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Sample records for von willebrand factor

  1. 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

  2. Of von Willebrand factor and platelets.

    Science.gov (United States)

    Bryckaert, Marijke; Rosa, Jean-Philippe; Denis, Cécile V; Lenting, Peter J

    2015-01-01

    Hemostasis and pathological thrombus formation are dynamic processes that require multiple adhesive receptor-ligand interactions, with blood platelets at the heart of such events. Many studies have contributed to shed light on the importance of von Willebrand factor (VWF) interaction with its platelet receptors, glycoprotein (GP) Ib-IX-V and αIIbβ3 integrin, in promoting primary platelet adhesion and aggregation following vessel injury. This review will recapitulate our current knowledge on the subject from the rheological aspect to the spatio-temporal development of thrombus formation. We will also discuss the signaling events generated by VWF/GPIb-IX-V interaction, leading to platelet activation. Additionally, we will review the growing body of evidence gathered from the recent development of pathological mouse models suggesting that VWF binding to GPIb-IX-V is a promising target in arterial and venous pathological thrombosis. Finally, the pathological aspects of VWF and its impact on platelets will be addressed.

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

    Czech Academy of Sciences Publication Activity Database

    Abdelmagid, N.; Bereczky-Veress, B.; Atanur, S.; Musilová, Alena; Zídek, Václav; Saba, L.; Warnecke, A.; Khademi, M.; Studahl, M.; Aurelius, E.; Hjalmarsson, A.; Garcia-Dias, A.; Denis, C. V.; Bergström, T.; Sköldenberg, B.; Kockum, I.; Aitman, T.; Hübner, N.; Olsson, T.; Pravenec, Michal; Diez, M.

    2016-01-01

    Roč. 11, č. 5 (2016), e0155832 E-ISSN 1932-6203 R&D Projects: GA MŠk(CZ) 7E10067; GA MŠk(CZ) LL1204 Institutional support: RVO:67985823 Keywords : Von Willebrand Factor gene * Herpes simplex encephalitis * rat * humans Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.806, year: 2016

  4. 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

    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.

  5. 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

    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...... 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...

  6. Von Willebrand factor regulation of blood vessel formation.

    Science.gov (United States)

    Randi, Anna M; Smith, Koval E; Castaman, Giancarlo

    2018-06-04

    Several important physiological processes, from permeability to inflammation to haemostasis, take place at the vessel wall and are regulated by endothelial cells (EC). Thus, proteins that have been identified as regulators of one process are increasingly found to be involved in other vascular functions. Such is the case for Von Willebrand Factor (VWF), a large glycoprotein best known for its critical role in haemostasis. In vitro and in vivo studies have shown that lack of VWF causes enhanced vascularisation, both constitutively and following ischemia. This evidence is supported by studies on blood outgrowth endothelial cells (BOEC) from patients with lack of VWF synthesis (type 3 von Willebrand disease [VWD]). The molecular pathways are likely to involve VWF binding partners, such as integrin αvβ3, and components of Weibel Palade bodies (WPB), such as Angiopoietin-2 and Galectin-3, whose storage is regulated by VWF; these converge on the master regulator of angiogenesis and endothelial homeostasis, vascular endothelial growth factor (VEGF) signalling. Recent studies suggest that the roles of VWF may be tissue-specific. The ability of VWF to regulate angiogenesis has clinical implications for a subset of VWD patients with severe, intractable gastrointestinal bleeding due to vascular malformations. In this article, we review the evidence showing that VWF is involved in blood vessel formation, discuss the role of VWF high molecular weight multimers in regulating angiogenesis, and the value of studies on BOEC in developing a precision medicine approach to validate novel treatments for angiodysplasia in congenital VWD and acquired von Willebrand syndrome. Copyright © 2018 American Society of Hematology.

  7. von Willebrand factor, Jedi knight of the bloodstream.

    Science.gov (United States)

    Springer, Timothy A

    2014-08-28

    When blood vessels are cut, the forces in the bloodstream increase and change character. The dark side of these forces causes hemorrhage and death. However, von Willebrand factor (VWF), with help from our circulatory system and platelets, harnesses the same forces to form a hemostatic plug. Force and VWF function are so closely intertwined that, like members of the Jedi Order in the movie Star Wars who learn to use "the Force" to do good, VWF may be considered the Jedi knight of the bloodstream. The long length of VWF enables responsiveness to flow. The shape of VWF is predicted to alter from irregularly coiled to extended thread-like in the transition from shear to elongational flow at sites of hemostasis and thrombosis. Elongational force propagated through the length of VWF in its thread-like shape exposes its monomers for multimeric binding to platelets and subendothelium and likely also increases affinity of the A1 domain for platelets. Specialized domains concatenate and compact VWF during biosynthesis. A2 domain unfolding by hydrodynamic force enables postsecretion regulation of VWF length. Mutations in VWF in von Willebrand disease contribute to and are illuminated by VWF biology. I attempt to integrate classic studies on the physiology of hemostatic plug formation into modern molecular understanding, and point out what remains to be learned. © 2014 by The American Society of Hematology.

  8. [Homocysteine and von Willebrand factor in chronic alcoholism].

    Science.gov (United States)

    Koriakin, A M; Epifantseva, N N; Dadyka, I V; Gorbatovskiĭ, Ia A

    2010-04-01

    The levels of homocysteine (HC) and von Willebrand factor (VWF) as cardiovascular risk factors were studied in patients with Stage II chronic alcoholism. Forty-one men with Stage II chronic alcoholism without clinical signs of somatic and infectious diseases were examined. Their median age was 37 (range 32-40) years; the alcoholization period was 12 (range 8-17) years. Plasma HC and VWF (amount and activity) levels were determined. In 63.4% of chronic alcoholic patients, HC levels was twice as high as in the controls; in 80.6%, both the content and activity of VWF were increased. There was no correlation between the levels of HC and VWF. Vascular endothelial damage concurrent with hyperhomocysteinemia increases a cardiovascular risk in patients with Stage II chronic alcoholism.

  9. Value of Von Willebrand Factor as a Predictor for Osteoporosis Development in Women with Hypothyroidism

    Directory of Open Access Journals (Sweden)

    I.V. Pankiv

    2015-08-01

    Full Text Available The paper presents the study of the value of von Willebrand factor as a marker of endothelial dysfunction for osteoporosis development and for prediction of risk of its formation in women with hypothyroidism. Postmenopausal women with hypothyroidism have significant increase of von Willebrand factor at lumbar osteopenia. High concentrations of von Willebrand factor in women with hypothyroidism follows to consider it as a predictor for osteoporosis development. Increased level of С-reactive protein belongs to the unfavorable prognostic signs in relation to the decline of bone mineral density for patients with primary hypothyroidism.

  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...... 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. Evaluation of von Willebrand factor during pregnancy, lactation and oestrous cycle in bitches affected and unaffected by von Willebrand disease.

    Science.gov (United States)

    Mattoso, C R S; Takahira, R K; Beier, S L; Araujo, J P; Corrente, J E

    2013-06-01

    Plasmatic concentrations of von Willebrand Factor (vWF) increase during pregnancy in humans and dogs; however the mechanism of such increase is still not well defined. The aims of this study were: (i) to evaluate changes in vWF concentration during pregnancy and during the subsequent oestrous cycle in bitches affected and unaffected by von Willebrand Disease (vWD); (ii) to correlate the vWF levels and cortisol levels in both groups. Seven vWD affected (GI) and nine unaffected (GII) bitches were used. The animals were assessed during pregnancy, parturition, lactation and non-gestational oestrous cycle in 11 moments (Pregnancy 1, Pregnancy 2, Parturition, Lactation 1, Lactation 2, Lactation 3, Anestrus, Proestrus, Oestrus, Diestrus 1, and Diestrus 2). The following tests were performed; measurement of von Willebrand factor antigen (vWF:Ag), albumin and cortisol. In both groups, vWF concentration remained stable during the non-gestational oestrous cycle, but increased during pregnancy, with the highest value observed at parturition. Increases of 70% and 124% in vWF were seen in GI and GII, respectively, compared to anestrus. No correlation was found between vWF and cortisol. Values of vWF:Ag changed during pregnancy, with a peak at parturition, both in vWD affected and unaffected animals. Values of vWF were not altered in the different phases of the oestrous cycle following pregnancy in both groups. Evaluation of vWF during pregnancy can cause false negative results for vWD, but assessment can be performed at any point in the oestrous cycle of non-pregnant bitches. © 2012 Blackwell Verlag GmbH.

  12. Phenotypic correction of von Willebrand disease type 3 blood-derived endothelial cells with lentiviral vectors expressing von Willebrand factor

    Science.gov (United States)

    De Meyer, Simon F.; Vanhoorelbeke, Karen; Chuah, Marinee K.; Pareyn, Inge; Gillijns, Veerle; Hebbel, Robert P.; Collen, Désiré; Deckmyn, Hans; VandenDriessche, Thierry

    2006-01-01

    Von Willebrand disease (VWD) is an inherited bleeding disorder, caused by quantitative (type 1 and 3) or qualitative (type 2) defects in von Willebrand factor (VWF). Gene therapy is an appealing strategy for treatment of VWD because it is caused by a single gene defect and because VWF is secreted into the circulation, obviating the need for targeting specific organs or tissues. However, development of gene therapy for VWD has been hampered by the considerable length of the VWF cDNA (8.4 kb [kilobase]) and the inherent complexity of the VWF protein that requires extensive posttranslational processing. In this study, a gene-based approach for VWD was developed using lentiviral transduction of blood-outgrowth endothelial cells (BOECs) to express functional VWF. A lentiviral vector encoding complete human VWF was used to transduce BOECs isolated from type 3 VWD dogs resulting in high-transduction efficiencies (95.6% ± 2.2%). Transduced VWD BOECs efficiently expressed functional vector-encoded VWF (4.6 ± 0.4 U/24 hour per 106 cells), with normal binding to GPIbα and collagen and synthesis of a broad range of multimers resulting in phenotypic correction of these cells. These results indicate for the first time that gene therapy of type 3 VWD is feasible and that BOECs are attractive target cells for this purpose. PMID:16478886

  13. Association of von Willebrand factor blood levels with exercise hypertension.

    Science.gov (United States)

    Nikolic, Sonja B; Adams, Murray J; Otahal, Petr; Edwards, Lindsay M; Sharman, James E

    2015-05-01

    A hypertensive response to moderate intensity exercise (HRE) is associated with increased cardiovascular risk. The mechanisms of an HRE are unclear, although previous studies suggest this may be due to haemostatic and/or haemodynamic factors. We investigated the relationships between an HRE with haemostatic and hemodynamic indices. Sixty-four participants (57 ± 10 years, 71 % male) with indication for exercise stress testing underwent cardiovascular assessment at rest and during moderate intensity exercise, from which 20 participants developed an HRE (defined as moderate exercise systolic BP ≥ 170 mmHg/men and ≥ 160 mmHg/women). Rest, exercise and post-exercise blood samples were analysed for haemostatic markers, including von Willebrand factor (vWf), and haemodynamic measures of brachial and central blood pressure (BP), aortic stiffness and systemic vascular resistance index (SVRi). HRE participants had higher rest vWf compared with normotensive response to exercise (NRE) participants (1,927 mU/mL, 95 % CI 1,240-2,615, vs. 1,129 mU/mL, 95 % CI 871-1,386; p = 0.016). vWf levels significantly decreased from rest to post-exercise in HRE participants (p = 0.005), whereas vWf levels significantly increased from rest to exercise in NRE participants (p = 0.030). HRE participants also had increased triglycerides, rest BP, aortic stiffness and exercise SVRi (p HRE at moderate intensity.

  14. Modeling Shear Induced Von Willebrand Factor Binding to Collagen

    Science.gov (United States)

    Dong, Chuqiao; Wei, Wei; Morabito, Michael; Webb, Edmund; Oztekin, Alparslan; Zhang, Xiaohui; Cheng, Xuanhong

    2017-11-01

    Von Willebrand factor (vWF) is a blood glycoprotein that binds with platelets and collagen on injured vessel surfaces to form clots. VWF bioactivity is shear flow induced: at low shear, binding between VWF and other biological entities is suppressed; for high shear rate conditions - as are found near arterial injury sites - VWF elongates, activating its binding with platelets and collagen. Based on parameters derived from single molecule force spectroscopy experiments, we developed a coarse-grain molecular model to simulate bond formation probability as a function of shear rate. By introducing a binding criterion that depends on the conformation of a sub-monomer molecular feature of our model, the model predicts shear-induced binding, even for conditions where binding is highly energetically favorable. We further investigate the influence of various model parameters on the ability to predict shear-induced binding (vWF length, collagen site density and distribution, binding energy landscape, and slip/catch bond length) and demonstrate parameter ranges where the model provides good agreement with existing experimental data. Our results may be important for understanding vWF activity and also for achieving targeted drug therapy via biomimetic synthetic molecules. National Science Foundation (NSF),Division of Mathematical Sciences (DMS).

  15. 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.

  16. A study of the effect of ethamsylate (Dicynene) on the bleeding time, von Willebrand factor level and fibrinolysis in patients with von Willebrand's disease.

    Science.gov (United States)

    Hutton, R A; Hales, M; Kernoff, P B

    1988-12-22

    Nine patients with clinically moderate or severe Type I von Willebrand's disease were treated for 2 weeks with ethamsylate (2 g/day in four equal doses) and with a matched placebo in a randomised double-blind trial. Template bleeding time, von Willebrand factor activity (ristocetin co-factor) and antigen, euglobulin lysis time and type I tissue plasminogen activator inhibitor were determined before and at the end of each treatment period. None of these parameters showed any significant change attributable to ethamsylate. Thus, despite the fact that five patients thought subjectively that their bleeding symptoms improved during ethamsylate treatment compared to only one while on placebo, we obtained no evidence that the drug was of benefit to patients with von Willebrand's disease.

  17. Von Willebrand disease protects against arterial thrombosis

    NARCIS (Netherlands)

    Sanders, Y.V.; Eikenboom, J.C.; De Wee, E.M.; Van Der Bom, J.G.; Cnossen, M.H.; Degenaar-Dujardin, M.E.; Fijnvandraat, K.; Kamphuisen, P.W.; Laros-Van Gorkum, B.A.; Meijer, K.; Mauser -Bunschoten, E.P.; Leebee k, F.W.

