs. 55.89±1.26, both P<0.01] and the concentration of t-PA (μg/L) was markedly decreased in thrombin challenge group (15.15±1.41 vs. 34.29±1.22, P<0.01). Compared with the thrombin challenge group, the concentrations of vWF and PAI-1 [vWF: (9.48±0.64)%, (8.57±0.50)%, (7.97±0.44)%; PAI-1: 58.30±0.90, 62.69±1.01,67. 47±1.28] were substantially decreased, and that of t-PA (32. 59±1.46, 26. 40±0. 82, 21. 06±1.13) was markedly increased (all P<0. 01) in the high, medium, low concentration Hirudo extract groups. These results showed that the Hirudo extract could significantly inhibit the release of vWF and PAI-1, and enhance the release of t-PA from HUVECs induced by thrombin. Conclusion The Hirudo extract has a noticeable effect of anticoagulation. Its mechanism may be related to the

  16. Expression of vascular endo- thelial growth factor in rat uterus during peri- implantation

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The first distinct mark of rodent implantation is the increased vascular permeability and significant angiogenesis at the sites of blastocyst implantation, but its mechanism is not clearly defined. Vascular endothelial growth factor (VEGF) is the key mediator for angiogenesis during embryogenesis and adult span and also serves as a vascular permeability factor. The aim of this study is to explore VEGF regulation mechanism and the possible role that VEGF plays in implantation by studying the VEGF expression and angio-genesis in the rat uterus during estrous cycle, ovarioecto-mized and peri-implantation stages using in situ message RNA hybridization and confocal laser scanning techniques. The results indicated that VEGF was regulated by ovarian steroid hormones. VEGF expression before implantation was localized at luminal epithelium, shifted to stroma as implan-tation initiated and extensively located at the decidualizing stroma region after implantation. Bandeiraea simplicifolia-1 (BS-1) agglutinin and antibody against von Willebrand fac-tor (vWF) were used to mark the endothelial cells and blood vessels. The results showed that the active angiogenesis oc-curred during the implantation process and this effect was probably mediated by VEGF. The results suggest that under the regulation of ovarian steroid hormones, VEGF plays an essential role in angiogenesis and increasing vascular perme-ability in endometrium, which are necessary for successful implantation.

  17. 血管性血友病因子及P-选择素对狼疮肾炎患者疾病严重程度的评估作用研究%Value of Von Willebrand Factor and P-selectin in Assessing Severity of Illness in Lupus Nephritis Patients

    Institute of Scientific and Technical Information of China (English)

    杨军; 郭明好; 刘云; 张燕

    2013-01-01

    Objective To explore the value of von Willebrand Factor ( vWF ) and P - selectin in assessing severity of illness in lupus nephritis patients. Methods The level of vWF and P - selectin in 46 cases of lupus nephritis were determined. Disease activity index, renal histological activity index, and disease chronicity index were compared between the study group ( lupus nephritis patients ) and the control group ( 10 cases of health checkups ) . Results There were 5 cases of type Ⅱ lupus nephritis, 12 cases of type Ⅲ , 20 cases of type Ⅳ , and 9 cases of type V. Patients of type Ⅳ lupus nephritis had the highest disease activity index, renal histological activity index, and disease chronic index, while type Ⅱ had the lowest. The expression of vWF and P - selectin in type Ⅳ and V lupus nephritis patients were higher than that of type Ⅱ and type Ⅲ ( P < 0. 05 ) and that of the control group ( P <0. 05 ). Correlation analysis showed that vWF was positively correlated with renal histological activity index, and nearly correlated with disease activity index. P - selectin was positively correlated with disease activity index, renal histological activity index, and disease chronicity index. Conclusion The expression of vWF and P - selectin indicates disease activity and severity in lupus nephritis patients, therefore can be used as a marker to guide clinical therapy.%目的 研究血管性血友病因子(vWF)及P-选择素对狼疮肾炎患者疾病严重程度的评估作用.方法 检测我院46例狼疮肾炎患者vWF及P-选择素水平,测量疾病活动指数(SLEDAI)、肾组织活动指数、疾病慢性指数,并与健康体检者进行对比分析.结果 纳入狼疮肾炎患者Ⅱ型5例,Ⅲ型12例,Ⅳ型20例,Ⅴ型9例.不同分型的狼疮肾炎患者SLEDAI评分、肾组织活动指数均以Ⅳ型最高,Ⅱ型最低.vWF、P-选择素在Ⅳ及Ⅴ型狼疮肾炎患者中表达水平最高,且与其他两组患者相比差异有统计学意义(P<0

  18. Challenges of the management of severe hemophilia A with inhibitors: two case reports emphasizing the potential interest of a high-purity human Factor VIII/von Willebrand factor concentrate and individually tailored prophylaxis guided by thrombin-generation test.

    Science.gov (United States)

    Mathieu, Sophie; Crampe, Carine; Dargaud, Yesim; Lavigne-Lissalde, Géraldine; Escuriola-Ettingshausen, Carmen; Tardy, Brigitte; Meley, Roland; Thouvenin, Sandrine; Stephan, Jean L; Berger, Claire

    2015-12-01

    Severe hemophilia A is an X-linked bleeding disorder. Immune tolerance induction (ITI) is the best strategy of treatment when patients develop inhibitors. The objective is to illustrate the benefit of a high-purity human factor VIII/von Willebrand factor (VWF) concentrate (Octanate) in the management of ITI. We also wanted to raise the potential interest of laboratory assays such as thrombin-generation test (TGT) and epitope mapping. Two patients were treated during ITI, first with a recombinant FVIII and then with plasma-derived factor VIII without success, and, finally, with Octanate. Bypassing agents were used based on the results of TGT. Epitope mapping was performed during ITI therapy. These observations suggest the potential contribution of Octanate in the management of ITI in difficult cases. The use of bypassing agents can be necessary in prophylaxis or to treat bleedings, and may be guided by TGT results. Epitope mapping is used to describe the inhibitor. This article shows a decrease of the inhibitor directed against the C2 domain after initiation of Octanate. A high-purity human factor VIII/von Willebrand factor concentrate (Octanate) may be a valuable therapeutical option for ITI therapy. TGT and epitope mapping could be of help in the management of ITI.

  19. Conventional rapid latex agglutination in estimation of von Willebrand factor: method revisited and potential clinical applications.

    Science.gov (United States)

    Mahat, Marianor; Abdullah, Wan Zaidah; Hussin, Che Maraina Che

    2014-01-01

    Measurement of von Willebrand factor antigen (VWF : Ag) levels is usually performed in a specialised laboratory which limits its application in routine clinical practice. So far, no commercial rapid test kit is available for VWF : Ag estimation. This paper discusses the technical aspect of latex agglutination method which was established to suit the purpose of estimating von Willebrand factor (VWF) levels in the plasma sample. The latex agglutination test can be performed qualitatively and semiquantitatively. Reproducibility, stability, linearity, limit of detection, interference, and method comparison studies were conducted to evaluate the performance of this test. Semiquantitative latex agglutination test was strongly correlated with the reference immunoturbidimetric assay (Spearman's rho = 0.946, P agglutination test and the reference assay. Using the scoring system for the rapid latex test, no agglutination is with 0% VWF : Ag (control negative), 1+ reaction is equivalent to 150% VWF : Ag (when comparing with immunoturbidimetric assay). The findings from evaluation studies suggest that latex agglutination method is suitable to be used as a rapid test kit for the estimation of VWF : Ag levels in various clinical conditions associated with high levels and low levels of VWF : Ag.

  20. Conventional Rapid Latex Agglutination in Estimation of von Willebrand Factor: Method Revisited and Potential Clinical Applications

    Directory of Open Access Journals (Sweden)

    Marianor Mahat

    2014-01-01

    Full Text Available Measurement of von Willebrand factor antigen (VWF : Ag levels is usually performed in a specialised laboratory which limits its application in routine clinical practice. So far, no commercial rapid test kit is available for VWF : Ag estimation. This paper discusses the technical aspect of latex agglutination method which was established to suit the purpose of estimating von Willebrand factor (VWF levels in the plasma sample. The latex agglutination test can be performed qualitatively and semiquantitatively. Reproducibility, stability, linearity, limit of detection, interference, and method comparison studies were conducted to evaluate the performance of this test. Semiquantitative latex agglutination test was strongly correlated with the reference immunoturbidimetric assay (Spearman’s rho = 0.946, P150% VWF : Ag (when comparing with immunoturbidimetric assay. The findings from evaluation studies suggest that latex agglutination method is suitable to be used as a rapid test kit for the estimation of VWF : Ag levels in various clinical conditions associated with high levels and low levels of VWF : Ag.

  1. ADAMTS13 predicts renal and cardiovascular events in type 2 diabetic patients and response to therapy.

    Science.gov (United States)

    Rurali, Erica; Noris, Marina; Chianca, Antonietta; Donadelli, Roberta; Banterla, Federica; Galbusera, Miriam; Gherardi, Giulia; Gastoldi, Sara; Parvanova, Aneliya; Iliev, Ilian; Bossi, Antonio; Haefliger, Carolina; Trevisan, Roberto; Remuzzi, Giuseppe; Ruggenenti, Piero

    2013-10-01

    In patients with diabetes, impaired ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13) proteolysis of highly thrombogenic von Willebrand factor (VWF) multimers may accelerate renal and cardiovascular complications. Restoring physiological VWF handling might contribute to ACE inhibitors' (ACEi) reno- and cardioprotective effects. To assess how Pro618Ala ADAMTS13 variants and related proteolytic activity interact with ACEi therapy in predicting renal and cardiovascular complications, we genotyped 1,163 normoalbuminuric type 2 diabetic patients from BErgamo NEphrologic DIabetes Complications Trial (BENEDICT). Interaction between Pro618Ala and ACEi was significant in predicting both renal and combined renal and cardiovascular events. The risk for renal or combined events versus reference Ala carriers on ACEi progressively increased from Pro/Pro homozygotes on ACEi (hazard ratio 2.80 [95% CI 0.849-9.216] and 1.58 [0.737-3.379], respectively) to Pro/Pro homozygotes on non-ACEi (4.77 [1.484-15.357] and 1.99 [0.944-4.187]) to Ala carriers on non-ACEi (8.50 [2.416-29.962] and 4.00 [1.739-9.207]). In a substudy, serum ADAMTS13 activity was significantly lower in Ala carriers than in Pro/Pro homozygotes and in case subjects with renal, cardiovascular, or combined events than in diabetic control subjects without events. ADAMTS13 activity significantly and negatively correlated with all outcomes. In patients with diabetes, ADAMTS13 618Ala variant associated with less proteolytic activity, higher risk of chronic complications, and better response to ACEi therapy. Screening for Pro618Ala polymorphism may help identify patients with diabetes at highest risk who may benefit the most from early reno- and cardioprotective therapy.

  2. Optimisation of the Factor VIII yield in mammalian cell cultures by reducing the membrane bound fraction

    DEFF Research Database (Denmark)

    Kolind, Mille Petersen; Nørby, Peder Lisby; Berchtold, Martin Werner

    2011-01-01

    and forms the tenase complex together with clotting Factor IX. In vitro, during serum free production of recombinant FVIII (rFVIII), production cells also expose PS, and since vWF is not present to hinder interaction of secreted rFVIII with PS, rFVIII is partly associated with the cell membrane...... of active membrane bound rFVIII to the culture medium. Moreover, the attachment of rFVIII to cell membranes of un-transfected HEK293 cells was studied in the presence of compounds that competes for interactions between rFVIII and PS. Competitive assays between iodinated rFVIII (¹²5I-rFVIII) and annexin V...... or ortho-phospho-L-serine (OPLS) demonstrated that annexin V and OPLS were able to reduce the membrane bound fraction of rFVIII by 70% and 30%, respectively. Finally, adding OPLS to CHO cells stably expressing FVIII increased the yield by 50%. Using this new knowledge, the recovery of rFVIII could...

  3. Glial cell line-derived neurotrophic factor induced the differentiation of amniotic fluid-derived stem cells into vascular endothelial-like cells in vitro.

    Science.gov (United States)

    Zhang, Ruyu; Lu, Ying; Li, Ju; Wang, Jia; Liu, Caixia; Gao, Fang; Sun, Dong

    2016-02-01

    Amniotic fluid-derived stem cells (AFSCs) are a novel source of stem cells that are isolated and cultured from second trimester amniocentesis. Glial cell line-derived neurotrophic factor (GDNF) acts as a tissue morphogen and regulates stem cell proliferation and differentiation. This study investigated the effect of an adenovirus-mediated GDNF gene, which was engineered into AFSCs, on the cells' biological properties and whether GDNF in combination with AFSCs can be directionally differentiated into vascular endothelial-like cells in vitro. AFSCs were isolated and cultured using the plastic adherence method in vitro and identified by the transcription factor Oct-4, which is the primary marker of pluripotent stem cells. AFSCs were efficiently transfected by a GFP-labeled plasmid system of an adenovirus vector carrying the GDNF gene (Ad-GDNF-GFP). Transfected AFSCs stably expressed GDNF. Transfected AFSCs were cultured in endothelial growth medium-2 containing vascular endothelial growth factor. After 1 week, AFSCs were positive for von Willebrand factor (vWF) and CD31, which are markers of endothelial cells, and the recombinant GDNF group was significantly higher than undifferentiated controls and the GFP only group. These results demonstrated that AFSCs differentiated into vascular endothelial-like cells in vitro, and recombinant GDNF promoted differentiation. The differentiation-induced AFSCs may be used as seed cells to provide a new manner of cell and gene therapies for transplantation into the vascular injury site to promote angiogenesis.

  4. Haemostatic factors, lipoproteins and long-term mortality in a multi-ethnic population of Gujarati, African-Caribbean and European origin.

    Science.gov (United States)

    Anderson, S G; Hutchings, D C; Heald, A H; Anderson, C D; Sanders, T A B; Cruickshank, J K

    2014-09-01

    To examine the relations between haemostatic factors and lipoproteins with mortality in British Europeans, African-Caribbeans (AfC) and Gujarati Indians. A prospective cohort study of 331 subjects (40-79 years), followed-up over 26 years for mortality. Apolipoprotein-A1 (Apo-A1), apolipoprotein-B (Apo-B), factor VII coagulant activity (FVIIc), fibrinogen and von Willebrand Factor (vWF) were measured at baseline in 118 Europeans, 100 AfC and 113 Gujaratis. Aortic pulse wave velocity (aPWV) was measured in 174 participants. 147 (44.4%) subjects died during a median of 24 years follow-up with 69 cardiovascular deaths. Women at baseline had higher, and AfC males the lowest FVIIc and Apo-A1 levels. Baseline age-sex and ethnicity adjusted FVIIc levels were higher in those who died (131.0 vs. 117.4%; P = 0.048). In similarly adjusted partial correlations, Apo-A1 was inversely related to arterial stiffness (ρ = -0.23, P = 0.04). Over the 26 years follow-up, participants below the median (i.e. with lower concentration) of FVIIc, Fibrinogen, Apo-B and vWF had better survival rates than those with higher concentrations; those with higher concentrations of Apo-A1 had better survival. In Cox multivariable regression analyses including sex, ethnicity and aPWV, independently increased risk of all-cause mortality came only from SBP (per 5 mmHg); P = 0.011), age (per year); P < 0.0001 and FVIIc at 7% (per 10-unit; HR 1.07 (1.02, 1.12); P = 0.008. Separately, Apo-A1 (HR 0.12 (0.02, 0.75; P = 0.029) was independently associated with a very significant 88% reduction in all-cause mortality. Despite a relatively small sample size, long-term follow-up suggests an independent effect of the prothrombotic state (via FVIIc) and apo-A1 (a constituent of HDL) on mortality. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  5. Post-operative thrombotic thrombocytopenic purpura: a review.

    Science.gov (United States)

    Naqvi, T A; Baumann, M A; Chang, J C

    2004-02-01

    Post-operative thrombotic thrombocytopenic purpura (TTP) is a recently recognised life-threatening clinical syndrome with considerable similarity to classic TTP in presentation and response to early treatment with plasma exchange. To date, 29 cases of TTP associated with surgery have been reported. The majority of cases have complicated vascular surgeries, with a few cases seen following gastrointestinal or orthopaedic procedures. Characteristically, patients develop microangiopathic haemolytic anaemia and consumptive thrombocytopenia 5 to 9 days following surgery with variable presence of fever, impaired renal function and altered mental status. The pathogenesis of post-operative TTP is speculative but may involve the release of large amounts of high-molecular-weight von Willebrand factor (vWF) multimers due to endothelial damage resulting from surgery in the setting of marginal levels of vWF-cleaving enzyme. The myriad of common post-surgical complications that may present with clinical manifestations similar to TTP may result in confusion with the potential for delay in the initiation of life-saving plasma-exchange therapy. It is important that physicians be alert to the phenomenon of post-operative TTP so that prompt recognition and treatment will prevent serious morbidity or mortality.

  6. Effects of Modified Qing'e Pill () on expression of adiponectin, bone morphogenetic protein 2 and coagulation-related factors in patients with nontraumatic osteonecrosis of femoral head.

    Science.gov (United States)

    Li, Cheng-Gang; Shen, Lin; Yang, Yan-Ping; Xu, Xiao-Juan; Shuai, Bo; Ma, Chen

    2017-03-01

    To observe the regulation of Chinese herbal medicine, Modifified Qing'e Pill (, MQEP), on the expression of adiponectin, bone morphogenetic protein 2 (BMP2), osteoprotegerin (OPG) and other potentially relevant risk factors in patients with nontraumatic osteonecrosis of the femoral head (ONFH). A total of 96 patients with nontraumatic ONFH were unequal randomly divided into treatment group (60 cases) and control group (36 cases). The treatment group were treated with MQEP while the control group were treated with simulated pills. Both groups were given caltrate D. Six months were taken as a treatment course. Patients were followed up every 2 months. The levels of plasma adiponectin, BMP2, OPG, von Willebrand factor (vWF), von Willebrand factor cleaving protease (vWF-cp), plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator (tPA), C-reactive protein (CRP), blood rheology, bone mineral density (BMD) of the femoral head and Harris Hip Score were measured before and after treatment. After 6 months of treatment, compared with the control group, patients in the treatment group had signifificantly higher adiponectin and BMP2 levels (Padiponectin showed a positive association with BMP2 (r=0.231, P=0.003) and a negative association with PAI-1 (r=-0.159, Padiponectin, regulating bone metabolism and improving the hypercoagulation state, which may provide an experimental base for its clinical effects.

  7. The Effect of Carbon Dioxide Insufflation Applied at Different Pressures and Periods on Thrombotic Factors.

    Science.gov (United States)

    Sen, Mehmet Celal; Turkyilmaz, Zafer; Sonmez, Kaan; Karabulut, Ramazan; Kaya, Zuhre; Yenicesu, Idil; Gursel, Turkiz; Basaklar, Abdullah Can

    2016-03-01

    The aim of this experimantal study which is applied on rats, is to determine the differences on the clotting factors over the application of low and high intraabdominal pressure (IAP) values in different periods of time in carbon dioxide (CO2) pneumoperitoneum. Thirty rats were randomized into five groups (n = 6): a control group (Group K) and 1 h and 6 mm Hg IAP (Group A), 2 h and 6 mm Hg IAP (Group B), 1 h and 12 mm Hg IAP (Group C) and 2 h and 12 mm Hg IAP were created with CO2 pneumoperitoneum (Group D). At the end of the experiment, plasma samples taken from subjects and fibrinogen, FII (prothrombin), FV, FVII, FVIII, FIX, FX, FXI, FXII, von willebrand's factor (vWF), ristocetin cofactor, protein C, protein S, antithrombin III (AT III) levels are studied. There were statistically significant differences in the mean levels of FII, FV, FVII, FVIII, FIX, FX, FXI, FXII, and protein S between the groups. A hypercoagulable state occurred with the following: increase in the coagulation parameters compared to the control group; increase in FVII in the group only Group C; decrease in AT III in all groups compared to the control group; decrease in protein C in the group only XII Group D compared to control group; decrease in protein S in all groups except group D compared to control group. CO2 insufflation predisposes to thromboembolic events both by inducing coagulation factors and by suppressing the fibrinolytic system contrary to the controversies in the literature.

  8. Nanomechanical Contribution of Collagen and von Willebrand Factor A in Marine Underwater Adhesion and Its Implication for Collagen Manipulation.

    Science.gov (United States)

    Yoo, Hee Young; Huang, Jun; Li, Lin; Foo, Mathias; Zeng, Hongbo; Hwang, Dong Soo

    2016-03-14

    Recent works on mussel adhesion have identified a load bearing matrix protein (PTMP1) containing von Willebrand factor (vWF) with collagen binding capability that contributes to the mussel holdfast by manipulating mussel collagens. Using a surface forces apparatus, we investigate for the first time, the nanomechanical properties of vWF-collagen interaction using homologous proteins of mussel byssus, PTMP1 and preCollagens (preCols), as collagen. Mimicking conditions similar to mussel byssus secretion (pH < 5.0) and seawater condition (pH 8.0), PTMP1 and preCol interact weakly in the "positioning" phase based on vWF-collagen binding and strengthen in "locked" phase due to the combined effects of electrostatic attraction, metal binding, and mechanical shearing. The progressive enhancement of binding between PTMP1 with porcine collagen under the aforementioned conditions is also observed. The binding mechanisms of PTMP1-preCols provide insights into the molecular interaction of the mammalian collagen system and the development of an artificial extracellular matrix based on collagens.

  9. Multiple factors contribute to the peripheral induction of cerebral beta-amyloidosis

    NARCIS (Netherlands)

    Eisele, Y.S.; Fritschi, S.K.; Hamaguchi, T.; Obermüller, U.; Füger, P.; Skodras, A.; Schäfer, C.; Odenthal, J.; Heikenwalder, M.; Staufenbiel, M.; Jucker, M.

    2014-01-01

    Deposition of aggregated amyloid-beta (Abeta) peptide in brain is an early event and hallmark pathology of Alzheimer's disease and cerebral Abeta angiopathy. Experimental evidence supports the concept that Abeta multimers can act as seeds and structurally corrupt other Abeta peptides by a

  10. Synergism of matrix stiffness and vascular endothelial growth factor on mesenchymal stem cells for vascular endothelial regeneration.

    Science.gov (United States)

    Wingate, Kathryn; Floren, Michael; Tan, Yan; Tseng, Pi Ou Nancy; Tan, Wei

    2014-09-01

    Mesenchymal stem cells (MSCs) hold tremendous potential for vascular tissue regeneration. Research has demonstrated that individual factors in the cell microenvironment such as matrix elasticity and growth factors regulate MSC differentiation to vascular lineage. However, it is not well understood how matrix elasticity and growth factors combine to direct the MSC fate. This study examines the combined effects of matrix elasticity and vascular endothelial growth factor (VEGF) on both MSC differentiation into endothelial lineage and MSC paracrine signaling. MSCs were seeded in soft nanofibrous matrices with or without VEGF, and in Petri dishes with or without VEGF. Only MSCs seeded in three-dimensional soft matrices with VEGF showed significant increases in the expression of endothelial markers (vWF, eNOS, Flt-1, and Flk-1), while eliminating the expression of smooth muscle marker (SM-α-actin). MSCs cultured in VEGF alone on two-dimensional dishes showed increased expression of both early-stage endothelial and smooth muscle markers, indicating immature vascular differentiation. Furthermore, MSCs cultured in soft matrices with VEGF showed faster upregulation of endothelial markers compared with MSCs cultured in VEGF alone. Paracrine signaling studies found that endothelial cells cultured in the conditioned media from MSCs differentiated in the soft matrix and VEGF condition exhibited increased migration and formation of capillary-like structures. These results demonstrate that VEGF and soft matrix elasticity act synergistically to guide MSC differentiation into mature endothelial phenotype while enhancing paracrine signaling. Therefore, it is critical to control both mechanical and biochemical factors to safely regenerate vascular tissues with MSCs.

  11. Clinical phenotype in genetically confirmed von Willebrand disease type 2N patients reflects a haemophilia A phenotype

    NARCIS (Netherlands)

    Meegeren, M.E.R. van; Mancini, T.L.; Schoormans, S.C.M.; Haren, B.J.T. van; Duren, C. van; Diekstra, A.; Laros-van Gorkom, B.A.P.; Brons, P.P.; Simons, A.; Hoefsloot, L.H.; Heerde, W.L. van

    2015-01-01

    INTRODUCTION: Von Willebrand disease (VWD) type 2N is characterized by a defective binding of factor VIII (FVIII) to von Willebrand factor (VWF) resulting in diminished plasma FVIII levels and a clinical phenotype mimicking mild haemophilia A. Several mutations in the FVIII binding site of VWF have

  12. Hepatocyte Growth Factor Effects on Mesenchymal Stem Cells Derived from Human Arteries: A Novel Strategy to Accelerate Vascular Ulcer Wound Healing

    Directory of Open Access Journals (Sweden)

    Sabrina Valente

    2016-01-01

    Full Text Available Vascular ulcers are a serious complication of peripheral vascular disease, especially in diabetics. Several approaches to treat the wounds are proposed but they show poor outcomes and require long healing times. Hepatocyte Growth Factor/Scatter Factor (HGF/SF is a pleiotropic cytokine exerting many biological activities through the c-Met receptor. This study was aimed at verifying whether HGF/SF influences proliferation, migration, and angiogenesis on mesenchymal stem cells isolated from human arteries (hVW-MSCs. hVW-MSCs were exposed to NIBSC HGF/SF (2.5, 5, 10, and 70 ng/mL from 6 hrs to 7 days. HGF and c-MET mRNA and protein expression, cell proliferation (Alamar Blue and Ki–67 assay, migration (scratch and transwell assays, and angiogenesis (Matrigel were investigated. hVW-MSCs displayed stemness features and expressed HGF and c-MET. HGF/SF did not increase hVW-MSC proliferation, whereas it enhanced the cell migration, the formation of capillary-like structures, and the expression of angiogenic markers (vWF, CD31, and KDR. The HGF/SF effects on hVW-MSC migration and angiogenic potential are of great interest to accelerate wound healing process. Local delivery of HGF/SF could therefore improve the healing of unresponsive vascular ulcers.

  13. Hepatocyte Growth Factor Effects on Mesenchymal Stem Cells Derived from Human Arteries: A Novel Strategy to Accelerate Vascular Ulcer Wound Healing.

    Science.gov (United States)

    Valente, Sabrina; Ciavarella, Carmen; Pasanisi, Emanuela; Ricci, Francesca; Stella, Andrea; Pasquinelli, Gianandrea

    2016-01-01

    Vascular ulcers are a serious complication of peripheral vascular disease, especially in diabetics. Several approaches to treat the wounds are proposed but they show poor outcomes and require long healing times. Hepatocyte Growth Factor/Scatter Factor (HGF/SF) is a pleiotropic cytokine exerting many biological activities through the c-Met receptor. This study was aimed at verifying whether HGF/SF influences proliferation, migration, and angiogenesis on mesenchymal stem cells isolated from human arteries (hVW-MSCs). hVW-MSCs were exposed to NIBSC HGF/SF (2.5, 5, 10, and 70 ng/mL) from 6 hrs to 7 days. HGF and c-MET mRNA and protein expression, cell proliferation (Alamar Blue and Ki-67 assay), migration (scratch and transwell assays), and angiogenesis (Matrigel) were investigated. hVW-MSCs displayed stemness features and expressed HGF and c-MET. HGF/SF did not increase hVW-MSC proliferation, whereas it enhanced the cell migration, the formation of capillary-like structures, and the expression of angiogenic markers (vWF, CD31, and KDR). The HGF/SF effects on hVW-MSC migration and angiogenic potential are of great interest to accelerate wound healing process. Local delivery of HGF/SF could therefore improve the healing of unresponsive vascular ulcers.

  14. Corruption Factors

    OpenAIRE

    Polterovich, Victor

    1998-01-01

    Among the factors that give rise to corruption, it is suggested that three groups be distinguished: fundamental factors rooted in the imperfection of economic institutions and economic policy, organizational factors ("weakness of the government"), and societal factors that depend on the prehistory and are connected with the mass culture and norms of bureaucratic behavior. A model in which corruption equilibrium is supported by non-optimum tax policy or by slow technical progress is compared w...

  15. Complement activation, endothelial dysfunction, insulin resistance and chronic heart failure

    DEFF Research Database (Denmark)

    Bjerre, M.; Kistorp, C.; Hansen, T.K.

    2010-01-01

    CRP), endothelial activation (soluble E-selectin, sEsel)), endothelial damage/dysfunction (von Willebrand factor, vWf) and insulin resistance (IR) and prognosis in CHF remains unknown. Design. We investigated the association(s) between plasma sMAC, hsCRP, sEsel, vWf and IR (assessed by homeostatic model assessment...