    Background and Aims: Von Willebrand disease (VWD) is caused by reduced levels of or dysfunctional von Willebrand factor (VWF) and is characterized by a bleeding tendency. It is well known that individuals with high VWF levels have a higher risk for arterial thrombosis. Although it has never been

  18. Differential proteolytic activation of factor VIII-von Willebrand factor complex by thrombin

    International Nuclear Information System (INIS)

    Hill-Eubanks, D.C.; Parker, C.G.; Lollar, P.

    1989-01-01

    Blood coagulation factor VIII (fVIII) is a plasma protein that is decreased or absent in hemophilia A. It is isolated as a mixture of heterodimers that contain a variably sized heavy chain and a common light chain. Thrombin catalyzes the activation of fVIII in a reaction that is associated with cleavages in both types of chain. The authors isolated a serine protease from Bothrops jararacussu snake venom that catalyzes thrombin-like heavy-chain cleavage but not light-chain cleavage in porcine fVIII as judged by NaDodSO 4 /PAGE and N-terminal sequence analysis. Using a plasma-free assay of the ability of activated 125 I-fVIII to function as a cofactor in the activation of factor X by factor IXa, they found that fVIII is activated by the venom enzyme. The venom enzyme-activated fVIII was isolated in stable form by cation-exchange HPLC. von Willebrand factor inhibited venom enzyme-activated fVIII but not thrombin-activated fVIII. These results suggest that the binding of fVIII to von Willebrand factor depends on the presence of an intact light chain and that activated fVIII must dissociate from von Willebrand factor to exert its cofactor effect. Thus, proteolytic activation of fVIII-von Willebrand factor complex appears to be differentially regulated by light-chain cleavage to dissociate the complex and heavy-chain cleavage to activate the cofactor function

  19. 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...

  20. Differential effects of the loss of intrachain- versus interchain-disulfide bonds in the cystine-knot domain of von Willebrand factor on the clinical phenotype of von Willebrand disease

    NARCIS (Netherlands)

    Tjernberg, Pernilla; Vos, Hans L.; Spaargaren-van Riel, Caroline C.; Luken, Brenda M.; Voorberg, Jan; Bertina, Rogier M.; Eikenboom, Jeroen C. J.

    2006-01-01

    Von Willebrand factor (VWF) contains a large number of cysteine residues, which all form disulfide bonds. Mutations of cysteines located in the cystine-knot (CK) domain of VWF have been identified in both qualitative type 2A (IID) and quantitative type 3 von Willebrand disease (VWD). Our objective

  1. Dynamics of von Willebrand factor reactivity in sickle cell disease during vaso-occlusive crisis and steady state

    NARCIS (Netherlands)

    Sins, J. W. R.; Schimmel, M.; Luken, B. M.; Nur, E.; Zeerleder, S. S.; van Tuijn, C. F. J.; Brandjes, D. P. M.; Kopatz, W. F.; Urbanus, R. T.; Meijers, J. C. M.; Biemond, B. J.; Fijnvandraat, K.

    2017-01-01

    Background: Endothelial activation plays a central role in the pathophysiology of vaso-occlusion in sickle cell disease (SCD), facilitating adhesive interactions with circulating blood cells. Upon activation, various adhesive molecules are expressed, including von Willebrand factor (VWF). Increased

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

    NARCIS (Netherlands)

    J.E. van Loon (Janine ); M.A.H. Sonneveld (Michelle); S.F.E. Praet (Stephan); M.P.M. de Maat (Moniek); F.W.G. Leebeek (Frank)

    2014-01-01

    textabstractBackground: 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

  3. Single molecule force spectroscopy data and BD- and MD simulations on the blood protein von Willebrand factor

    Directory of Open Access Journals (Sweden)

    Sandra Posch

    2016-09-01

    Full Text Available We here give information for a deeper understanding of single molecule force spectroscopy (SMFS data through the example of the blood protein von Willebrand factor (VWF. It is also shown, how fitting of rupture forces versus loading rate profiles in the molecular dynamics (MD loading-rate range can be used to demonstrate the qualitative agreement between SMFS and MD simulations. The recently developed model by Bullerjahn, Sturm, and Kroy (BSK was used for this demonstration. Further, Brownian dynamics (BD simulations, which can be utilized to estimate the lifetimes of intramolecular VWF interactions under physiological shear, are described. For interpretation and discussion of the methods and data presented here, we would like to directly point the reader to the related research paper, “Mutual A domain interactions in the force sensing protein von Willebrand Factor” (Posch et al., 2016 [1]. Keywords: Atomic force microscopy, Single molecule force spectroscopy, Molecular dynamics simulation, Brownian dynamics simulation, von Willebrand factor

  4. Doença de von Willebrand e anestesia Enfermedad de von Willebrand y anestesia Von Willebrand's disease and anesthesia

    Directory of Open Access Journals (Sweden)

    Fabiano Timbó Barbosa

    2007-06-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A doença de von Willebrand ocorre devido à mutação no cromossomo 12 e é caracterizada por deficiência qualitativa ou quantitativa do fator de von Willebrand. A diversidade de mutações leva ao aparecimento das mais variadas manifestações clínicas possibilitando a divisão dos pacientes em vários tipos e subtipos clínicos. A coagulopatia se manifesta basicamente através da disfunção plaquetária associada à diminuição dos níveis séricos do fator VIII coagulante. O objetivo dessa revisão foi mostrar os cuidados relacionados aos pacientes portadores da doença de von Willebrand durante o período perioperatório. CONTEÚDO: Foram definidas as características da doença de von Willebrand quanto à fisiopatologia, à classificação, ao diagnóstico laboratorial, ao tratamento atual e aos cuidados com o manuseio do paciente no período perioperatório. CONCLUSÕES: A doença de von Willebrand é o distúrbio hemorrágico hereditário mais comum, porém ela é subdiagnosticada pela complexidade da própria doença. A correta classificação do paciente, o uso apropriado da desmopressina e a transfusão do fator de von Willebrand são medidas fundamentais para a realização do procedimento anestésico bem-sucedido.JUSTIFICATIVA Y OBJETIVOS: La enfermedad de von Willebrand ocurre debido a la mutación en el cromosoma 12 y se caracteriza por la deficiencia cualitativa o cuantitativa del factor de von Willebrand. La diversidad de mutaciones conlleva al aparecimiento de las más variadas manifestaciones clínicas posibilitando la división de los pacientes en varios tipos y subtipos clínicos. La coagulopatía se manifiesta básicamente a través de la disfunción plaquetaria asociada con la disminución de los niveles séricos del factor VIII coagulante. El objetivo de esa revisión fue mostrar los cuidados relacionados con las pacientes portadoras de la enfermedad de von Willebrand durante el per

  5. Profile of von Willebrand factor antigen and von Willebrand factor propeptide in an overall TIA and ischaemic stroke population and amongst subtypes.

    Science.gov (United States)

    Tobin, W O; Kinsella, J A; Kavanagh, G F; O'Donnell, J S; McGrath, R T; Tierney, S; Egan, B; Feeley, T M; Coughlan, T; Collins, D R; O'Neill, D; Murphy, Sjx; Lim, S J; Murphy, R P; McCabe, Djh

    2017-04-15

    Von Willebrand factor propeptide (VWF:Ag II) is proposed to be a more sensitive marker of acute endothelial activation than von Willebrand factor antigen (VWF:Ag). Simultaneous data on VWF:Ag and VWF:Ag II profiles are very limited following TIA and ischaemic stroke. In this prospective, observational, case-control study, plasma VWF:Ag and VWF:Ag II levels were quantified in 164 patients≤4weeks of TIA or ischaemic stroke (baseline), and then ≥14days (14d) and ≥90days (90d) later, and compared with those from 27 healthy controls. TIA and stroke subtyping was performed according to the TOAST classification. The relationship between VWF:Ag and VWF:Ag II levels and platelet activation status was assessed. 'Unadjusted' VWF:Ag and VWF:Ag II levels were higher in patients at baseline, 14d and 90d than in controls (p≤0.03). VWF:Ag levels remained higher in patients than controls at baseline (p≤0.03), but not at 14d or 90d after controlling for differences in age or hypertension, and were higher in patients at baseline and 90d after controlling for smoking status (p≤0.04). 'Adjusted' VWF:Ag II levels were not higher in patients than controls after controlling for age, hypertension or smoking (p≥0.1). Patients with symptomatic carotid stenosis (N=46) had higher VWF:Ag and VWF:Ag II levels than controls at all time-points (p≤0.002). There was no significant correlation between platelet activation status and VWF:Ag or VWF:Ag II levels. VWF:Ag and VWF:Ag II levels are increased in an overall TIA and ischaemic stroke population, especially in patients with recently symptomatic carotid stenosis. VWF:Ag II was not superior to VWF:Ag at detecting acute endothelial activation in this cohort and might reflect timing of blood sampling in our study. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. 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.

  7. Aging and ABO blood type influence von Willebrand factor and factor VIII levels through interrelated mechanisms.

    Science.gov (United States)

    Albánez, S; Ogiwara, K; Michels, A; Hopman, W; Grabell, J; James, P; Lillicrap, D

    2016-05-01

    Essentials von Willebrand factor (VWF) and factor VIII (FVIII) levels are modulated by age and ABO status. The effect of aging and ABO blood type on VWF and FVIII was assessed in 207 normal individuals. Aging and ABO blood type showed combined and bidirectional influences on VWF and FVIII levels. Aging and ABO blood type influence VWF levels through both secretion and clearance mechanisms. Background The effect of aging and ABO blood type on plasma levels of von Willebrand factor (VWF) and factor VIII (FVIII) have been widely reported; however, a comprehensive analysis of their combined effect has not been performed and the mechanisms responsible for the age-related changes have not been determined. Objectives To assess the influence of aging and ABO blood type on VWF and FVIII levels, and to evaluate the contribution of VWF secretion and clearance to the age-related changes. Methods A cross-sectional observational study was performed in a cohort of 207 normal individuals, whose levels of VWF, FVIII, VWF propeptide (VWFpp), VWFpp/VWF:Ag ratio and blood type A antigen content on VWF (A-VWF) were quantified. Results Aging and ABO blood type exerted interrelated effects on VWF and FVIII plasma levels, because the age-related increase in both proteins was significantly higher in type non-O individuals (β = 0.011 vs. 0.005). This increase with age in non-O subjects drove the differences between blood types in VWF levels, as the mean difference increased from 0.13 U/mL in the young to 0.57 U/mL in the old. Moreover, A-VWF was associated with both VWF antigen (β = 0.29; 95% confidence interval [CI], 0.09, 0.50) and VWF clearance (β = -0.15; 95% CI, -0.25, -0.06). We also documented an effect of ABO blood type on VWF secretion with aging, as old individuals with blood type non-O showed higher levels of VWFpp (mean difference 0.29 U/mL). Conclusions Aging and ABO blood type have an interrelated effect on VWF and FVIII levels, where the effect of one is significantly

  8. 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 V...

  9. Dynamics of von Willebrand factor reactivity in sickle cell disease during vaso-occlusive crisis and steady state

    NARCIS (Netherlands)

    Sins, J. W.R.; Schimmel, Marein; Luken, Brenda M.; Nur, Erfan; Zeerleder, S.; van Tuijn, Charlotte F. J.; Brandjes, Dees P. M.; Kopatz, W. F.; Urbanus, R. T.; Meijers, Joost C. M.; Biemond, B. J.; Fijnvandraat, K.

    2017-01-01

    Essentials The role of von Willebrand Factor (VWF) in the pathophysiology of sickle cell disease is unclear. We assessed markers of VWF during admission for vaso-occlusive crisis (VOC) and steady state. VWF reactivity was higher during VOC and was associated with inflammation and neutrophil

  10. Expression of von Willebrand factor and caldesmon in the placental tissues of pregnancies complicated with intrauterine growth restriction.

    Science.gov (United States)

    Göksever Çelik, Hale; Uhri, Mehmet; Yildirim, Gökhan

    2017-11-02

    The decreased placental perfusion is the underlying reason for intrauterine growth restriction that in turn leads to reduced placental perfusion and ischemia. However, there are several issues to be understood in the pathophysiology of intrauterine growth restriction. We aimed to study whether any compensatory response in placental vascular bed occur in pregnancies complicated with intrauterine growth restriction by the immunohistochemical staining of von Willebrand factor and caldesmon in placental tissues. A total of 103 pregnant women was enrolled in the study including 50 patients who were complicated with IUGR and 50 uncomplicated control patients. The study was designed in a prospective manner. All placentas were also stained with von Willebrand factor and caldesmon monoclonal kits. The immunohistochemical staining of von Willebrand factor and caldesmon expressions in placental tissues were different between normal and intrauterine growth restriction group. The percentages of 2+ and 3+ von Willebrand factor expression were higher in the intrauterine growth restriction group comparing with the normal group, although the difference was not statistically significant. The intensity of caldesmon expression was significantly lower in the intrauterine growth restriction group in comparison with the normal group (p intrauterine growth restriction which is a hypoxic condition. But newly formed vessels are immature and not strong enough. Our study is important to clarify the pathophysiology and placental compensatory responses in intrauterine growth restriction.

  11. Regulation of plasma von Willebrand factor [version 1; referees: 3 approved

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    Karl C Desch

    2018-01-01

    Full Text Available Von Willebrand factor (VWF is a multimeric plasma glycoprotein that plays a central role in the initiation of blood coagulation. Through interactions between its specific functional domains, the vascular wall, coagulation factor VIII, and platelet receptors, VWF maintains hemostasis by binding to platelets and delivering factor VIII to the sites of vascular injury. In the healthy human population, plasma VWF levels vary widely. The important role of VWF is illustrated by individuals at the extremes of the normal distribution of plasma VWF concentrations where individuals with low VWF levels are more likely to present with mucocutaneous bleeding. Conversely, people with high VWF levels are at higher risk for venous thromboembolic disease, stroke, and coronary artery disease. This report will summarize recent advances in our understanding of environmental influences and the genetic control of VWF plasma variation in healthy and symptomatic populations and will also highlight the unanswered questions that are currently driving this field of study.