  16. The role of ADAMTS13 in acute myocardial infarction : Cause or consequence?

    NARCIS (Netherlands)

    Teunissen, Paul F.; Kamp, Otto; Kamphuisen, Pieter Willem; Meijers, Joost; Tijssen, Ruben; Eerenberg, Elise S.; Jansen, Matthijs F.; Niessen, Hans W.; Van Royen, Niels

    2015-01-01

    BACKGROUND ADAMTS13 is a metalloprotease that cleaves von Willebrand factor (VWF), thereby reducing its prothrombotic properties. There is considerable evidence that VWF levels increase and ADAMTS13 levels decrease in STEMI patients. It is unclear if this contributes to no reflow, infarct size and i

  17. El factoring

    Directory of Open Access Journals (Sweden)

    Alberto Rosenthal

    1988-04-01

    Full Text Available RESUMEN El artículo  presenta, una conceptualización general de lo que es el factoring, el origen del mismo, su evolución y hace una clasificación de los distintos tipos de factoring.

  18. Robust factorization

    DEFF Research Database (Denmark)

    Aanæs, Henrik; Fisker, Rune; Åström, Kalle;

    2002-01-01

    Factorization algorithms for recovering structure and motion from an image stream have many advantages, but they usually require a set of well-tracked features. Such a set is in generally not available in practical applications. There is thus a need for making factorization algorithms deal...... effectively with errors in the tracked features. We propose a new and computationally efficient algorithm for applying an arbitrary error function in the factorization scheme. This algorithm enables the use of robust statistical techniques and arbitrary noise models for the individual features....... These techniques and models enable the factorization scheme to deal effectively with mismatched features, missing features, and noise on the individual features. The proposed approach further includes a new method for Euclidean reconstruction that significantly improves convergence of the factorization algorithms...

  19. Conjugation with RGD Peptides and Incorporation of Vascular Endothelial Growth Factor Are Equally Efficient for Biofunctionalization of Tissue-Engineered Vascular Grafts

    Directory of Open Access Journals (Sweden)

    Larisa V. Antonova

    2016-11-01

    Full Text Available The blend of poly(3-hydroxybutyrate-co-3-hydroxyvalerate (PHBV and poly(ε-caprolactone (PCL has recently been considered promising for vascular tissue engineering. However, it was shown that PHBV/PCL grafts require biofunctionalization to achieve high primary patency rate. Here we compared immobilization of arginine–glycine–aspartic acid (RGD-containing peptides and the incorporation of vascular endothelial growth factor (VEGF as two widely established biofunctionalization approaches. Electrospun PHBV/PCL small-diameter grafts with either RGD peptides or VEGF, as well as unmodified grafts were implanted into rat abdominal aortas for 1, 3, 6, and 12 months following histological and immunofluorescence assessment. We detected CD31+/CD34+/vWF+ cells 1 and 3 months postimplantation at the luminal surface of PHBV/PCL/RGD and PHBV/PCL/VEGF, but not in unmodified grafts, with the further observation of CD31+CD34−vWF+ phenotype. These cells were considered as endothelial and produced a collagen-positive layer resembling a basement membrane. Detection of CD31+/CD34+ cells at the early stages with subsequent loss of CD34 indicated cell adhesion from the bloodstream. Therefore, either conjugation with RGD peptides or the incorporation of VEGF promoted the formation of a functional endothelial cell layer. Furthermore, both modifications increased primary patency rate three-fold. In conclusion, both of these biofunctionalization approaches can be considered as equally efficient for the modification of tissue-engineered vascular grafts.

  20. El factoring

    Directory of Open Access Journals (Sweden)

    Alberto Rosenthal

    2015-04-01

    Full Text Available RESUMEN Se presenta la segunda parte del artículo aparecido en  el número 6 de la revista EAN. Su contenido es complementario a lo expuesto en dicho número, en está aparecen las ventajas del factoring, conveniencias, limitaciones así como la forma  de efectuar un factor en Colombia,  su necesidad, incidencia económica, etc.

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

    Science.gov (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

    2016-06-01

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

  2. Reversal of ischemic cardiomyopathy with Sca-1+ stem cells modified with multiple growth factors.

    Directory of Open Access Journals (Sweden)

    Ning Li

    Full Text Available BACKGROUND: We hypothesized that bone marrow derived Sca-1+ stem cells (BM Sca-1+ transduced with multiple therapeutic cytokines with diverse effects will induce faster angiomyogenic differentiation in the infarcted myocardium. METHODS AND RESULTS: BM Sca-1+ were purified from transgenic male mice expressing GFP. Plasmids encoding for select quartet of growth factors, i.e., human IGF-1, VEGF, SDF-1α and HGF were prepared and used for genetic modification of Sca-1+ cells (GFSca-1+. Scramble transfected cells (ScSca-1+ were used as a control. RT-PCR and western blotting showed significantly higher expression of the growth factors in GFSca-1+. Besides the quartet of the therapeutic growth factors, PCR based growth factor array showed upregulation of multiple angiogenic and prosurvival factors such as Ang-1, Ang-2, MMP9, Cx43, BMP2, BMP5, FGF2, and NGF in GFSca-1+ (p<0.01 vs ScSca-1+. LDH and TUNEL assays showed enhanced survival of GFSca-1+ under lethal anoxia (p<0.01 vs ScSca-1+. MTS assay showed significant increased cell proliferation in GFSca-1+ (p<0.05 vs ScSca-1+. For in vivo study, female mice were grouped to receive the intramyocardial injection of 15 μl DMEM without cells (group-1 or containing 2.5 × 10(5 ScSca-1+ (group-2 or GFSca-1+ (group-3 immediately after coronary artery ligation. As indicated by Sry gene, a higher survival of GFSca-1+ in group-3 on day 4 (2.3 fold higher vs group-2 was observed with massive mobilization of stem and progenitor cells (cKit+, Mdr1+, Cxcr4+ cells. Heart tissue sections immunostained for actinin and Cx43 at 4 weeks post engraftment showed extensive myofiber formation and expression of gap junctions. Immunostaining for vWF showed increased blood vessel density in both peri-infarct and infarct regions in group-3. Infarct size was attenuated and the global heart function was improved in group-3 as compared to group-2. CONCLUSIONS: Administration of BM Sca-1+ transduced with multiple genes is a novel

  3. Nonparametric Identification of Glucose-Insulin Process in IDDM Patient with Multi-meal Disturbance

    Science.gov (United States)

    Bhattacharjee, A.; Sutradhar, A.

    2012-12-01

    Modern close loop control for blood glucose level in a diabetic patient necessarily uses an explicit model of the process. A fixed parameter full order or reduced order model does not characterize the inter-patient and intra-patient parameter variability. This paper deals with a frequency domain nonparametric identification of the nonlinear glucose-insulin process in an insulin dependent diabetes mellitus patient that captures the process dynamics in presence of uncertainties and parameter variations. An online frequency domain kernel estimation method has been proposed that uses the input-output data from the 19th order first principle model of the patient in intravenous route. Volterra equations up to second order kernels with extended input vector for a Hammerstein model are solved online by adaptive recursive least square (ARLS) algorithm. The frequency domain kernels are estimated using the harmonic excitation input data sequence from the virtual patient model. A short filter memory length of M = 2 was found sufficient to yield acceptable accuracy with lesser computation time. The nonparametric models are useful for closed loop control, where the frequency domain kernels can be directly used as the transfer function. The validation results show good fit both in frequency and time domain responses with nominal patient as well as with parameter variations.

  4. Parallel detection of antigen-specific T cell responses by combinatorial encoding of MHC multimers

    DEFF Research Database (Denmark)

    Andersen, Rikke Sick; Kvistborg, Pia; Frøsig, Thomas Mørch;

    2012-01-01

    -dimensional combinatorial matrix, these eight fluorochromes are combined to generate 28 unique two-color codes. By the use of combinatorial encoding, a large number of different T cell populations can be detected in a single sample. The method can be used for T cell epitope mapping, and also for the monitoring of CD8...

  5. Data analysis as a source of variability of the HLA-peptide multimer assay

    DEFF Research Database (Denmark)

    Gouttefangeas, Cécile; Chan, Cliburn; Attig, Sebastian

    2015-01-01

    Multiparameter flow cytometry is an indispensable method for assessing antigen-specific T cells in basic research and cancer immunotherapy. Proficiency panels have shown that cell sample processing, test protocols and data analysis may all contribute to the variability of the results obtained by ....... We show that this automated method can circumvent difficulties inherent to manual gating strategies and is broadly applicable for experiments performed with heterogeneous protocols and reagents.......Multiparameter flow cytometry is an indispensable method for assessing antigen-specific T cells in basic research and cancer immunotherapy. Proficiency panels have shown that cell sample processing, test protocols and data analysis may all contribute to the variability of the results obtained...... by laboratories performing ex vivo T cell immune monitoring. In particular, analysis currently relies on a manual, step-by-step strategy employing serial gating decisions based on visual inspection of one- or two-dimensional plots. It is therefore operator dependent and subjective. In the context of continuing...

  6. Rhabdomyosarcome paratesticulaire (RMSP) multimétastatique : à propos d’un cas

    Science.gov (United States)

    Bennani, Hassan; Ziouziou, Imad; El Ghanmi, Jihad; Karmouni, Tarik; El Khader, Khalid; Koutani, Abdellatif; Andaloussi, Ahmed Iben Attya

    2014-01-01

    Résumé Nous rapportons, dans le présent article, le cas clinique d’un RMSP découvert à un stade tardif chez un adolescent, dans le but de confirmer l’évolution fatale de cette pathologie au potentiel métastatique « affreux ». Nous discutons aussi les causes du retard diagnostique, l’implication du sous-type histologique comme facteur pronostique et la place de la chimiothérapie dans le traitement des formes évoluées de la maladie. PMID:25295143

  7. Experimental and Theoretical Investigation of Sodiated Multimers of Steroid Epimers with Ion Mobility-Mass Spectrometry

    Science.gov (United States)

    Chouinard, Christopher D.; Cruzeiro, Vinícius Wilian D.; Roitberg, Adrian E.; Yost, Richard A.

    2017-02-01

    Ion mobility-mass spectrometry (IM-MS) has recently seen increased use in the analysis of small molecules, especially in the field of metabolomics, for increased breadth of information and improved separation of isomers. In this study, steroid epimers androsterone and trans-androsterone were analyzed with IM-MS to investigate differences in their relative mobilities. Although sodiated monomers exhibited very similar collision cross-sections (CCS), baseline separation was observed for the sodiated dimer species (RS = 1.81), with measured CCS of 242.6 and 256.3 Å2, respectively. Theoretical modeling was performed to determine the most energetically stable structures of solution-phase and gas-phase monomer and dimer structures. It was revealed that these epimers differ in their preferred dimer binding mode in solution phase: androsterone adopts a R=O - Na+ - OH—R' configuration, whereas trans-androsterone adopts a R=O - Na+ - O=R' configuration. This difference contributes to a significant structural variation, and subsequent CCS calculations based on these structures relaxed in the gas phase were in agreement with experimentally measured values (ΔCCS 5%). Additionally, these calculations accurately predicted the relative difference in mobility between the epimers. This study illustrates the power of combining experimental and theoretical results to better elucidate gas-phase structures.

  8. Theranostic Value of Multimers: Lessons Learned from Trimerization of Neurotensin Receptor Ligands and Other Targeting Vectors

    Directory of Open Access Journals (Sweden)

    Simone Maschauer

    2017-03-01

    Full Text Available Neurotensin receptor 1 (NTS1 is overexpressed on a variety of cancer entities; for example, prostate cancer, ductal pancreatic adenocarcinoma, and breast cancer. Therefore, it represents an interesting target for the diagnosis of these cancers types by positron emission tomography (PET [...

  9. Branca de Neve multim?dia: a personagem na literatura, no cinema e nos quadrinhos

    OpenAIRE

    Miranda., Allana Dilene de Ara?jo de

    2011-01-01

    Objetivando estudar a categoria personagem e sua manifesta??o em tr?s diferentes m?dias, este trabalho analisa Branca de Neve e sua constru??o na literatura, no cinema, e nas hist?rias em quadrinhos. O corpus utilizado foi o conto Branca de Neve e os sete an?es, assinado pelos irm?os Wilhelm e Jacob Grimm; a anima??o de 1937, produzida pelos est?dios Disney, hom?nima; e o primeiro volume da miniss?rie As mil e uma noites, derivada da revista mensal F?bulas, de Bill Willingham. Nos tr?s primei...

  10. Self-assembling SAS-6 multimer is a core centriole building block.

    Science.gov (United States)

    Gopalakrishnan, Jayachandran; Guichard, Paul; Smith, Andrew H; Schwarz, Heinz; Agard, David A; Marco, Sergio; Avidor-Reiss, Tomer

    2010-03-19

    Centrioles are conserved microtubule-based organelles with 9-fold symmetry that are essential for cilia and mitotic spindle formation. A conserved structure at the onset of centriole assembly is a "cartwheel" with 9-fold radial symmetry and a central tubule in its core. It remains unclear how the cartwheel is formed. The conserved centriole protein, SAS-6, is a cartwheel component that functions early in centriole formation. Here, combining biochemistry and electron microscopy, we characterize SAS-6 and show that it self-assembles into stable tetramers, which serve as building blocks for the central tubule. These results suggest that SAS-6 self-assembly may be an initial step in the formation of the cartwheel that provides the 9-fold symmetry. Electron microscopy of centrosomes identified 25-nm central tubules with repeating subunits and show that SAS-6 concentrates at the core of the cartwheel. Recombinant and native SAS-6 self-oligomerizes into tetramers with approximately 6-nm subunits, and these tetramers are components of the centrosome, suggesting that tetramers are the building blocks of the central tubule. This is further supported by the observation that elevated levels of SAS-6 in Drosophila cells resulted in higher order structures resembling central tubule morphology. Finally, in the presence of embryonic extract, SAS-6 tetramers assembled into high density complexes, providing a starting point for the eventual in vitro reconstruction of centrioles.

  11. Folding Landscape of Mutant Huntingtin Exon1: Diffusible Multimers, Oligomers and Fibrils, and No Detectable Monomer.

    Directory of Open Access Journals (Sweden)

    Bankanidhi Sahoo

    Full Text Available Expansion of the polyglutamine (polyQ track of the Huntingtin (HTT protein above 36 is associated with a sharply enhanced risk of Huntington's disease (HD. Although there is general agreement that HTT toxicity resides primarily in N-terminal fragments such as the HTT exon1 protein, there is no consensus on the nature of the physical states of HTT exon1 that are induced by polyQ expansion, nor on which of these states might be responsible for toxicity. One hypothesis is that polyQ expansion induces an alternative, toxic conformation in the HTT exon1 monomer. Alternative hypotheses posit that the toxic species is one of several possible aggregated states. Defining the nature of the toxic species is particularly challenging because of facile interconversion between physical states as well as challenges to identifying these states, especially in vivo. Here we describe the use of fluorescence correlation spectroscopy (FCS to characterize the detailed time and repeat length dependent self-association of HTT exon1-like fragments both with chemically synthesized peptides in vitro and with cell-produced proteins in extracts and in living cells. We find that, in vitro, mutant HTT exon1 peptides engage in polyQ repeat length dependent dimer and tetramer formation, followed by time dependent formation of diffusible spherical and fibrillar oligomers and finally by larger, sedimentable amyloid fibrils. For expanded polyQ HTT exon1 expressed in PC12 cells, monomers are absent, with tetramers being the smallest molecular form detected, followed in the incubation time course by small, diffusible aggregates at 6-9 hours and larger, sedimentable aggregates that begin to build up at 12 hrs. In these cell cultures, significant nuclear DNA damage appears by 6 hours, followed at later times by caspase 3 induction, mitochondrial dysfunction, and cell death. Our data thus defines limits on the sizes and concentrations of different physical states of HTT exon1 along the reaction profile in the context of emerging cellular distress. The data provide some new candidates for the toxic species and some new reservations about more well-established candidates. Compared to other known markers of HTT toxicity, nuclear DNA damage appears to be a relatively early pathological event.

  12. Behavioral factors.

    Science.gov (United States)

    Zero, D T; Lussi, A

    2006-01-01

    During and after an erosive challenge, behavioral factors play a role in modifying the extent of erosive tooth wear. The manner that dietary acids are introduced into the mouth (gulping, sipping, use of a straw) will affect how long the teeth are in contact with the erosive challenge. The frequency and duration of exposure to an erosive agent is of paramount importance. Night-time exposure (e.g. baby bottle-feeding) to erosive agents may be particularly destructive because of the absence of salivary flow. Health-conscious individuals tend to ingest acidic drinks and juices more frequently and tend to have higher than average oral hygiene. While good oral hygiene is of proven value in the prevention of periodontal disease and dental caries, frequent toothbrushing with abrasive oral hygiene products may enhance erosive tooth wear. Unhealthy lifestyles such as consumption of designer drugs, alcopops and alcohol abuse are other important behavioral factors.

  13. Factor analysis

    CERN Document Server

    Gorsuch, Richard L

    2013-01-01

    Comprehensive and comprehensible, this classic covers the basic and advanced topics essential for using factor analysis as a scientific tool in psychology, education, sociology, and related areas. Emphasizing the usefulness of the techniques, it presents sufficient mathematical background for understanding and sufficient discussion of applications for effective use. This includes not only theory but also the empirical evaluations of the importance of mathematical distinctions for applied scientific analysis.

  14. High-Affinity DNA Aptamer Generation Targeting von Willebrand Factor A1-Domain by Genetic Alphabet Expansion for Systematic Evolution of Ligands by Exponential Enrichment Using Two Types of Libraries Composed of Five Different Bases.

    Science.gov (United States)

    Matsunaga, Ken-Ichiro; Kimoto, Michiko; Hirao, Ichiro

    2017-01-11

    The novel evolutionary engineering method ExSELEX (genetic alphabet expansion for systematic evolution of ligands by exponential enrichment) provides high-affinity DNA aptamers that specifically bind to target molecules, by introducing an artificial hydrophobic base analogue as a fifth component into DNA aptamers. Here, we present a newer version of ExSELEX, using a library with completely randomized sequences consisting of five components: four natural bases and one unnatural hydrophobic base, 7-(2-thienyl)imidazo[4,5-b]pyridine (Ds). In contrast to the limited number of Ds-containing sequence combinations in our previous library, the increased complexity of the new randomized library could improve the success rates of high-affinity aptamer generation. To this end, we developed a sequencing method for each clone in the enriched library after several rounds of selection. Using the improved library, we generated a Ds-containing DNA aptamer targeting von Willebrand factor A1-domain (vWF) with significantly higher affinity (KD = 75 pM), relative to those generated by the initial version of ExSELEX, as well as that of the known DNA aptamer consisting of only the natural bases. In addition, the Ds-containing DNA aptamer was stabilized by introducing a mini-hairpin DNA resistant to nucleases, without any loss of affinity (KD = 61 pM). This new version is expected to consistently produce high-affinity DNA aptamers.

  15. Role of transcription factor CCAAT/enhancer-binding protein alpha in human fetal liver cell types in vitro.

    Science.gov (United States)

    Gerlach, Jörg C; Over, Patrick; Foka, Hubert G; Turner, Morris E; Thompson, Robert L; Gridelli, Bruno; Schmelzer, Eva

    2015-08-01

    The transcription factor CCAAT/enhancer-binding protein alpha (C/EBPα) has been shown to play an important role in liver development, cell proliferation and differentiation. It is, however, largely unknown if C/EBPα regulates cell differentiation and proliferation differently in the diverse cell types of the human liver. We investigated the role of C/EBPα in primary human fetal liver cells and liver cell subpopulations in vitro using a 3-D perfusion bioreactor as an advanced in vivo-like human organ culture model. Human fetal liver cells were investigated in vitro. C/EBPα gene expression was knocked down using siRNA or overexpressed by plasmid transfection. Cell type-specific gene expression was studied, cell populations and their proliferation were investigated, and metabolic parameters were analyzed. When C/EBPα gene expression was knocked down, we observed a significantly reduced expression of typical endothelial, hematopoietic and mesenchymal genes such as CD31, vWF, CD90, CD45 and α-smooth muscle actin in fetal cells. The intracellular expression of hepatic proteins and genes for liver-specific serum proteins α-fetoprotein and albumin were reduced, their protein secretion was increased. Fetal endothelial cell numbers were reduced and hepatoblast numbers were increased. C/EBPα overexpression in fetal cells resulted in increased endothelial numbers, but did not affect mesenchymal cell types or hepatoblasts. We demonstrated that the effects of C/EBPα are specific for the different human fetal liver cell types, using an advanced 3-D perfusion bioreactor as a human in vivo-like model. © 2014 The Japan Society of Hepatology.

  16. Establishment of canine hemangiosarcoma xenograft models expressing endothelial growth factors, their receptors, and angiogenesis-associated homeobox genes

    Directory of Open Access Journals (Sweden)

    Maruo Kouji

    2009-10-01

    Full Text Available Abstract Background Human hemangiosarcoma (HSA tends to have a poor prognosis; its tumorigenesis has not been elucidated, as there is a dearth of HSA clinical specimens and no experimental model for HSA. However, the incidence of spontaneous HSA is relatively high in canines; therefore, canine HSA has been useful in the study of human HSA. Recently, the production of angiogenic growth factors and their receptors in human and canine HSA has been reported. Moreover, the growth-factor environment of HSA is very similar to that of pathophysiological angiogenesis, which some homeobox genes regulate in the transcription of angiogenic molecules. In the present study, we established 6 xenograft canine HSA tumors and detected the expression of growth factors, their receptors, and angiogenic homeobox genes. Methods Six primary canine HSAs were xenografted to nude mice subcutaneously and serially transplanted. Subsequently, the expressions of vascular endothelial growth factor (VEGF-A, basic fibroblast growth factors (bFGF, flt-1 and flk-1 (receptors of VEGF-A, FGFR-1, and angiogenic homeobox genes HoxA9, HoxB3, HoxB7, HoxD3, Pbx1, and Meis1 were investigated in original and xenograft tumors by histopathology, immunostaining, and reverse transcription polymerase chain reaction (RT-PCR, using canine-specific primer sets. Results Histopathologically, xenograft tumors comprised a proliferation of neoplastic cells that were varied in shape, from spindle-shaped and polygonal to ovoid; some vascular-like structures and vascular clefts of channels were observed, similar to those in the original tumors. The expression of endothelial markers (CD31 and vWF was detected in xenograft tumors by immunohistochemistry and RT-PCR. Moreover, the expression of VEGF-A, bFGF, flt-1, flk-1, FGFR-1, HoxA9, HoxB3, HoxB7, HoxD3, Pbx1, and Meis1 was detected in xenograft tumors. Interestingly, expressions of bFGF tended to be higher in 3 of the xenograft HSA tumors than in the

  17. 瑞舒伐他汀对急性脑梗死患者血浆血管性假血友病因子和血栓调节蛋白水平的影响%Influence of rosuvastatin on von wilebrand factor and plasma thrombomodulin (TM) levels of acute cerebral infarction patients

    Institute of Scientific and Technical Information of China (English)

    王波; 王海英; 甘慧玲; 罗利飞; 林莉

    2014-01-01

    Objective To discuss the effect of rosuvastatin on von wilebrand factor and plasma thrombomodu-lin ( TM) levels of acute cerebral infarction patients. Methods 76 cases of acute cerebral infarction patients from June 2012 to May 2013 in our hospital were divided into observation group and control group. The patients of the two groups were given basic treatment like intracranial pressure control,blood pressure and blood sugar maintenance,anti-platelet aggregation,brain cells nutrition etc. The patients of the observation group were given 100 mg rosuvastatin tablets per time,once daily for 2 weeks at the same time. The changes of vWF and TM levels in plasma of patients of the two groups were compared before and after medical treatment,and the curative effect and security were carried on as well. Results After 2 weeks′ medical treatment,the vWF and TM level of the two groups declined obviously than before treatment(P0. 05). Conclusion Rosuvastatin has reliable curative effect on acute cerebral infarction with high security,whose mechanism of action is to reduce vWF and TM level in plasma,protect and improve the vascular endothelial function.%目的:探讨瑞舒伐他汀对急性脑梗死患者血浆血管性假血友病因子( vWF)和血栓调节蛋白( TM)水平的影响。方法选择2012年6月至2013年5月我院收治的急性脑梗死患者76例,随机分为观察组和对照组,每组38例。两组患者均予以控制颅内压、维持血压、血糖、抗血小板聚集和营养脑细胞等治疗。观察组在此基础上加用瑞舒伐他汀片10 mg/次,1次/d,连用2周。观察两组患者治疗前后血浆vWF、TM水平变化,并观察临床疗效及安全性。结果治疗2周后,两组患者血浆vWF和TM水平较治疗前明显降低( P0.05)。结论瑞舒伐他汀治疗急性脑梗死临床疗效确切,安全性较好,其作用机制与其降低血浆vWF和TM水平,从而保护及改善患者的血管内皮功能密切相关。

  18. 阿托伐他汀对高血压患者C反应蛋白及其他炎性因子的影响%Effects of atorvastatin on levels of C-reactive protein and other inflammatory factors in patients with hypertension

    Institute of Scientific and Technical Information of China (English)

    吴静; 吴钢; 王梅平; 林昭敏; 胡志坚

    2010-01-01

    Objective To identify the effects of atorvastatin on high-sensitivity C-reactive protein (hs-CRP), yon willebrand factor (vWF), P-selectin, low-density lipoprotein-cholesterol (LDL-C)and carotid intima-media thickness (IMT) of patients with essential hypertension. Methods One hundred and fifty-one patients with mild hypertension were randomly divided into 3 groups: 10 mg atorvastatin, amlodipine and benazepril were daily delivered to group A (n=50); 20 mg atorvastatin,amlodipine and benazepril were daily delivered to group B (n=61); and amlodipine and benazepril were daily delivered to control group (n=40). All patients were assessed for the levels of hs-CRP, vWF,P-selectin, LDL-C and IMT at the baseline and every 3 months. The observation period lasted for 1 y and statistical analysis was performed on these collected data. Results As compared with that in the control group, significant reduction was identified on the levels of hs-CRP, vWF, P-selectin, LDL-C and IMT in group A and group B (P<0.05). Correlation analysis discovered that the changes of levels of hs-CRP, VWF, P-selectin and IMT did not correlate with the reduction of LDL-C. Conclusion The progression of atherosclerosis can be delayed by atorvastatin in patients with hypertension, which is probably independent from its lipid-lowering function.%目的 观察阿托伐他汀对高血压患者超敏C反应蛋白(hs-CRP)、血管性假血友病因子(vWF)、P-选择素、低密度脂蛋白胆固醇(LDL-C)及颈动脉内膜-中层厚度(IMT)的影响.方法 151例高血压患者按治疗方法分为3组,50例用10 mg阿托伐他汀+氨氯地平+贝那普利治疗,61例用20mg阿托伐他汀+氨氯地平+贝那普利治疗,对照组40例采用氨氯地平+贝那普利治疗;每3个月检测患者hs-CRP、LDL-C、vWF及P-选择素等指标变化.共观察1年,并对结果进行统计学分析.结果 (1)10 mg和20 mg阿托伐他汀组hs-CRP、LDL-C、vWF、P-选择素及IMT均较对照组下

  19. Global Factor Trade with Differentiated Factor Prices and Factor Intensities

    OpenAIRE

    Yun-kwong Kwok

    2004-01-01

    Relaxing the assumption of internationally identical factor intensity techniques in the HOV model creates two challenges. First, computing actual factor intensity techniques of different countries requires detailed input-output tables and factor usage data, which are not always available. Second, determinants of the factor intensity technique differences across countries need to be identified. This paper explores the role of relative factor price differences in the determination of factor int...

  20. Successful Aortic Aneurysm Repair in a Woman with Severe von Willebrand (Type 3 Disease

    Directory of Open Access Journals (Sweden)

    Victoria Campbell

    2015-01-01

    Full Text Available von Willebrand disease type 3 (VWD3 is a rare but the most severe form of von Willebrand disease; it is due to almost complete lack of von Willebrand factor activity (VWF:RCo. It is inherited as autosomal recessive trait; whilst heterozygote carriers have mild, or no symptoms, patients with VWD3 show severe bleeding symptoms. In the laboratory, this is characterised by undetectable VWF:Ag, VWF:RCo, and reduced levels of factor VIII < 0.02 IU/dL. The bleeding is managed with von Willebrand/FVIII factor concentrate replacement therapy. In this rare but challenging case we report on the successful excision and repair of an ascending aortic aneurysm following adequate VWF/FVIII factor concentrate replacement using Haemate-P.