  12. The Molecular Genetics of von Willebrand Disease

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    Ergül Berber

    2012-12-01

    Full Text Available Quantitative and/or qualitative deficiency of von Willebrand factor (vWF is associated with the most common inherited bleeding disease von Willebrand disease (vWD. vWD is a complex disease with clinical and genetic heterogeneity. Incomplete penetrance and variable expression due to genetic and environmental factors contribute to its complexity. vWD also has a complex molecular pathogenesis. Some vWF gene mutations are associated with the affected vWF biosynthesis and multimerization, whereas others are associated with increased clearance and functional impairment. Moreover, in addition to a particular mutation, type O blood may result in the more severe phenotype. The present review aimed to provide a summary of the current literature on the molecular genetics of vWD.

  13. The molecular genetics of von Willebrand disease.

    Science.gov (United States)

    Berber, Ergül

    2012-12-01

    Quantitative and/or qualitative deficiency of von Willebrand factor (vWF) is associated with the most common inherited bleeding disease von Willebrand disease (vWD). vWD is a complex disease with clinical and genetic heterogeneity. Incomplete penetrance and variable expression due to genetic and environmental factors contribute to its complexity. vWD also has a complex molecular pathogenesis. Some vWF gene mutations are associated with the affected vWF biosynthesis and multimerization, whereas others are associated with increased clearance and functional impairment. Moreover, in addition to a particular mutation, type O blood may result in the more severe phenotype. The present review aimed to provide a summary of the current literature on the molecular genetics of vWD. None declared.

  14. Increased active von Willebrand factor during disease development in the aging diabetic patient population.

    Science.gov (United States)

    Chen, Shuang Feng; Xia, Zuo Li; Han, Ji Ju; Wang, Yi Ting; Wang, Ji Yue; Pan, Shao Dong; Wu, Ya Ping; Zhang, Bin; Li, Guang Yao; Du, Jing Wei; Gao, Hen Qiang; de Groot, Philip G; de Laat, Bas; Hollestelle, Martine J

    2013-02-01

    Type 2 diabetes is known to cause endothelial activation resulting in the secretion of von Willebrand factor (VWF). We have shown that levels of VWF in a glycoprotein Ib-binding conformation are increased in specific clinical settings. The aim of the current study is to investigate whether active VWF levels increase during aging and the development of diabetes within the population of patients suffering from type 2 diabetes. Patients and controls were divided into two groups based on age: older and younger than 60 years of age. VWF antigen, VWF propeptide, VWF activation factor and total active VWF were measured. Patients older than 60 years of age had increased levels of total active VWF, VWF activation factor and VWF propeptide compared to younger patients and controls. All measured VWF parameters were associated with age in diabetic patients. Total active VWF and VWF propeptide correlated with the period of being diagnosed with diabetes. Regression analyses showed that especially the VWF activation factor was strongly associated with diabetes in patients older than 60 years of age. In conclusion, we found that the conformation of VWF could be involved in the disease process of diabetes and that the VWF in a glycoprotein Ib-binding conformation could play a role as risk marker during the development of diabetes in combination with an increase in age. Our study shows that the active quality of VWF was more important than the quantity.

  15. The structure of the TFIIH p34 subunit reveals a von Willebrand factor A like fold.

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    Dominik R Schmitt

    Full Text Available RNA polymerase II dependent transcription and nucleotide excision repair are mediated by a multifaceted interplay of subunits within the general transcription factor II H (TFIIH. A better understanding of the molecular structure of TFIIH is the key to unravel the mechanism of action of this versatile protein complex within these vital cellular processes. The importance of this complex becomes further evident in the context of severe diseases like xeroderma pigmentosum, Cockayne's syndrome and trichothiodystrophy, that arise from single point mutations in TFIIH subunits. Here we describe the structure of the p34 subunit of the TFIIH complex from the eukaryotic thermophilic fungus Chaetomium thermophilum. The structure revealed that p34 contains a von Willebrand Factor A (vWA like domain, a fold which is generally known to be involved in protein-protein interactions. Within TFIIH p34 strongly interacts with p44, a positive regulator of the helicase XPD. Putative protein-protein interfaces are analyzed and possible binding sites for the p34-p44 interaction suggested.

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

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    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

  17. Taq I polymorphism in the 5' region of the von Willebrand Factor (vWF) gene

    Energy Technology Data Exchange (ETDEWEB)

    Lavergne, J M; Bahnak, B R; Assouline, Z; Pietu, G; Kerbiriou-Nabias, D; Meulien, P; Pavirani, A; Meyer, D

    1988-03-25

    pvWFIPC8 is a 2.28 Kb partial cDNA clone for human von Willebrand factor (vWF) isolated from a human lung cDNA library and inserted into the EcoRI site of pUC9. The sequence includes the last 1330 nucleotides that encode for vWF propeptide and 950 nucleotides that encode for mature vWF. Taq I (TCGA) identifies plural invariant bands and two variant bands with alleles at 2.3 (Al) and 1.0 (A2). The frequency was determined in 33 unrelated European and North American caucasians. The extreme 3' region of pvWFIPC8 corresponds to the 5' boundary of an area that could possibly hybridize with similar sequences on human chromosome 22. The 5' 1.74 Kb portion of pvWFIPC8 generated by Bam HI digestion that corresponds to sequences only on chromosome 12 also demonstrates the polymorphism. Co-dominant segregation was demonstrated in 6 families of 48 individuals.

  18. Von Willebrand Factor as a Novel Player in Valvular Heart Disease: From Bench to Valve Replacement.

    Science.gov (United States)

    Gragnano, Felice; Crisci, Mario; Bigazzi, Maurizio Cappelli; Bianchi, Renatomaria; Sperlongano, Simona; Natale, Francesco; Fimiani, Fabio; Concilio, Claudia; Cesaro, Arturo; Pariggiano, Ivana; Diana, Vincenzo; Limongelli, Giuseppe; Cirillo, Plinio; Russo, Mariagiovanna; Golia, Enrica; Calabrò, Paolo

    2018-02-01

    von Willebrand Factor (vWF) is a well-known mediator of hemostasis and vascular inflammation. Its dynamic modulation in the bloodstream, according to hemodynamic conditions, makes it an appealing biomarker in patients with valvular heart disease (VHD). Recent studies highlight the close connection between vWF and VHD, with possible implications in the pathogenesis of VHD, promoting valve aging and calcification or favoring the development of infective endocarditis. Moreover, vWF has been recently proposed as a new diagnostic and prognostic tool in patients with valve stenosis or regurgitation, showing a strict correlation with severity of valve disease, outcome, and bleeding (Heyde syndrome). A novel role for vWF is also emerging in patients undergoing percutaneous or surgical valve repair/replacement to select and stratify patients, evaluate periprocedural bleeding risk, and detect procedural complications. We also report our single-center experience, suggesting, for the first time, possible clinical implications for vWF in percutaneous mitral valve repair (MitraClip). This review summarizes recent advances in the role of vWF in VHD with an updated overview going from bench to operating room.

  19. Pattern of von Willebrand factor in hypertensive patients in Lagos, Nigeria

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    Ann Abiola Ogbenna

    2018-01-01

    Full Text Available Background and Objective: Hypertension alone accounts for 50% of death from stroke. Its ability to induce endothelial dysfunction leads to the release of von Willebrand factor (vWF, a prothrombotic glycoprotein. The increase secretion of vWF may account for increased risk of stroke in hypertensive disorders. This study aimed to determine the vWF:antigen (Ag levels among hypertensives and assess its relationship with blood pressure and occurrence of stroke in hypertensives. Subjects and Methods: The study included 66 hypertensives, 33 with stroke (HS and 33 without stroke (HWS, and 33 controls matched for age and sex. Structured questionnaires were used to obtain biodata and clinical information. Blood pressure was taken after 15 min rest. Four milliliters of blood was collected into 0.1 ml of 3.2% trisodium citrate for vWF:Ag assay and 4 ml into K-ethylenediaminetetraacetic acid anticoagulant bottles for blood grouping and erythrocyte sedimentation rate. Data were analyzed with SPSS version 21. Confidence interval was set at 95%. Results: Mean vWF:Ag levels were significantly higher in hypertensives compared with nonhypertensives (P = 0.005, but no statistically significant difference was observed between HS and HWS (P = 0.874. A positive correlation of vWF with systolic blood pressure was observed (r = 0.335, P = 0.001. Conclusion: Our study suggests that higher systolic blood pressure is associated with higher levels of endothelial activation and release of vWF.

  20. Thrombomodulin and von Willebrand factor as markers of radiation-induced endothelial injury

    International Nuclear Information System (INIS)

    Zhou Quansheng; Zhao Yimin; Li Peixia; Bai Xia; Ruan Changgeng

    1992-02-01

    Cultured confluent human umbilical vein endothelial cells were irradiated in vitro by 60 Co-gamma ray at doses from 0 to 50 Gy. After irradiation Thrombomodulin in the supernatants of endothelial cell culture medium, on the surface of the cells and within the cells was measured at different times over six days. At twenty-four hours after irradiation, an increase in the release of Thrombomodulin and von Willebrand factor from irradiated endothelial cells and an increase in the number of molecules and the activity of Thrombomodulin on the surface of the cells were observed, which were radiation-dose dependent. The capacity of the cells to produce and release Thrombomodulin was decreased from two to six days after exposure to 60 Co-gamma ray. Our data indicate that radiation can injure endothelial cells and that Thrombomodulin may be as a marker of radiation-induced endothelial cell injury. The relationship between dysfunction of irradiated endothelial cells and the pathological mechanisms of acute radiation sickness are discussed

  1. Neuropeptide delivery to the brain: a von Willebrand factor signal peptide to direct neuropeptide secretion

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    de Backer Marijke WA

    2010-08-01

    Full Text Available Abstract Background Multiple neuropeptides, sometimes with opposing functions, can be produced from one precursor gene. To study the roles of the different neuropeptides encoded by one large precursor we developed a method to overexpress minigenes and establish local secretion. Results We fused the signal peptide from the Von Willebrand Factor (VWF to a furin site followed by a processed form of the Agouti related protein (AgRP, AgRP83-132 or α-melanocyte stimulating hormone. In vitro, these minigenes were secreted and biologically active. Additionally, the proteins of the minigenes were not transported into projections of primary neurons, thereby ensuring local release. In vivo administration of VWF-AgRP83-132 , using an adeno-associated viral vector as a delivery vehicle, into the paraventricular hypothalamus increased body weight and food intake of these rats compared to rats which received a control vector. Conclusions This study demonstrated that removal of the N-terminal part of full length AgRP and addition of a VWF signal peptide is a successful strategy to deliver neuropeptide minigenes to the brain and establish local neuropeptide secretion.

  2. Elevated plasma factor VIII enhances venous thrombus formation in rabbits: contribution of factor XI, von Willebrand factor and tissue factor.

    Science.gov (United States)

    Sugita, Chihiro; Yamashita, Atsushi; Matsuura, Yunosuke; Iwakiri, Takashi; Okuyama, Nozomi; Matsuda, Shuntaro; Matsumoto, Tomoko; Inoue, Osamu; Harada, Aya; Kitazawa, Takehisa; Hattori, Kunihiro; Shima, Midori; Asada, Yujiro

    2013-07-01

    Elevated plasma levels of factor VIII (FVIII) are associated with increased risk of deep venous thrombosis. The aim of this study is to elucidate how elevated FVIII levels affect venous thrombus formation and propagation in vivo. We examined rabbit plasma FVIII activity, plasma thrombin generation, whole blood coagulation, platelet aggregation and venous wall thrombogenicity before and one hour after an intravenous infusion of recombinant human FVIII (rFVIII). Venous thrombus induced by the endothelial denudation of rabbit jugular veins was histologically assessed. Thrombus propagation was evaluated as indocyanine green fluorescence intensity. Argatroban, a thrombin inhibitor, and neutralised antibodies for tissue factor (TF), factor XI (FXI), and von Willebrand factor (VWF) were infused before or after thrombus induction to investigate their effects on venous thrombus formation or propagation. Recombinant FVIII (100 IU/kg) increased rabbit plasma FVIII activity two-fold and significantly enhanced whole blood coagulation and total plasma thrombin generation, but did not affect initial thrombin generation time, platelet aggregation and venous wall thrombogenicity. The rFVIII infusion also increased the size of venous thrombus 1 hour after thrombus induction. Argatroban and the antibodies for TF, FXI or VWF inhibited such enhanced thrombus formation and all except TF suppressed thrombus propagation. In conclusion, elevated plasma FVIII levels enhance venous thrombus formation and propagation. Excess thrombin generation by FXI and VWF-mediated FVIII recruitment appear to contribute to the growth of FVIII-driven venous thrombus.

  3. Fluid-phase immunoradiometric assay for the detection of qualitative abnormalities of factor VIII/von Willebrand factor in variants of von Willebrand's disease

    International Nuclear Information System (INIS)

    Girma, J.P.; Ardaillou, N.; Meyer, D.; Lavergne, J.M.; Larrieu, M.J.