  1. Correction of diabetic erectile dysfunction with adipose derived stem cells modified with the vascular endothelial growth factor gene in a rodent diabetic model.

    Directory of Open Access Journals (Sweden)

    Guihua Liu

    Full Text Available The aim of this study was to determine whether adipose derived stem cells (ADSCs expressing vascular endothelial growth factor (VEGF gene can improve endothelial function, recover the impaired VEGF signaling pathway and enhance smooth muscle contents in a rat diabetic erectile dysfunction (DED model. DED rats were induced via intraperitoneal injection of streptozotocin (40 mg/kg, and then screened by apomorphine (100 µg/kg. Five groups were used (n = 12/group-Group 1 (G1: intracavernous injection of lentivirus-VEGF; G2: ADSCs injection; G3: VEGF-expressing ADSCs injection; G4: Phosphate buffered saline injection; G1-G4 were DED rats; G5: normal rats. The mean arterial pressure (MAP and intracavernosal pressure (ICP were measured at days 7 and 28 after the injections. The components of the VEGF system, endothelial, smooth muscle, pericytes markers in cavernoursal tissue were assessed. On day 28 after injection, the group with intracavernosum injection of ADSCs expressing VEGF displayed more efficiently and significantly raised ICP and ICP/MAP (p<0.01 than those with ADSCs or lentivirus-VEGF injection. Western blot and immunofluorescent analysis demonstrated that improved erectile function by ADSCs-VEGF was associated with increased expression of endothelial markers (VEGF, VEGF R1, VEGF R2, eNOS, CD31 and vWF, smooth muscle markers (a-actin and smoothelin, and pericyte markers (CD146 and NG2. ADSCs expressing VEGF produced a therapeutic effect and restored erectile function in diabetic rats by enhancing VEGF-stimulated endothelial function and increasing the contents of smooth muscle and pericytes.

  2. [Endothelin-1 in pathogenesis of Raynaud's syndrome].

    Science.gov (United States)

    Knapik-Kordecka, M; Adamiec, R; Ciosek, W

    2001-06-01

    Endothelin is an endogenous vasoconstrictor and plays an important role in pathogenesis of Raynaud's phenomenon. Plasma endothelin-1 (ET-1) and von Willebrand factor (vWF) concentrations following cold exposure in 52 patients with Raynaud's phenomenon were measured. Statistically significant increase of ET-1 and vWF was found in the study group in compare to healthy volunteers. There was positive correlation between ET-1 and vWF in those cases. The dates suggest that ET-changes indicates a vasospastic effect on vascular injury. Treatment with endothelin-receptor antagonist may prevent structural changes in vessel well.

  3. The 80th anniversary of von Willebrand's disease: history, management and research.

    Science.gov (United States)

    Federici, A B; Berntorp, E; Lee, C A

    2006-11-01

    The history of von Willebrand's disease (VWD) is fascinating because it demonstrates how good clinical observations, genetic studies and biochemical skills can improve basic understanding of a disease and its management. The continuous efforts of scientists and clinicians during the last 80 years have significantly improved the knowledge of von Willebrand factor (VWF) structure and function and the management of VWD. Diagnosis of phenotype and genotype is now available in many countries and treatment is becoming more specific according to the VWD type. Any therapeutic agents must correct the dual defect of haemostasis, i.e. the abnormal platelet adhesion due to reduced and/or dysfunctional and low levels of factor VIII (FVIII) associated with VWF defects. Desmopressin (DDAVP) is the treatment of choice for type 1 VWD because it induces release of VWF from cellular compartments. Plasma virally inactivated VWF concentrates containing FVIII are effective and safe in patients unresponsive to DDAVP. There are advanced plans to develop a recombinant VWF but this product will require the concomitant administration of FVIII for the control of acute bleeds. Basic research studies on cellular biology, biochemistry and immunology have confirmed the role of VWF as a crucial participant in both haemostasis and thrombosis as its main biological activity is to support platelet adhesion-aggregation in the circulation. Retrospective and prospective clinical research studies, including bleeding history and laboratory markers for diagnosis as well as the use of DDAVP and VWF concentrates to manage or prevent bleeds in patients with VWD have been essential to provide general guidelines for VWD management. The large number of publications quoting VWD and VWF emphasizes the important role of VWF in medicine.

  4. Factores de riesgo relacionados al uso de drogas ilegales: perspectiva crítica de familiares y personas cercanas en un centro de salud público en San Pedro Sula, Honduras Fatores de risco relacionados ao uso de drogas ilegais, perspectiva crítica de familiares e pessoas próximas, em um centro da saúde público em San Pedro Sula, Honduras Risk factors related to the use of illegal drugs: the critial perspective of drug users' relatives and acquaintances at a public health center in San Pedro Sula, Honduras

    Directory of Open Access Journals (Sweden)

    Gladys Magdalena Rodríguez Funes

    2009-01-01

    Full Text Available En este estudio, se presentan datos cuantitativos del estudio multicéntrico, multimétodos, de corte transversal realizado en un centro de salud público en San Pedro Sula, en Honduras. Su objetivo es describir la perspectiva crítica que tienen los familiares o personas, que se consideran afectadas por tener a alguien cercano que usa o ha usado drogas ilegales, con relación a factores de riesgo. Los datos se obtuvieron mediante una encuesta con 100 entrevistados. La mayor parte de las personas informantes eran mujeres pobres con baja escolaridad. Los consumidores eran en su mayoría hombres con edad promedio de 23,3 años. La droga más usada fue la marihuana (78% seguida de crack/cocaína (72%, pegamento/inhalantes (27%, alucinógenos (éxtasis/LSD (3%, anfetaminas/estimulantes (1% y heroína (1%. Los factores de riesgo identificados fueron la experiencia previa con alcohol/tabaco, el tener amigos/amigas que usan drogas, la falta de conocimiento, la baja autoestima , la edad, entre otros factores personales, familiares y sociales. Se concluye que es necesario fortalecer las medidas de prevención y protección.São apresentados, aqui, dados quantitativos de um estudo multicêntrico, multimétodos, de corte transversal, realizado em um centro de saúde pública em San Pedro Sula, Honduras. O objetivo foi descrever a perspectiva crítica dos membros da família ou pessoas que se sentem afetadas por terem alguém próximo que usa ou usou drogas ilegais, em relação aos fatores de risco. Os dados foram coletados através de questionário aplicado em 100 indivíduos. A maioria era composta por mulheres pobres, com pouca escolaridade. Os consumidores eram majoritariamente varões, com idade média de 23,3 anos. A droga mais utilizada foi a maconha (78%, seguida por crack/cocaína (72%, cola/inalantes (27%, alucinógenos (ecstasy/LSD (3%, anfetaminas/estimulantes (1%, heroína (1%. Entre os fatores de risco identificados estão: experi

  5. Factor II deficiency

    Science.gov (United States)

    ... if one or more of these factors are missing or are not functioning like they should. Factor II is one such coagulation factor. Factor II deficiency runs in families (inherited) and is very rare. Both parents must ...

  6. Factor VII deficiency

    Science.gov (United States)

    ... if one or more of these factors are missing or are not functioning like they should. Factor VII is one such coagulation factor. Factor VII deficiency runs in families (inherited) and is very rare. Both parents must ...

  7. Heart disease - risk factors

    Science.gov (United States)

    Heart disease - prevention; CVD - risk factors; Cardiovascular disease - risk factors; Coronary artery disease - risk factors; CAD - risk ... a certain health condition. Some risk factors for heart disease you cannot change, but some you can. ...

  8. Thyroid Cancer Risk Factors

    Science.gov (United States)

    ... Prevented? Thyroid Cancer Causes, Risk Factors, and Prevention Thyroid Cancer Risk Factors A risk factor is anything that ... Cancer? Can Thyroid Cancer Be Prevented? More In Thyroid Cancer About Thyroid Cancer Causes, Risk Factors, and Prevention ...

  9. Increased von Willebrand factor, P-selectin and fibrin content in occlusive thrombus resistant to lytic therapy.

    Science.gov (United States)

    Sambola, Antonia; García Del Blanco, Bruno; Ruiz-Meana, Marisol; Francisco, Jaume; Barrabés, José A; Figueras, Jaume; Bañeras, Jordi; Otaegui, Imanol; Rojas, Angeles; Vilardosa, Úrsula; Montaner, Joan; García-Dorado, David

    2016-06-01

    Therapeutic fibrinolysis is ineffective in 40 % of ST-segment elevation acute myocardial infarction (STEMI) patients, but understanding of the mechanisms is incomplete. It was our aim to compare the composition of coronary thrombus in lysis-resistant STEMI patients with that of lysis-sensitive patients. Intracoronary thrombi (n=64) were obtained by aspiration in consecutive STEMI patients. Of them, 20 had received fibrinolysis and underwent rescue percutaneous coronary intervention (r-PCI, lysis-resistant patients) and 44 underwent primary PCI (p-PCI). Lysis-sensitivity was determined in vitro by clot permeability measurements and turbidimetric lysis in plasma of 44 patients undergoing p-PCI and 20 healthy donors. Clot-lysis sensitivity was defined as a clot-lysis time not greater than 1 SD over the mean of healthy donors. Coronary thrombus composition in 20 lysis-resistant and in 20 lysis-sensitive patients was analysed by immunofluorescence with confocal microscopy. Plasma biomarkers (P-selectin, VWF, PAI-1, t-PA, D-dimer, TF pathway markers, plasmin and CD34+) were measured simultaneously on peripheral blood. Lysis-resistant clots had higher levels of fibrin (p=0.02), P-selectin (p=0.03) and VWF (p=0.01) than lysis-sensitive clots. Among thrombi obtained ≤ 6 hours after onset of symptoms, those from lysis-resistant patients showed a higher content in fibrin than those from p-PCI patients (p=0.01). Plasma PAI-1 (p=0.02) and D-dimer levels were significantly higher (p=0.003) in lysis-resistant patients, whereas plasmin levels were lower (p=0.03). Multivariate analysis showed the content of fibrin and VWF within thrombus as predictors of thrombolysis resistance. In conclusion, coronary thrombi in STEMI patients resistant to fibrinolysis are characterised by higher fibrin, P-selectin and VWF content than lysis-sensitive thrombi.

  10. Cascade filtration for TTP: an effective alternative to plasma exchange with cryodepleted plasma.

    Science.gov (United States)

    Bruni, R; Giannini, G; Lercari, G; Bo, A; Florio, G; De Luigi, M C; Marmont, A; Gobbi, A; Damasio, E; Valbonesi, M

    1999-12-01

    TTP remains enigmatic both in terms of etiology and management. The most recent approach is aggressive plasma exchange (PE) employing cryopoor plasma for replacement, based on the pathogenetic relevance given to exceedingly large Von Willebrand (VWF) multimers in the determination of the syndrome with normalization during remission. PE with fresh frozen plasma (FFP) is better than FFP infusion as shown by a recent Canadian study, supporting the theory that to treat TTP an offending circulating agent needs to be removed from the patient's plasma in contrast to the hypothesis that a missing factor is to be given along with FFP. A more recent hypothesis is supported by the results of studies published by the end of 1998 [Moake J, Chintagumpala M, Turner N et al. Blood 1994;84:490-97; Moake J, McPherson PD. Am J Med 1989;87: 3-9N] which would show that TTP is mediated by auto-antibodies to VWF-cleaving protease, or is the result of deficiency of the protease ascribed to abnormalities in its production, function or survival. Plasmapheresis without plasma infusion is relatively ineffective perhaps because it does not increase the protease activity. Cascade filtration (CF) is the autologous counterpart of plasmapheresis. It has been used by our group since 1980 to remove from patients plasma macromolecules such as VWF, fibrinogen, LDL and circulatory immune complexes (CIC). After secondary filtration, the autologous plasma has a composition which is very similar to that of allogeneic plasma after cryoprecipitation, a product which used in the management of TTP. Based on this knowledge, in 1994 we began to use CF in the treatment of TTP patients. In the beginning (7 patients) CF was combined with a decreasing number of conventional PEs using allogeneic plasma for substitution. Lately only CF with some plasma supplementation has been used in the last 9 cases. From a clinical point of view our 16 patients achieved remission after a number of treatments (11 +/- 7) that

  11. Risk Factors and Prevention

    Science.gov (United States)

    ... Factors & Prevention Back to Patient Resources Risk Factors & Prevention Even people who look healthy and free of ... as possible. Share: The Normal Heart Risk Factors & Prevention Heart Diseases & Disorders Substances & Heart Rhythm Disorders Symptoms & ...

  12. Risk Factors for Scleroderma

    Science.gov (United States)

    ... You are here: Home For Patients Risk Factors Risk Factors for Scleroderma The cause of scleroderma is ... what biological factors contribute to scleroderma pathogenesis. Genetic Risk Scleroderma does not tend to run in families ...

  13. Factor V deficiency

    Science.gov (United States)

    ... When certain blood clotting factors are low or missing, your blood does not clot properly. Factor V deficiency is rare. It may be caused by: A defective Factor V gene passed down through families (inherited) An antibody that interferes with normal Factor ...

  14. Foundations of factor analysis

    CERN Document Server

    Mulaik, Stanley A

    2009-01-01

    Introduction Factor Analysis and Structural Theories Brief History of Factor Analysis as a Linear Model Example of Factor AnalysisMathematical Foundations for Factor Analysis Introduction Scalar AlgebraVectorsMatrix AlgebraDeterminants Treatment of Variables as Vectors Maxima and Minima of FunctionsComposite Variables and Linear Transformations Introduction Composite Variables Unweighted Composite VariablesDifferentially Weighted Composites Matrix EquationsMulti

  15. The VITRO Score (Von Willebrand Factor Antigen/Thrombocyte Ratio as a New Marker for Clinically Significant Portal Hypertension in Comparison to Other Non-Invasive Parameters of Fibrosis Including ELF Test.

    Directory of Open Access Journals (Sweden)

    Stephanie Hametner

    Full Text Available Clinically significant portal hypertension (CSPH, defined as hepatic venous pressure gradient (HVPG ≥10 mmHg, causes major complications. HVPG is not always available, so a non-invasive tool to diagnose CSPH would be useful. VWF-Ag can be used to diagnose. Using the VITRO score (the VWF-Ag/platelet ratio instead of VWF-Ag itself improves the diagnostic accuracy of detecting cirrhosis/ fibrosis in HCV patients.This study tested the diagnostic accuracy of VITRO score detecting CSPH compared to HVPG measurement.All patients underwent HVPG testing and were categorised as CSPH or no CSPH. The following patient data were determined: CPS, D'Amico stage, VITRO score, APRI and transient elastography (TE.The analysis included 236 patients; 170 (72% were male, and the median age was 57.9 (35.2-76.3; 95% CI. Disease aetiology included ALD (39.4%, HCV (23.4%, NASH (12.3%, other (8.1% and unknown (11.9%. The CPS showed 140 patients (59.3% with CPS A; 56 (23.7% with CPS B; and 18 (7.6% with CPS C. 136 patients (57.6% had compensated and 100 (42.4% had decompensated cirrhosis; 83.9% had HVPG ≥10 mmHg. The VWF-Ag and the VITRO score increased significantly with worsening HVPG categories (P<0.0001. ROC analysis was performed for the detection of CSPH and showed AUC values of 0.92 for TE, 0.86 for VITRO score, 0.79 for VWF-Ag, 0.68 for ELF and 0.62 for APRI.The VITRO score is an easy way to diagnose CSPH independently of CPS in routine clinical work and may improve the management of patients with cirrhosis.

  16. Spotlight on the human factor: building a foundation for the future of haemophilia A management: report from a symposium on human recombinant FVIII at the World Federation of Hemophilia World Congress, Melbourne, Australia on 12 May 2014.

    Science.gov (United States)

    Kessler, C; Oldenburg, J; Ettingshausen, C Escuriola; Tiede, A; Khair, K; Négrier, C; Klamroth, R

    2015-01-01

    Inhibitor development is the most serious and challenging complication in the treatment of severe haemophilia A. Up to 38% of such patients develop inhibitors with current recombinant factor VIII (rFVIII) products produced in hamster cell lines. Human-cl rhFVIII is a new generation fully sulfated B-domain-deleted FVIII coagulant glycoprotein, which is generated from a human cell line. Thus, there are no non-human epitopes which would be potentially immunogenic. This molecule has significantly higher VWF-binding affinity compared with existing full-length rFVIII produced in hamster cell lines. The development aim of Human-cl rhFVIII is to address the challenges of FVIII inhibitors and frequent infusions during prophylaxis. Human-cl rhFVIII's mean half-life is very comparable to some of the newer products which involve modification of the FVIII molecule to extend the circulating half-life. There are promising data concerning the use of a personalized prophylaxis regimen with Human-cl rhFVIII. Preliminary data indicate a median dosing interval of 3.5 days with 66.7% of the patients on a twice per week or fewer infusions schedule combined with a low bleeding rate and no increased FVIII consumption when compared to standard prophylaxis. No product-specific laboratory assay is required to monitor the coagulation activity for Human-cl rhFVIII. The results of registration clinical trials with Human-cl rhFVIII as well as the ongoing studies in previously untreated patients (NuProtect) and personalized prophylaxis study in previously treated patients (NuPreviq), will be discussed. The manufacturer has received marketing authorization for Human-cl rhFVIII in Europe and Canada under the name Nuwiq(®) and plans to launch it in the USA and globally in 2015.

  17. ISS Payload Human Factors

    Science.gov (United States)

    Ellenberger, Richard; Duvall, Laura; Dory, Jonathan

    2016-01-01

    The ISS Payload Human Factors Implementation Team (HFIT) is the Payload Developer's resource for Human Factors. HFIT is the interface between Payload Developers and ISS Payload Human Factors requirements in SSP 57000. ? HFIT provides recommendations on how to meet the Human Factors requirements and guidelines early in the design process. HFIT coordinates with the Payload Developer and Astronaut Office to find low cost solutions to Human Factors challenges for hardware operability issues.

  18. Assembly and activation of alternative complement components on endothelial cell-anchored ultra-large von Willebrand factor links complement and hemostasis-thrombosis.

    Directory of Open Access Journals (Sweden)

    Nancy A Turner

    Full Text Available BACKGROUND: Vascular endothelial cells (ECs express and release protein components of the complement pathways, as well as secreting and anchoring ultra-large von Willebrand factor (ULVWF multimers in long string-like structures that initiate platelet adhesion during hemostasis and thrombosis. The alternative complement pathway (AP is an important non-antibody-requiring host defense system. Thrombotic microangiopathies can be associated with defective regulation of the AP (atypical hemolytic-uremic syndrome or with inadequate cleavage by ADAMTS-13 of ULVWF multimeric strings secreted by/anchored to ECs (thrombotic thrombocytopenic purpura. Our goal was to determine if EC-anchored ULVWF strings caused the assembly and activation of AP components, thereby linking two essential defense mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: We quantified gene expression of these complement components in cultured human umbilical vein endothelial cells (HUVECs by real-time PCR: C3 and C5; complement factor (CF B, CFD, CFP, CFH and CFI of the AP; and C4 of the classical and lectin (but not alternative complement pathways. We used fluorescent microscopy, monospecific antibodies against complement components, fluorescent secondary antibodies, and the analysis of >150 images to quantify the attachment of HUVEC-released complement proteins to ULVWF strings secreted by, and anchored to, the HUVECs (under conditions of ADAMTS-13 inhibition. We found that HUVEC-released C4 did not attach to ULVWF strings, ruling out activation of the classical and lectin pathways by the strings. In contrast, C3, FB, FD, FP and C5, FH and FI attached to ULVWF strings in quantitative patterns consistent with assembly of the AP components into active complexes. This was verified when non-functional FB blocked the formation of AP C3 convertase complexes (C3bBb on ULVWF strings. CONCLUSIONS/SIGNIFICANCE: AP components are assembled and activated on EC-secreted/anchored ULVWF multimeric

  19. Bayesian Exploratory Factor Analysis

    DEFF Research Database (Denmark)

    Conti, Gabriella; Frühwirth-Schnatter, Sylvia; Heckman, James J.;

    2014-01-01

    This paper develops and applies a Bayesian approach to Exploratory Factor Analysis that improves on ad hoc classical approaches. Our framework relies on dedicated factor models and simultaneously determines the number of factors, the allocation of each measurement to a unique factor, and the corr......This paper develops and applies a Bayesian approach to Exploratory Factor Analysis that improves on ad hoc classical approaches. Our framework relies on dedicated factor models and simultaneously determines the number of factors, the allocation of each measurement to a unique factor......, and the corresponding factor loadings. Classical identification criteria are applied and integrated into our Bayesian procedure to generate models that are stable and clearly interpretable. A Monte Carlo study confirms the validity of the approach. The method is used to produce interpretable low dimensional aggregates...

  20. Une réalisation de l’apprentissage partagé dans un environnement multimédia Une réalisation de l’apprentissage partagé dans un environnement multimédia

    Directory of Open Access Journals (Sweden)

    Colette Mrowa-Hopkins

    2000-12-01

    Full Text Available Dans la mesure où l’utilisation des technologies nouvelles est adaptée aux besoins d’un apprentissage individualisé, les enseignants de langues sont contraints de réévaluer leur propre savoir-faire pédagogique. Il convient de se demander dans quelle mesure la dynamique sociale qui caractérise les échanges dans un climat de travail en collaboration autour de l’ordinateur peut être plus enrichissante pour l’apprentissage des langues. Plus particulièrement, en ce qui nous concerne, dans quelle mesure cette dynamique peut favoriser la performance orale par rapport à un travail de groupe dans une classe traditionnelle. Le présent article offre une perspective nouvelle sur le potentiel d’apprentissage que peut apporter l’utilisation des technologies de l’information et de la communication.This paper attempts, firstly, to document the nature of the linguistic exchanges between pairs of intermediate and advanced students of French who engage in interactive tasks in a CALL environment; and, secondly, it examines the extent to which that interaction is relevant to second-language learning by way of comparison with a small-group, task-based, interaction in a traditional oral class, involving students of the same level of competence. In a search for methods for describing and evaluating CALL use, this exploratory investigation provides support for the adoption of an ’interactionist’ perspective which claims that the language of the participants is central to learning, and that the use of discourse analysis methods is helpful. It is anticipated that computer-mediated interaction shares with a traditional face-to-face contact many of the same interactional features which are believed to make oral negotiation beneficial to learning. However, as this small-scale study suggests, the potential of computer-mediated interaction to facilitate language learning is seen as stemming from a combination of the interactive features of conversation with reflective aspects of learning as participants co-construct knowledge with their more or less experienced peers.

  1. Proteomic screen identifies IGFBP7 as a novel component of endothelial cell-specific Weibel-Palade bodies.

    Science.gov (United States)

    van Breevoort, Dorothee; van Agtmaal, Ellen L; Dragt, Bieuwke S; Gebbinck, Jacqueline Klein; Dienava-Verdoold, Ilze; Kragt, Astrid; Bierings, Ruben; Horrevoets, Anton J G; Valentijn, Karine M; Eikenboom, Jeroen C; Fernandez-Borja, Mar; Meijer, Alexander B; Voorberg, Jan

    2012-05-04

    Vascular endothelial cells contain unique storage organelles, designated Weibel-Palade bodies (WPBs), that deliver inflammatory and hemostatic mediators to the vascular lumen in response to agonists like thrombin and vasopressin. The main component of WPBs is von Willebrand factor (VWF), a multimeric glycoprotein crucial for platelet plug formation. In addition to VWF, several other components are known to be stored in WPBs, like osteoprotegerin, monocyte chemoattractant protein-1 and angiopoetin-2 (Ang-2). Here, we used an unbiased proteomics approach to identify additional residents of WPBs. Mass spectrometry analysis of purified WPBs revealed the presence of several known components such as VWF, Ang-2, and P-selectin. Thirty-five novel candidate WPB residents were identified that included insulin-like growth factor binding protein-7 (IGFBP7), which has been proposed to regulate angiogenesis. Immunocytochemistry revealed that IGFBP7 is a bona fide WPB component. Cotransfection studies showed that IGFBP7 trafficked to pseudo-WPB in HEK293 cells. Using a series of deletion variants of VWF, we showed that targeting of IGFBP7 to pseudo-WPBs was dependent on the carboxy-terminal D4-C1-C2-C3-CK domains of VWF. IGFBP7 remained attached to ultralarge VWF strings released upon exocytosis of WPBs under flow. The presence of IGFBP7 in WPBs highlights the role of this subcellular compartment in regulation of angiogenesis.

  2. Risk Factors for Thrombosis

    Institute of Scientific and Technical Information of China (English)

    包承鑫

    2002-01-01

    @@ Thrombotic disease is a multifactorial disease, multiple interactions between genetic and environmental factors contribute to the development of the disease.This review summarized some risk factors reported for arterial thrombosis and venous thrombosis in recent few years.

  3. Factoring Polynomials and Fibonacci.

    Science.gov (United States)

    Schwartzman, Steven

    1986-01-01

    Discusses the factoring of polynomials and Fibonacci numbers, offering several challenges teachers can give students. For example, they can give students a polynomial containing large numbers and challenge them to factor it. (JN)

  4. Coagulation Factors Test

    Science.gov (United States)

    ... be limited. Home Visit Global Sites Search Help? Coagulation Factors Share this page: Was this page helpful? ... else I should know? How is it used? Coagulation factor testing is performed to determine if a ...

  5. Annual Adjustment Factors

    Data.gov (United States)

    Department of Housing and Urban Development — The Department of Housing and Urban Development establishes the rent adjustment factors - called Annual Adjustment Factors (AAFs) - on the basis of Consumer Price...

  6. Analyse de Aider les élèves à comprendre - Du texte au multimédia

    Directory of Open Access Journals (Sweden)

    Carole Renard

    2006-04-01

    Full Text Available Cet ouvrage, qui met à contribution différents spécialistes, fait le point sur "l'activité de comprendre" du point de vue de la psychologie cognitive[]. Il est destiné aux enseignants et pointe la diversité des situations de compréhension tout en donnant des pistes d'enseignement possibles - tout du moins de sensibilisation - de cette activité. Nous avons conservé le découpage de l'ouvrage pour rendre compte du contenu des différents articles qui le composent et avons réservé nos critiques à ...

  7. Disseny d'un entorn multimèdia i telemàtic aplicat a la Comptabilitat de Costos

    Directory of Open Access Journals (Sweden)

    Juan Luis Gandía Cabedo

    2008-12-01

    Full Text Available El objetivo de este trabajo es desarrollar un modelo virtual-presencial que favorezca un aprendizaje controlado y dirigido por el profesor y donde el estudiante sea el protagonista de su proceso formativo. Las características del entorno multimedia y telemático propuesto se desarrolla sobre la plataforma de e-learning Moodle, si bien los recursos ofrecidos por la misma han sido ampliados con tres innovaciones relevantes: i el gestor de contenidos, que permite integrar audio, video, documentos, imágenes y cuestionarios; ii Un generador automatizado de ejercicios autoevaluables, que permite la elaboración de enunciados individualizados para cada estudiante y su solución; iii Una ficha de estudiante que permite integrar los resultados obtenidos de las diferentes actividades evaluables: cuestionarios, consultas, talleres, foros, casos prácticos o simulaciones.

  8. Large-scale detection of antigen-specific T cells using peptide-MHC-I multimers labeled with DNA barcodes

    DEFF Research Database (Denmark)

    Bentzen, Amalie Kai; Marquard, Andrea Marion; Lyngaa, Rikke Birgitte

    2016-01-01

    cell therapy in melanoma patients, we observe a greater number of melanoma-specific T-cell populations compared with cytometry-based approaches. Furthermore, we detect neoepitope-specific T cells in tumor-infiltrating lymphocytes and peripheral blood from patients with non-small cell lung cancer...

  9. Développement des services multimédia de la bibliothèque du CERN rapport de stage

    CERN Document Server

    Boigey, Myriam; Vigen, Jens

    1997-01-01

    Multimedia allows new possibilities in specialised scientific libraries, such as CERN Library. So, this report presents some exemples showing this. The point is focused over the diversity of media (electronic, video) but also the possibility to propose new services and to make the information access easier for the users. (in french)

  10. The mitochondrial calcium uniporter is a multimer that can include a dominant-negative pore-forming subunit.

    Science.gov (United States)

    Raffaello, Anna; De Stefani, Diego; Sabbadin, Davide; Teardo, Enrico; Merli, Giulia; Picard, Anne; Checchetto, Vanessa; Moro, Stefano; Szabò, Ildikò; Rizzuto, Rosario

    2013-08-28

    Mitochondrial calcium uniporter (MCU) channel is responsible for Ruthenium Red-sensitive mitochondrial calcium uptake. Here, we demonstrate MCU oligomerization by immunoprecipitation and Förster resonance energy transfer (FRET) and characterize a novel protein (MCUb) with two predicted transmembrane domains, 50% sequence similarity and a different expression profile from MCU. Based on computational modelling, MCUb includes critical amino-acid substitutions in the pore region and indeed MCUb does not form a calcium-permeable channel in planar lipid bilayers. In HeLa cells, MCUb is inserted into the oligomer and exerts a dominant-negative effect, reducing the [Ca(2+)]mt increases evoked by agonist stimulation. Accordingly, in vitro co-expression of MCUb with MCU drastically reduces the probability of observing channel activity in planar lipid bilayer experiments. These data unveil the structural complexity of MCU and demonstrate a novel regulatory mechanism, based on the inclusion of dominant-negative subunits in a multimeric channel, that underlies the fine control of the physiologically and pathologically relevant process of mitochondrial calcium homeostasis.