    1979-01-01

    Antigenic reactivity of F.VIII/WF in variants of von Willebrand's disease (vWd) was studied with both fluid-phase and solid-phase immunoradiometric assays. Two different (rabbit and goat) 125 I-labeled specific antibodies against purified F.VIII/WF were used in both their divalent (lgG) and their monovalent (Fab fragment) forms. Dose-response curves obtained by reacting a constant amount of antibody with serial dilutions of plasmas from normal or homozygous vWd demonstrated the specificity of the test. The accuracy was significantly higher with 125 I-Fab fragments of goat anti-F.VIII/WF antiserum than intact goat lgG or rabbit lgG or Fab fragments. The significant decrease of the slope of the dose-response curves obtained with plasma from variants of vWd has been interpreted as due to the presence of abnormal F.VIII/WF molecules with decreased antigenic reactivity. A similar anomaly was found in cryosupernatant prepared from normal plasma, paralleling similarities demonstrated between variants of vWd and cryosupernatant. Results of experiments performed by reacting constant plasma dilutions from control or variants of vWd and varying concentrations of anti-F.VIII/WF Fab fragments (rabbit or goat) confirmed the decreased antigenic reactivity of variant F.VIII/WF

  4. Complex changes in von Willebrand factor-associated parameters are acquired during uncomplicated pregnancy.

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    Danielle N Drury-Stewart

    Full Text Available The coagulation protein von Willebrand Factor (VWF is known to be elevated in pregnancy. However, the timing and nature of changes in VWF and associated parameters throughout pregnancy are not well understood.To better understand the changes in VWF provoked by pregnancy, we studied VWF-associated parameters in samples collected over the course of healthy pregnancies.We measured VWF antigen (VWF:Ag, VWF propeptide (VWFpp, Factor VIII (FVIII, and ADAMTS13 activity in samples collected from 46 women during pregnancy and at non-pregnant baseline. We also characterized pregnant vs. non-pregnant VWF multimer structure in 21 pregnancies, and performed isoelectric focusing (IEF of VWF in two pregnancies which had samples from multiple trimesters.VWF:Ag and FVIII levels were significantly increased during pregnancy. ADAMTS13 activity was unchanged. VWFpp levels increased much later in pregnancy than VWF:Ag, resulting in a progressive decrease in VWFpp:Ag ratios. FVIII:VWF ratios also decreased in pregnancy. Most pregnancies exhibited a clear loss of larger VWF multimers and altered VWF triplet structure. Further evidence of acquired VWF qualitative changes in pregnancy was found in progressive, reversible shifts in VWF IEF patterns over gestation.These data support a new view of pregnancy in which VWF can acquire qualitative changes associated with advancing gestational age. Modeling supports a scenario in which both increased VWF production and doubling of the VWF half-life would account for the data observed. We propose that gestation induces a prolongation in VWF survival, which likely contributes to increased total VWF levels and altered VWF structure.

  5. Unconjugated Bilirubin Inhibits Proteolytic Cleavage of von Willebrand Factor by ADAMTS13 Protease

    Science.gov (United States)

    Lu, Rui-Nan; Yang, Shangbin; Wu, Haifeng M.; Zheng, X. Long

    2015-01-01

    Summary Background Bilirubin is a yellow breakdown product of heme catabolism. Increased serum levels of unconjugated bilirubin are conditions commonly seen in premature neonates and adults with acute hemolysis including thrombotic microangiopathy. Previous studies have shown that unconjugated bilirubin lowers plasma ADAMTS13 activity, but the mechanism is not fully understood. Objectives The study is to determine whether unconjugated bilirubin directly inhibits the cleavage of von Willebrand factor (VWF) and its analogs by ADAMTS13. Methods Fluorogenic, SELDI-TOF mass spectrometric assay, and Western blotting analyses were employed to address this question. Results Unconjugated bilirubin inhibits the cleavage of F485-rVWF73-H, D633-rVWF73-H, and GST-rVWF71-11K by ADAMTS13 in a concentration-dependent manner with a half-maximal inhibitory concentration (IC50) of ~13 μM, ~70 μM, and ~17 μM, respectively. Unconjugated bilirubin also dose-dependently inhibits the cleavage of multimeric VWF by ADAMTS13 under denaturing conditions. The inhibitory activity of bilirubin on the cleavage of D633-rVWF73-H and multimeric VWF, but not F485-rVWF73-H, was eliminated after incubation with bilirubin oxidase that converts bilirubin to biliverdin. Furthermore, plasma ADAMTS13 activity in patients with hyperbilirubinemia is lower prior to than after treatment with bilirubin oxidase. Conclusions unconjugated bilirubin directly inhibits ADAMTS13’s ability to cleave both peptidyl and native VWF substrates in addition to its interference with certain fluorogenic assays. Our findings may help proper interpretation of ADAMTS13 results under pathological conditions. Whether elevated serum unconjugated bilirubin has an adverse effect in vivo remains to be determined in our future study. PMID:25782102

  6. Increased metastatic potential of tumor cells in von Willebrand factor-deficient mice.

    Science.gov (United States)

    Terraube, V; Pendu, R; Baruch, D; Gebbink, M F B G; Meyer, D; Lenting, P J; Denis, C V

    2006-03-01

    The key role played by von Willebrand factor (VWF) in platelet adhesion suggests a potential implication in various pathologies, where this process is involved. In cancer metastasis development, tumor cells interact with platelets and the vessel wall to extravasate from the circulation. As a potential mediator of platelet-tumor cell interactions, VWF could influence this early step of tumor spread and therefore play a role in cancer metastasis. To investigate whether VWF is involved in metastasis development. In a first step, we characterized the interaction between murine melanoma cells B16-BL6 and VWF in vitro. In a second step, an experimental metastasis model was used to compare the formation of pulmonary metastatic foci in C57BL/6 wild-type and VWF-null mice following the injection of B16-BL6 cells or Lewis lung carcinoma cells. In vitro adhesion assays revealed that VWF is able to promote a dose-dependent adhesion of B16-BL6 cells via its Arg-Gly-Asp (RGD) sequence. In the experimental metastasis model, we found a significant increase in the number of pulmonary metastatic foci in VWF-null mice compared with the wild-type mice, a phenotype that could be corrected by restoring VWF plasma levels. We also showed that increased survival of the tumor cells in the lungs during the first 24 h in the absence of VWF was the cause of this increased metastasis. These findings suggest that VWF plays a protective role against tumor cell dissemination in vivo. Underlying mechanisms remain to be investigated.

  7. 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.

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

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    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.

  9. Diagnosis and management of von Willebrand disease: guidelines for primary care.

    Science.gov (United States)

    Yawn, Barbara; Nichols, William L; Rick, Margaret E

    2009-12-01

    Von Willebrand disease is an inherited condition characterized by deficiency of von Willebrand factor, which is essential in hemostasis. The National Heart, Lung, and Blood Institute has released new evidence-based guidelines for the diagnosis and management of the disease. There are three major subtypes of von Willebrand disease, classified as partial quantitative deficiency (low levels) of von Willebrand factor (type 1), qualitative deficiency (type 2), or virtually complete deficiency (type 3). Diagnosis is usually made by reviewing the patient's personal and family history of bleeding and by clinical evaluation for more common reasons for bleeding, supplemented with laboratory tests. Assessment may be used to determine bleeding risk before surgery and other invasive procedures, and to diagnose reasons for unexplained hemorrhaging. Von Willebrand factor levels of 30 IU per dL or lower are required for the definite diagnosis of inherited von Willebrand disease. Persons with levels of 30 to 50 IU per dL may not have the disease, but may need agents to increase von Willebrand factor levels during invasive procedures or childbirth. Treatment is tailored to the subtype of the disease: increasing plasma concentration of von Willebrand factor by releasing endogenous stores with desmopressin or replacing nonexistent or ineffective von Willebrand factor by using human plasma-derived, viral-inactivated concentrates; treatment is often combined with hemostatic agents that have mechanisms other than increasing von Willebrand factor. Regular prophylaxis is seldom required, and treatment is initiated before planned invasive procedures or in response to bleeding.

  10. Detection of von Willebrand factor and tissue factor in platelets-fibrin rich coronary thrombi in acute myocardial infarction.

    Science.gov (United States)

    Yamashita, Atsushi; Sumi, Takahiro; Goto, Shinya; Hoshiba, Yasunari; Nishihira, Kensaku; Kawamoto, Riichirou; Hatakeyama, Kinta; Date, Haruhiko; Imamura, Takuroh; Ogawa, Hisao; Asada, Yujiro

    2006-01-01

    The rapid closure of coronary arteries due to occlusive thrombi is the major cause of acute myocardial infarction. However, the mechanisms of coronary thrombus formation have not been elucidated. We immunohistochemically assessed the localizations and their changes over time of glycoprotein IIb/IIIa, fibrin, von Willebrand factor (vWF), and tissue factor (TF), after the onset of chest pain (platelets, fibrin, vWF, and TF from the early phase of onset, and glycoprotein IIb/IIIa and fibrin were closely associated with vWF and TF, respectively. vWF and/or TF may contribute to occlusive thrombus formation and be novel therapeutic candidates for treating patients with coronary thrombosis.

  11. Exercise-induced shear stress is associated with changes in plasma von Willebrand factor in older humans

    OpenAIRE

    Gonzales, Joaquin U.; Thistlethwaite, John R.; Thompson, Benjamin C.; Scheuermann, Barry W.

    2009-01-01

    Shear stress is the frictional force of blood against the endothelium, a stimulus for endothelial activation and the release of von Willebrand factor (vWF). This study tested the hypothesis that the increase in shear stress associated with exercise correlates with plasma vWF. Young (n = 14, 25.7 ± 5.4 y) and older (n = 13, 65.6 ± 10.7 y) individuals participated in 30 min of dynamic handgrip exercise at a moderate intensity. Brachial artery diameter and blood flow were measured using ultrasou...

  12. Comparative analysis of von Willebrand factor profiles after implantation of left ventricular assist device and total artificial heart.

    Science.gov (United States)

    Reich, H J; Morgan, J; Arabia, F; Czer, L; Moriguchi, J; Ramzy, D; Esmailian, F; Lam, L; Dunhill, J; Volod, O

    2017-08-01

    Essentials Bleeding is a major source of morbidity during mechanical circulatory support. von Willebrand factor (VWF) multimer loss may contribute to bleeding. Different patterns of VWF multimer loss were seen with the two device types. This is the first report of total artificial heart associated VWF multimer loss. Background Bleeding remains a challenge during mechanical circulatory support and underlying mechanisms are incompletely understood. Functional von Willebrand factor (VWF) impairment because of loss of high-molecular-weight multimers (MWMs) produces acquired von Willebrand disease (VWD) after left ventricular assist device (LVAD). Little is known about VWF multimers with total artificial hearts (TAHs). Here, VWF profiles with LVADs and TAHs are compared using a VWD panel. Methods VWD evaluations for patients with LVAD or TAH (2013-14) were retrospectively analyzed and included: VWF activity (ristocetin cofactor, VWF:RCo), VWF antigen (VWF:Ag), ratio of VWF:RCo to VWF:Ag, and quantitative VWF multimeric analysis. Results Twelve patients with LVADs and 12 with TAHs underwent VWD evaluation. All had either normal (47.8%) or elevated (52.2%) VWF:RCo, normal (26.1%) or elevated (73.9%) VWF:Ag and 50.0% were disproportional (ratio ≤ 0.7). Multimeric analysis showed abnormal patterns in all patients with LVADs: seven with high MWM loss; five with highest MWM loss. With TAH, 10/12 patients had abnormal patterns: all with highest MWM loss. High MWM loss correlated with presence of LVAD and highest MWM loss with TAH. Increased low MWMs were detected in 22/24. Conclusion Using VWF multimeric analysis, abnormalities after LVAD or TAH were detected that would be missed with measurements of VWF level alone: loss of high MWM predominantly in LVAD, loss of highest MWM in TAH, and elevated levels of low MWM in both. This is the first study to describe TAH-associated highest MWM loss, which may contribute to bleeding. © 2017 International Society on Thrombosis and

  13. Translational Medicine Advances in von Willebrand Disease

    Science.gov (United States)

    Lillicrap, David

    2014-01-01

    Following the recognition of von Willebrand disease (VWD) in 1926 and the cloning of the gene for von Willebrand factor (VWF) in 1985, significant advances have been made in our fundamental knowledge of both the disease and the protein. Some of this new knowledge has also begun to impact the clinical management of VWD. First, the progressive increase in our understanding of the molecular genetic basis of VWD has resulted in rational applications of molecular testing to complement the current range of phenotypic tests for VWD. These molecular genetic strategies are most effectively directed at the prenatal diagnosis of type 3 VWD and confirmatory testing for types 2B and 2N disease. In contrast, the use of molecular testing to clarify the diagnosis of type 1 VWD is of marginal benefit, at best. In terms of VWD therapies, a new recombinant VWF concentrate has recently completed successful clinical trials and is now awaiting more widespread application. There have even been some pre-clinical successes with VWF gene transfer although the clinical rationale for this therapeutic strategy needs careful consideration. Much more remains to be learnt about the biology of VWF and further translational advances for the enhancement of VWD care will inevitably be realized. PMID:23809112

  14. Von Willebrand protein binds to extracellular matrices independently of collagen.

    OpenAIRE

    Wagner, D D; Urban-Pickering, M; Marder, V J

    1984-01-01

    Von Willebrand protein is present in the extracellular matrix of endothelial cells where it codistributes with fibronectin and types IV and V collagen. Bacterial collagenase digestion of endothelial cells removed fibrillar collagen, but the pattern of fibronectin and of von Willebrand protein remained undisturbed. Exogenous von Willebrand protein bound to matrices of different cells, whether rich or poor in collagen. von Willebrand protein also decorated the matrix of cells grown in the prese...

  15. 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 MEASURE...

  16. Acquired von Willebrand syndrome: A rare disorder of heterogeneous etiology

    Directory of Open Access Journals (Sweden)

    P Kasatkar

    2013-01-01

    Full Text Available Context: Acquired von Willebrand syndrome (AVWS is a rare bleeding disorder that mimics the inherited form of von Willebrand disease (VWD in terms of laboratory findings and clinical presentation. Aims: To study the etiology of acquired VWD. Settings and Design: The patients referred from various hospitals in and out of Mumbai were included in the study. Materials and Methods: Six patients with AVWS diagnosed at this center over the last 10 years were analyzed against 171 patients with inherited VWD. The differential diagnosis of AVWS was made based on reduced levels of von Willebrand antigen and von Willebrand ristocetin cofactor, decrease in ristocetin induced platelet aggregation, absence of correction in mixing studies with no prior history of bleeding problems and a negative family history for bleeding disorders. Results: In three patients, the disease was associated with systematic lupus erythematosus, out of which one was also associated with Kikuchi lymphadenitis and second with autoimmune hemolytic anemia. Fourth case was associated with hypothyroidism and fifth was a case of dermatitis and vitiligo. The last patient was a case of hemophilia A with Burkitts lymphoma, who developed autoantibodies to von Willebrand factor. Except two patients, all other patients responded to immune suppressive therapy with corticosteroids, while the patient with hypothyroidism responded to oral thyroxine. Conclusion: AVWS is a rare condition and may often be missed or diagnosed as inherited disease associated with heterogeneous disease conditions.

  17. 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

    The purpose of this prospective study was to investigate platelet function using in vitro tests based on both high and low shear rates and von Willebrand factor (vWf) multimeric composition in dogs with cardiac disease and turbulent high-velocity blood flow. Client-owned asymptomatic, untreated d...