  11. Mark Briggs, Manuel de journalisme web. Blogs, réseaux sociaux, multimédia, info mobile

    OpenAIRE

    Toppé, Gilbert

    2015-01-01

    L’ouvrage comporte onze chapitres, dont le premier consiste en une large introduction (pp. 2-8) aux systèmes de l’information numérique et à son vocabulaire. Les autres sont essentiellement des points de mise en pratique du journalisme web. Le volume est un livre-outil, un guide d’utilisateur, à l’attention des journalistes web, avec des schémas, des figures et des cas pratiques. C’est pourquoi, Mark Briggs commence par expliquer le fonctionnement du journalisme web : usage de l’internet qu’i...

  12. Environmental factors in autism

    OpenAIRE

    Andreas Martin Grabrucker

    2013-01-01

    Autism is a neurodevelopmental disorders characterized by impairments in communication and social behavior, and by repetitive behaviors. Although genetic factors might be largely responsible for the occurrence of autism they cannot fully account for all cases and it is likely that in addition to a certain combination of autism-related genes, specific environmental factors might act as risk factors triggering the development of autism. Thus, the role of environmental factors in autism is an im...

  13. Environmental Factors in Autism

    OpenAIRE

    Andreas M. Grabrucker

    2013-01-01

    Autism is a neurodevelopmental disorders characterized by impairments in communication and social behavior, and by repetitive behaviors. Although genetic factors might be largely responsible for the occurrence of autism they cannot fully account for all cases and it is likely that in addition to a certain combination of autism-related genes, specific environmental factors might act as risk factors triggering the development of autism. Thus, the role of environmental factors in autism is an im...

  14. Mesonic Form Factors

    Energy Technology Data Exchange (ETDEWEB)

    Frederic D. R. Bonnet; Robert G. Edwards; George T. Fleming; Randal Lewis; David Richards

    2003-07-22

    We have started a program to compute the electromagnetic form factors of mesons. We discuss the techniques used to compute the pion form factor and present preliminary results computed with domain wall valence fermions on MILC asqtad lattices, as well as Wilson fermions on quenched lattices. These methods can easily be extended to rho-to-gamma-pi transition form factors.

  15. Multilevel Mixture Factor Models

    Science.gov (United States)

    Varriale, Roberta; Vermunt, Jeroen K.

    2012-01-01

    Factor analysis is a statistical method for describing the associations among sets of observed variables in terms of a small number of underlying continuous latent variables. Various authors have proposed multilevel extensions of the factor model for the analysis of data sets with a hierarchical structure. These Multilevel Factor Models (MFMs)…

  16. Bayesian Exploratory Factor Analysis

    DEFF Research Database (Denmark)

    Conti, Gabriella; Frühwirth-Schnatter, Sylvia; Heckman, James J.

    2014-01-01

    This paper develops and applies a Bayesian approach to Exploratory Factor Analysis that improves on ad hoc classical approaches. Our framework relies on dedicated factor models and simultaneously determines the number of factors, the allocation of each measurement to a unique factor......, and the corresponding factor loadings. Classical identification criteria are applied and integrated into our Bayesian procedure to generate models that are stable and clearly interpretable. A Monte Carlo study confirms the validity of the approach. The method is used to produce interpretable low dimensional aggregates...

  17. 基质细胞衍生因子-1α和白细胞介素-1β诱导淋巴管内皮表型的作用%Effect of stromal cell derived factor-1αand interleukin-1βon inducing vascular endothelial cells expressing lymphatic phenotype

    Institute of Scientific and Technical Information of China (English)

    索宁; 王雪颖; 杨春林; 周辉; 李菲; 张宗璞; 万芳竹; 田铧

    2014-01-01

    目的:探讨基质细胞衍生因子-1α( SDF-1α)及白细胞介素-1β( IL-1β)诱导内皮细胞表达淋巴管表型的作用。方法 SDF-1α和IL-1β分别诱导内皮细胞株CRL-1730,用Real-time PCR、Western blotting 及免疫细胞化学等方法检测其内皮及淋巴管标志物,的表达情况。结果 SDF-1α诱导培养之后,CRL-1730细胞株的内皮细胞标志物血管性血友病因子(vWF)、血管内皮钙黏蛋白(VE-cadherin)、血管内皮生长因子受体(VEGFR)2随其浓度增高而表达降低,淋巴管标志物平足蛋白( podoplanin )、同源异形盒蛋白-1( Prox-1)和淋巴管内皮透明质酸受体-1(LYVE-1)随其浓度增高而表达增高。 IL-1β诱导之后,CRL-1730细胞株的vWF、VEGFR2和podoplanin、prox-1、LYVE-1的变化趋势同SDF-1α,而VE-cadherin的表达量基本不变。结论 SDF-1α和IL-1β都能够诱导血管内皮细胞表达淋巴管标志物。%Objective To investigate the effect of stromal cell-derived factor-1α( SDF-1α) and interleukin ( IL-1β) on inducing vascular endothelial cells to express lymphatic phenotype .Methods The CRL-1730 cell line was cultured and treated with SDF-1αor IL-1β.The expression of endothelial cell markers and lymphatic endothelial cell markers were investigated with Real-time PCR, Western blotting and immunocytochemistry .Results In CRL-1730 cell line, endothelial cell markers such as voln willebrand factor ( vWF ) , VE-cadherin , vascular endothelial growth factor receptor(VEGFR)2, were dose dependently down-regulated after SDF-1αstimulation, while lymphatic phenotypes such as Prox-1, podoplanin and lymphatic vessel endothelial hyaluronan receptor-1(LYVE-1), were dose-dependently up-regulated after SDF-1αstimulation.The changes of vWF, VEGFR2 and podoplanin, Prox-1, LYVE-1 expression after IL-1βstimulation was similar to that after SDF-1αwhile expression of VE-cadherin changed slightly .Conclusion SDF-1αand IL-1

  18. Analytic Couple Modeling Introducing Device Design Factor, Fin Factor, Thermal Diffusivity Factor, and Inductance Factor

    Science.gov (United States)

    Mackey, Jon; Sehirlioglu, Alp; Dynys, Fred

    2014-01-01

    A set of convenient thermoelectric device solutions have been derived in order to capture a number of factors which are previously only resolved with numerical techniques. The concise conversion efficiency equations derived from governing equations provide intuitive and straight-forward design guidelines. These guidelines allow for better device design without requiring detailed numerical modeling. The analytical modeling accounts for factors such as i) variable temperature boundary conditions, ii) lateral heat transfer, iii) temperature variable material properties, and iv) transient operation. New dimensionless parameters, similar to the figure of merit, are introduced including the device design factor, fin factor, thermal diffusivity factor, and inductance factor. These new device factors allow for the straight-forward description of phenomenon generally only captured with numerical work otherwise. As an example a device design factor of 0.38, which accounts for thermal resistance of the hot and cold shoes, can be used to calculate a conversion efficiency of 2.28 while the ideal conversion efficiency based on figure of merit alone would be 6.15. Likewise an ideal couple with efficiency of 6.15 will be reduced to 5.33 when lateral heat is accounted for with a fin factor of 1.0.

  19. Explicit correlation factors

    Science.gov (United States)

    Johnson, Cole M.; Hirata, So; Ten-no, Seiichiro

    2017-09-01

    We analyze the performance of 17 different correlation factors in explicitly correlated second-order many-body perturbation calculations for correlation energies. Highly performing correlation factors are found to have near-universal shape and size in the short range of electron-electron distance (0 1.5 a.u.) is insignificant insofar as the factor becomes near constant, leaving an orbital expansion to describe decoupled electrons. An analysis based on a low-rank Taylor expansion of the correlation factor seems limited, except that a negative second derivative with the value of around -1.3 a.u. correlates with high performance.

  20. Rh Factor Blood Test

    Science.gov (United States)

    Tests and Procedures Rh factor blood test By Mayo Clinic Staff Rhesus (Rh) factor is an inherited protein found on the surface of ... If your blood has the protein, you're Rh positive. If your blood lacks the protein, you' ...

  1. Baryon form factors

    CERN Document Server

    Kubis, B; Meißner, Ulf G; Mei{\\ss}ner, Ulf-G.

    1999-01-01

    We calculate the form factors of the baryon octet in the framework of heavy baryon chiral perturbation theory. The calculated charge radius of the show that kaon loop effects can play a significant role in the neutron electric form factor. Furthermore. we derive generalized Caldi-Pagels relations between various charge radii which are free of chiral loop effects.

  2. Overview of environmental factors

    Science.gov (United States)

    Purvis, C. K.

    1989-01-01

    The orbital environment is complex, dynamic, and comprised of both natural and system-induced components. Several environment factors are important for materials. Materials selection/suitability determination requires consideration of each and all factors, including synergisms among them. Understanding and evaluating these effects will require ground testing, modeling, and focused flight experimentation.

  3. The Transcription Factor Encyclopedia

    DEFF Research Database (Denmark)

    Yusuf, Dimas; Butland, Stefanie L; Swanson, Magdalena I

    2012-01-01

    ABSTRACT: Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130...

  4. Factors of schizoid personality.

    Science.gov (United States)

    Raine, A; Allbutt, J

    1989-02-01

    The increasing use of schizoid personality scales with normals has led to a number of validation studies, but to date there are no published analyses of the factorial structure of these scales. This study presents results of factor analyses of schizoid personality scales in an initial attempt to delineate their factorial structure. Questionnaires were administered to 114 male and female undergraduates and factor analysed using Varimax, Quartimax, and Oblique rotations. A two-factor varimax solution yielded a first factor accounting for 49 per cent of total unrotated variance with high (0.70 to 0.91) loadings from Hallucinatory predisposition, Perceptual aberration, Schizophrenism, STA and STB scales, and was interpreted as reflecting a general factor of schizoid personality disorder. Psychoticism and Social anhedonia loaded on a second factor accounting for 20 per cent of the variance which was uncorrelated (r = 0.09) with factor 1. This factor solution was closely replicated using quartimax and oblimin rotation criteria. It is concluded that Social anhedonia and Psychoticism represent a separate dimension from other scales which reflect the more positive features of schizoid personality.

  5. Evaluation of coagulation factors and platelet function from an off-line modified ultrafiltration technique for post-cardiopulmonary bypass circuit blood recovery.

    Science.gov (United States)

    Beckmann, S; Lynn, P; Miller, S; Harris, R; DiMarco, R F; Ross, J E

    2013-05-01

    Modified ultrafiltration (MUF) is a technique that hemoconcentrates residual CPB circuit blood and the patient at the same time. Hemoconcentration and MUF are Class 1-A recommendations in the anesthesia and surgical blood conservation guidelines. This study evaluated the off-line MUF process of the Hemobag (HB, Global Blood Resources, Somers, CT, USA) to quantitate coagulation factor levels, platelet (PLT) count and function in one facility and cellular growth factor concentrations of the final product that were transfused to the patient in another facility In two cardiac surgery facilities, after decannulation, the extracorporeal circuit (ECC) blood from 22 patients undergoing cardiac surgery was processed with the HB device. In eleven patients from the first facility by the study design, blood samples for coagulation factor levels and PLT aggregation were drawn from the reservoir of the MUF device pre- and post-processing. The samples (n = 11) were sent to a reference laboratory where testing for prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), reptilase time, fibrinogen, clotting factors II, V, VII, VIII, IX, X, ADAMTS-13, protein C, protein S, antithrombin III, von Willebrand Factor (vWF), and platelet (PLT) aggregation were performed. A portion of the final concentrated HB blood samples (n = 5-10) from the second facility by design were evaluated for transforming and platelet-derived cellular growth factor concentrations. On average, approximately 800 - 2000 mls of whole blood were removed from the ECC post-CPB for processing in the HB device. After processing, there was, on the average, approximately 300 - 950 mls of concentrated whole blood salvaged for reinfusion. The PT and INR were significantly lower in the post-processing product compared to the pre-processing samples while the aPTT times were not significantly different. All coagulation factors and natural anti-coagulants were significantly

  6. Role of Nitric Oxide Isoforms in Vascular and Alveolar Development and Lung Injury in Vascular Endothelial Growth Factor Overexpressing Neonatal Mice Lungs.

    Directory of Open Access Journals (Sweden)

    Mansoor A Syed

    Full Text Available The role of vascular endothelial growth factor (VEGF-induced 3 different nitric oxide synthase (NOS isoforms in lung development and injury in the newborn (NB lung are not known. We hypothesized that VEGF-induced specific NOS pathways are critical regulators of lung development and injury.We studied NB wild type (WT, lung epithelial cell-targeted VEGF165 doxycycline-inducible overexpressing transgenic (VEGFTG, VEGFTG treated with a NOS1 inhibitor (L-NIO, VEGFTG x NOS2-/- and VEGFTG x NOS3+/- mice in room air (RA for 7 postnatal (PN days. Lung morphometry (chord length, vascular markers (Ang1, Ang2, Notch2, vWF, CD31 and VE-cadherin, cell proliferation (Ki67, vascular permeability, injury and oxidative stress markers (hemosiderin, nitrotyrosine and 8-OHdG were evaluated.VEGF overexpression in RA led to increased chord length and vascular markers at PN7, which were significantly decreased to control values in VEGFTG x NOS2-/- and VEGFTG x NOS3+/- lungs. However, we found no noticeable effect on chord length and vascular markers in the VEGFTG / NOS1 inhibited group. In the NB VEGFTG mouse model, we found VEGF-induced vascular permeability in the NB murine lung was partially dependent on NOS2 and NOS3-signaling pathways. In addition, the inhibition of NOS2 and NOS3 resulted in a significant decrease in VEGF-induced hemosiderin, nitrotyrosine- and 8-OHdG positive cells at PN7. NOS1 inhibition had no significant effect.Our data showed that the complete absence of NOS2 and partial deficiency of NOS3 confers protection against VEGF-induced pathologic lung vascular and alveolar developmental changes, as well as injury markers. Inhibition of NOS1 does not have any modulating role on VEGF-induced changes in the NB lung. Overall, our data suggests that there is a significant differential regulation in the NOS-mediated effects of VEGF overexpression in the developing mouse lung.

  7. Factorized Graph Matching.

    Science.gov (United States)

    Zhou, Feng; de la Torre, Fernando

    2015-11-19

    Graph matching (GM) is a fundamental problem in computer science, and it plays a central role to solve correspondence problems in computer vision. GM problems that incorporate pairwise constraints can be formulated as a quadratic assignment problem (QAP). Although widely used, solving the correspondence problem through GM has two main limitations: (1) the QAP is NP-hard and difficult to approximate; (2) GM algorithms do not incorporate geometric constraints between nodes that are natural in computer vision problems. To address aforementioned problems, this paper proposes factorized graph matching (FGM). FGM factorizes the large pairwise affinity matrix into smaller matrices that encode the local structure of each graph and the pairwise affinity between edges. Four are the benefits that follow from this factorization: (1) There is no need to compute the costly (in space and time) pairwise affinity matrix; (2) The factorization allows the use of a path-following optimization algorithm, that leads to improved optimization strategies and matching performance; (3) Given the factorization, it becomes straight-forward to incorporate geometric transformations (rigid and non-rigid) to the GM problem. (4) Using a matrix formulation for the GM problem and the factorization, it is easy to reveal commonalities and differences between different GM methods. The factorization also provides a clean connection with other matching algorithms such as iterative closest point; Experimental results on synthetic and real databases illustrate how FGM outperforms state-of-the-art algorithms for GM. The code is available at http://humansensing.cs.cmu.edu/fgm.

  8. Risk Factors for Tuberculosis

    Directory of Open Access Journals (Sweden)

    Padmanesan Narasimhan

    2013-01-01

    Full Text Available The risk of progression from exposure to the tuberculosis bacilli to the development of active disease is a two-stage process governed by both exogenous and endogenous risk factors. Exogenous factors play a key role in accentuating the progression from exposure to infection among which the bacillary load in the sputum and the proximity of an individual to an infectious TB case are key factors. Similarly endogenous factors lead in progression from infection to active TB disease. Along with well-established risk factors (such as human immunodeficiency virus (HIV, malnutrition, and young age, emerging variables such as diabetes, indoor air pollution, alcohol, use of immunosuppressive drugs, and tobacco smoke play a significant role at both the individual and population level. Socioeconomic and behavioral factors are also shown to increase the susceptibility to infection. Specific groups such as health care workers and indigenous population are also at an increased risk of TB infection and disease. This paper summarizes these factors along with health system issues such as the effects of delay in diagnosis of TB in the transmission of the bacilli.

  9. Environmental factors in autism.

    Science.gov (United States)

    Grabrucker, Andreas M

    2012-01-01

    Autism is a neurodevelopmental disorders characterized by impairments in communication and social behavior, and by repetitive behaviors. Although genetic factors might be largely responsible for the occurrence of autism they cannot fully account for all cases and it is likely that in addition to a certain combination of autism-related genes, specific environmental factors might act as risk factors triggering the development of autism. Thus, the role of environmental factors in autism is an important area of research and recent data will be discussed in this review. Interestingly, the results show that many environmental risk factors are interrelated and their identification and comparison might unveil a common scheme of alterations on a contextual as well as molecular level. For example, both, disruption in the immune system and in zinc homeostasis may affect synaptic transmission in autism. Thus, here, a model is proposed that interconnects the most important and scientifically recognized environmental factors. Moreover, similarities in how these risk factors impact synapse function are discussed and a possible influence on an already well described genetic pathway leading to the development of autism via zinc homeostasis is proposed.

  10. Environmental factors in autism

    Directory of Open Access Journals (Sweden)

    Andreas Martin Grabrucker

    2013-01-01

    Full Text Available Autism is a neurodevelopmental disorders characterized by impairments in communication and social behavior, and by repetitive behaviors. Although genetic factors might be largely responsible for the occurrence of autism they cannot fully account for all cases and it is likely that in addition to a certain combination of autism-related genes, specific environmental factors might act as risk factors triggering the development of autism. Thus, the role of environmental factors in autism is an important area of research and recent data will be discussed in this review. Interestingly, the results show that many environmental risk factors are interrelated and their identification and comparison might unveil a common scheme of alterations on a contextual as well as molecular level. For example, both, disruption in the immune system and in zinc homeostasis may affect synaptic transmission in autism. Thus, here, a model is proposed that interconnects the most important and scientifically recognized environmental factors. Moreover, similarities in how these risk factors impact synapse function are discussed and a possible influence on an already well described genetic pathway leading to the development of autism via zinc homeostasis is proposed.

  11. Factor V Leiden thrombophilia.

    Science.gov (United States)

    Kujovich, Jody Lynn

    2011-01-01

    Factor V Leiden is a genetic disorder characterized by a poor anticoagulant response to activated Protein C and an increased risk for venous thromboembolism. Deep venous thrombosis and pulmonary embolism are the most common manifestations, but thrombosis in unusual locations also occurs. The current evidence suggests that the mutation has at most a modest effect on recurrence risk after initial treatment of a first venous thromboembolism. Factor V Leiden is also associated with a 2- to 3-fold increased relative risk for pregnancy loss and possibly other obstetric complications, although the probability of a successful pregnancy outcome is high. The clinical expression of Factor V Leiden is influenced by the number of Factor V Leiden alleles, coexisting genetic and acquired thrombophilic disorders, and circumstantial risk factors. Diagnosis requires the activated Protein C resistance assay (a coagulation screening test) or DNA analysis of the F5 gene, which encodes the Factor V protein. The first acute thrombosis is treated according to standard guidelines. Decisions regarding the optimal duration of anticoagulation are based on an individualized assessment of the risks for venous thromboembolism recurrence and anticoagulant-related bleeding. In the absence of a history of thrombosis, long-term anticoagulation is not routinely recommended for asymptomatic Factor V Leiden heterozygotes, although prophylactic anticoagulation may be considered in high-risk clinical settings. In the absence of evidence that early diagnosis reduces morbidity or mortality, decisions regarding testing at-risk family members should be made on an individual basis.

  12. Two-factor authentication

    CERN Document Server

    Stanislav, Mark

    2015-01-01

    During the book, readers will learn about the various technical methods by which two-factor authentication is implemented, security concerns with each type of implementation, and contextual details to frame why and when these technologies should be used. Readers will also be provided with insight about the reasons that two-factor authentication is a critical security control, events in history that have been important to prove why organization and individual would want to use two factor, and core milestones in the progress of growing the market.

  13. Teratogenic factors affect transcription factor expression.

    Science.gov (United States)

    Kojima, Takuya; Asano, Shinya; Takahashi, Naoki

    2013-01-01

    Chemical compounds are produced every day, many with adverse effects on human health, and hence it is vital to predict the risks to humans simply, rapidly, and accurately. Teratogens have a serious impact on fetal development. This has been studied mainly by phenotypic analysis of experimental animals. However, since phenotypes can vary within different species, we established a new evaluation system based on our recent finding that teratogens influence Hox gene expression in mice. Similarly to the Hox gene expression changes, the expression patterns of several transcription factors involved in development, including the Dlx, Irx, Sall, and T-box families, were altered after 6 h of exposure to retinoic acid (RA) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The expression changes in Dlx4, Dlx6, Irx5, Sall2, Sall3, Sall4, Tbx10, and Tbx22 were linked to teratogen-induced phenotypes, and our results indicate that expression changes in developmental transcription factors can help to predict teratogenic risk.

  14. Pseudo (Platelet-type von Willebrand disease in pregnancy: a case report

    Directory of Open Access Journals (Sweden)

    Grover Neetu

    2013-01-01

    Full Text Available Abstract Background Pseudo (platelet-type-von Willebrand disease is a rare autosomal dominant bleeding disorder caused by an abnormal function of the glycoprotein lb protein; the receptor for von Willebrand factor. This leads to an increased removal of VWF multimers from the circulation as well as platelets and this results in a bleeding diathesis. Worldwide, less than 50 patients are reported with platelet type von Willebrand disease (PT-VWD. Case presentation We describe the management of platelet type von Willebrand disease in pregnancy of a 26 year old Caucasian primigravida. The initial diagnosis was made earlier following a significant haemorrhage post tonsillectomy several years prior to pregnancy. The patient was managed under a multidisciplinary team which included obstetricians, haematologists, anaesthetists and neonatologists. Care plans were made for the ante- natal, intra-partum and post-partum periods in partnership with the patient. The patient’s platelet count levels dropped significantly during the antenatal period. This necessitated the active exclusion of other causes of thrombocytopenia in pregnancy. A vaginal delivery was desired and plans were made for induction of labour at 38 weeks of gestation with platelet cover in view of the progressive fall of the platelet count. The patient however went into spontaneous labour on the day of induction. She was transfused two units of platelets before delivery. She had an unassisted vaginal delivery of a healthy baby. The successful antenatal counselling has encouraged the diagnosis of the same condition in her mother and sister. We found this to be a particularly interesting case as well as challenging to manage due to its rarity. Psuedo von Willebrand disease in pregnancy can be confused with a number of other differential diagnoses, such as gestational thrombocutopenia, idiopathatic thrombocytopenia, thrombotic thrombocytopenic purpura and pre-eclampsia; all need consideration

  15. TMDs, universality and factorization

    CERN Document Server

    D'Alesio, Umberto

    2011-01-01

    We present a short overview on transverse momentum dependent parton distribution and fragmentation functions, giving their partonic interpretation and ways to access them. We then discuss the issue of their universality and its connection to factorization in perturbative QCD.

  16. Factor V Leiden

    Science.gov (United States)

    ... increase your chance of developing abnormal blood clots (thrombophilia), usually in your veins. Most people with factor ... sharp tools. References Bauer KA. Management of inherited thrombophilia. http://www.uptodate.com/home. Accessed June 6, ...

  17. New microbial growth factor

    Science.gov (United States)

    Bok, S. H.; Casida, L. E., Jr.

    1977-01-01

    A screening procedure was used to isolate from soil a Penicillium sp., two bacterial isolates, and a Streptomyces sp. that produced a previously unknown microbial growth factor. This factor was an absolute growth requirement for three soil bacteria. The Penicillium sp. and one of the bacteria requiring the factor, an Arthrobacter sp., were selected for more extensive study concerning the production and characteristics of the growth factor. It did not seem to be related to the siderochromes. It was not present in soil extract, rumen fluid, or any other medium component tested. It appears to be a glycoprotein of high molecular weight and has high specific activity. When added to the diets for a meadow-vole mammalian test system, it caused an increased consumption of diet without a concurrent increase in rate of weight gain.

  18. Factors Affecting Wound Healing

    Science.gov (United States)

    Guo, S.; DiPietro, L.A.

    2010-01-01

    Wound healing, as a normal biological process in the human body, is achieved through four precisely and highly programmed phases: hemostasis, inflammation, proliferation, and remodeling. For a wound to heal successfully, all four phases must occur in the proper sequence and time frame. Many factors can interfere with one or more phases of this process, thus causing improper or impaired wound healing. This article reviews the recent literature on the most significant factors that affect cutaneous wound healing and the potential cellular and/or molecular mechanisms involved. The factors discussed include oxygenation, infection, age and sex hormones, stress, diabetes, obesity, medications, alcoholism, smoking, and nutrition. A better understanding of the influence of these factors on repair may lead to therapeutics that improve wound healing and resolve impaired wounds. PMID:20139336

  19. Factor X assay

    Science.gov (United States)

    ... D, Neff AT. Rare coagulation factor deficiencies. In: Hoffman R, Benz EJ Jr, Silberstein LE, Heslop HE, ... Laboratory evaluation of hemostatic and thrombotic disorders. In: Hoffman R, Benz EJ Jr, Silberstein LE, Heslop HE, ...

  20. Factor XII assay

    Science.gov (United States)

    ... D, Neff AT. Rare coagulation factor deficiencies. In: Hoffman R, Benz EJ Jr, Silberstein LE, Heslop HE, ... Laboratory evaluation of hemostatic and thrombotic disorders. In: Hoffman R, Benz EJ Jr, Silberstein LE, Heslop HE, ...

  1. Rheumatoid Factors: Clinical Applications

    Directory of Open Access Journals (Sweden)

    Francesca Ingegnoli

    2013-01-01

    Full Text Available Rheumatoid factors are antibodies directed against the Fc region of immunoglobulin G. First detected in patients with rheumatoid arthritis 70 years ago, they can also be found in patients with other autoimmune and nonautoimmune conditions, as well as in healthy subjects. Rheumatoid factors form part of the workup for the differential diagnosis of arthropathies. In clinical practice, it is recommended to measure anti-cyclic citrullinated peptide antibodies and rheumatoid factors together because anti-cyclic citrullinated peptide antibodies alone are only moderately sensitive, and the combination of the two markers improves diagnostic accuracy, especially in the case of early rheumatoid arthritis. Furthermore, different rheumatoid factor isotypes alone or in combination can be helpful when managing rheumatoid arthritis patients, from the time of diagnosis until deciding on the choice of therapeutic strategy.

  2. Heart Disease Risk Factors

    Science.gov (United States)

    ... Hearts® WISEWOMAN Program Other Chronic Disease Topics Diabetes Nutrition Obesity Physical Activity Stroke Heart Disease Risk Factors Recommend ... Hearts® WISEWOMAN Program Other Chronic Disease Topics Diabetes Nutrition Obesity Physical Activity Stroke File Formats Help: How do ...

  3. Human Factors Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — Purpose: The purpose of the Human Factors Laboratory is to further the understanding of highway user needs so that those needs can be incorporated in roadway design,...

  4. Factors Affecting Wound Healing

    OpenAIRE

    Guo, S.; DiPietro, L A

    2010-01-01

    Wound healing, as a normal biological process in the human body, is achieved through four precisely and highly programmed phases: hemostasis, inflammation, proliferation, and remodeling. For a wound to heal successfully, all four phases must occur in the proper sequence and time frame. Many factors can interfere with one or more phases of this process, thus causing improper or impaired wound healing. This article reviews the recent literature on the most significant factors that affect cutane...

  5. FGF growth factor analogs

    Science.gov (United States)

    Zamora, Paul O [Gaithersburg, MD; Pena, Louis A [Poquott, NY; Lin, Xinhua [Plainview, NY; Takahashi, Kazuyuki [Germantown, MD

    2012-07-24

    The present invention provides a fibroblast growth factor heparin-binding analog of the formula: ##STR00001## where R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, X, Y and Z are as defined, pharmaceutical compositions, coating compositions and medical devices including the fibroblast growth factor heparin-binding analog of the foregoing formula, and methods and uses thereof.

  6. Brain derived neurotrophic factor

    DEFF Research Database (Denmark)

    Mitchelmore, Cathy; Gede, Lene

    2014-01-01

    Brain Derived Neurotrophic Factor (BDNF) is a neurotrophin with important functions in neuronal development and neuroplasticity. Accumulating evidence suggests that alterations in BDNF expression levels underlie a variety of psychiatric and neurological disorders. Indeed, BDNF therapies are curre......Brain Derived Neurotrophic Factor (BDNF) is a neurotrophin with important functions in neuronal development and neuroplasticity. Accumulating evidence suggests that alterations in BDNF expression levels underlie a variety of psychiatric and neurological disorders. Indeed, BDNF therapies...

  7. General Factors in Graphs.

    Science.gov (United States)

    1986-07-01

    conjectured that the general factor problem can be solved in polynomial time when, in each Bi, all the gaps (if any) have length one. We prove this conjecture...exactly bi edges incident with node i, for each i. This problem is well-solved. A polynomial algorithm is known (Edmonds and Johnson (1970)) as well as a...powerful theorem to characterize the existence of solutions ( Tutte (1952)). The following generalization of the factor problem was studied by Lovtsz

  8. Factors Impacting Knowledge Sharing

    DEFF Research Database (Denmark)

    Schulzmann, David; Slepniov, Dmitrij

    The purpose of this paper is to examine various factors affecting knowledge sharing at the R&D center of a Western MNE in China. The paper employs qualitative methodology and is based on the action research and case study research techniques. The findings of the paper advance our understanding...... about factors that affect knowledge sharing. The main emphasis is given to the discussion on how to improve knowledge sharing in global R&D organizations....

  9. Los factores de riesgo

    Directory of Open Access Journals (Sweden)

    Justo Senado Dumoy

    1999-01-01

    Full Text Available Sobre el fundamento filosófico de los conceptos de la Dialéctica Materialista, se presenta un análisis en relación con el concepto e interpretación de los Factores de Riesgo.A analysis on the concept and interpretation of risk factors is presented based on the philosophical foundation of the concepts of materialist dialectics.

  10. Factors affecting emotional divorce

    Directory of Open Access Journals (Sweden)

    Karim Said Shabanlou

    2016-03-01

    Full Text Available Emotional Divorce is the most important factor in the rupture of the most fundamental structures of society, the family.Due to the sensitivity and position of the familyAnd its functions specifically to investigate the factors underlying emotional divorce has of particular importance.Emotional Divorce phenomenon is not a single factor, but rather a set of related factors together led to Emotional Divorce.In this paper the role of psychological factors such as early maladaptive schemas, negative body image, perfectionism is discussed on an emotional divorce.Also quality of life and family relationships of couples with emotional divorce,Such as quality of health, sexual dissatisfaction, ignoring the needs, expectations and opinions of women by men or vice versa,And also social and economic factors such as subcultures families, couples, the quality of social relationships, social networks couple,Economic situation of the families of the couple, financial crisis, unemployment and economic revenues couples studied and some suggestions are presented based on the findings.

  11. CATTELL AND EYSENCK FACTOR SCORES RELATED TO COMREY PERSONALITY FACTORS.

    Science.gov (United States)

    Comrey, A L; Duffy, K E

    1968-10-01

    The Eysenck Personality Inventory, the Cattell 16 PF Inventory, and the Comrey Personality Inventory were administered to 272 volunteers. Eysenck and Cattell factor scores were correlated with scores over homogeneous item groups (FHIDs) which define the Comrey test factors. This matrix was factor analyzed to relate the Eysenck and Cattell factor scores to the factor structure underlying the Comrey test. The Eysenck Neuroticism, Comrey Neuroticism, and Cattell second-order Anxiety factors appeared to match. The Eysenck Introversion and the Comrey Shyness factors also matched. The 16 Cattell primary factors overlapped but did not match with the Comrey factors.

  12. Breast cancer risk factors

    Directory of Open Access Journals (Sweden)

    Marzena Kamińska

    2015-09-01

    Full Text Available Breast cancer is the most frequently diagnosed neoplastic disease in women around menopause often leading to a significant reduction of these women’s ability to function normally in everyday life. The increased breast cancer incidence observed in epidemiological studies in a group of women actively participating in social and professional life implicates the necessity of conducting multidirectional studies in order to identify risk factors associated with the occurrence of this type of neoplasm. Taking the possibility of influencing the neoplastic transformation process in individuals as a criterion, all the risk factors initiating the process can be divided into two groups. The first group would include inherent factors such as age, sex, race, genetic makeup promoting familial occurrence of the neoplastic disease or the occurrence of benign proliferative lesions of the mammary gland. They all constitute independent parameters and do not undergo simple modification in the course of an individual’s life. The second group would include extrinsic factors conditioned by lifestyle, diet or long-term medical intervention such as using oral hormonal contraceptives or hormonal replacement therapy and their influence on the neoplastic process may be modified to a certain degree. Identification of modifiable factors may contribute to development of prevention strategies decreasing breast cancer incidence.

  13. [Prognostic factors in resuscitation].

    Science.gov (United States)

    Bahloul, F; Le Gall, J R; Loirat, P; Alperovitch, A; Patois, E

    1988-10-08

    The outcome from intensive care is known to be influenced by such factors as age, previous health status, severity of the disease and diagnosis. In order to assess the influence of each individual factor, 3,687 patients from 38 French intensive care units were studied. For each patient were recorded: age, simplified acute physiological score (SAPS), previous health status, diagnosis, type of intensive care unit (medicine, scheduled or elective surgery) and immediate outcome. Each of these factors was found to influence the immediate survival rate. A multivariate analysis ranked the factors in the following order: SAPS, age, type of intensive care unit and previous health status. Diagnosis played a role in the prognosis since with a 10-15 points SAPS mortality was nil for drug overdose, 12 per cent for chronic obstructive pulmonary disease and 38 per cent for cardiogenic shock. However, a single diagnosis was made in only 37 per cent of the patients, as against 3 diagnoses in 17 per cent and 4 diagnoses or more in 7 per cent. When the type of intensive care unit was considered, the mean death rate was 20 per cent in medicine, 27 per cent in scheduled surgery and 5 per cent in elective surgery (P less than 0.001). Since this study showed a definite influence of each of the four factors on immediate survival, intensive care patients can be described and classified according to this system. However, it must be stressed that individual prognoses are extremely vague.

  14. Geothermal Plant Capacity Factors

    Energy Technology Data Exchange (ETDEWEB)

    Greg Mines; Jay Nathwani; Christopher Richard; Hillary Hanson; Rachel Wood

    2015-01-01

    The capacity factors recently provided by the Energy Information Administration (EIA) indicated this plant performance metric had declined for geothermal power plants since 2008. Though capacity factor is a term commonly used by geothermal stakeholders to express the ability of a plant to produce power, it is a term frequently misunderstood and in some instances incorrectly used. In this paper we discuss how this capacity factor is defined and utilized by the EIA, including discussion on the information that the EIA requests from operations in their 923 and 860 forms that are submitted both monthly and annually by geothermal operators. A discussion is also provided regarding the entities utilizing the information in the EIA reports, and how those entities can misinterpret the data being supplied by the operators. The intent of the paper is to inform the facility operators as the importance of the accuracy of the data that they provide, and the implications of not providing the correct information.

  15. Multi-factor authentication

    Energy Technology Data Exchange (ETDEWEB)

    Hamlet, Jason R; Pierson, Lyndon G

    2014-10-21

    Detection and deterrence of spoofing of user authentication may be achieved by including a cryptographic fingerprint unit within a hardware device for authenticating a user of the hardware device. The cryptographic fingerprint unit includes an internal physically unclonable function ("PUF") circuit disposed in or on the hardware device, which generates a PUF value. Combining logic is coupled to receive the PUF value, combines the PUF value with one or more other authentication factors to generate a multi-factor authentication value. A key generator is coupled to generate a private key and a public key based on the multi-factor authentication value while a decryptor is coupled to receive an authentication challenge posed to the hardware device and encrypted with the public key and coupled to output a response to the authentication challenge decrypted with the private key.

  16. The focus factor

    DEFF Research Database (Denmark)

    Nicolaisen, Jeppe; Frandsen, Tove Faber

    2015-01-01

    Introduction. We present a new bibliometric indicator to measure journal specialisation over time, named the focus factor. This new indicator is based on bibliographic coupling and counts the percentage of re-citations given in subsequent years. Method. The applicability of the new indicator....... To validate re-citations as caused by specialisation, other possible causes were measured and correlated (obsolescence, journal self-citations and number of references). Results. The results indicate that the focus factor is capable of distinguishing between general and specialised journals and thus...... effectively measures the intended phenomenon (i.e., journal specialisation). Only weak correlations were found between journal re-citations and obsolescence, journal self-citations, and number of references. Conclusions. The focus factor successfully measures journal specialisation over time. Measures based...

  17. La adolescencia: factores criticos

    Directory of Open Access Journals (Sweden)

    Noé Ardila Espinel

    1980-01-01

    Full Text Available Ten factors, tbat are considered by several psychologists as sensitive and characterístíc of the adolescent period, were tested by means of a Lykert type scale of 50 ítems, Seventy-eight subjects divided in three groups (U·13 years, early adolescence; 14·17 years, middle adolescence; 18-22 years, late adolescence answered the scale, Results índicate age differences. The factors that are in conflict duríng the middle adolescente are: emotional control, self control, social behavior, logical thinking, tendeney toward independency, economic índependency, family índependency, relígíous independency, rules conflict,and affective development, The factors change in direction before, during, and after adolescence

  18. Model Correction Factor Method

    DEFF Research Database (Denmark)

    Christensen, Claus; Randrup-Thomsen, Søren; Morsing Johannesen, Johannes

    1997-01-01

    The model correction factor method is proposed as an alternative to traditional polynomial based response surface techniques in structural reliability considering a computationally time consuming limit state procedure as a 'black box'. The class of polynomial functions is replaced by a limit...... statebased on an idealized mechanical model to be adapted to the original limit state by the model correction factor. Reliable approximations are obtained by iterative use of gradient information on the original limit state function analogously to previous response surface approaches. However, the strength...... of the model correction factor method, is that in simpler form not using gradient information on the original limit state function or only using this information once, a drastic reduction of the number of limit state evaluation is obtained together with good approximations on the reliability. Methods...

  19. Orthogonal factorizations of digraphs

    Institute of Scientific and Technical Information of China (English)

    Guizhen LIU

    2009-01-01

    Let G be a digraph with vertex set V(G) and arc set E(G) and let g = (g-,g+) and f = (f-, f+) be pairs of positive integer-valued functions defined on V(G) such that g-(x) ≤ f-(x) and g+(x) ≤ f+(x) for each x ∈ V(G). A (g, f)-factor of G is a spanning subdigraph H of G such that g-(x) ≤ idH(x) ≤ f-(x) and g+(x) ≤ odu(x) ≤ f+(x) for each x ∈ V(H); a (g, f)-factorization of G is a partition of E(G) into arc-disjoint (g, f)-factors. Let = {F1,F2,...,Fm} and H be a factorization and a subdigraph of G, respectively, is called k-orthogonal to H if each FI, 1 ≤ I ≤ m, has exactly k arcs in common with H. In this paper it is proved that every (mg+m-1, mf-m+1)-digraph has a (g, f)-factorization k-orthogonal to any given subdigraph with km arcs if k ≤ min{g-(x),g+(x)} for any x ∈ V(G) and that every (mg, mf)-digraph has a (g, f)-factorization orthogonal to any given directed m-star if 0 ≤ g(x) ≤ f(x) for any x ∈ V(G). The results in this paper are in some sense best possible.

  20. Factores de riesgo psicosocial

    OpenAIRE

    Fernández, Borja

    2012-01-01

    Tras un año de estudio de la Prevención de Riesgos Laborales he podido ir adquiriendo, todavía más, una clara concienciación sobre el estudio, supresión y mejora de los factores de riesgo que afectan a los trabajadores en la ejecución de su trabajo. Algo que es fácil de darse cuenta al entrar en profundidad en estas cuestiones, es de la escasa conciencia que tienen las organizaciones y los trabajadores sobre lo perjudiciales que pueden ser para su salud los factores de riesgo ergonómicos. ...

  1. Graph factors modulo k

    DEFF Research Database (Denmark)

    Thomassen, Carsten

    2014-01-01

    We prove a general result on graph factors modulo k . A special case says that, for each natural number k , every (12k−7)-edge-connected graph with an even number of vertices contains a spanning subgraph in which each vertex has degree congruent to k modulo 2k.......We prove a general result on graph factors modulo k . A special case says that, for each natural number k , every (12k−7)-edge-connected graph with an even number of vertices contains a spanning subgraph in which each vertex has degree congruent to k modulo 2k....

  2. Endodontic surgery prognostic factors.

    Science.gov (United States)

    Azarpazhooh, Amir; Shah, Prakesh S

    2011-01-01

    Medline, (PubMed) and the Cochrane databases together with hand searching of the following journals: Journal of Endodontics, International Endodontic Journal, Oral Surgery Oral Medicine Oral Pathology (name changed to Oral Surgery Oral Medicine Oral Pathology Oral Radiology and Endodontics in 1995), Endodontics and Dental Traumatology (name changed to Dental Traumatology in 2001), Journal of Oral and Maxillofacial Surgery, and International Journal of Oral and Maxillofacial Surgery. Clinical studies evaluating apical surgery with placement of a root-end filling were included. Studies on apical surgery with orthograde root canal filling or about apicectomy alone without root-end filling were excluded, as were experimental and animal studies. Only studies with ≥ ten patients with a minimum six month follow-up period and clearly defined radiographic and clinical healing criteria, with healing reported for at least two categories of a specific prognostic factor were accepted. Studies reporting in English, German, French, Spanish, Italian, Portuguese and Scandinavian languages were included. All studies were assessed separately by two of the three authors, with disagreements resolved by discussion. Prognostic factors were divided into patient related, tooth-related or treatment-related factors. The reported percentages of healed teeth were pooled per category. The statistical method of Mantel-Haenszel was applied to estimate the odds ratios and their 95% confidence intervals. Homogeneity was assessed using Woolf's test. With regard to tooth-related factors, the following were identified as predictors of healing: absence of preoperative pain or signs, good density of the root canal filling and a periapical lesion size of ≤ 5 mm. With regard to treatment-related factors, teeth treated with the use of an endoscope tended to have higher healed rates than teeth treated without the use of an endoscope. Although the clinician may be able to control treatment

  3. STEREOTYPICAL FACTORS IN TOURISM

    Directory of Open Access Journals (Sweden)

    Cristina-Elena ALBU

    2013-06-01

    Full Text Available International tourism has grown rapidly nowdays, contributing to the growth of the global economy. The purpose of this essay is to identify and analyze stereotypical factors in the development of strategies concerning the offer for the tourism industry: the image of a tourist destination, brand, country of origin and customer behaviour. Documentary study was the research method used: representative articles were analysed, as recent as possible, to determine the factors mentioned above. Professionals in the industry of tourism need to understand cultural differences between tourists, as well as those of the host country, to be able to create tourist reception offers that live up to the standards expected by clients.

  4. The transcription factor encyclopedia.

    Science.gov (United States)

    Yusuf, Dimas; Butland, Stefanie L; Swanson, Magdalena I; Bolotin, Eugene; Ticoll, Amy; Cheung, Warren A; Zhang, Xiao Yu Cindy; Dickman, Christopher T D; Fulton, Debra L; Lim, Jonathan S; Schnabl, Jake M; Ramos, Oscar H P; Vasseur-Cognet, Mireille; de Leeuw, Charles N; Simpson, Elizabeth M; Ryffel, Gerhart U; Lam, Eric W-F; Kist, Ralf; Wilson, Miranda S C; Marco-Ferreres, Raquel; Brosens, Jan J; Beccari, Leonardo L; Bovolenta, Paola; Benayoun, Bérénice A; Monteiro, Lara J; Schwenen, Helma D C; Grontved, Lars; Wederell, Elizabeth; Mandrup, Susanne; Veitia, Reiner A; Chakravarthy, Harini; Hoodless, Pamela A; Mancarelli, M Michela; Torbett, Bruce E; Banham, Alison H; Reddy, Sekhar P; Cullum, Rebecca L; Liedtke, Michaela; Tschan, Mario P; Vaz, Michelle; Rizzino, Angie; Zannini, Mariastella; Frietze, Seth; Farnham, Peggy J; Eijkelenboom, Astrid; Brown, Philip J; Laperrière, David; Leprince, Dominique; de Cristofaro, Tiziana; Prince, Kelly L; Putker, Marrit; del Peso, Luis; Camenisch, Gieri; Wenger, Roland H; Mikula, Michal; Rozendaal, Marieke; Mader, Sylvie; Ostrowski, Jerzy; Rhodes, Simon J; Van Rechem, Capucine; Boulay, Gaylor; Olechnowicz, Sam W Z; Breslin, Mary B; Lan, Michael S; Nanan, Kyster K; Wegner, Michael; Hou, Juan; Mullen, Rachel D; Colvin, Stephanie C; Noy, Peter John; Webb, Carol F; Witek, Matthew E; Ferrell, Scott; Daniel, Juliet M; Park, Jason; Waldman, Scott A; Peet, Daniel J; Taggart, Michael; Jayaraman, Padma-Sheela; Karrich, Julien J; Blom, Bianca; Vesuna, Farhad; O'Geen, Henriette; Sun, Yunfu; Gronostajski, Richard M; Woodcroft, Mark W; Hough, Margaret R; Chen, Edwin; Europe-Finner, G Nicholas; Karolczak-Bayatti, Magdalena; Bailey, Jarrod; Hankinson, Oliver; Raman, Venu; LeBrun, David P; Biswal, Shyam; Harvey, Christopher J; DeBruyne, Jason P; Hogenesch, John B; Hevner, Robert F; Héligon, Christophe; Luo, Xin M; Blank, Marissa Cathleen; Millen, Kathleen Joyce; Sharlin, David S; Forrest, Douglas; Dahlman-Wright, Karin; Zhao, Chunyan; Mishima, Yuriko; Sinha, Satrajit; Chakrabarti, Rumela; Portales-Casamar, Elodie; Sladek, Frances M; Bradley, Philip H; Wasserman, Wyeth W

    2012-01-01

    Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130 mini review articles on pertinent human, mouse and rat TFs. Notable features of the TFe website include a high-quality PDF generator and web API for programmatic data retrieval. TFe aims to rapidly educate scientists about the TFs they encounter through the delivery of succinct summaries written and vetted by experts in the field. TFe is available at http://www.cisreg.ca/tfe.

  5. The Transcription Factor Encyclopedia

    DEFF Research Database (Denmark)

    Yusuf, Dimas; Butland, Stefanie L; Swanson, Magdalena I

    2012-01-01

    mini review articles on pertinent human, mouse and rat TFs. Notable features of the TFe website include a high-quality PDF generator and web API for programmatic data retrieval. TFe aims to rapidly educate scientists about the TFs they encounter through the delivery of succinct summaries written......ABSTRACT: Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130...

  6. Factors stimulating content marketing

    Directory of Open Access Journals (Sweden)

    Naser Azad

    2016-02-01

    Full Text Available This paper presents an empirical investigation to determine factors influencing on content marketing in banking industry. The study designs a questionnaire consists of 40 questions in Likert scale and distributes it among 550 randomly selected regular customers of Bank Mellat in city of Tehran, Iran and 400 properly filled questionnaires are collected. Cronbach alphas for all components of the survey are well above desirable level. Using principle component analysis with Varimax rotation, the study has determined six factors influencing the most on content marketing including organization, details, having new ideas, quality, sensitivity and power while the last component contains only two subcomponents and is removed from the study.

  7. Human factors in network security

    OpenAIRE

    Jones, Francis B.

    1991-01-01

    Human factors, such as ethics and education, are important factors in network information security. This thesis determines which human factors have significant influence on network security. Those factors are examined in relation to current security devices and procedures. Methods are introduced to evaluate security effectiveness by incorporating the appropriate human factors into network security controls

  8. Introduction to human factors

    Energy Technology Data Exchange (ETDEWEB)

    Winters, J.M.

    1988-03-01

    Some background is given on the field of human factors. The nature of problems with current human/computer interfaces is discussed, some costs are identified, ideal attributes of graceful system interfaces are outlined, and some reasons are indicated why it's not easy to fix the problems. (LEW)

  9. Irrational factor races

    Indian Academy of Sciences (India)

    Sneha Chaubey; Milenda Lanius; Alexandru Zaharescu

    2014-11-01

    We investigate the behavior of the sum of the irrational factor function over arithmetic progressions. We first establish a general asymptotic formula for such a sum, and then obtain some further results in the case of arithmetic progressions 3 ± 1.

  10. Affective Factors: Anxiety

    Science.gov (United States)

    Tasnimi, Mahshad

    2009-01-01

    Affective factors seem to play a crucial role in success or failure in second language acquisition. Negative attitudes can reduce learners' motivation and harm language learning, while positive attitudes can do the reverse. Discovering students' attitudes about language will help both teacher and student in teaching learning process. Anxiety is…

  11. Hyperglycemia: a prothrombotic factor?

    NARCIS (Netherlands)

    B.A. Lemkes; J. Hermanides; J.H. Devries; F. Holleman; J.C.M. Meijers; J.B.L. Hoekstra

    2010-01-01

    Diabetes mellitus is characterized by a high risk of atherothrombotic events. What is more, venous thrombosis has also been found to occur more frequently in this patient group. This prothrombotic condition in diabetes is underpinned by laboratory findings of elevated coagulation factors and impaire

  12. FRUIT NUTRITIVE FACTOR NETWORK

    Institute of Scientific and Technical Information of China (English)

    Yanqing QU; Yumei JIANG; Daren HE

    2009-01-01

    As an research example of the widely existing cooperation-competition systems, the authors present an empirical investigation on a fruit nutritive factor network. It is described by a node-weighted bipartite graph. The fruit nutritive factors are defined as the nodes, and two nodes are connected by an edge if at least one fruit contains these two nutritive factors. The fruits are defined as the collaboration acts. The node-weight Writ, which signifies the "importance degree" of each actor node, is defined as the content of a nutritive factor in a fruit. The empirical investigation results show some unique features.The node-weight distributions take so-called "shifted power law" function forms, but the act-weight distribution takes a normal form. The degree and act-degree distributions show impulsive-spectrum like forms. These observations may be helpful for the study of fruits. The network description method proposed in this article may be universal for a kind of cooperation-competition systems.

  13. Environmental factors and leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Brandt, L.

    1985-01-01

    Investigations on the association between environmental hazards and the development of various types of leukaemia are reviewed. Regarding acute non-lymphocytic leukaemia (ANLL) exposure to ionizing radiation is a well-documented risk factor. According to several recent studies exposure to strong electromagnetic fields may be suspected to be of etiologic importance for ANLL. There is evidence that occupational handling of benzene is a risk factor and other organic solvents may also be leukaemogenic. Occupational exposure to petrol products has been proposed to be a risk factor although the hazardous substances have not yet been defined. Results of cytogenetic studies in ANLL suggest that exposure to certain environmental agents may be associated with relatively specific clonal chromosome aberrations. Exposure in utero to ionizing radiation has been proposed to be a risk factor for acute lymphocytic leukaemia (ALL) in children. Unlike ANLL there seems at present to be little evidence that ALL is related to exposure to some chemicals. Chronic myeloid leukaemia (CML) may follow exposure to high doses of ionizing radiation whereas such exposure seems to be of insignificant importance for the development of chronic lymphocytic leukaemia (CLL). According to some studies an abnormally high incidence of CLL may be found among farmers in the USA. These results have not been confirmed in Scandinavian studies. There seems to be little evidence that CML or CLL are related to occupational handling of some chemicals. 35 references.

  14. Factor Analysis and AIC.

    Science.gov (United States)

    Akaike, Hirotugu

    1987-01-01

    The Akaike Information Criterion (AIC) was introduced to extend the method of maximum likelihood to the multimodel situation. Use of the AIC in factor analysis is interesting when it is viewed as the choice of a Bayesian model; thus, wider applications of AIC are possible. (Author/GDC)

  15. eta ' transition form factors

    NARCIS (Netherlands)

    Amo Sanchez, del P.; Raven, H.G.; Snoek, H.; BaBar, Collaboration

    2011-01-01

    eta((')) transition form factors in the momentum-transfer range from 4 to 40 GeV(2). The analysis is based on 469 fb(-1) of integrated luminosity collected at PEP-II with the BABAR detector at e(+)e(-) center-of-mass energies near 10.6 GeV.

  16. Ceramide triggers Weibel-Palade body exocytosis.

    Science.gov (United States)

    Bhatia, Rinky; Matsushita, Kenji; Yamakuchi, Munekazu; Morrell, Craig N; Cao, Wangsen; Lowenstein, Charles J

    2004-08-06

    The sphingolipid ceramide mediates a variety of stress responses, including vascular inflammation and thrombosis. Activated endothelial cells release Weibel-Palade bodies, granules containing von Willebrand factor (vWF) and P-selectin, which induce leukocyte rolling and platelet adhesion and aggregation. We hypothesized that ceramide induces vascular inflammation and thrombosis in part by triggering Weibel-Palade body exocytosis. We added ceramide to human aortic endothelial cells and assayed Weibel-Palade body exocytosis by measuring the concentration of vWF released into the media. Exogenous ceramide induces vWF release from endothelial cells in a dose-dependent manner. Activators of endogenous ceramide production, neutral sphingomyelinase, or tumor necrosis factor-alpha also induce Weibel-Palade body exocytosis. We next studied NO effects on ceramide-induced Weibel-Palade body exocytosis because NO can inhibit vascular inflammation. The NO donor S-nitroso-N-acetylpenicillamine decreases ceramide-induced vWF release in a dose-dependent manner, whereas the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester increases ceramide-induced vWF release. In summary, our findings show that endogenous ceramide triggers Weibel-Palade body exocytosis, and that endogenous NO inhibits ceramide-induced exocytosis. These data suggest a novel mechanism by which ceramide induces vascular inflammation and thrombosis.

  17. Efficacy and safety of rVIII-Singlechain : Results of a phase 1/3 multicenter clinical trial in severe hemophilia A

    NARCIS (Netherlands)

    Mahlangu, Johnny; Kuliczkowski, Kazimierz; Karim, Faraizah Abdul; Stasyshyn, Oleksandra; Kosinova, Marina V.; Lepatan, Lynda Mae; Skotnicki, Aleksander; Boggio, Lisa N.; Klamroth, Robert; Oldenburg, Johannes; Hellmann, Andrzej; Santagostino, Elena; Baker, Ross I.; Fischer, Kathelijn; Gill, Joan C.; P'Ng, Stephanie; Chowdary, Pratima; Escobar, Miguel A.; Khayat, Claudia Djambas; Rusen, Luminita; Bensen-Kennedy, Debra; Blackman, Nicole; Limsakun, Tharin; Veldman, Alex; Ledger, Katie St; Pabinger, Ingrid

    2016-01-01

    Recombinant VIII (rVIII)-SingleChain is a novel B-domain–truncated recombinant factor VIII (rFVIII), comprised of covalently bonded factor VIII (FVIII) heavy and light chains. It was designed to have a higher binding affinity for von Willebrand factor (VWF). This phase 1/3 study investigated the eff

  18. Identificar Factores de Riesgo

    Directory of Open Access Journals (Sweden)

    Luis Carlos Silva Ayçaguer

    2005-01-01

    Full Text Available Se exponen el contexto histórico y las condiciones en que se ha configurado lo que podría caracterizarse como una verdadera "cacería de factores de riesgo" en la epidemiología contemporánea. Entre otros problemas, se ha extendido la práctica de encarar el problema de la determinación o identificación de factores de riesgo a través de un ritual estadístico que roza la caricatura y, lo más importante, que la mayor parte de las veces no conduce a conseguir el objetivo de la investigación, ni a obtener nuevos conocimientos. El trabajo caracteriza dicho ritual y examina críticamente sus pasos. Se realiza una detallada discusión de la endeblez metodológica de tal procedimiento y se ilustra profusamente su empleo.