  18. The impact of statin therapy on plasma levels of von Willebrand factor antigen. Systematic review and meta-analysis of randomised placebo-controlled trials

    NARCIS (Netherlands)

    Sahebkar, Amirhossein; Serban, Corina; Ursoniu, Sorin; Mikhailidis, Dimitri P.; Undas, Anetta; Lip, Gregory Y. H.; Bittner, Vera; Ray, Kausik; Watts, Gerald F.; Hovingh, G. Kees; Rysz, Jacek; Kastelein, John J. P.; Banach, Maciej

    2016-01-01

    Increased plasma levels of von Willebrand factor antigen (vWF:Ag) are associated with high risk of coronary artery disease. The effect of statin therapy on vWF:Ag levels remains uncertain. Therefore the aim of this meta-analysis was to evaluate the effect of statin therapy on vWF:Ag Levels. A

  19. Binding of von Willebrand factor to collagen type III: role of specific amino acids in the collagen binding domain of vWF and effects of neighboring domains

    NARCIS (Netherlands)

    van der Plas, R. M.; Gomes, L.; Marquart, J. A.; Vink, T.; Meijers, J. C.; de Groot, P. G.; Sixma, J. J.; Huizinga, E. G.

    2000-01-01

    Binding of von Willebrand Factor (vWF) to sites of vascular injury is the first step of hemostasis. Collagen types I and III are important binding sites for vWF. We have previously determined the three-dimensional structure of the collagen binding A3 domain of vWF (Huizinga et al., Structure 1997;

  20. Von willebrand factor cleaving protease activity in the physiopathology of microangiopathic disorders Detección de la actividad de la proteasa que cliva al factor von Willebrand en la patofisiología de las microangiopatías

    Directory of Open Access Journals (Sweden)

    M. M. Amaral

    2003-04-01

    Full Text Available The von Willebrand factor cleaving protease (VWFCP modulates the von Willebrand factor (VWF multimeric size in normal plasma. VWFCP activity levels are decreased in different physiological and pathologic situations. Different techniques have been developed to unfold the purified VWF (perfusion at high shear rate, dialysis against urea in nitrocellulose filters, to detect the VWFCP activity on it (multimeric analysis of VWF, collagen binding to VWF assay and to use the patient plasma both as the source of the enzyme and substrate. In this paper we compared the above mentioned methods with new ones: normal plasma dialyzed on membranes instead of purified VWF, dialysis of the samples against urea in tubing instead of nitrocellulose filters, and sonicated plasma to remove the endogenous VWF. The perfusion assay and detection by multimeric analysis showed a limit of detection (25% of VWFCP activity. Dialysis against urea in both supports and detection by multimeric analysis, showed a better limit of detection (3%, but the recovery of the samples was not as efficient in nitrocellulose filters as it was in tubing. The detection by collagen binding to VWF has more advantages because it allows to analyze more samples than the multimeric analysis does in the same assay. The dialysis of plasma by membranes to obtain the source of exogenous VWF requires no complex equipment. The method, which uses patient plasma as the source of the enzyme and substrate, was inapplicable in our experience because the values could not be interpolated in the reference curve.La proteasa que cliva al factor von Willebrand (VWFCP controla el tamaño multimérico del factor von Willebrand (VWF en plasma normal. Sus niveles se encuentran disminuidos en diferentes situaciones fisiológicas y patológicas. Diferentes técnicas se desarrollaron para desplegar al VWF purificado (perfusión a alta fuerza de cizallamiento, diálisis contra urea en filtros de nitrocelulosa, para detectar

  1. An immunoradiometric assay for procoagulant factor VIII antigen: results in haemophilia, von Willebrand's disease and fetal plasma and serum

    International Nuclear Information System (INIS)

    Peake, I.R.; Bloom, A.L.; Giddings, J.C.; Ludlam, C.A.

    1979-01-01

    An immunoradiometric assay (IRMA) has been developed based on the inhibitor which arose in a polytransfused severe haemophiliac. The two-site IRMA measured antigens closely associated with the procoagulant parts of the factor VIII complex, which are termed FVIIIC antigens or FVIIICAG. FVIIICAG was present in normal plasma and also, at a slightly lower concentration, in normal serum. In 37 patients with haemophilia A, 36 had FVIIICAG levels of less than 10% of the normal plasma pool. In patients with von Willebrand's disease the levels of FVIIIC and FVIIICAG were in good agreement, both before and after treatment with cryoprecipitate or DDAVP. FVIIICAG was relatively stable in plasma at 37 0 C and could also be detected in cord and fetal serum. The assay is of potential value for detecting reduced levels of factor VIII, for carrier detection and for the prenatal diagnosis of haemophilia. (author)

  2. Testosterone and acute stress are associated with fibrinogen and von Willebrand factor in African men: the SABPA study.

    Science.gov (United States)

    Malan, Nicolaas T; von Känel, Roland; Schutte, Alta E; Huisman, Hugo W; Schutte, Rudolph; Smith, Wayne; Mels, Carina M; Kruger, Ruan; Meiring, Muriel; van Rooyen, Johannes M; Malan, Leoné

    2013-10-12

    Low testosterone, acute and chronic stress and hypercoagulation are all associated with hypertension and hypertension-related diseases. The interaction between these factors and future risk for coronary artery disease in Africans has not been fully elucidated. In this study, associations of testosterone, acute cardiovascular and coagulation stress responses with fibrinogen and von Willebrand factor in African and Caucasian men in a South African cohort were investigated. Cardiovascular variables were studied by means of beat-to-beat and ambulatory blood pressure monitoring. Fasting serum-, salivary testosterone and citrate coagulation markers were obtained from venous blood samples. Acute mental stress responses were evoked with the Stroop test. The African group demonstrated a higher cardiovascular risk compared to Caucasian men with elevated blood pressure, low-grade inflammation, chronic hyperglycemia (HbA1c), lower testosterone levels, and elevated von Willebrand factor (VWF) and fibrinogen levels. Blunted testosterone acute mental stress responses were demonstrated in African males. In multiple regression analyses, higher circulating levels of fibrinogen and VWF in Africans were associated with a low T environment (R(2) 0.24-0.28; p≤0.01), but only circulating fibrinogen in Caucasians. Regarding endothelial function, a low testosterone environment and a profile of augmented α-adrenergic acute mental stress responses (diastolic BP, D-dimer and testosterone) were associated with circulating VWF levels in Africans (Adj R(2) 0.24; pstress, salivary testosterone, D-dimer and vascular responses existed in African males in their association with circulating VWF but no interdependence of the independent variables occurred with fibrinogen levels. © 2013.

  3. Establishment and characterization of a new and stable collagen-binding assay for the assessment of von Willebrand factor activity

    Science.gov (United States)

    Ni, Y; Nesrallah, J; Agnew, M; Geske, F J; Favaloro, E J

    2013-01-01

    Introduction Laboratory diagnosis of von Willebrand disease (VWD) requires determination of both von Willebrand factor (VWF) protein levels and activity. Current VWF activity tests include the ristocetin cofactor assay and the collagen-binding assay (VWF:CB). The goal of this investigation is to characterize a new collagen-binding assay and to determine its effectiveness in identifying VWD. Methods Analytical studies were carried out to characterize the performance of a new VWF:CB ELISA. Additionally, samples from a normal population were tested as were well-characterized type 1 and type 2 VWD samples. Results Repeatability and within-laboratory precision studies resulted in coefficients of variation (CVs) of ≤11%. A linear range of 1–354% (0.01–3.54 IU/mL) was determined, along with a limit of detection and a lower limit of quantitation of 1.6% and 4.0% (0.016 and 0.04 IU/mL), respectively. Samples tested from apparently healthy individuals resulted in a normal range of 54–217% (0.54–2.17 IU/mL). Known VWD type 1 and type 2 samples were also analyzed by the ELISA, with 99% of samples having VWF:CB below the normal reference range and an estimated 96% sensitivity and 87% specificity using a VWF collagen-binding/antigen cutoff ratio of 0.50. Conclusion This new VWF:CB ELISA provides an accurate measure of collagen-binding activity that aids in the diagnosis and differentiation of type 1 from type 2 VWD. PMID:23107512

  4. Relationship between ABO blood groups and von Willebrand factor, ADAMTS13 and factor VIII in patients undergoing hemodialysis.

    Science.gov (United States)

    Rios, Danyelle R A; Fernandes, Ana Paula; Figueiredo, Roberta C; Guimarães, Daniela A M; Ferreira, Cláudia N; Simões E Silva, Ana C; Carvalho, Maria G; Gomes, Karina B; Dusse, Luci Maria Sant' Ana

    2012-05-01

    Several studies have demonstrated that non-O blood groups subjects present an increased VTE risk as compared to those carrying O blood group. The aim of this study was to investigate the ABO blood groups influence on factor VIII (FVIII) activity, von Willebrand factor (VWF), and ADAMTS13 plasma levels in patients undergoing hemodialysis (HD). Patients undergoing HD (N=195) and 80 healthy subjects (control group) were eligible for this cross-sectional study. The ABO blood group phenotyping was performed by the reverse technique. FVIII activity was measured through coagulometric method, and VWF and ADAMTS13 antigens were assessed by ELISA. FVIII activity and VWF levels were significantly higher and ADAMTS13 levels was decreased in HD patients, as compared to healthy subjects (P blood groups showed a significant increase in FVIII activity (P = 0.001) and VWF levels (P blood group. However, no significant difference was observed in ADAMTS13 levels (P = 0.767). In the control group, increased in FVIII activity (P = 0.001) and VWF levels (P = 0.002) and decreased in ADAMTS13 levels (P = 0.005) were observed in subjects carrying non-O blood groups as compared to carriers of O blood group.Our data confirmed that ABO blood group is an important risk factor for increased procoagulant factors in plasma, as FVIII and VWF. Admitting the possible role of kidneys in ADAMTS13 synthesis or on its metabolism, HD patients were not able to increase ADAMTS13 levels in order to compensate the increase of VWF levels mediated by ABO blood groups. Considering that non-O blood groups constitute a risk factor for thrombosis, it is reasonable to admit that A, B and AB HD patients need a careful and continuous follow-up in order to minimize thrombotic events.

  5. Association of ABO blood groups with von Willebrand factor, factor VIII and ADAMTS-13 in patients with lung cancer.

    Science.gov (United States)

    Liu, Xia; Chen, Xiaogang; Yang, Jiezuan; Guo, Renyong

    2017-09-01

    Coagulative and fibrinolytic disorders appear to be associated with the development of lung cancer. The aim of the present study was to determine plasma levels of von Willebrand factor (VWF) and a disintegrin and metalloproteinase with a thrombospondin type 1 motif 13 (ADAMTS-13), and factor VIII (FVIII) activity, in association with O and non-O blood groups in patients with lung cancer. Plasma levels of VWF and ADAMTS-13, and FVIII activity were measured in 115 patients with lung cancer and 98 healthy subjects. Phenotyping of the ABO blood groups was also performed for the two groups. Significantly increased VWF levels and FVIII activity, as well as significantly decreased ADAMTS-13 levels, were observed in patients with distant metastasis as compared with those without distant metastasis and the healthy controls. Plasma VWF levels and FVIII activity were significantly increased in subjects with non-O type blood compared with those with type O blood in the two groups. However, a significant decrease in ADAMTS-13 levels was observed only in the control group among those with non-O type blood, compared with those with type O blood. The results of the present study indicate that increased VWF and decreased ADAMTS-13 levels facilitate the invasiveness and metastasis of lung cancer. Non-O blood groups constitute a risk factor for increased VWF and FVIII in plasma. Continued monitoring of VWF and ADAMTS-13 levels, and of FVIII activity in patients with lung cancer with distinct blood groups may help to minimize the incidence of thrombotic events and improve assessment of disease progression.

  6. 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.

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

    Science.gov (United States)

    van Loon, Janine E; Sonneveld, Michelle A H; Praet, Stephan F E; de Maat, Moniek P M; Leebeek, Frank W G

    2014-01-01

    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] (pexercise (median increase 43% and 12%, both pexercise (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.

  8. DEEP VEIN THROMBOSIS IN PATIENT WITH VON WILLEBRAND DISEASE

    Directory of Open Access Journals (Sweden)

    V. A. Elykomov

    2016-01-01

    Full Text Available Objective: to identify the possible factors of thrombogenic risk and ways of its prevention in patients with von Willebrand disease.Case description. Patient X., 42 years old, who suffers from von Willebrand disease type 3 with 5-years of age. Asked on reception to the traumatologist in the polyclinic of the Regional Hospital with pain in the left hip joint. Recommended planned operative treatment in the Altai Regional Clinical Hospital. Preoperative preparation included the infusion of concentrate of von Willebrand factor and coagulation factor VIII. Operation – cement total arthroplasty of the left hip joint. In the postoperative period analgesic treatment, elastic compression of the lower extremities, iron supplements, also conducted infusion of concentrate of von Willebrand factor and coagulation factor VIII for 20 days and thromboprophylactic with dabigatran. On the 3rd day after the operation the patient revealed deep vein thrombosis of the femoral segment (floating clot.Results. The patient was operated for emergency indications in the Department of endovascular surgery – installation of venous cava filter “Volan”. Dabigatran is cancelled, appointed clexane for 3 months. In our clinical example the patient lacked risk factors of pulmonary embolism as obesity, age, smoking, prolonged immobilization, estrogen therapy. Overdose of factor VIII were not observed – the level of factor did not exceed 135 % on transfusions. At the same time, the patient was found polymorphisms in the genes ITGA2, FGB, MTHFR, MTR – heterozygote, MTRR – mutant homozygote, which may indicate the genetic factors of thrombogenic risk. Also a significant risk factor was massive surgical intervention (total hip replacement. Despite preventive measures (elastic compression, thromboprophylactic dabigatran, early activation we cannot to avoid thrombotic complications.Conclusion. This article presents a case demonstrating a thrombotic complication in patients

  9. The thrombospondin-1 N700S polymorphism is associated with early myocardial infarction without altering von Willebrand factor multimer size.

    Science.gov (United States)

    Zwicker, Jeffrey I; Peyvandi, Flora; Palla, Roberta; Lombardi, Rossana; Canciani, Maria Teresa; Cairo, Andrea; Ardissino, Diego; Bernardinelli, Luisa; Bauer, Kenneth A; Lawler, Jack; Mannucci, Pier

    2006-08-15

    The N700S polymorphism of thrombospondin-1 (TSP-1) has been identified as a potential genetic risk factor for myocardial infarction (MI). In a large case-control study of 1425 individuals who survived a myocardial infarction prior to age 45, the N700S polymorphism was a significant risk factor for myocardial infarction in both homozygous (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.1-3.3, P = .01) and heterozygous carriers of the S700 allele (OR 1.4, 95% CI 1.1-3.3, P = .01). TSP-1 has been shown to reduce von Willebrand factor (VWF) multimer size, and the domain responsible for VWF-reducing activity has been localized to the calcium-binding C-terminal sequence. As the N700S polymorphism was previously shown to alter the function of this domain, we investigated whether the altered VWF-reducing activity of TSP-1 underlies the observed prothrombotic phenotype. The TSP1 N700S polymorphism did not influence VWF multimer size in patients homozygous for either allele nor was there a significant reduction of VWF multimer size following incubation with recombinant N700S fragments or platelet-derived TSP-1.

  10. Von Willebrand's disease in the German shepherd dog : clinical communication

    Directory of Open Access Journals (Sweden)

    R.G. Lobetti

    2000-07-01

    Full Text Available Two litters of Germanshepherd dogs were evaluated for a haemorrhagic tendency that was characterised by excessive bleeding from the umbilicus at birth, haemorrhage and haematoma formation at vaccination, excessive bruising, and lameness due to haemarthrosis. Platelet counts, clotting times and Von Willebrand's factor (VWF assays were assessed in all dogs. Factor VIII determination was performed in 1 puppy and its parents. Based on the clotting times and VWF assay, 6 puppies (4 male and 2 female showed type I Von Willebrand's disease (VWD, 5 (4 male and 1 female possible type II VWD, and 4 were unaffected. One puppy with possible type II VWD had very low factor VIII activity; its sire had a normal factor activity, whereas the dam was in the low-normal range. This article reports type I and possible type II VWD in 2 related litters of German shepherd dogs, the latter being rare in German shepherd dogs.

  11. 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.

  12. Factor VIII and von Willebrand factor co-delivery by endothelial cells

    NARCIS (Netherlands)

    Bouwens, E.A.M.|info:eu-repo/dai/nl/314061894

    2011-01-01

    A defect in coagulation factor VIII (FVIII) results in the inherited bleeding disorder hemophilia A. Current treatment of hemophilia A is hampered by the need of frequent administration of costly FVIII products. Therefore gene therapy is an attractive alternative for protein replacement to treat

  13. Analysis of von Willebrand factor A domain-related protein (WARP polymorphism in temperate and tropical Plasmodium vivax field isolates

    Directory of Open Access Journals (Sweden)

    Zakeri Sedigheh

    2009-06-01

    Full Text Available Abstract Background The identification of key molecules is crucial for designing transmission-blocking vaccines (TBVs, among those ookinete micronemal proteins are candidate as a general class of malaria transmission-blocking targets. Here, the sequence analysis of an extra-cellular malaria protein expressed in ookinetes, named von Willebrand factor A domain-related protein (WARP, is reported in 91 Plasmodium vivax isolates circulating in different regions of Iran. Methods Clinical isolates were collected from north temperate and southern tropical regions in Iran. Primers have been designed based on P. vivax sequence (ctg_6991 which amplified a fragment of about 1044 bp with no size variation. Direct sequencing of PCR products was used to determine polymorphism and further bioinformatics analysis in P. vivax sexual stage antigen, pvwarp. Results Amplified pvwarp gene showed 886 bp in size, with no intron. BLAST analysis showed a similarity of 98–100% to P. vivax Sal-I strain; however, Iranian isolates had 2 bp mismatches in 247 and 531 positions that were non-synonymous substitution [T (ACT to A (GCT and R (AGA to S (AGT] in comparison with the Sal-I sequence. Conclusion This study presents the first large-scale survey on pvwarp polymorphism in the world, which provides baseline data for developing WARP-based TBV against both temperate and tropical P. vivax isolates.

  14. Exercise-induced shear stress is associated with changes in plasma von Willebrand factor in older humans.

    Science.gov (United States)

    Gonzales, Joaquin U; Thistlethwaite, John R; Thompson, Benjamin C; Scheuermann, Barry W

    2009-07-01

    Shear stress is the frictional force of blood against the endothelium, a stimulus for endothelial activation and the release of von Willebrand factor (vWF). This study tested the hypothesis that the increase in shear stress associated with exercise correlates with plasma vWF. Young (n = 14, 25.7 +/- 5.4 years) and older (n = 13, 65.6 +/- 10.7 years) individuals participated in 30 min of dynamic handgrip exercise at a moderate intensity. Brachial artery diameter and blood flow were measured using ultrasound Doppler and blood samples were collected before, immediately after, and following 30 min of recovery from exercise with plasma levels of vWF. Plasma levels of vWF increased (P exercise. The change in plasma vWF was linearly correlated with the increase in shear stress during exercise in older individuals (post-exercise: r = 0.78, 30 min recovery: r = 0.77, P < 0.01), but no association was found in the young individuals. These changes in plasma levels of vWF in humans suggest that aging influences endothelial activation and hemostasis.

  15. Space and Time Resolved Detection of Platelet Activation and von Willebrand Factor Conformational Changes in Deep Suspensions.

    Science.gov (United States)

    Biasetti, Jacopo; Sampath, Kaushik; Cortez, Angel; Azhir, Alaleh; Gilad, Assaf A; Kickler, Thomas S; Obser, Tobias; Ruggeri, Zaverio M; Katz, Joseph

    2017-01-01

    Tracking cells and proteins' phenotypic changes in deep suspensions is critical for the direct imaging of blood-related phenomena in in vitro replica of cardiovascular systems and blood-handling devices. This paper introduces fluorescence imaging techniques for space and time resolved detection of platelet activation, von Willebrand factor (VWF) conformational changes, and VWF-platelet interaction in deep suspensions. Labeled VWF, platelets, and VWF-platelet strands are suspended in deep cuvettes, illuminated, and imaged with a high-sensitivity EM-CCD camera, allowing detection using an exposure time of 1 ms. In-house postprocessing algorithms identify and track the moving signals. Recombinant VWF-eGFP (rVWF-eGFP) and VWF labeled with an FITC-conjugated polyclonal antibody are employed. Anti-P-Selectin FITC-conjugated antibodies and the calcium-sensitive probe Indo-1 are used to detect activated platelets. A positive correlation between the mean number of platelets detected per image and the percentage of activated platelets determined through flow cytometry is obtained, validating the technique. An increase in the number of rVWF-eGFP signals upon exposure to shear stress demonstrates the technique's ability to detect breakup of self-aggregates. VWF globular and unfolded conformations and self-aggregation are also observed. The ability to track the size and shape of VWF-platelet strands in space and time provides means to detect pro- and antithrombotic processes.

  16. von Willebrand factor as a novel noninvasive predictor of portal hypertension and esophageal varices in hepatitis B patients with cirrhosis.

    Science.gov (United States)

    Wu, Hao; Yan, Shiping; Wang, Guangchuan; Cui, Shaobo; Zhang, Chunqing; Zhu, Qiang

    2015-01-01

    At present, there is no perfect noninvasive method to assess portal hypertension and esophageal varices. Early predicting esophageal varices can provide evidence for managing cirrhotic patients. We aimed to further investigate von Willebrand factor (vWF) as a noninvasive predictor of portal hypertension, especially of esophageal varices. A total of 60 hepatitis B patients with cirrhosis and 45 healthy subjects were enrolled in this study. Levels of six markers were examined. All patients underwent hepatic venous pressure gradient (HVPG) and esophagogastroduodenoscopy. We evaluated the performance of six factors for diagnosis of portal hypertension and esophageal varices. The vWF levels in liver tissues were observed by immunohistochemistry. Correlations between the level of vWF in liver tissues and HVPG and between levels of vWF in tissues and plasma were examined. Cutoff values of plasma vWF (1510.5 mU/mL and 1701 mU/mL) showed high positive predictive value (PPV, 90.2% and 87.5%) in predicting clinically significant portal hypertension and severe portal hypertension. Cutoff values of vWF (1414 mU/ml and 1990 mU/mL, PPV 90.3% and 86.3%, respectively) were provided to detect the presence and degree of esophageal varices. Linear correlations were observed between levels of vWF in liver tissues and HVPG (r(2) = 0.552, p portal hypertension and esophageal varices in hepatitis B patients with cirrhosis. Increased levels of vWF in liver tissues may induce the elevated plasma vWF levels, but molecular mechanism is needed for further study.

  17. Von Willebrand's disease: case report and review of literature.

    Science.gov (United States)

    Echahdi, Hanae; El Hasbaoui, Brahim; El Khorassani, Mohamed; Agadr, Aomar; Khattab, Mohamed

    2017-01-01

    Von Willebrand Disease (VWD) is the most common human inherited bleeding disorder due to a defect of Von Willebrand Factor (VWF), which a glycoprotein crucial for platelet adhesion to the subendothelium after vascular injury. VWD include quantitative defects of VWF, either partial (type 1 with VWF levels < 50 IU/dL) or virtually total (type 3 with undetectable VWF levels) and also qualitative defects of VWF (type 2 variants with discrepant antigenic and functional VWF levels). The most bleeding forms of VWD usually do not concern type 1 patients with the mildest VWF defects (VWF levels between 30 and 50IU/dL). Von willebrand factor is a complex multimeric protein with two functions: it forms a bridge between the platelets and areas of vascular damage and it binds to and stabilizes factor VIII, which is necessary for the clotting cascade. By taking a clinical history of bleeding (mucocutaneous bleeding symptoms suggestive of a primary haemostatic disorder, a quantitative or qualitative abnormality of VWF is possible) it is important to think about VWD and to make the appropriate diagnosis. If the VWD is suspected diagnostic tests should include an activated partial thromboplastin time, bleeding time, factor VIII: C Ristocetin cofactor and vWF antigen. Additional testing of ristocetin induced plattlet adhesion (RIPA) the multimeric structure and collagen binding test and genanalysis allow diagnosing the different types of von. Willebrand Disease. The treatment of choice in mild forms is the synthetic agent desmopressin. In patients with severe type 1, type 2B, 2N and type 3 or in people who do not response to desmopressin, the appropriate treatment is a factor VIII concentrate that is rich of VWF. We report a case of infant in 27-month-old boy who had been referred due to haemorrhagic shock. His birth histories, his familie's social history and developmental milestones were unremarkable. He was born at full term with no antenatal or perinatal complications. Prior to

  18. Elevated Factor VIII and von Willebrand Factor Levels Predict Unfavorable Outcome in Stroke Patients Treated with Intravenous Thrombolysis

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    Noémi Klára Tóth

    2018-01-01

    Full Text Available IntroductionPlasma factor VIII (FVIII and von Willebrand factor (VWF levels have been associated with the rate and severity of arterial thrombus formation and have been linked to outcomes following thrombolytic therapy in acute myocardial infarction patients. Here, we aimed to investigate FVIII and VWF levels during the course of thrombolysis in acute ischemic stroke (AIS patients and to find out whether they predict long-term outcomes.Materials and methodsStudy population included 131 consecutive AIS patients (median age: 69 years, 60.3% men who underwent i.v. thrombolysis with recombinant tissue plasminogen activator (rt-PA. Blood samples were taken on admission, 1 and 24 h after rt-PA administration to measure FVIII activity and VWF antigen levels. Neurological deficit of patients was determined according to the National Institutes of Health Stroke Scale (NIHSS. ASPECT scores were assessed using computer tomography images taken before and 24 h after thrombolysis. Intracranial hemorrhage was classified according to the European Cooperative Acute Stroke Study (ECASS II criteria. Long-term functional outcome was determined at 90 days after the event by the modified Rankin scale (mRS.ResultsVWF levels on admission were significantly elevated in case of more severe AIS [median and IQR values: NIHSS <6:189.6% (151.9–233.2%; NIHSS 6–16: 199.6% (176.4–250.8%; NIHSS >16: 247.8% (199.9–353.8%, p = 0.013]; similar, but non-significant trend was observed for FVIII levels. FVIII and VWF levels correlated well on admission (r = 0.748, p < 0.001 but no significant correlation was found immediately after thrombolysis (r = 0.093, p = 0.299, most probably due to plasmin-mediated FVIII degradation. VWF levels at all investigated occasions and FVIII activity before and 24 h after thrombolysis were associated with worse 24 h post-lysis ASPECT scores. In a binary backward logistic regression analysis including age, gender

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

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    Ramesh Tati

    2017-02-01

    Full Text Available 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. Von Willebrand factor indicates bacterial translocation, inflammation, and procoagulant imbalance and predicts complications independently of portal hypertension severity.

    Science.gov (United States)

    Mandorfer, M; Schwabl, P; Paternostro, R; Pomej, K; Bauer, D; Thaler, J; Ay, C; Quehenberger, P; Fritzer-Szekeres, M; Peck-Radosavljevic, M; Trauner, M; Reiberger, T; Ferlitsch, A

    2018-04-01

    Elevated plasma von Willebrand factor antigen (vWF) has been shown to indicate the presence of clinically significant portal hypertension, and thus, predicts the development of clinical events in patients with cirrhosis. To investigate the impact of bacterial translocation and inflammation on vWF, as well as the association between vWF and procoagulant imbalance. Moreover, we assessed whether vWF predicts complications of cirrhosis, independent of the severity of portal hypertension. Our study population comprised 225 patients with hepatic venous pressure gradient (HVPG) ≥ 10 mm Hg without active bacterial infections or hepatocellular carcinoma. vWF correlated with markers of bacterial translocation (lipopolysaccharide-binding protein [LBP; ρ = 0.201; P = 0.021]), inflammation (interleukin 6 [IL-6; ρ = 0.426; P protein [CRP; ρ = 0.249; P protein C ratio; ρ = 0.507; P model for transplant-free mortality. Finally, the independent prognostic value of vWF/CRP groups for mortality was confirmed by competing risk analysis. Our results demonstrate that vWF is not only a marker of portal hypertension but also independently linked to bacterial translocation, inflammation and procoagulant imbalance, which might explain its HVPG-independent association with most clinical events. Prognostic groups based on vWF/CRP efficiently discriminate between patients with a poor 5-year survival and patients with a favourable prognosis. © 2018 John Wiley & Sons Ltd.