  19. Smad transcription factors.

    Science.gov (United States)

    Massagué, Joan; Seoane, Joan; Wotton, David

    2005-12-01

    Smad transcription factors lie at the core of one of the most versatile cytokine signaling pathways in metazoan biology-the transforming growth factor-beta (TGFbeta) pathway. Recent progress has shed light into the processes of Smad activation and deactivation, nucleocytoplasmic dynamics, and assembly of transcriptional complexes. A rich repertoire of regulatory devices exerts control over each step of the Smad pathway. This knowledge is enabling work on more complex questions about the organization, integration, and modulation of Smad-dependent transcriptional programs. We are beginning to uncover self-enabled gene response cascades, graded Smad response mechanisms, and Smad-dependent synexpression groups. Our growing understanding of TGFbeta signaling through the Smad pathway provides general principles for how animal cells translate complex inputs into concrete behavior.

  20. Precipitating factors of asthma.

    Science.gov (United States)

    Lee, T H

    1992-01-01

    Asthma is characterised by bronchial hyperresponsiveness. This feature of the asthmatic diathesis predisposes patients to wheezing in response to a number of different factors. These precipitating factors include specific allergen acting via sensitised mediator cells through an IgE-dependent mechanism. There are irritants which may work through a non-specific manner, or stimuli such as exercise and hyperventilation, which probably also act through mediator release via a non-IgE-dependent manner. The mechanism whereby physical stimuli such as exercise induce bronchoconstriction is of interest, because it increases the context in which the mast cell may participate in acute asthmatic bronchoconstriction. Respiratory infections also commonly provoke asthma, especially in infants and may, indeed, precipitate the asthmatic state itself. Finally, drugs can often trigger asthma attacks and the mechanisms of asthma precipitated by non-steroidal anti-inflammatory drugs such as aspirin have been the subject of recent research.

  1. Helicopter human factors

    Science.gov (United States)

    Hart, Sandra G.

    1988-01-01

    The state-of-the-art helicopter and its pilot are examined using the tools of human-factors analysis. The significant role of human error in helicopter accidents is discussed; the history of human-factors research on helicopters is briefly traced; the typical flight tasks are described; and the noise, vibration, and temperature conditions typical of modern military helicopters are characterized. Also considered are helicopter controls, cockpit instruments and displays, and the impact of cockpit design on pilot workload. Particular attention is given to possible advanced-technology improvements, such as control stabilization and augmentation, FBW and fly-by-light systems, multifunction displays, night-vision goggles, pilot night-vision systems, night-vision displays with superimposed symbols, target acquisition and designation systems, and aural displays. Diagrams, drawings, and photographs are provided.

  2. [Streptococcus pyogenes pathogenic factors].

    Science.gov (United States)

    Bidet, Ph; Bonacorsi, S

    2014-11-01

    The pathogenicity of ß-hemolytic group A streptococcus (GAS) is particularly diverse, ranging from mild infections, such as pharyngitis or impetigo, to potentially debilitating poststreptococcal diseases, and up to severe invasive infections such as necrotizing fasciitis or the dreaded streptococcal toxic shock syndrome. This variety of clinical expressions, often radically different in individuals infected with the same strain, results from a complex interaction between the bacterial virulence factors, the mode of infection and the immune system of the host. Advances in comparative genomics have led to a better understanding of how, following this confrontation, GAS adapts to the immune system's pressure, either peacefully by reducing the expression of certain virulence factors to achieve an asymptomatic carriage, or on the contrary, by overexpressing them disproportionately, resulting in the most severe forms of invasive infection.

  3. Power factor compensation

    Energy Technology Data Exchange (ETDEWEB)

    Barra R, Felipe [Schneider Electric Chile (Chile)

    2010-07-01

    Every company is looking for ways to increase productivity as a way to gain a competitive advantage. Energy is a significant element in making any product and so it is important to assess production processes from an energy perspective. This paper discusses the impact of power factor compensation on energy efficiency. The life cycle solution for energy efficiency involves optimization of active energy using automation and regulation. A brief explanation is given of how each component of a company plays a part in this cycle. Examples include simulations and analysis, modeling, performance monitoring facilities, and environmental sustainability. Reactive energy suppliers and the installation of capacitors are also explained. Types of compensation include fixed and automation compensations. Economic advantages include a reduction in the electricity bill and active energy consumption. Technical advantages include reduction in voltage drop and an increase in available power. The power correction factor also improves reliability and contributes to conservation of the environment.

  4. On braid monodromy factorizations

    Energy Technology Data Exchange (ETDEWEB)

    Kharlamov, V M [Institut de Recherche Matematique Avanee Universite Louis Pasteur et CNRS 7 rue Rene Descartes (France); Kulikov, Vik S [Steklov Mathematical Institute, Russian Academy of Sciences (Russian Federation)

    2003-06-30

    We introduce and develop a language of semigroups over the braid groups to study the braid monodromy factorizations (bmf's) of plane algebraic curves and other related objects. As an application, we give a new proof of Orevkov's theorem on the realization of bmf's over a disc by algebraic curves and show that the complexity of such a realization cannot be bounded in terms of the types of factors of the bmf. We also prove that the type of a bmf distinguishes Hurwitz curves with singularities of inseparable type up to H-isotopy and J-holomorphic cuspidal curves in CP{sup 2} up to symplectic isotopy.

  5. The focus factor

    DEFF Research Database (Denmark)

    Nicolaisen, Jeppe; Frandsen, Tove Faber

    2015-01-01

    is demonstrated on a selection of general science journals and on a selection of medical journals. The reference lists of each journal are compared year by year, and the percentage of re-citations is calculated by dividing the number of re-citations with the total number of citations each year. Analysis......Introduction. We present a new bibliometric indicator to measure journal specialisation over time, named the focus factor. This new indicator is based on bibliographic coupling and counts the percentage of re-citations given in subsequent years. Method. The applicability of the new indicator....... To validate re-citations as caused by specialisation, other possible causes were measured and correlated (obsolescence, journal self-citations and number of references). Results. The results indicate that the focus factor is capable of distinguishing between general and specialised journals and thus...

  6. Cross-culturally recurrent personality factors : Analyses of three factors

    NARCIS (Netherlands)

    De Raad, B; Peabody, D

    2005-01-01

    This study proceeds from an earlier one that examined the 'Big Five' factors (Peabody & De Raad, 2002). That study considered the substantive nature of five factors from six European psycholexical studies. The results supported Big Five Factor III (Conscientiousness), but Factors I (Extraversion) an

  7. Information security factors systematization

    OpenAIRE

    Янченко, Вадим Николавевич; Ивченко, Александр Владимирович; Залога, Вильям Александрович; Дынник, Оксана Дмитриевна

    2015-01-01

    In this article the necessity of solving the theoretical and practical task, aimed on development the methodological basis for elaboration and implementation of information security management system, has been considered. Based on research results of scientific works and the requirements in the field of information security management the universal multilevel system of information security factors of organizations (enterprises) in the wood properties form was offered by using quality control ...

  8. The malingering factor.

    Science.gov (United States)

    Williams, J Michael

    2011-04-01

    The influence of malingering and suboptimal performance on neuropsychological tests has become a major interest of clinical neuropsychologists. Methods to detect malingering have focused on specialized tests or embedded patterns associated with malingering present in the conventional neuropsychology tests. There are two stages to the study of their validity. The first stage involves whether the method can discriminate malingering subjects from those who are not malingering. In the second stage, they must be examined for their relationship to the conventional tests used to establish impairment and disability. Constantinou, Bauer, Ashendorf, Fisher, and McCaffrey (2005. Is poor performance on recognition memory effort measures indicative of generalized poor performance on neuropsychological tests? Archives of Clinical Neuropsychology, 20, 191-198.) conducted the only study in which correlations are presented between a commonly used symptom validity test, the Test of Memory Malingering (TOMM) and the subtests of the Wechsler Adult Intelligence Scale-Revised (WAIS-R). A factor analysis was conducted using these correlations. It revealed a clear malingering factor that explained significant variance in the TOMM and the WAIS-R subtests. The relationship of malingering with cognitive tests is complex: some tests are sensitive to malingering and others are not. Factor analysis can summarize the magnitude of variance associated with each test and reveal the patterns of inter-relationships between malingering and clinical tests. The analysis also suggested that malingering assessment methods could be improved by the addition of timing the responses.

  9. Risk Factors for Cholelithiasis.

    Science.gov (United States)

    Pak, Mila; Lindseth, Glenda

    2016-01-01

    Gallstone disease is one of the most common public health problems in the United States. Approximately 10%-20% of the national adult populations currently carry gallstones, and gallstone prevalence is rising. In addition, nearly 750,000 cholecystectomies are performed annually in the United States; direct and indirect costs of gallbladder surgery are estimated to be $6.5 billion. Cholelithiasis is also strongly associated with gallbladder, pancreatic, and colorectal cancer occurrence. Moreover, the National Institutes of Health estimates that almost 3,000 deaths (0.12% of all deaths) per year are attributed to complications of cholelithiasis and gallbladder disease. Although extensive research has tried to identify risk factors for cholelithiasis, several studies indicate that definitive findings still remain elusive. In this review, predisposing factors for cholelithiasis are identified, the pathophysiology of gallstone disease is described, and nonsurgical preventive options are discussed. Understanding the risk factors for cholelithiasis may not only be useful in assisting nurses to provide resources and education for patients who are diagnosed with gallstones, but also in developing novel preventive measures for the disease.

  10. Nucleon Electromagnetic Form Factors

    Energy Technology Data Exchange (ETDEWEB)

    Kees de Jager

    2004-08-01

    Although nucleons account for nearly all the visible mass in the universe, they have a complicated structure that is still incompletely understood. The first indication that nucleons have an internal structure, was the measurement of the proton magnetic moment by Frisch and Stern (1933) which revealed a large deviation from the value expected for a point-like Dirac particle. The investigation of the spatial structure of the nucleon, resulting in the first quantitative measurement of the proton charge radius, was initiated by the HEPL (Stanford) experiments in the 1950s, for which Hofstadter was awarded the 1961 Nobel prize. The first indication of a non-zero neutron charge distribution was obtained by scattering thermal neutrons off atomic electrons. The recent revival of its experimental study through the operational implementation of novel instrumentation has instigated a strong theoretical interest. Nucleon electro-magnetic form factors (EMFFs) are optimally studied through the exchange of a virtual photon, in elastic electron-nucleon scattering. The momentum transferred to the nucleon by the virtual photon can be selected to probe different scales of the nucleon, from integral properties such as the charge radius to scaling properties of its internal constituents. Polarization instrumentation, polarized beams and targets, and the measurement of the polarization of the recoiling nucleon have been essential in the accurate separation of the charge and magnetic form factors and in studies of the elusive neutron charge form factor.

  11. Human Factors Review Plan

    Energy Technology Data Exchange (ETDEWEB)

    Paramore, B.; Peterson, L.R. (eds.)

    1985-12-01

    ''Human Factors'' is concerned with the incorporation of human user considerations into a system in order to maximize human reliability and reduce errors. This Review Plan is intended to assist in the assessment of human factors conditions in existing DOE facilities. In addition to specifying assessment methodologies, the plan describes techniques for improving conditions which are found to not adequately support reliable human performance. The following topics are addressed: (1) selection of areas for review describes techniques for needs assessment to assist in selecting and prioritizing areas for review; (2) human factors engineering review is concerned with optimizing the interfaces between people and equipment and people and their work environment; (3) procedures review evaluates completeness and accuracy of procedures, as well as their usability and management; (4) organizational interface review is concerned with communication and coordination between all levels of an organization; and (5) training review evaluates training program criteria such as those involving: trainee selection, qualification of training staff, content and conduct of training, requalification training, and program management.

  12. Accidents - personal factors

    Energy Technology Data Exchange (ETDEWEB)

    Zaitsev, S.L.; Tsygankov, A.V.

    1982-03-01

    This paper evaluates influence of selected personal factors on accident rate in underground coal mines in the USSR. Investigations show that so-called organizational factors cause from 80 to 85% of all accidents. About 70% of the organizational factors is associated with social, personal and economic features of personnel. Selected results of the investigations carried out in Donbass mines are discussed. Causes of miner dissatisfaction are reviewed: 14% is caused by unsatisfactory working conditions, 21% by repeated machine failures, 16% by forced labor during days off, 14% by unsatisfactory material supply, 16% by hard physical labor, 19% by other reasons. About 25% of miners injured during work accidents are characterized as highly professionally qualified with automatic reactions, and about 41% by medium qualifications. About 60% of accidents is caused by miners with less than a 3 year period of service. About 15% of accidents occurs during the first month after a miner has returned from a leave. More than 30% of accidents occurs on the first work day after a day or days off. Distribution of accidents is also presented: 19% of accidents occurs during the first 2 hours of a shift, 36% from the second to the fourth hour, and 45% occurs after the fourth hour and before the shift ends.

  13. Molecular factors in migraine

    Science.gov (United States)

    Kowalska, Marta; Prendecki, Michał; Kozubski, Wojciech; Lianeri, Margarita; Dorszewska, Jolanta

    2016-01-01

    Migraine is a common neurological disorder that affects 11% of adults worldwide. This disease most likely has a neurovascular origin. Migraine with aura (MA) and more common form - migraine without aura (MO) – are the two main clinical subtypes of disease. The exact pathomechanism of migraine is still unknown, but it is thought that both genetic and environmental factors are involved in this pathological process. The first genetic studies of migraine were focused on the rare subtype of MA: familial hemiplegic migraine (FHM). The genes analysed in familial and sporadic migraine are: MTHFR, KCNK18, HCRTR1, SLC6A4, STX1A, GRIA1 and GRIA3. It is possible that migraine is a multifactorial disease with polygenic influence. Recent studies have shown that the pathomechanisms of migraine involves both factors responsible for immune response and oxidative stress such as: cytokines, tyrosine metabolism, homocysteine; and factors associated with pain transmission and emotions e.g.: serotonin, hypocretin-1, calcitonin gene-related peptide, glutamate. The correlations between genetic variants of the HCRTR1 gene, the polymorphism 5-HTTLPR and hypocretin-1, and serotonin were observed. It is known that serotonin inhibits the activity of hypocretin neurons and may affect the appearance of the aura during migraine attack. The understanding of the molecular mechanisms of migraine, including genotype-phenotype correlations, may contribute to finding markers important for the diagnosis and treatment of this disease. PMID:27191890

  14. Perinatal risk factors for strabismus

    DEFF Research Database (Denmark)

    Torp-Pedersen, Tobias; Boyd, Heather A; Poulsen, Gry;

    2010-01-01

    Little is known about the aetiological factors underlying strabismus. We undertook a large cohort study to investigate perinatal risk factors for strabismus, overall and by subtype.......Little is known about the aetiological factors underlying strabismus. We undertook a large cohort study to investigate perinatal risk factors for strabismus, overall and by subtype....

  15. Milestones and Impact Factors

    Directory of Open Access Journals (Sweden)

    Grandjean Philippe

    2010-07-01

    Full Text Available Abstract Environmental Health has just received its first Impact Factor by Thomson ISI. At a level of 2.48, this achievement is quite satisfactory and places Environmental Health in the top 25% of environmental science journals. When the journal was launched in 2002, it was still unclear whether the Open Access publishing model could be made into a viable commercial enterprise within the biomedical field. During the past eight years, Open Access journals have become widely available, although still covering only about 15% of journal titles. Major funding agencies and institutions, including prominent US universities, now require that researchers publish in Open Access journals. Because of the profound role of scientific journals for the sharing of results and communication between researchers, the advent of Open Access may be of as much significance as the transition from handwriting to printing via moveable type. As Environmental Health is an electronic Open Access journal, the numbers of downloads at the journal website can be retrieved. The top-20 list of articles most frequently accessed shows that all of them have been downloaded over 10,000 times. Back in 2002, the first article published was accessed only 49 times during the following month. A year later, the server had over 1,000 downloads per month, and now the total number of monthly downloads approaches 50,000. These statistics complement the Impact Factor and confirm the viability of Open Access in our field of research. The advent of digital media and its decentralized mode of distribution - the internet - have dramatically changed the control and financing of scientific information dissemination, while facilitating peer review, accelerating editorial handling, and supporting much needed transparency. Both the meaning and means of "having an impact" are therefore changing, as will the degree and way in which scientific journals remain "factors" in that impact.

  16. Milestones and impact factors.

    Science.gov (United States)

    Ozonoff, David M; Grandjean, Philippe

    2010-07-08

    Environmental Health has just received its first Impact Factor by Thomson ISI. At a level of 2.48, this achievement is quite satisfactory and places Environmental Health in the top 25% of environmental science journals. When the journal was launched in 2002, it was still unclear whether the Open Access publishing model could be made into a viable commercial enterprise within the biomedical field. During the past eight years, Open Access journals have become widely available, although still covering only about 15% of journal titles. Major funding agencies and institutions, including prominent US universities, now require that researchers publish in Open Access journals. Because of the profound role of scientific journals for the sharing of results and communication between researchers, the advent of Open Access may be of as much significance as the transition from handwriting to printing via moveable type. As Environmental Health is an electronic Open Access journal, the numbers of downloads at the journal website can be retrieved. The top-20 list of articles most frequently accessed shows that all of them have been downloaded over 10,000 times. Back in 2002, the first article published was accessed only 49 times during the following month. A year later, the server had over 1,000 downloads per month, and now the total number of monthly downloads approaches 50,000. These statistics complement the Impact Factor and confirm the viability of Open Access in our field of research. The advent of digital media and its decentralized mode of distribution - the internet - have dramatically changed the control and financing of scientific information dissemination, while facilitating peer review, accelerating editorial handling, and supporting much needed transparency. Both the meaning and means of "having an impact" are therefore changing, as will the degree and way in which scientific journals remain "factors" in that impact.

  17. A New Factorization Method to Factorize RSA Public Key Encryption

    Directory of Open Access Journals (Sweden)

    Bhagvant Ram Ambedkar

    2011-11-01

    Full Text Available The security of public key encryption such as RSA scheme relied on the integer factoring problem. The security of RSA algorithm is based on positive integer N, because each transmitting node generates pair of keys such as public and private. Encryption and decryption of any message depends on N. Where, N is the product of two prime numbers and pair of key generation is dependent on these prime numbers. The factorization of N is very intricate. In this paper a New Factorization method is proposed to obtain the factor of positive integer N. The proposed work focuses on factorization of all trivial and nontrivial integer numbers and requires fewer steps for factorization process of RSA modulus N. The New Factorization method is based on Pollard rho factorization method. Experimental results shown that factorization speed is fast as compare existing methods.

  18. Cultural Factors in Reading

    Institute of Scientific and Technical Information of China (English)

    孔敏

    2005-01-01

    Reading is a basic ability in learning English and reading comprehension exercise is a common way to assess this ability.Since reading is a communicative activity between author and reader in written form,there are some different rules and regulations of this communication in different countries.Therefore,cultural factors,existing in reading,decide,help,and influence the percentage of the right answers.This article attempts to analyze the effects of cultural differences in reading and the barriers in comprehension,and aims to improve students awareness of cultural differences in reading.

  19. Human Factors Model

    Science.gov (United States)

    1993-01-01

    Jack is an advanced human factors software package that provides a three dimensional model for predicting how a human will interact with a given system or environment. It can be used for a broad range of computer-aided design applications. Jack was developed by the computer Graphics Research Laboratory of the University of Pennsylvania with assistance from NASA's Johnson Space Center, Ames Research Center and the Army. It is the University's first commercial product. Jack is still used for academic purposes at the University of Pennsylvania. Commercial rights were given to Transom Technologies, Inc.

  20. Platelet dysfunction in thrombosis patients treated with vitamin K antagonists and recurrent bleeding.

    Directory of Open Access Journals (Sweden)

    Paola E J van der Meijden

    Full Text Available BACKGROUND: Recurrent bleeding can complicate the treatment of thrombosis patients with vitamin K antagonists (VKA, even at a well-regulated level of anticoagulation. In this proof-of-principle study, we investigated whether alterations in platelet function or von Willebrand factor (vWf contribute to a bleeding phenotype in these patients. METHODS: In this case-control study 33 well-regulated patients without bleeding events (controls and 33 patients with recurrent bleeding (cases were retrospectively included. Thrombin generation and vWf were determined in plasma. Platelet function was assessed by light transmission aggregometry and flow cytometry using a validated panel of agonists. RESULTS: Thrombin generation was similarly reduced in controls and cases, in comparison to normal plasma. Plasma vWf level was above the normal range in 85% of controls and 67% of the cases. vWf activity was similarly increased in all patients in comparison to healthy volunteers. Platelet aggregation was in the normal range for almost all patients irrespective of the type of agonist. However, in response to a low collagen dose, platelets from 21% of controls and 27% of cases showed diminished responses. Agonist-induced secretion of alpha- and dense-granules or integrin αIIbβ3 activation were affected in platelets from neither controls nor cases. CONCLUSION: Recurrent bleeding in well-controlled patients on VKA therapy is not explained by anti-hemostatic changes in platelet or vWf function.

  1. Content delivery to newly forming Weibel-Palade bodies is facilitated by multiple connections with the Golgi apparatus.

    Science.gov (United States)

    Mourik, Marjon J; Faas, Frank G A; Zimmermann, Hans; Voorberg, Jan; Koster, Abraham J; Eikenboom, Jeroen

    2015-05-28

    Weibel-Palade bodies (WPBs) comprise an on-demand storage organelle within vascular endothelial cells. It's major component, the hemostatic protein von Willebrand factor (VWF), is known to assemble into long helical tubules and is hypothesized to drive WPB biogenesis. However, electron micrographs of WPBs at the Golgi apparatus show that these forming WPBs contain very little tubular VWF compared with mature peripheral WPBs, which raises questions on the mechanisms that increase the VWF content and facilitate vesicle growth. Using correlative light and electron microscopy and electron tomography, we investigated WPB biogenesis in time. We reveal that forming WPBs maintain multiple connections to the Golgi apparatus throughout their biogenesis. Also by volume scanning electron microscopy, we confirmed the presence of these connections linking WPBs and the Golgi apparatus. From electron tomograms, we provided evidence that nontubular VWF is added to WPBs, which suggested that tubule formation occurs in the WPB lumen. During this process, the Golgi membrane and clathrin seem to provide a scaffold to align forming VWF tubules. Overall, our data show that multiple connections with the Golgi facilitate content delivery and indicate that the Golgi appears to provide a framework to determine the overall size and dimensions of newly forming WPBs.

  2. Auxin response factors.

    Science.gov (United States)

    Chandler, John William

    2016-05-01

    Auxin signalling involves the activation or repression of gene expression by a class of auxin response factor (ARF) proteins that bind to auxin response elements in auxin-responsive gene promoters. The release of ARF repression in the presence of auxin by the degradation of their cognate auxin/indole-3-acetic acid repressors forms a paradigm of transcriptional response to auxin. However, this mechanism only applies to activating ARFs, and further layers of complexity of ARF function and regulation are being revealed, which partly reflect their highly modular domain structure. This review summarizes our knowledge concerning ARF binding site specificity, homodimer and heterodimer multimeric ARF association and cooperative function and how activator ARFs activate target genes via chromatin remodelling and evolutionary information derived from phylogenetic comparisons from ARFs from diverse species. ARFs are regulated in diverse ways, and their importance in non-auxin-regulated pathways is becoming evident. They are also embedded within higher-order transcription factor complexes that integrate signalling pathways from other hormones and in response to the environment. The ways in which new information concerning ARFs on many levels is causing a revision of existing paradigms of auxin response are discussed.

  3. β3 Integrin Haplotype Influences Gene Regulation and Plasma von Willebrand Factor Activity

    Science.gov (United States)

    Payne, Katie E; Bray, Paul F; Grant, Peter J; Carter, Angela M

    2008-01-01

    The Leu33Pro polymorphism of the gene encoding β3 integrin (ITGB3) is associated with acute coronary syndromes and influences platelet aggregation. Three common promoter polymorphisms have also been identified. The aims of this study were to (1) investigate the influence of the ITGB3 −400C/A, −425A/C and −468G/A promoter polymorphisms on reporter gene expression and nuclear protein binding and (2) determine genotype and haplotype associations with platelet αIIbβ3 receptor density. Promoter haplotypes were introduced into an ITGB3 promoter-pGL3 construct by site directed mutagenesis and luciferase reporter gene expression analysed in HEL and HMEC-1 cells. Binding of nuclear proteins was assessed by electrophoretic mobility shift assay. The association of ITGB3 haplotype with platelet αIIbβ3 receptor density was determined in 223 subjects. Species conserved motifs were identified in the ITGB3 promoter in the vicinity of the 3 polymorphisms. The GAA, GCC, AAC, AAA and ACC constructs induced ~50% increased luciferase expression relative to the GAC construct in both cell types. Haplotype analysis including Leu33Pro indicated 5 common haplotypes; no associations between ITGB3 haplotypes and receptor density were found. However, the GCC-Pro33 haplotype was associated with significantly higher vWF activity (128.6 [112.1–145.1]%) compared with all other haplotypes (107.1 [101.2–113.0]%, p=0.02). In conclusion, the GCC-Pro33 haplotype was associated with increased vWF activity but not with platelet αIIbβ3 receptor density, which may indicate ITGB3 haplotype influences endothelial function. PMID:18045606

  4. Robust and Sparse Factor Modelling

    DEFF Research Database (Denmark)

    Croux, Christophe; Exterkate, Peter

    Factor construction methods are widely used to summarize a large panel of variables by means of a relatively small number of representative factors. We propose a novel factor construction procedure that enjoys the properties of robustness to outliers and of sparsity; that is, having relatively few...... nonzero factor loadings. Compared to the traditional factor construction method, we find that this procedure leads to a favorable forecasting performance in the presence of outliers and to better interpretable factors. We investigate the performance of the method in a Monte Carlo experiment...

  5. Eukaryotic transcription factors

    DEFF Research Database (Denmark)

    Staby, Lasse; O'Shea, Charlotte; Willemoës, Martin

    2017-01-01

    Gene-specific transcription factors (TFs) are key regulatory components of signaling pathways, controlling, for example, cell growth, development, and stress responses. Their biological functions are determined by their molecular structures, as exemplified by their structured DNA-binding domains...... targeting specific cis-acting elements in genes, and by the significant lack of fixed tertiary structure in their extensive intrinsically disordered regions. Recent research in protein intrinsic disorder (ID) has changed our understanding of transcriptional activation domains from 'negative noodles' to ID...... them to participate in large interactomes, how they use only a few hydrophobic residues, short sequence motifs, prestructured motifs, and coupled folding and binding for their interactions with co-activators, and how their accessibility to post-translational modification affects their interactions...

  6. Pion form factor

    Energy Technology Data Exchange (ETDEWEB)

    Ryong Ji, C.; Pang, A.; Szczepaniak, A. [North Carolina State Univ., Raleigh, NC (United States)

    1994-04-01

    It is pointed out that the correct criterion to define the legal PQCD contribution to the exclusive processes in the lightcone perturbative expansion should be based on the large off-shellness of the lightcone energy in the intermediate states. In the lightcone perturbative QCD calculation of the pion form factor, the authors find that the legal PQCD contribution defined by the lightcone energy cut saturates in the smaller Q{sup 2} region compared to that defined by the gluon four-momentum square cut. This is due to the contribution by the highly off-energy-shell gluons in the end point regions of the phase space, indicating that the gluon four-momentum-square cut may have cut too much to define the legal PQCD.

  7. Unity power factor converter

    Science.gov (United States)

    Wester, Gene W. (Inventor)

    1980-01-01

    A unity power factor converter capable of effecting either inversion (dc-to-dc) or rectification (ac-to-dc), and capable of providing bilateral power control from a DC source (or load) through an AC transmission line to a DC load (or source) for power flow in either direction, is comprised of comparators for comparing the AC current i with an AC signal i.sub.ref (or its phase inversion) derived from the AC ports to generate control signals to operate a switch control circuit for high speed switching to shape the AC current waveform to a sine waveform, and synchronize it in phase and frequency with the AC voltage at the AC ports, by selectively switching the connections to a series inductor as required to increase or decrease the current i.

  8. Asma: factores precipitantes

    OpenAIRE

    Pimenta, José Eduardo da Silva Maia Ferreira

    2009-01-01

    A asma é uma doença pulmonar crónica caracterizada por obstrução das vias aéreas, inflamação e hiperreactividade brônquica. A asma afecta cerca de 150 milhões de pessoas de todas as idades no Mundo. Em Portugal calcula-se que atinja cerca de 600.000 pessoas incluindo crianças e adultos, calculando-se que afecte cerca de 11% das crianças e 5% dos adultos. A asma é uma doença que provavelmente resulta de uma interacção complexa entre múltiplos factores ambientais e influências...