  1. Nordic Haemophilia Council's practical guidelines on diagnosis and management of von Willebrand disease

    DEFF Research Database (Denmark)

    Lassila, Riitta; Holme, Pål André; Landorph, Andrea

    2011-01-01

    Von Willebrand disease (VWD) is the most common inherited bleeding disorder characterized by spontaneous or tissue injury-related, mostly mucocutaneous, bleeding events. VWD affects both males and females and is caused by quantitative or qualitative deficiency of Von Willebrand factor. The diagno......Von Willebrand disease (VWD) is the most common inherited bleeding disorder characterized by spontaneous or tissue injury-related, mostly mucocutaneous, bleeding events. VWD affects both males and females and is caused by quantitative or qualitative deficiency of Von Willebrand factor...... subtyping may also be problematic. This article summarizes the guidelines of the Nordic Haemophilia Council (NHC), which are intended to serve as a practical tool and provide the standards for diagnosing and treating VWD patients. The complete Nordic Guidelines on VWD are available at the NHC Web site (http://nordhemophilia.org)....

  2. A pilot study of homocyst(e)ine levels in essential hypertension: relationship to von Willebrand factor, an index of endothelial damage.

    Science.gov (United States)

    Lip, G Y; Edmunds, E; Martin, S C; Jones, A F; Blann, A D; Beevers, D G

    2001-07-01

    An interaction between homocyst(e)ine and the endothelium in hypertensive patients may promote thrombogenesis and atherogenesis, leading to adverse cardiovascular events. We hypothesized that homocyst(e)ine levels are abnormal in patients with essential hypertension, and that this may be related to an adverse effect on the vascular endothelium. Accordingly, we compared plasma levels of homocyst(e)ine and von Willebrand factor (marking endothelial damage) in 83 patients (43 men; mean age 54 +/- standard deviation 15.9 years) with essential hypertension (> 160/90 mm Hg), with levels in 25 healthy normotensive controls (13 men; mean age 56+/-11.8 years). Baseline levels of the markers and other clinical indices were then related to adverse cardiovascular events at follow-up. Plasma homocyst(e)ine (P = .0001) and von Willebrand factor (P = .031) levels were significantly higher in hypertensives compared to controls. After a mean follow-up of 76 patients for 45 months (range, 1 to 66 months), 17 subjects experienced an end point of either cardiovascular death (n = 10) or adverse cardiovascular event (n = 7). Comparing these 17 with the 59 free of an end point, the former were older (P = .0002) and had a longer duration of known hypertension (P = .018). There was a nonsignificant trend toward higher median plasma homocyst(e)ine levels in the patients sustaining a vascular end point (P = .07). In this pilot study, we suggest that essential hypertension may be associated with increased plasma homocyst(e)ine levels, but that this amino acid is unrelated to endothelial damage (von Willebrand factor), clinical indices, or prognosis.

  3. Elevated levels of plasma von Willebrand factor and the risk of macro- and microvascular disease in type 2 diabetic patients with microalbuminuria

    DEFF Research Database (Denmark)

    Gaede, P; Vedel, P; Parving, H H

    2001-01-01

    BACKGROUND: The purpose of this study was to examine the concept suggesting that microalbuminuria in combination with high levels of plasma von Willebrand factor is a stronger predictor for cardiovascular disease and microvascular complications than microalbuminuria alone in type 2 diabetic...... patients. METHODS: One hundred and sixty patients with type 2 diabetes mellitus and persistent microalbuminuria were followed for an average of 3.8 (SD 0.3) years. 70% of the patients were treated with angiotensin converting enzyme (ACE)-inhibitors. Patients in this subanalysis were divided into two groups...... nephropathy or progression in diabetic retinopathy than microalbuminuria alone in patients with type 2 diabetes and persistent microalbuminuria....

  4. Associations Between Diabetic Retinopathy and Plasma Levels of High-sensitive C-reactive Protein or Von Willebrand Factor in Long-term Type 1 Diabetic Patients

    DEFF Research Database (Denmark)

    Laursen, Jonas Vejvad Nørskov; Hoffmann, Stine Skovbo; Green, Anders

    2013-01-01

    .27 IU/ml (0.79-2.07 IU/ml), respectively. No or minimal DR (ETDRS-levels 10-20) was found in 16.4%, mild DR (ETDRS-level 35) in 19.4%, moderate DR (ETDRS-levels 43-47) in 11.0%, and 53.2% had proliferative diabetic retinopathy (PDR) corresponding to ETDRS-level 60 or more. In an age- and sex......Purpose: To evaluate high-sensitive C-reactive protein (hs-CRP) and von Willebrand factor as possible plasma markers of diabetic retinopathy in a population-based cohort of type 1 diabetic patients. Materials and Methods: This was a cross-sectional study of 201 type 1 diabetic patients from...... a population-based cohort from Fyn County, Denmark. Plasma levels of hs-CRP and von Willebrand factor antigen were measured and related to the level of diabetic retinopathy (DR) as evaluated by dilated nine-field 45 degree monoscopic fundus photos captured by Topcon TRC-NWS6 and graded according to the Early...

  5. Prophylaxis escalation in severe von Willebrand disease: A prospective study from the von Willebrand Disease Prophylaxis Network

    NARCIS (Netherlands)

    T.C. Abshire (Thomas Calvin); J. Cox-Gill; C.L. Kempton; F.W.G. Leebeek (Frank); M. Carcao (M.); P. Kouides (P.); S. Donfield (S.); E. Berntorp

    2015-01-01

    textabstractBackground: Treatment of mucosal bleeding (epistaxis, gastrointestinal bleeding, and menorrhagia) and joint bleeding remains problematic in clinically severe von Willebrand disease (VWD). Patients are often unresponsive to treatment (e.g. desmopressin or antifibrinolytic therapy) and may

  6. von Willebrand Factor Test

    Science.gov (United States)

    ... with infections, inflammation, trauma, and with physical and emotional stressors. They are also increased with pregnancy and with the use of estrogen medications such as oral contraceptives. Is there anything else I should know? A ...

  7. Changes in bleeding patterns in von Willebrand disease after institution of long-term replacement therapy : results from the von Willebrand Disease Prophylaxis Network

    NARCIS (Netherlands)

    Holm, Elena; Abshire, Thomas C; Bowen, Joel; Álvarez, M Teresa; Bolton-Maggs, Paula; Carcao, Manuel; Federici, Augusto B; Gill, Joan Cox; Halimeh, Susan; Kempton, Christine; Key, Nigel S; Kouides, Peter; Lail, Alice; Landorph, Andrea; Leebeek, Frank; Makris, Michael; Mannucci, Pier; Mauser-Bunschoten, Eveline P; Nugent, Diane; Valentino, Leonard A; Winikoff, Rochelle; Berntorp, Erik

    Clinically, the leading symptom in von Willebrand disease (VWD) is bleeding, chiefly of mucosal type, for example, epistaxis, gingival, or gastrointestinal bleeding, and menorrhagia. In severe forms of VWD with secondary deficiency of factor VIII, spontaneous joint bleeding, resembling that observed

  8. Influences of ABO blood group, age and gender on plasma coagulation factor VIII, fibrinogen, von Willebrand factor and ADAMTS13 levels in a Chinese population.

    Science.gov (United States)

    Wang, Zongkui; Dou, Miaomiao; Du, Xi; Ma, Li; Sun, Pan; Cao, Haijun; Ye, Shengliang; Jiang, Peng; Liu, Fengjuan; Lin, Fangzhao; Zhang, Rong; Li, Changqing

    2017-01-01

    ABO blood group is a hereditary factor of plasma levels of coagulation factor VIII (FVIII) and von Willebrand factor (VWF). Age and gender have been shown to influence FVIII, VWF, fibrinogen (Fbg), and ADAMTS13 (A disintegrin and metalloprotease with thrombospondin type 1 motif, 13). We investigated the effects of ABO type, age, and gender on plasma levels of FVIII, Fbg, VWF, and ADAMTS13 in a Chinese population. A total of 290 healthy volunteers were eligible for this study. ABO blood group was determined by indirect technique. FVIII:C and Fbg were measured by clotting assays. VWF antigen (VWF:Ag), collagen-binding activity (VWF:CBA), and ADAMTS13 antigen were assessed by ELISA, whereas VWF ristocetin cofactor activity (VWF:Rcof) was performed by agglutination of platelets with ristocetin. Mean FVIII:C and VWF levels (VWF:Ag, VWF:CBA, and VWF:Rcof) were significantly higher in non-O than in O type subjects ( p  blood group, age, and gender showed different effects on plasma levels of FVIII:C, Fbg, VWF:Ag, VWF:CBA, VWF:Rcof, and ADAMTS13 antigen. These new data on a Chinese population are quite helpful to compare with other ethnic groups.

  9. 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.

  10. Use of routine histopathology and factor VIII-related antigen/von Willebrand factor immunohistochemistry to differentiate primary hemangiosarcoma of bone from telangiectatic osteosarcoma in 54 dogs.

    Science.gov (United States)

    Giuffrida, M A; Bacon, N J; Kamstock, D A

    2017-12-01

    Hemangiosarcoma (HSA) of bone and telangiectatic osteosarcoma (tOSA) can appear similar histologically, but differ in histogenesis (malignant endothelial cells versus osteoblasts), and may warrant different treatments. Immunohistochemistry (IHC) for endothelial cell marker factor VIII-related antigen/von Willebrand factor (FVIII-RAg/vWF) is a well-documented ancillary test to confirm HSA diagnoses in soft tissues, but its use in osseous HSA is rarely described. Archived samples of 54 primary appendicular bone tumours previously diagnosed as HSA or tOSA were evaluated using combination routine histopathology (RHP) and IHC. Approximately 20% of tumours were reclassified on the basis of FVIII-RAg/vWF immunoreactivity, typically from an original diagnosis of tOSA to a reclassified diagnosis of HSA. No sample with tumour osteoid clearly identified on RHP was immunopositive for FVIII-RAg/vWF. RHP alone was specific but not sensitive for diagnosis of HSA, compared with combination RHP and IHC. Routine histopathological evaluation in combination with FVIII-RAg/vWF IHC can help differentiate canine primary appendicular HSA from tOSA. © 2016 John Wiley & Sons Ltd.

  11. Descripción de un inmunoensayo enzimático que reconoce anticuerpos anti-factor VIII/von Willebrand obtenidos a partir de hibridomas múridos Description of an enzime immunoassay that recognizes anti-factor VIII/von Willebrand antibodies obtained from murine hybridomas

    Directory of Open Access Journals (Sweden)

    Renée González Sampedro

    1999-04-01

    Full Text Available Se describe un inmunoensayo enzimático (ELISA que detecta anticuerpos anti-Factor-VIII/von Willebrand (FVIII/vW, con una relación de enlace > 5, que permite reconocer dichos anticuerpos tempranamente en los cultivos de hibridomas múridos. Para la adsorción de las placas del inmunoensayo se utilizaron preparados semipurificados de FVIII/vW obtenidos en Cuba. Se inmunizaron ratones Balb/c con la finalidad de generar los anticuerpos monoclonales detectados por este ELISA. Se obtuvo un clon con crecimiento estable y varios subclones positivos por el ELISA con actividad biológica específica de anticuerpos inhibidores de FVIIIAn enzime immunoassay (ELISA that detects anti-Factor VIII/von Willebrand (FVIII/vw antibodies with a binding relationship > 5 that allows the early recognition of such antibodies in the cultures of murine hybridomas is described. Semipurified preparations of FVIII/vw obtained in Cuba were used for the adsorption of the immunoassay plates. Balb/c mice were immunized in order to generate the monoclonal antibodies detected by this ELISA. A clone with stable growth and several positive subclones were obtained by ELISA with specific biological activity of FVIII-inhibiting antibodies

  12. Von-Willebrand Disease Presenting as Intractable Epistaxis after Nasal Polypectomy

    Directory of Open Access Journals (Sweden)

    Jeong Jin Park

    2014-01-01

    Full Text Available Von-Willebrand disease (VWD is one of the platelet dysfunction disorders that results from a deficiency of Von-Willebrand factor, which is essential for hemostasis. VWD patients typically have normal laboratory results on screening for bleeding disorders. To suspect and diagnose VWD, a careful review of past medical history and laboratory tests is critical. A 59-year-old male patient presented with intractable nasal bleeding after nasal polypectomy. The bleeding was controlled by platelet transfusion, and he was later diagnosed with VWD.

  13. Molecular cloning of the human gene for von Willebrand factor and identification of the transcription initiation site

    International Nuclear Information System (INIS)

    Collins, C.J.; Underdahl, J.P.; Levene, R.B.; Ravera, C.P.; Morin, M.J.; Dombalagian, M.J.; Ricca, G.; Livingston, D.M.; Lynch, D.C.