  9. Psychosomatic factors in pruritus.

    Science.gov (United States)

    Tey, Hong Liang; Wallengren, Joanna; Yosipovitch, Gil

    2013-01-01

    Pruritus and psyche are intricately and reciprocally related, with psychophysiological evidence and psychopathological explanations helping us to understand their complex association. Their interaction may be conceptualized and classified into 3 groups: pruritic diseases with psychiatric sequelae, pruritic diseases aggravated by psychosocial factors, and psychiatric disorders causing pruritus. Management of chronic pruritus is directed at treating the underlying causes and adopting a multidisciplinary approach to address the dermatologic, somatosensory, cognitive, and emotional aspects. Pharmcotherapeutic agents that are useful for chronic pruritus with comorbid depression and/or anxiety comprise selective serotonin reuptake inhibitors, mirtazapine, tricyclic antidepressants (amitriptyline and doxepin), and anticonvulsants (gabapentin, pregabalin); the role of neurokinin receptor-1 antagonists awaits verification. Antipsychotics are required for treating itch and formication associated with schizophrenia and delusion of parasitosis (including Morgellons disease). Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Nucleon Electromagnetic Form Factors

    Energy Technology Data Exchange (ETDEWEB)

    Marc Vanderhaeghen; Charles Perdrisat; Vina Punjabi

    2007-10-01

    There has been much activity in the measurement of the elastic electromagnetic proton and neutron form factors in the last decade, and the quality of the data has greatly improved by performing double polarization experiments, in comparison with previous unpolarized data. Here we review the experimental data base in view of the new results for the proton, and neutron, obtained at JLab, MAMI, and MIT-Bates. The rapid evolution of phenomenological models triggered by these high-precision experiments will be discussed, including the recent progress in the determination of the valence quark generalized parton distributions of the nucleon, as well as the steady rate of improvements made in the lattice QCD calculations.

  11. Tiled QR factorization algorithms

    CERN Document Server

    Bouwmeester, Henricus; Langou, Julien; Robert, Yves

    2011-01-01

    This work revisits existing algorithms for the QR factorization of rectangular matrices composed of p-by-q tiles, where p >= q. Within this framework, we study the critical paths and performance of algorithms such as Sameh and Kuck, Modi and Clarke, Greedy, and those found within PLASMA. Although neither Modi and Clarke nor Greedy is optimal, both are shown to be asymptotically optimal for all matrices of size p = q^2 f(q), where f is any function such that \\lim_{+\\infty} f= 0. This novel and important complexity result applies to all matrices where p and q are proportional, p = \\lambda q, with \\lambda >= 1, thereby encompassing many important situations in practice (least squares). We provide an extensive set of experiments that show the superiority of the new algorithms for tall matrices.

  12. Milestones and impact factors

    DEFF Research Database (Denmark)

    Ozonoff, David M; Grandjean, Philippe

    2010-01-01

    universities, now require that researchers publish in Open Access journals. Because of the profound role of scientific journals for the sharing of results and communication between researchers, the advent of Open Access may be of as much significance as the transition from handwriting to printing via moveable...... type. As Environmental Health is an electronic Open Access journal, the numbers of downloads at the journal website can be retrieved. The top-20 list of articles most frequently accessed shows that all of them have been downloaded over 10,000 times. Back in 2002, the first article published...... was accessed only 49 times during the following month. A year later, the server had over 1,000 downloads per month, and now the total number of monthly downloads approaches 50,000. These statistics complement the Impact Factor and confirm the viability of Open Access in our field of research. The advent...

  13. Helicopter Human Factors

    Science.gov (United States)

    Hart, Sandra G.; Sridhar, Banavar (Technical Monitor)

    1995-01-01

    Even under optimal conditions, helicopter flight is a most demanding form of human-machine interaction, imposing continuous manual, visual, communications, and mental demands on pilots. It is made even more challenging by small margins for error created by the close proximity of terrain in NOE flight and missions flown at night and in low visibility. Although technology advances have satisfied some current and proposed requirements, hardware solutions alone are not sufficient to ensure acceptable system performance and pilot workload. However, human factors data needed to improve the design and use of helicopters lag behind advances in sensor, display, and control technology. Thus, it is difficult for designers to consider human capabilities and limitations when making design decisions. This results in costly accidents, design mistakes, unrealistic mission requirements, excessive training costs, and challenge human adaptability. NASA, in collaboration with DOD, industry, and academia, has initiated a program of research to develop scientific data bases and design principles to improve the pilot/vehicle interface, optimize training time and cost, and maintain pilot workload and system performance at an acceptable level. Work performed at Ames, and by other research laboratories, will be reviewed to summarize the most critical helicopter human factors problems and the results of research that has been performed to: (1) Quantify/model pilots use of visual cues for vehicle control; (2) Improve pilots' performance with helmet displays of thermal imagery and night vision goggles for situation awareness and vehicle control; (3) Model the processes by which pilots encode maps and compare them to the visual scene to develop perceptually and cognitively compatible electronic map formats; (4) Evaluate the use of spatially localized auditory displays for geographical orientation, target localization, radio frequency separation; (5) Develop and flight test control

  14. Helicopter Human Factors

    Science.gov (United States)

    Hart, Sandra G.; Sridhar, Banavar (Technical Monitor)

    1995-01-01

    Even under optimal conditions, helicopter flight is a most demanding form of human-machine interaction, imposing continuous manual, visual, communications, and mental demands on pilots. It is made even more challenging by small margins for error created by the close proximity of terrain in NOE flight and missions flown at night and in low visibility. Although technology advances have satisfied some current and proposed requirements, hardware solutions alone are not sufficient to ensure acceptable system performance and pilot workload. However, human factors data needed to improve the design and use of helicopters lag behind advances in sensor, display, and control technology. Thus, it is difficult for designers to consider human capabilities and limitations when making design decisions. This results in costly accidents, design mistakes, unrealistic mission requirements, excessive training costs, and challenge human adaptability. NASA, in collaboration with DOD, industry, and academia, has initiated a program of research to develop scientific data bases and design principles to improve the pilot/vehicle interface, optimize training time and cost, and maintain pilot workload and system performance at an acceptable level. Work performed at Ames, and by other research laboratories, will be reviewed to summarize the most critical helicopter human factors problems and the results of research that has been performed to: (1) Quantify/model pilots use of visual cues for vehicle control; (2) Improve pilots' performance with helmet displays of thermal imagery and night vision goggles for situation awareness and vehicle control; (3) Model the processes by which pilots encode maps and compare them to the visual scene to develop perceptually and cognitively compatible electronic map formats; (4) Evaluate the use of spatially localized auditory displays for geographical orientation, target localization, radio frequency separation; (5) Develop and flight test control

  15. Factor Rotation and Standard Errors in Exploratory Factor Analysis

    Science.gov (United States)

    Zhang, Guangjian; Preacher, Kristopher J.

    2015-01-01

    In this article, we report a surprising phenomenon: Oblique CF-varimax and oblique CF-quartimax rotation produced similar point estimates for rotated factor loadings and factor correlations but different standard error estimates in an empirical example. Influences of factor rotation on asymptotic standard errors are investigated using a numerical…

  16. von Willebrand disease and aging : an evolving phenotype

    NARCIS (Netherlands)

    Sanders, Y. V.; Giezenaar, M. A.; Laros-van Gorkom, B. A. P.; Meijer, K.; van der Bom, J. G.; Cnossen, M. H.; Nijziel, M. R.; Ypma, P. F.; Fijnvandraat, K.; Eikenboom, J.; Mauser-Bunschoten, E. P.; Leebeek, F. W. G.

    2014-01-01

    Background: Because the number of elderly von Willebrand disease (VWD) patients is increasing, the pathophysiology of aging in VWD has become increasingly relevant. Objectives: To assess age-related changes in von Willebrand factor (VWF) and factor VIII (FVIII) levels and to compare age-related diff

  17. Clinical and laboratory diagnosis of von Willebrand disease : A synopsis of the 2008 NHLBI/NIH guidelines

    NARCIS (Netherlands)

    Nichols, William L.; Rick, Margaret E.; Ortel, Thomas L.; Montgomery, Robert R.; Sadler, J. Evan; Yawn, Barbara P.; James, Andra H.; Hultin, Mae B.; Manco-Johnson, Marilyn J.; Weinstein, Mark

    2009-01-01

    Von Willebrand factor (VWF) mediates blood platelet adhesion and accumulation at sites of blood vessel injury, and also carries coagulation factor VIII (FVIII) that is important for generating procoagulant activity. Von Willebrand disease (VWD), the most common inherited bleeding disorder, affects m

  18. Establishment of an assay for active von Willebrand factor in plasma and its application%血浆活化血管性vWF测定方法的建立与应用

    Institute of Scientific and Technical Information of China (English)

    韩纪举; 潘少东; 吴亚平; de GROOT Evelyn; de GROOT Philip G; 王云; 蔡洪信; 赵晓民; 夏作理

    2010-01-01

    机制提供重要依据.%Objective To establish an double-antibody sandwich method to detect the amount of active vWF in the plasma of healthy people and diabetic patients.Methods A double-antibody sandwich method has been established using llama-derived anti-active vWF antibody and horseradish peroxidaselabelled rabbit anti-human vWF polyclonal antibodies.The study randomly selected 66 healthy people,30 diabetic patients,10 cases of von Willebrand disease 2B(vWD-2B),5 cases of congenital thrombotic thrombocytopenic purpura(TIP),13 cases of acquired TIPs and 13 cases of malaria.The activated vWF level were described as the ratio of absorbance value(A)representing activated vWF value using AU/vWFa-11 antibody-based ELISA method to the concentrations of vWF antigen.At the same time,the absorbance values representing the concentrations of active vWF were measured when the concentrations of vWF antigen were 62,125,250μg/L respectively.The data were analyzed with GraphPad Prism 4 software.Under the premise of reaching a good linear regression,plasma active vWF values were calculated as the slope ratio of the sample plasma to the standard plasma.Accordingly to the ratio evaluated the levels of active vWF in plasma.Results The coefficients of variation(CVs)for intra assays were 4.21%,4.98% and 6.32% respectively.The CVs for interassays were 6.34%,7.02% and 7.69% respectively.In healthy adults,the level of active vWF in plasma was 0.74±0.35.There was no significant difference of the vWF levels[male (7.29±5.15)×10~3μg/L,female(9.42±4.67)×10~3μg/L]and active vWF levels(male 0.74±0.34,female 0.73±0.35)between male and female in healthy people(t=1.35,0.04,P>0.05).The vWF levels of the group over 40 years old[(10.64±5.39)×10~3μg/L]were higher than these below 40 years old[(6.11 ±2.84)×10~3 μL)(t=8.24,P < 0.01)],but there was no significant difference of the active vWF levels difference between these groups(over 40 years old 0.70±0.38,under 40 years old 0.78 ± 0.29,t=1.02,P>0.05).The plasma

  19. ADJUSTMENT FACTORS AND ADJUSTMENT STRUCTURE

    Institute of Scientific and Technical Information of China (English)

    Tao Benzao

    2003-01-01

    In this paper, adjustment factors J and R put forward by professor Zhou Jiangwen are introduced and the nature of the adjustment factors and their role in evaluating adjustment structure is discussed and proved.

  20. EAMJ Risk Factors 10.indd

    African Journals Online (AJOL)

    2010-02-02

    Feb 2, 2010 ... Several factors have been suggested as independent risk factors for their ... Conclusions: Current standard regimens in resource-limited countries are associated .... Summary of outcomes and fate of all the ADRs:The most.

  1. R-Factor for Alaska

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The rainfall-runoff erosivity factor (R-Factor) quantifies the effects of raindrop impacts and reflects the amount and rate of runoff associated with the rain. The...

  2. FACTORING TO FIT OFF DIAGONALS.

    Science.gov (United States)

    imply an upper bound on the number of factors. When applied to somatotype data, the method improved substantially on centroid solutions and indicated a reinterpretation of earlier factoring studies. (Author)

  3. Factores de crecimiento IV: Factor de crecimiento epidérmico,Factores estimuladores de colonias, Neurotropinas Growth factors: epidermal growth factor, colony stimulating factors and neurotropins

    Directory of Open Access Journals (Sweden)

    Hilda Norha Jaramillo Londoño

    1999-02-01

    Full Text Available En esta cuarta entrega sobre los factores de crecimiento se revisan el factor de crecimiento epidérmico (EGF, los factores estimuladores de colonias (CSF y las neurotropinas. Como se ha venido presentando en las anteriores entregas, se hace referencia a su estructura bioquímica, su mecanismo de acción, sus efectos biológicos y sus interacciones. Las neurotropinas y el EGF, por tratarse de factores que actúan predominantemente en el microambiente tisular, no pueden manejarse en el contexto de concentraciones circulantes, situación que sí es factible para los CSF. De otro lado, se revisan los mecanismos de las neurotropinas en el sistema nervioso. In this fourth review of growth factors we summarize, as in previous papers, topics related to biochemical structure, mechanisms of action, biological effects and cross-interactions for epidermal growth factor (EGF, colony stimulating factors (CSF and neurotropins. Since the effects of EGF and neurotropins are exerted predominantly at the microenvironment level, they can not be evaluated by means of its circulating levels, a fact that could be possible for CSFs.

  4. Plasma factor XIII and platelet factor XIII in hyperlipaemia.

    Science.gov (United States)

    Cucuianu, M P; Miloszewski, K; Porutiu, D; Losowsky, M S

    1976-12-31

    Plasma factor XIII activity measured by a quantitative assay was found to be significantly higher in hypertriglyceridaemic patients (type IV and combined hyperlipoproteinaemia), as compared to normolipaemic controls. No such elevation in plasma factor XIII activity was found in patients with type Ha hyperlipaemia. Plasma pseudocholinesterase was found to parallel the elevated factor XIII activity in hypertriglyceridaemic subjects. In contrast, platelet factor XIII activity was not raised in hyperlipaemic subjects, and plasma factor XIII was found to be normal in a normolipaemic subjects with thrombocythaemia. It was concluded that there is no significant contribution from platelets to plasma factor XIII activity, and that the observed increase in plasma factor XIII in hypertriglyceridaemia results from enhanced hepatic synthesis of the enzyme.

  5. Effects of breed, gender, exercise and white-coat effect on markers of endothelial function in dogs

    DEFF Research Database (Denmark)

    Moesgaard, Sophia Gry; Holte, A.V.; Mogensen, T.;

    2007-01-01

    This study examines how systemic biomarkers of endothelial function and nitric oxide metabolism are affected by exercise in dogs. Furthermore, breed variation and white-coat effect have been tested by sampling three different dog breeds both in their home and in a clinical setting. Short...... significantly higher when the sample was taken in the laboratory cf. at home, whereas ADMA and L-arginine were significantly lower. In conclusion, both short-term exercise and white-coat effect influence several plasma markers of endothelial function depending also on the breed and gender of the dogs......-term exercise increased plasma nitrate and nitrite (NOx) and von Willebrand factor (vWf). There was significant difference between Pointers and the small dog breeds Cairn Terriers and Cavalier King Charles Spaniels in the general plasma levels of vWf and asymmetric dimethylarginine (ADMA9. NOx and vWf were...

  6. Molecular requirements for sorting of the chemokine interleukin-8/CXCL8 to endothelial Weibel-Palade bodies.

    Science.gov (United States)

    Hol, Johanna; Küchler, Axel M; Johansen, Finn-Eirik; Dalhus, Bjørn; Haraldsen, Guttorm; Oynebråten, Inger

    2009-08-28

    Sorting of proteins to Weibel-Palade bodies (WPB) of endothelial cells allows rapid regulated secretion of leukocyte-recruiting P-selectin and chemokines as well as procoagulant von Willebrand factor (VWF). Here we show by domain swap studies that the exposed aspartic acid in loop 2 (Ser(44)-Asp(45)-Gly(46)) of the CXC chemokine interleukin (IL)-8 is crucial for targeting to WPB. Loop 2 also governs sorting of chemokines to alpha-granules of platelets, but the fingerprint of the loop 2 of these chemokines differs from that of IL-8. On the other hand, loop 2 of IL-8 closely resembles a surface-exposed sequence of the VWF propeptide, the region of VWF that directs sorting of the protein to WPB. We conclude that loop 2 of IL-8 constitutes a critical signal for sorting to WPB and propose a general role for this loop in the sorting of chemokines to compartments of regulated secretion.

  7. Human Factors in Marine Casualties

    Directory of Open Access Journals (Sweden)

    Jelenko Švetak

    2002-05-01

    Full Text Available Human factors play an important role in the origin of accidents,and it is commonly claimed that between seventy andninety-five percent of industrial and transport accidents involvehuman factors, see Figure 1.Some authorities, however, claim that ultimately, all accidentsinvolve human factors.

  8. Investing in systematic factor premiums

    NARCIS (Netherlands)

    Koedijk, Kees G.; Slager, Alfred M. H.; Stork, P.A.

    2016-01-01

    In this paper we investigate and evaluate factor investing in the US and Europe for equities and bonds. We show that factor-based portfolios generally produce comparable or better portfolios than market indices. We expand the analysis to other asset classes and factors, work with other optimisation

  9. Factors Affecting Children Learning English

    Institute of Scientific and Technical Information of China (English)

    李楠

    2002-01-01

    By reviewing the literature, the author points out some theoretical defects of the CPH on which the policy was based. CPH is the conceptualization formulation of the maturational constraints for SLA. The paper, based on the reality of China, put forward some suggestion, which includes the time factor, the teacher's factor and the content factor.

  10. Phonological Awareness: Factors of Influence

    Science.gov (United States)

    Frohlich, Linda Paulina; Petermann, Franz; Metz, Dorothee

    2013-01-01

    Early child development is influenced by various genetic and environmental factors. This study aims to identify factors that affect the phonological awareness of preschool and first grade children. Based on a sample of 330 German-speaking children (mean age = 6.2 years) the following domains were evaluated: Parent factors, birth and pregnancy,…

  11. Social networks and factor markets

    DEFF Research Database (Denmark)

    Abay, Kibrom Araya; Kahsay, Goytom Abraha; Berhane, Guush

    In the absence of well-established factor markets, the role of indigenous institutions and social networks can be substantial for mobilizing factors for agricultural production. We investigate the role of an indigenous social network in Ethiopia, the iddir, in facilitating factor market...

  12. Factor Analysis of Intern Effectiveness

    Science.gov (United States)

    Womack, Sid T.; Hannah, Shellie Louise; Bell, Columbus David

    2012-01-01

    Four factors in teaching intern effectiveness, as measured by a Praxis III-similar instrument, were found among observational data of teaching interns during the 2010 spring semester. Those factors were lesson planning, teacher/student reflection, fairness & safe environment, and professionalism/efficacy. This factor analysis was as much of a…

  13. Factor analysis and missing data

    NARCIS (Netherlands)

    Kamakura, WA; Wedel, M

    2000-01-01

    The authors study the estimation of factor models and the imputation of missing data and propose an approach that provides direct estimates of factor weights without the replacement of missing data with imputed values. First, the approach is useful in applications of factor analysis in the presence

  14. Risks factoring business: accounting measurement

    Directory of Open Access Journals (Sweden)

    Z.V. Gutsaylyuk

    2015-06-01

    Full Text Available The paper carried out the identification of risk factors for the development of possible accounting software management. Studied theoretical and methodological aspects of the risk classification of factoring operations in the part of the risk assessment factors. It is proposed to consider the risks factors as the risk that is acceptable controlled by accounting instruments and the risks that can not be taken into account in the accounting records. To minimize the risk factor, accounting-driven tools, a method of self-insurance, which is a factor in the creation of provision for factoring transactions designed to cover unexpected expenses and losses. Provision for factoring factor will establish more stable conditions of financial activity and avoid the fluctuations of profit factor in relation to the writing off of losses on factoring operatsіyam.Developed proposals allow for further research to improve the organizational and methodological basis of accounting and analysis of information as a basis for providing risk management factor, particularly in terms of improving the evaluation questions such risks and their qualitative and quantitative analysis.

  15. STEC:O111-HUS complicated by acute encephalopathy in a young girl was successfully treated with a set of hemodiafiltration, steroid pulse, and soluble thrombomodulin under plasma exchange.

    Science.gov (United States)

    Yada, Noritaka; Fujioka, Masayuki; Bennett, Charles L; Inoki, Kazuya; Miki, Toyokazu; Watanabe, Akihiko; Yoshida, Toshiko; Hayakawa, Masaki; Matsumoto, Masanori; Fujimura, Yoshihiro

    2015-04-01

    We report a 14-year-old girl, who developed shigatoxin-producing E. coli (STEC)-HUS complicated by encephalopathy. She was successfully treated with hemodiafiltration, high-dose methylprednisolone pulse therapy, and soluble recombinant thrombomodulin under plasma exchange. von Willebrand factor multimers analysis provides potential insights into how the administered therapies might facilitate successful treatment of STEC-HUS.

  16. Human Factors in Training

    Science.gov (United States)

    Barshi, Immanuel; Byrne, Vicky; Arsintescu, Lucia; Connell, Erin

    2010-01-01

    Future space missions will be significantly longer than current shuttle missions and new systems will be more complex than current systems. Increasing communication delays between crews and Earth-based support means that astronauts need to be prepared to handle the unexpected on their own. As crews become more autonomous, their potential span of control and required expertise must grow to match their autonomy. It is not possible to train for every eventuality ahead of time on the ground, or to maintain trained skills across long intervals of disuse. To adequately prepare NASA personnel for these challenges, new training approaches, methodologies, and tools are required. This research project aims at developing these training capabilities. By researching established training principles, examining future needs, and by using current practices in space flight training as test beds, both in Flight Controller and Crew Medical domains, this research project is mitigating program risks and generating templates and requirements to meet future training needs. Training efforts in Fiscal Year 09 (FY09) strongly focused on crew medical training, but also began exploring how Space Flight Resource Management training for Mission Operations Directorate (MOD) Flight Controllers could be integrated with systems training for optimal Mission Control Center (MCC) operations. The Training Task addresses Program risks that lie at the intersection of the following three risks identified by the Project: 1) Risk associated with poor task design; 2) Risk of error due to inadequate information; and 3) Risk associated with reduced safety and efficiency due to poor human factors design.

  17. Proteolytic factors in exosomes.

    Science.gov (United States)

    Shimoda, Masayuki; Khokha, Rama

    2013-05-01

    Exosomes are small microvesicles secreted from the late endosomal compartment of cells. Although an increasing body of evidence indicates that they play a pivotal role in cell-to-cell communication, the biological functions of exosomes are far from fully understood. Recent work has revealed detailed proteomic profiles of exosomes from cell lines and body fluids, which may provide clues to understanding their biological significance and general importance in human diseases. Metalloproteinases include the cell surface-anchored sheddases a disintegrin and metalloproteinases, as well as cell surface-bound and soluble matrix metalloproteinases and these extracellular proteases have been detected in exosomes by proteomic analyses. Exosomes play a key role in the transfer of proteins to other cells and metalloproteinases may provide a novel platform where ectodomain shedding by these membrane proteases alters the makeup of the recipient cell's surface. This review aims to address some of the facets of exosome biology with particular emphasis on the proteolytic factors and we discuss their potential involvement in human diseases, especially tumor biology.

  18. Tissue factor pathway inhibitor endocytosis.

    Science.gov (United States)

    Schwartz, A L; Broze, G J

    1997-10-01

    Tissue factor pathway inhibitor (TFPI), a 42 kD protein, provides the physiological inhibition of tissue factor initiated coagulation by inhibition of both factor Xa and factor VIIa/tissue factor. In plasma, most TFPI is lipoprotein bound with an additional "releasable" pool bound to the endothelial cell surface. TFPI clearance is via receptor mediated endocytosis into liver. Heparin sulfate proteoglycans and LRP (low density lipoprotein receptor-related protein), an extremely large (∼600 kD) cell surface protein, primarily mediate this clearance, although additional TFPI binding sites and endocytosis pathways exist. (Trends Cardiovasc Med 1997; 7:234-239). © 1997, Elsevier Science Inc.

  19. Congenital thrombotic thrombocytopenic purpura caused by new compound heterozygous mutations of the ADAMTS13 gene

    DEFF Research Database (Denmark)

    Rank, Cecilie Utke; Kremer Hovinga, Johanna; Taleghani, Magnus Mansouri

    2014-01-01

    Upshaw-Schulman syndrome (USS) is due to severe congenital deficiency of von Willebrand factor (VWF)-cleaving protease ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 domains, nr 13) activity resulting in the presence of unusually large forms of VWF in the circulation...... of A) leading to p.R1123H. This case report confirms the importance of the analysis of the ADAMTS13 activity and its inhibitor in patients who have episodes of TTP, with a very low platelet count and sometimes without the classic biochemical signs of hemolysis....

  20. A factor analysis to detect factors influencing building national brand

    Directory of Open Access Journals (Sweden)

    Naser Azad

    Full Text Available Developing a national brand is one of the most important issues for development of a brand. In this study, we present factor analysis to detect the most important factors in building a national brand. The proposed study uses factor analysis to extract the most influencing factors and the sample size has been chosen from two major auto makers in Iran called Iran Khodro and Saipa. The questionnaire was designed in Likert scale and distributed among 235 experts. Cronbach alpha is calculated as 84%, which is well above the minimum desirable limit of 0.70. The implementation of factor analysis provides six factors including “cultural image of customers”, “exciting characteristics”, “competitive pricing strategies”, “perception image” and “previous perceptions”.

  1. 重组人碱性成纤维细胞生长因子结构类似物在大肠杆菌中的高效稳定表达研究%High and stable expression of an analog of human basic fibroblast growth factor in Escherichia coli

    Institute of Scientific and Technical Information of China (English)

    陈琼玉; 孙奋勇; 陈小佳; 谢秋玲; 孙晋华; 洪岸

    2006-01-01

    AIM: To obtain a high and stable expression analog of human basic fibroblast growth factor by genetic engineering. METHODS: The cysteins 78 and 96 of natural hbFGF polypeptide was substituted with serines by means of site-directed mutagenesis. Using pET- 3c as vector, the mutated polynucleotide was cloned and then transferred into BL21 (DE3)plysS. After induction by IPTG, the analog was obtained and analyzed by SDS - PAGE. RESULTS: After purification the form of soluble mutant increased remarkably but the forms of dimmer and higher multimer were reduced greatly to no more than 8% of the total recombinant protein. By MTT assay, the analog showed the same biological activity. This new analog represented a desirable complementation for native hbFGF to develop pharmaceutical drug in clinical use. CONCLUSION: Substitution of certain amino acids of polypeptide without altering native protein' s bioactivity to get the analog is an effective means to increase stability of foreign protein and its solubility in E. coli.%目的:用基因工程的方法获得高效稳定表达的重组人碱性成纤维细胞生长因子结构类似物.方法:利用定点突变技术,将天然hbFGF的第78与96位半胱氨酸替换为丝氨酸,通过载体pET-3c,突变基因被克隆并转化至大肠杆菌BL21(DE3)plysS,IPTG诱导表达后,SDS-PAGE分析蛋白表达结果.结果:纯化后突变蛋白的可溶性成分大幅度增加,而二聚体与多聚体显著减少至纯化后总蛋白的8%以下.MTT法的结果表明,结构类似物蛋白具有良好的生物学活性.这种新的结构类似物蛋白能较好地替代天然hbFGF在临床上的使用.结论:在不影响生物学活性的条件下,对个别氨基酸残基进行突变以获得新的结构类似物的方法,能够有效提高外源蛋白在大肠杆菌中表达的稳定性及可溶性.

  2. The population factor.

    Science.gov (United States)

    Kats, G

    1983-01-01

    Reducing population growth is essentil to Egypt's broader efforts to improve facilities, services, and the phsycial quality of life. Although a family planning program has existed since the mid-1950s, the 2.7% annual rate of population growth has not changed in 30 years. Nasser and the other "free officers" who seized power in 1952 became concerned about the adverse effects of the rapidly growing population, but perhaps out of concern with a possible religious backlash, they confined themselves to launching studies and subsidizing several dozen private family planning clinics. From 1962-72, the number of private clinics grew from 28 to 480, and family planning was introduced in government healthclinics in 1965. Such clinics are mainly located in rural areas and are staffed by doctors and other personnel who are not members of the local community and are not very effective at promoting family planning. Local girls and women called Rayadet were recruited to promote the idea to birth control in local communities. By 1970, 12.6% of Egyptians were using reliable contraception. A national survey 12 years later found 34% using contraception, buth the figure seems high. Approximately 60-65% of eligible couples would need to practice birth control for Egypt to reach a less than 1% annuel increase. The Egyptian government hopes to slow population growth to 1% by the year 2000, but major problems of motivation remain especially among the rural poor. Several factors may lead to success of the family planning effort: 1) financial and technical support from international family planning sources has grown rapidley and is likely to remain high; 2) the mortality rate has dropped from 17.8/1000 in 1952 to about half that level, while the rate of natural increase is about the same, suggesting that future reductions in the birth rate will translate to a reduced rate of natural increase, and that parents will be less reluctant to practice faimly planning if there is a greater chance

  3. Risk factors for periodontal disease.

    Science.gov (United States)

    Genco, Robert J; Borgnakke, Wenche S

    2013-06-01

    Risk factors play an important role in an individual's response to periodontal infection. Identification of these risk factors helps to target patients for prevention and treatment, with modification of risk factors critical to the control of periodontal disease. Shifts in our understanding of periodontal disease prevalence, and advances in scientific methodology and statistical analysis in the last few decades, have allowed identification of several major systemic risk factors for periodontal disease. The first change in our thinking was the understanding that periodontal disease is not universal, but that severe forms are found only in a portion of the adult population who show abnormal susceptibility. Analysis of risk factors and the ability to statistically adjust and stratify populations to eliminate the effects of confounding factors have allowed identification of independent risk factors. These independent but modifiable, risk factors for periodontal disease include lifestyle factors, such as smoking and alcohol consumption. They also include diseases and unhealthy conditions such as diabetes mellitus, obesity, metabolic syndrome, osteoporosis, and low dietary calcium and vitamin D. These risk factors are modifiable and their management is a major component of the contemporary care of many periodontal patients. Genetic factors also play a role in periodontal disease and allow one to target individuals for prevention and early detection. The role of genetic factors in aggressive periodontitis is clear. However, although genetic factors (i.e., specific genes) are strongly suspected to have an association with chronic adult periodontitis, there is as yet no clear evidence for this in the general population. It is important to pursue efforts to identify genetic factors associated with chronic periodontitis because such factors have potential in identifying patients who have a high susceptibility for development of this disease. Many of the systemic risk factors

  4. Growth Factors in Synaptic Function

    Directory of Open Access Journals (Sweden)

    Vivian Yi Nuo Poon

    2013-09-01

    Full Text Available Synapses are increasingly recognized as key structures that malfunction in disorders like schizophrenia, mental retardation, and neurodegenerative diseases. The importance and complexity of the synapse has fuelled research into the molecular mechanisms underlying synaptogenesis, synaptic transmission, and plasticity. In this regard, neurotrophic factors such as netrin, Wnt, transforming growth factor-beta (TGF-beta, tumor necrosis factor-α (TNF-α, and others have gained prominence for their ability to regulate synaptic function. Several of these factors were first implicated in neuroprotection, neuronal growth, and axon guidance. However, their roles in synaptic development and function have become increasingly clear, and the downstream signaling pathways employed by these factors have begun to be elucidated. In this review, we will address the role of these factors and their downstream effectors in synaptic function in vivo and in cultured neurons.

  5. Factors Affecting Medical Service Quality.

    OpenAIRE

    Ali Mohammad Mosadeghrad

    2014-01-01

    A better understanding of factors influencing quality of medical service can pinpoint better strategies for quality assurance in medical services. This study aimed to identify factors affecting the quality of medical services provided by Iranian physicians.Exploratory in-depth individual interviews were conducted with sixty-four physicians working in various medical institutions in Iran.Individual, organizational and environmental factors enhance or inhibit the quality of medical services. Qu...

  6. Factors Affecting Medical Service Quality

    OpenAIRE

    Mosadeghrad, Ali Mohammad

    2014-01-01

    Abstract Background A better understanding of factors influencing quality of medical service can pinpoint better strategies for quality assurance in medical services. This study aimed to identify factors affecting the quality of medical services provided by Iranian physicians. Methods Exploratory in-depth individual interviews were conducted with sixty-four physicians working in various medical institutions in Iran. Results Individual, organizational and environmental factors enhance or inhib...

  7. Risk factors for thyroid cancer.

    Science.gov (United States)

    Nikiforov, Y E; Fagin, J A

    1997-01-01

    The potential risk factors for thyroid carcinoma development include genetic predisposition, exposure to therapeutic or environmental ionizing radiation, residence in areas of iodine deficiency or excess, history of preexisting benign thyroid disease, as well as hormonal and reproductive factors. In this review, we analyze some of the epidemiological data, as well as the possible molecular mechanisms by which certain environmental and genetic factors might predispose to thyroid tumorigenesis. (c) 1997, Elsevier Science Inc. (Trends Endocrinol Metab 1997; 8:20-25).

  8. Matrix Factorization and Matrix Concentration

    OpenAIRE

    Mackey, Lester

    2012-01-01

    Motivated by the constrained factorization problems of sparse principal components analysis (PCA) for gene expression modeling, low-rank matrix completion for recommender systems, and robust matrix factorization for video surveillance, this dissertation explores the modeling, methodology, and theory of matrix factorization.We begin by exposing the theoretical and empirical shortcomings of standard deflation techniques for sparse PCA and developing alternative methodology more suitable for def...

  9. Optimal Algorithm for Algebraic Factoring

    Institute of Scientific and Technical Information of China (English)

    支丽红

    1997-01-01

    This paper presents on optimized method for factoring multivariate polynomials over algebraic extension fields defined by an irreducible ascending set. The basic idea is to convert multivariate polynomials to univariate polynomials and algebraic extension fields to algebraic number fields by suitable integer substituteions.Then factorize the univariate polynomials over the algebraic number fields.Finally,construct mulativariate factors of the original polynomial by Hensel lemma and TRUEFACTOR test.Some examples with timing are included.

  10. Strange nucleon form-factors

    Science.gov (United States)

    Maas, F. E.; Paschke, K. D.

    2017-07-01

    A broad program measuring parity-violation in electron-nuclear scattering has now provided a large set of precision data on the weak-neutral-current form-factors of the proton. Under comparison with well-measured electromagnetic nucleon form-factors, these measurements reveal the role of the strange quark sea on the low-energy interactions of the proton through the strange-quark-flavor vector form-factors. This review will describe the experimental program and the implications of the global data for the strange-quark vector form-factors. We present here a new fit to the world data.

  11. Summable series and convergence factors

    CERN Document Server

    Moore, Charles N

    1938-01-01

    Fairly early in the development of the theory of summability of divergent series, the concept of convergence factors was recognized as of fundamental importance in the subject. One of the pioneers in this field was C. N. Moore, the author of the book under review.... Moore classifies convergence factors into two types. In type I he places the factors which have only the property that they preserve convergence for a convergent series or produce convergence for a summable series. In type II he places the factors which not only maintain or produce convergence but have the additional property that

  12. First course in factor analysis

    CERN Document Server

    Comrey, Andrew L

    2013-01-01

    The goal of this book is to foster a basic understanding of factor analytic techniques so that readers can use them in their own research and critically evaluate their use by other researchers. Both the underlying theory and correct application are emphasized. The theory is presented through the mathematical basis of the most common factor analytic models and several methods used in factor analysis. On the application side, considerable attention is given to the extraction problem, the rotation problem, and the interpretation of factor analytic results. Hence, readers are given a background of

  13. Schemes for Deterministic Polynomial Factoring

    CERN Document Server

    Ivanyos, Gábor; Saxena, Nitin

    2008-01-01

    In this work we relate the deterministic complexity of factoring polynomials (over finite fields) to certain combinatorial objects we call m-schemes. We extend the known conditional deterministic subexponential time polynomial factoring algorithm for finite fields to get an underlying m-scheme. We demonstrate how the properties of m-schemes relate to improvements in the deterministic complexity of factoring polynomials over finite fields assuming the generalized Riemann Hypothesis (GRH). In particular, we give the first deterministic polynomial time algorithm (assuming GRH) to find a nontrivial factor of a polynomial of prime degree n where (n-1) is a smooth number.

  14. Factorization method of quadratic template

    Science.gov (United States)

    Kotyrba, Martin

    2017-07-01

    Multiplication of two numbers is a one-way function in mathematics. Any attempt to distribute the outcome to its roots is called factorization. There are many methods such as Fermat's factorization, Dixońs method or quadratic sieve and GNFS, which use sophisticated techniques fast factorization. All the above methods use the same basic formula differing only in its use. This article discusses a newly designed factorization method. Effective implementation of this method in programs is not important, it only represents and clearly defines its properties.

  15. Social networks and factor markets

    DEFF Research Database (Denmark)

    Abay, Kibrom Araya; Kahsay, Goytom Abraha; Berhane, Guush

    In the absence of well-established factor markets, the role of indigenous institutions and social networks can be substantial for mobilizing factors for agricultural production. We investigate the role of an indigenous social network in Ethiopia, the iddir, in facilitating factor market...... sources. These results point out the roles non-market arrangements, such as social networks, can play in mitigating market inefficiencies in poor rural markets....... transactions among smallholder farmers. Using detailed longitudinal household survey data and employing a difference-in-differences approach, we find that iddir membership improves households’ access to factor markets. Specifically, we find that joining an iddir network improves households’ access to land...

  16. Women's Career Success: A Factor Analytic Study of Contributing Factors.

    Science.gov (United States)

    Gaskill, LuAnn Ricketts

    1991-01-01

    A survey of 466 women employed in retailing received 205 responses identifying (1) factors influencing the success and advancement of women in retailing and (2) how those factors differ for women in upper versus middle positions. Upper-level executives placed more importance on ambition and abilities; midlevel executives credited opportunity and…

  17. Factorized molecular wave functions: Analysis of the nuclear factor

    Energy Technology Data Exchange (ETDEWEB)

    Lefebvre, R., E-mail: roland.lefebvre@u-psud.fr [Institut des Sciences Moléculaires d’ Orsay, Bâtiment 350, UMR8214, CNRS- Université. Paris-Sud, 91405 Orsay, France and Sorbonne Universités, UPMC Univ Paris 06, UFR925, F-75005 Paris (France)

    2015-06-07

    The exact factorization of molecular wave functions leads to nuclear factors which should be nodeless functions. We reconsider the case of vibrational perturbations in a diatomic species, a situation usually treated by combining Born-Oppenheimer products. It was shown [R. Lefebvre, J. Chem. Phys. 142, 074106 (2015)] that it is possible to derive, from the solutions of coupled equations, the form of the factorized function. By increasing artificially the interstate coupling in the usual approach, the adiabatic regime can be reached, whereby the wave function can be reduced to a single product. The nuclear factor of this product is determined by the lowest of the two potentials obtained by diagonalization of the potential matrix. By comparison with the nuclear wave function of the factorized scheme, it is shown that by a simple rectification, an agreement is obtained between the modified nodeless function and that of the adiabatic scheme.

  18. Glycoprotein Ib-IX-V Complex Transmits Cytoskeletal Forces That Enhance Platelet Adhesion.

    Science.gov (United States)

    Feghhi, Shirin; Munday, Adam D; Tooley, Wes W; Rajsekar, Shreya; Fura, Adriane M; Kulman, John D; López, Jose A; Sniadecki, Nathan J

    2016-08-09

    Platelets bind to exposed vascular matrix at a wound site through a highly specialized surface receptor, glycoprotein (GP) Ib-IX-V complex, which recognizes von Willebrand factor (VWF) in the matrix. GPIb-IX-V is a catch bond for it becomes more stable as force is applied to it. After attaching to the wound site, platelets generate cytoskeletal forces to compact and reinforce the hemostatic plug. Here, we evaluated the role of the GPIb-IX-V complex in the transmission of cytoskeletal forces. We used arrays of flexible, silicone nanoposts to measure the contractility of individual platelets on VWF. We found that a significant proportion of cytoskeletal forces were transmitted to VWF through GPIb-IX-V, an unexpected finding given the widely held notion that platelet forces are transmitted exclusively through its integrins. In particular, we found that the interaction between GPIbα and the A1 domain of VWF mediates this force transmission. We also demonstrate that the binding interaction between GPIbα and filamin A is involved in force transmission. Furthermore, our studies suggest that cytoskeletal forces acting through GPIbα are involved in maintaining platelet adhesion when external forces are absent. Thus, the GPIb-IX-V/VWF bond is able to transmit force, and uses this force to strengthen the bond through a catch-bond mechanism. This finding expands our understanding of how platelets attach to sites of vascular injury, describing a new, to the best of our knowledge, mechanism in which the catch bonds of GPIb-IX-V/VWF can be supported by internal forces produced by cytoskeletal tension.

  19. FACTORING- CREDIT OPPORTUNITIES IN ROMANIA

    Directory of Open Access Journals (Sweden)

    ADELA IONESCU

    2013-05-01

    Full Text Available Capital is the main factor of production, business development becomes virtually impossible without taking into account the financial market and the resources it provides to businesses. Any business, regardless of its degree of development, is involving direct contact with financial markets, namely the institutions that mediate mobilization of capital and the services they provide. Understanding the functioning of the financial system, the specific financial mechanisms through which savings are allocated to support capital investments and the costs and risks involved is essential for the development of a solid base for business. In this context, factoring operations can support economic agents, allowing a transfer of commercial receivables from their holder to a factor who commits to their recovery and guarantee such operations even if temporary or permanent insolvency of the debtor . Thus, factoring is a complex technique in at least two aspects, of the debt and the transfer of credit. . Factoring is a means of financing business, especially export-import transactions, less known in Romania. Maybe because of poor business environment popularize the term is as little known as it was a few years ago the leasing. Present in Romanian legislation since 2002, factoring appears as a contract between one party (called adherent, providing goods or service and a banking company or a financial institution specialized (called factor, which the last one shall finance debts pursuing and preservation against credit risks and adherent gives factor by way of sale, debts arising from the sale of goods or services to third parties. The article is divided into three parts. In the first part we defined the concept of factoring and international factoring, then I presented the advantages and development of factoring in Romania, and the last part conclusions.

  20. Matrix factorizations and elliptic fibrations

    Science.gov (United States)

    Omer, Harun

    2016-09-01

    I use matrix factorizations to describe branes at simple singularities of elliptic fibrations. Each node of the corresponding Dynkin diagrams of the ADE-type singularities is associated with one indecomposable matrix factorization which can be deformed into one or more factorizations of lower rank. Branes with internal fluxes arise naturally as bound states of the indecomposable factorizations. Describing branes in such a way avoids the need to resolve singularities. This paper looks at gauge group breaking from E8 fibers down to SU (5) fibers due to the relevance of such fibrations for local F-theory GUT models. A purpose of this paper is to understand how the deformations of the singularity are understood in terms of its matrix factorizations. By systematically factorizing the elliptic fiber equation, this paper discusses geometries which are relevant for building semi-realistic local models. In the process it becomes evident that breaking patterns which are identical at the level of the Kodaira type of the fibers can be inequivalent at the level of matrix factorizations. Therefore the matrix factorization picture supplements information which the conventional less detailed descriptions lack.

  1. Factors associated with asthma control.

    NARCIS (Netherlands)

    Vries, M.P. de; Bemt, E.A.J.M. van den; Lince, S.; Muris, J.W.M.; Thoonen, B.P.A.; Schayck, C.P. van

    2005-01-01

    The aim of this study was to evaluate which factors are associated with asthma control experienced by asthma patients. In a cross-sectional study patients aged 16-60 years with mild to moderate asthma were selected. The influence of the following factors on asthma control was studied in a multivaria

  2. Factor analysis of multivariate data

    Digital Repository Service at National Institute of Oceanography (India)

    Fernandes, A.A.; Mahadevan, R.

    A brief introduction to factor analysis is presented. A FORTRAN program, which can perform the Q-mode and R-mode factor analysis and the singular value decomposition of a given data matrix is presented in Appendix B. This computer program, uses...

  3. Factors That Shape Design Thinking

    Science.gov (United States)

    Gray, Colin M.

    2013-01-01

    A wide range of design literature discusses the role of the studio and its related pedagogy in the development of design thinking. Scholars in a variety of design disciplines pose a number of factors that potentially affect this development process, but a full understanding of these factors as experienced from a critical pedagogy or student…

  4. Matrix factorizations and elliptic fibrations

    Directory of Open Access Journals (Sweden)

    Harun Omer

    2016-09-01

    Full Text Available I use matrix factorizations to describe branes at simple singularities of elliptic fibrations. Each node of the corresponding Dynkin diagrams of the ADE-type singularities is associated with one indecomposable matrix factorization which can be deformed into one or more factorizations of lower rank. Branes with internal fluxes arise naturally as bound states of the indecomposable factorizations. Describing branes in such a way avoids the need to resolve singularities. This paper looks at gauge group breaking from E8 fibers down to SU(5 fibers due to the relevance of such fibrations for local F-theory GUT models. A purpose of this paper is to understand how the deformations of the singularity are understood in terms of its matrix factorizations. By systematically factorizing the elliptic fiber equation, this paper discusses geometries which are relevant for building semi-realistic local models. In the process it becomes evident that breaking patterns which are identical at the level of the Kodaira type of the fibers can be inequivalent at the level of matrix factorizations. Therefore the matrix factorization picture supplements information which the conventional less detailed descriptions lack.

  5. Psychological Factors in English Study

    Institute of Scientific and Technical Information of China (English)

    吴西

    2015-01-01

    <正>1.Introduction The psychological factor that influences English study is dynamic,complex,and flexible.Its influence is not immediately known,but it rather accumulates over a period of time.It is inevitable that students have some psychological factors in learning English.Therefore,in the process of teaching,teachers

  6. Twisting formula of epsilon factors

    Indian Academy of Sciences (India)

    SAZZAD ALI BISWAS

    2017-09-01

    For characters of a non-Archimedean local field we have explicit formula for epsilon factors. But in general, we do not have any generalized twisting formula of epsilon factors. In this paper, we give a generalized twisting formula of epsilon factorsvia local Jacobi sums.

  7. Polynomial J-spectral factorization

    NARCIS (Netherlands)

    Kwakernaak, Huibert; Sebek, Michael

    1994-01-01

    Several algorithms are presented for the J-spectral factorization of a para-Hermitian polynomial matrix. The four algorithms that are discussed are based on diagonalization, successive factor extraction, interpolation, and the solution of an algebraic Riccati equation, respectively. The paper includ

  8. Kadison-Kastler stable factors

    DEFF Research Database (Denmark)

    Cameron, Jan; Christensen, Erik; Sinclair, Allan M.;

    2014-01-01

    It is proven that a pair of continuous finite von Neumann algebra factors are unitarily equivalent if sufficiently close and one satisfies a certain cohomological condition.......It is proven that a pair of continuous finite von Neumann algebra factors are unitarily equivalent if sufficiently close and one satisfies a certain cohomological condition....

  9. Quadratic prediction of factor scores

    NARCIS (Netherlands)

    Wansbeek, T

    1999-01-01

    Factor scores are naturally predicted by means of their conditional expectation given the indicators y. Under normality this expectation is linear in y but in general it is an unknown function of y. II is discussed that under nonnormality factor scores can be more precisely predicted by a quadratic

  10. Shell model and spectroscopic factors

    Energy Technology Data Exchange (ETDEWEB)

    Poves, P. [Madrid Univ. Autonoma and IFT, UAM/CSIC, E-28049 (Spain)

    2007-07-01

    In these lectures, I introduce the notion of spectroscopic factor in the shell model context. A brief review is given of the present status of the large scale applications of the Interacting Shell Model. The spectroscopic factors and the spectroscopic strength are discussed for nuclei in the vicinity of magic closures and for deformed nuclei. (author)

  11. Critical factors for EIA implementation

    DEFF Research Database (Denmark)

    Zhang, Jasmine; Kørnøv, Lone; Christensen, Per

    2013-01-01

    between different critical factors and how they relate to different stages in the EIA and thus influence the decision making process. After reviewing 33 refereed journal articles published between 1999 and 2011, we identified 203 notions of critical factors. Of these, 102 related to different stages...

  12. Shape Factor Modeling and Simulation

    Science.gov (United States)

    2016-06-01

    10 3. Shape Factor Distributions for Natural Fragments 12 3.1 Platonic Solids and Uniform Viewing from All Viewpoints 12 3.2 Natural Fragments from...12 Fig. 9 The 5 Platonic solids. ............................................................. 12 Fig. 10 Mean shape factor of...of the 5 Platonic solids............................................ 13 Table 3 Sequence of viewing angles in Icosahedron Gage

  13. Activity factors of the Korean exposure factors handbook.

    Science.gov (United States)

    Jang, Jae-Yeon; Jo, Soo-Nam; Kim, So-Yeon; Lee, Kyung-Eun; Choi, Kyung-Ho; Kim, Young-Hee

    2014-01-01

    Exposure factors based on the Korean population are required for making appropriate risk assessment. It is expected that handbooks for exposure factors will be applied in many fields, as well as by health department risk assessors. The present article describes the development of an exposure factors handbook that specifically focuses on human activities in situations involving the possible risk of exposure to environmental contaminants. We define majour exposure factors that represent behavioral patterns for risk assessment, including time spent on routine activities, in different places, on using transportation, and engaged in activities related to water contact including swimming, bathing and washing. Duration of residence and employment are also defined. National survey data were used to identify recommended levels of exposure factors in terms of time spent on routine activities and period of residence and employment. An online survey was conducted with 2073 subjects who were selected using a stratified random sampling method in order to develop a list of exposure factors for the time spent in different places and in performing water-related activities. We provide the statistical distribution of the variables, and report reference levels of average exposure based on the reliable data in our exposure factors handbook.

  14. 缺氧诱导因子-1α对创伤性脑损伤大鼠炎性反应和血管生成因子表达的影响%Effect of hypoxia-inducible factor-1α on inflammatory response and angiogenic factor expression in rats with traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    靳春杰; 方贵龙; 权伟; 江荣才; 张建宁

    2016-01-01

    brain injury (TBI).Methods The fluid percussion model was applied to induce TBI in rats.A total of 600 rats were divided into sham operation group,TBI group,TBI + HIF-1 α silence group and TBI + control virus group according to the random number table,with 150 rats in each.Virus-mediated HIF-1 α silence gene and control virus were delivered 24 h before the fluid percussion injury.After 3,7 and 14 d,brain injury area and morphological changes in injured region were detected by HE staining,expressions of vascular endothelial cell markers (vWF) and HIF-1 α were detected by Western blot method,and expressions of vascular endothelial growth factor (VEGF),matrix metalloproteinase-9 (MMP-9),tumor necrosis factor-α (TNF-α),interleukin 6 (IL-6) and nuclear factor-κB (NF-κB) in peripheral blood and brain tissue were detected by ELISA method.Rat neural function was dynamically assessed using the modified neurological severity score (mNSS).Results (1) Brain injury area and edema area in TBI + HIF-1 α silence group were higher than those in TBI group at all time points (P < 0.05).(2) Compared with sham operation group and TBI + control virus group,expression of HIF-1α in TBI group gradually increased and remained high at 7 and 14 d postinjury (P < 0.05).Compared with TBI group,expression of vWF in TBI + HIF-1αsilence group decreased at all time points (P < 0.05) and inhibited angiogenesis.(3) TBI + HIF-lα silence group versus TBI group showed remarkably decreased VEGF at all time points,increased expressions of TNF-α,IL-6 and NF-κB at all time point,and increased expression of MMP-9 at 7 and 14 d postinjury (all P <0.05).(4) TBI + HIF-1α silence group versus TBI group showed significant difference in mNSS at 7 and 14 d postinjury (all P < 0.05).Conclusions After TBI,high expression of HIF-1αcan facilitate vascular formation and inhibit inflammatory reaction related factor expression,inducing the mitigation of brain edema and brain injury

  15. Risk factors for suicidal behavior

    Directory of Open Access Journals (Sweden)

    Antonova A.A.

    2012-06-01

    Full Text Available

     

    The article presents data on risk factors that contribute to the development of suicidal behavior. The development of suicidal behavior is infuenced by a number of factors. These include — gender, age, residence, occupation, marital status, health status, etc. A number of studies indicated the impact of economic and social factors on the level of suicidal activity of the population. Observed relationship between mental disorders, substance abuse (particularly alcohol and suicide. In this case, the presence of numerous investigations in the feld of Suicidology, a number of problems still remains unsolved. Further study of issues relating to risk factors that infuence the development of suicidal behavior. Of particular note is the importance of “regional” risk factors that most infuence on the formation of suicidal behavior in a particular region.

  16. Universally conserved translation initiation factors.

    Science.gov (United States)

    Kyrpides, N C; Woese, C R

    1998-01-06

    The process by which translation is initiated has long been considered similar in Bacteria and Eukarya but accomplished by a different unrelated set of factors in the two cases. This not only implies separate evolutionary histories for the two but also implies that at the universal ancestor stage, a translation initiation mechanism either did not exist or was of a different nature than the extant processes. We demonstrate herein that (i) the "analogous" translation initiation factors IF-1 and eIF-1A are actually related in sequence, (ii) the "eukaryotic" translation factor SUI1 is universal in distribution, and (iii) the eukaryotic/archaeal translation factor eIF-5A is homologous to the bacterial translation factor EF-P. Thus, the rudiments of translation initiation would seem to have been present in the universal ancestor stage. However, significant development and refinement subsequently occurred independently on both the bacterial lineage and on the archaeal/eukaryotic line.

  17. [Risk factors for arterial disease].

    Science.gov (United States)

    Madoery, Roberto; Rubin, Graciela; Luquez, Hugo; Luquez, Cecilia; Cravero, Cecilia

    2004-01-01

    The risk factors of arterial disease (FREA) predict a future damage over the vascular system of the human body. Its detection are considered a key for the diagnostic as well as for the preventive and even curative strategies. For a long time, scientist considered those factors originated as a consecuence of large studies during the middle of the last century, with current validity up to our days. A simple classification spoke of them as traditionals. Further investigations described the so called new or emergents.factors that where joint together accordingly to their actions: coagulation factors, psicosocial, inflamatories and infectious. A recent classification, taking into account the type of impact, divided them into; causatives, predisposals and conditionals. Also, it was described a mechanism, the oxidative power, with consecuences over the endothelium, in the last part of the process. Before, another mechanism was described: the insulin resistance and the hiperinsulinism, bases for the Metabolic Syndrome, that includes a number of traditional risk factors.

  18. Coagulopathy in Cushing's syndrome.

    Science.gov (United States)

    Trementino, Laura; Arnaldi, Giorgio; Appolloni, Gloria; Daidone, Viviana; Scaroni, Carla; Casonato, Alessandra; Boscaro, Marco

    2010-01-01

    A hypercoagulable state and its consequent increased incidence of thromboembolic complications are reported in patients with Cushing's syndrome (CS). These alterations are related to cortisol excess that induces prothrombotic changes in blood by several and complex mechanisms including increased levels of clotting factors, mainly factor VIII and von Willebrand factor (VWF) and impaired fibrinolytic capacity. However, it has recently been observed that the increase in VWF levels is not a constant feature of CS and that VWF response to glucocorticoids is genetically determined and depends on the presence of particular polymorphisms in the VWF gene promoter. The risk of venous thromboembolism is moreover enhanced in patients with CS by additional endogenous and exogenous risk factors such as obesity, bed rest, surgery and invasive diagnostic procedures like inferior petrosal sinus (IPS) sampling. In line with all these data, patients with active CS should be treated as having a prothrombotic disorder and undergo antithrombotic prophylaxis during IPS sampling. Special care should be taken in the immediate perioperative period in order to avoid thromboembolic events. In the absence of prospective randomized trials, preventive antithrombotic treatment (best with heparin) during IPS sampling and low-dose heparin treatment early after surgery should be suggested.

  19. An endothelial storage granule for tissue-type plasminogen activator

    NARCIS (Netherlands)

    Emeis, J.J.; Eijnden van den - Schrauwen, Y.; Hoogen, C.M. van den; Priester, W. de; Westmuckett, A.; Lupu, F.

    1997-01-01

    In previous studies we have shown that, after stimulation by a receptor ligand such as thrombin, tissue-type plasminogen activator (tPA) and von Willebrand factor (vW(f)) will be acutely released from human umbilical vein endothelial cells (HUVEC). However, the mechanisms involved in the secretion o

  20. The fibrinolytic system in the hemolytic uremic syndrome: In vivo and in vitro studies

    NARCIS (Netherlands)

    Kar, N.C.A.J. van de; Hinsbergh, V.W.M. van; Brommer, E.J.P.; Monnens, L.A.H.

    1994-01-01

    Fibrinolytic parameters and von Willebrand factor (vWF) antigen were measured in the plasma of 10 patients with hemolytic uremic syndrome (HUS). Samples were taken at presentation and again 2 wk later, before and after infusion of 1-desamino-8-arginine vasopressin. Compared with the plasma values of