    1987-01-01

    A series of overlapping cosmid genomic clones have been isolated that contain the entire coding unit of the human gene for van Willebrand factor (vWf), a major component of the hemostatic system. The cloned segments span ≅ 175 kilobases of human DNA sequence, and hybridization analysis suggest that the vWf coding unit is ≅150 kilobases in length. Within one of these clones, the vWF transcription initiation site has been mapped and a portion of the vWf promoter region has been sequenced, revealing a typical TATA box, a downstream CCAAT box, and a perfect downstream repeat of the 8 base pairs containing the transcription start site. Sequencing of a segment of another genomic clone has revealed the vWF translation termination codon. Where tested, comparative restriction analysis of cloned and chromosomal DNA segments strongly suggests that no major alterations occurred during cloning and that there is only one complete copy of the vWf gene in the human haploid genome. Similar analyses of DNA from vWf-producing endothelial cells and nonexpressing leukocytes suggest that vWf gene expression is not accompanied by gross genomic rearrangements. In addition, there is significant homology of C-terminal coding sequences among the vWf genes of several vertebrate species

  14. Analysis of expression of von Willebrand factor, endothelin-1, vascular endothelial growth factor in Budd-Chiari syndrome with membranous obstruction

    International Nuclear Information System (INIS)

    Han Xinqiang; Zu Maoheng

    2011-01-01

    Objective: To investigate whether the injured vascular endothelial plays an important role in the membranous formation of the inferior vena cava (IVC). Methods: There were 40 cases of membranous obstruction of inferior vena cava (MOVC) in the experimental group and 40 arrhythmic inpatients in the control group from affiliated hospital. There were 23 males and 17 females in experimental group while 21 males and 19 females in control group, and the age were (41.8±8.1) yrs and (43.2± 7.6) yrs respectively. All of them had no anti-coagulation (clotting) drug history and smoking history, no hypertension, no pulmonary artery hypertension, no coronary heart disease, no valvular disease, no myocardial disease, no blood disease, no diabetes, no connective tissue disease and malignancy, and liver and renal function must be normal. And then the serum concentrations of von Willebrand factor (vWF), endothelin-l (ET-1), vascular endothelial growth factor (VEGF) were defined by enzyme-linked immunosorbent assay (ELISA). The results were analyzed with independent sample t-test. Results: In MOVC patients, the serum concentrations of vWF, ET-1 and VEGF [(37.8±6.6) μg/L, (31.9± 6.0) ng/L, (20.84±5.78) μg/L] were higher than those in the control group [(3.3±1.3) μg/L, (5.3±1.8) ng/L, (4.2±1.2) μg/L. t=32.65, 26.70, 17.85, P<0.01, respectively]. Conclusions: The injury of vascular endothelium is related to the formation of membrane in the IVC. (authors)

  15. Comparative study on collagen-binding enzyme-linked immunosorbent assay and ristocetin cofactor activity assays for detection of functional activity of von Willebrand factor.

    Science.gov (United States)

    Turecek, Peter L; Siekmann, Jürgen; Schwarz, Hans Peter

    2002-04-01

    For more than two decades, the ristocetin cofactor (RCo) assay, which measures the von Willebrand factor (vWF)-mediated agglutination of platelets in the presence of the antibiotic ristocetin, has been the most common method for measuring the functional activity of vWF. There is, however, general agreement among clinical analysts that this method has major practical disadvantages in performance and reproducibility. Today, collagen-binding assays (CBA) based on the enzyme-linked immunosorbent assay (ELISA) technique that measure the interaction of vWF and collagen are an alternative analytic procedure based on a more physiological function than that of the RCo procedure. We used both assay systems in a comparative study to assess the functional activity of vWF in plasma as well as in therapeutic preparations. We measured RCo activities of plasma from healthy donors and patients with different types of von Willebrand disease (vWD) and of vWF as a drug substance in factor (F) VIII/vWF concentrates using both the aggregometric and the macroscopic methods. In addition, we measured collagen-binding activity (vWF:CB) using a recently developed commercially available CBA system. To investigate the relation between the structure and the functional activity of vWF, we isolated vWF species with different numbers of multimers from FVIII/vWF concentrates by affinity chromatography on immobilized heparin. The vWF:RCo and vWF:CB of the different fractions were measured, and the multimeric structure of vWF was analyzed by sodium dodecyl sulfate (SDS) agarose gel electrophoresis. (vWF:CB and vWF:RCo are part of the nomenclature proposed by the International Society on Thrombosis and Hemostasis Scientific and Standardization Committee [ISTH SSC] subcommittee on von Willebrand factor, in Maastricht, Germany, June 16, 2000.) Measurement of functional vWF activity by CBA can be carried out with substantially higher interassay reproducibility than can measurement of RCo. Both assay

  16. 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

  17. Elevated levels of von Willebrand factor and high mobility group box 1 (HMGB1) are associated with disease severity and clinical outcome of scrub typhus.

    Science.gov (United States)

    Chen, Hongliu; Ning, Zong; Qiu, Ying; Liao, Yuanli; Chang, Haihua; Ai, Yuanyuan; Wei, Yinghua; Deng, Yiming; Shen, Ying

    2017-08-01

    This study aimed to investigate whether von Willebrand factor (vWF) and high mobility group box 1 (HMGB1) are associated with the severity and clinical outcome of scrub typhus and to seek novel biomarkers for surveillance and prediction of the prognosis of this infection. Serum concentrations of vWF and HMGB1 were measured twice by ELISA for scrub typhus patients (n=103), once prior to doxycycline therapy and then on day 7 of doxycycline therapy; concentrations were measured once for healthy controls (n=32). Among the total 103 patients enrolled, 38 had disease complicated by multiple organ dysfunction syndrome (MODS). Serum concentrations of vWF and HMGB1 were significantly higher in all the patients than in the healthy controls, both prior to doxycycline treatment and on day 7 of doxycycline treatment (pscrub typhus (area under the curve (AUC)=0.864, p=0.001, and AUC=0.862, p=0.001, respectively). Elevated levels of vWF and HMGB1 are associated with the severity and clinical outcome of scrub typhus. These represent possible new biomarkers for use in the assessment and prognostic prediction of this infection. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  18. Thrombomodulin, von Willebrand factor and E-selectin as plasma markers of endothelial damage/dysfunction and activation in pregnancy induced hypertension.

    Science.gov (United States)

    Nadar, Sunil K; Al Yemeni, Eman; Blann, Andrew D; Lip, Gregory Y H

    2004-01-01

    Endothelial disturbance (whether activation, dysfunction or damage) is a likely pathogenic mechanism in pre-eclampsia and pregnancy-induced hypertension (PIH). We set out to determine which of three plasma markers of endothelial disturbance, indicating endothelial activation (E-selectin) or damage/dysfunction (von Willebrand factor (vWf), soluble thrombomodulin), would provide the best discriminator of PIH compared to normotensive pregnancy. Cross-sectional study of 36 consecutive women with PIH (age 31+/-6 years) and 36 consecutive women with normotensive pregnancies (age 29+/-5 years) of similar parity. Plasma levels of vWf, E-selectin and thrombomodulin were measured using ELISA. As expected, women with PIH had significantly higher levels of plasma vWf (by 19%, p=0.003), E-selectin (by 40%, p<0.001) and thrombomodulin (by 61%, p=0.01) than normotensive women. However, on stepwise multiple regression analysis, only thrombomodulin was an independent significant predictor of the presence of PIH (p=0.023). We conclude that although vWf, E-selectin and thrombomodulin are all raised in PIH, only thrombomodulin was independently associated with PIH. This molecule could potentially be useful in monitoring and in providing clues in aetiology and pathophysiology, and may have implications for the clinical complications associated with PIH.

  19. Characterization of an entomopathogenic fungi target integument protein, Bombyx mori single domain von Willebrand factor type C, in the silkworm, Bombyx mori.

    Science.gov (United States)

    Han, F; Lu, A; Yuan, Y; Huang, W; Beerntsen, B T; Huang, J; Ling, E

    2017-06-01

    The insect cuticle works as the first line of defence to protect insects from pathogenic infections and water evaporation. However, the old cuticle must be shed in order to enter the next developmental stage. During each ecdysis, moulting fluids are produced and secreted into the area among the old and new cuticles. In a previous study, the protein Bombyx mori single domain von Willebrand factor type C (BmSVWC; BGIBMGA011399) was identified in the moulting fluids of Bo. mori and demonstrated to regulate ecdysis. In this study we show that in Bo. mori larvae, BmSVWC primarily locates to the integument (epidermal cells and cuticle), wing discs and head. During the moulting stage, BmSVWC is released into the moulting fluids, and is then produced again by epidermal cells after ecdysis. Fungal infection was shown to decrease the amount of BmSVWC in the cuticle, which indicates that BmSVWC is a target protein of entomopathogenic fungi. Thus, BmSVWC is mainly involved in maintaining the integrity of the integument structure, which serves to protect insects from physical damage and pathogenic infection. © 2017 The Royal Entomological Society.

  20. One-pot preparation of conducting composite containing abundant amino groups on electrode surface for electrochemical detection of von willebrand factor

    Science.gov (United States)

    Wang, Wen; Ma, Chao; Li, Yi; Liu, Baihui; Tan, Liang

    2018-03-01

    A one-pot protocol based on cyclic voltammetric scan was employed to prepare new conducting composite that was abundant in amino groups. The scanning electron microscope, atomic force microscope, X-ray photoelectron spectroscopy and infrared spectrum characterization demonstrate that poly(azure A), gold nanoparticles, chitosan and cysteine were immobilized simultaneously on glassy carbon electrode surface. Von Willebrand factor (vWF) antibody (Ab) was subsequently assembled by using glutaraldehyde to construct the Ab/composite-modified electrode. The capture of vWF could inhibit the charge transfer between the ferri-/ferrocyanide probe and the electrode and exert the negative effect on the electrochemical response of the dye polymer in the conducting composite due to the strong steric hindrance effect. The DPV peak current change before and after the immunoreaction was found to be proportional to the logarithm of the vWF concentration from 0.001 to 100 μg mL-1 with a detection limit of 0.4 ng mL-1. The proposed label-free electrochemical method was employed in the investigation on the release of vWF by oxidation-injured vascular endothelial cells. The experimental results exhibit that the vWF content in growth medium was increased when the oxidation injury of the cells was intensified in the presence of H2O2.

  1. D-dimer, factor VIII and von Willebrand factor predict a non-dipping pattern of blood pressure in hypertensive patients.

    Science.gov (United States)

    Agorasti, Athanasia; Trivellas, Theodoros; Mourvati, Efthimia; Papadopoulos, Vasilios; Tsatalas, Konstantinos; Vargemezis, Vasilios; Passadakis, Ploumis

    2013-06-01

    The aim of this study is to assess whether the haemostatic markers D-dimer, factor VIII (FVIII) and von Willebrand factor (VWF) are predictive of non-dipping status in treated hypertensive patients; so, as easy available laboratory data can predict non-dipping pattern and help with the selection of the patients whom circadian blood pressure should be re-examined. Forty treated hypertensive patients with essential hypertension were included in the study. Twenty-four-hour ambulatory blood pressure monitoring was performed in all patients. Daytime and nocturnal average systolic, diastolic and mean blood pressures were calculated. Patients were characterised as "non-dippers" on the basis of a less than 10 % decline in nocturnal blood pressure (BP); either systolic or diastolic or mean (MAP). D-dimer as marker of fibrinolytic function, FVIII activity and VWF antigen as marker of endothelial dysfunction were measured on plasma. The predictive efficiency was analysed by receiver operating characteristic (ROC) curves. Youden index was used for the estimation of the cut-off points and the associated values for sensitivity and 1-specificity. Plasma levels of D-dimer, FVIII and VWF were significantly higher in non-dippers as compared with dippers, irrespective of the classification used (BP index); all P AUC(ROC) = 0.697, 0.715 and 0.774), FVIII (AUC(ROC) = 0.714, 0.692 and 0.755) and VWF (AUC(ROC) = 0.706, 0.740 and 0.708) in distinguishing non-dipping pattern (systolic, diastolic or mean) in the study population; all P 168 ng/ml (sensitivity/1-specificity for systolic BP non-dippers of 0.789/0.381, for diastolic BP non-dippers 0.923/0.444 and for MAP non-dippers 0.875/0.375). In conclusion, D-dimer has a good predictive value for non-dipping pattern and the decision for the 24-h ambulatory blood pressure re-monitoring among dippers could rely on its values.

  2. Von Willebrand's Disease in Two Families of Doberman Pinschers

    OpenAIRE

    Johnstone, I. B.; Crane, S.

    1981-01-01

    The history, clinical symptoms and laboratory results in two families of Doberman pinschers with von Willebrand's disease are described. The affected animals illustrate the rather nonspecific bleeding problems that may be encountered in mild and moderate forms of this disease. In both families a bleeding diathesis was suspected when one member of the family underwent surgery with serious postoperative bleeding complications. These cases illustrate the importance of a thorough presurgical hist...

  3. von Willebrand factor and its cleaving protease ADAMTS13 balance in coronary artery vessels: Lessons learned from thrombotic thrombocytopenic purpura. A narrative review.

    Science.gov (United States)

    Morici, Nuccia; Cantoni, Silvia; Panzeri, Francesco; Sacco, Alice; Rusconi, Chiara; Stucchi, Miriam; Oliva, Fabrizio; Cattaneo, Marco

    2017-07-01

    Deficiency of the von Willebrand factor-cleaving protease ADAMTS13 is central to the pathophysiology of thrombotic thrombocytopenic purpura (TTP), a microangiopathic syndrome that presents as an acute medical emergency. In this review we will explore the evidence of a two-way relationship between TTP and ACS. Moreover, we will review the evidence emerged from epidemiological studies of an inverse relationship between the plasma levels of ADAMTS13 and the risk of ACS. Pubmed, MEDLINE and EMBASE, CINHAL, COCHRANE and Google Scholar databases were searched from inception to January 2017. The search yielded 43 studies representing 23 unique patient cases, 5 case series, 5 cohort studies and 10 case-control studies. Most ACS cases developing in the setting of TTP resolved with standard treatment of the underlying microangiopathy, with only a few requiring coronary invasive management. Antiplatelet therapy was not usually prescribed and all of the currently used P2Y 12 were felt to be a potential trigger for a TTP-like syndrome, although our review revealed that the occurrence of TTP in patients treated with new P2Y 12 antagonists is rare. Most studies confirmed the inverse association among ADAMTS13 levels and ACS. The heart is a definite target organ in TTP. The clinical spectrum of its involvement is probably influenced by local factors that add on to the systemic deficiency characteristic of TTP. It follows that patients with TTP should be carefully monitored for ACS events, especially when multiple risk factors for coronary disease exist. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. 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 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.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.AP components are assembled and activated on EC-secreted/anchored ULVWF multimeric strings. Our findings provide one possible molecular mechanism for clinical

  5. Cloning of the cDNA for murine von Willebrand factor and identification of orthologous genes reveals the extent of conservation among diverse species.

    Science.gov (United States)

    Chitta, Mohan S; Duhé, Roy J; Kermode, John C

    2007-05-01

    Interaction of von Willebrand factor (VWF) with circulating platelets promotes hemostasis when a blood vessel is injured. The A1 domain of VWF is responsible for the initial interaction with platelets and is well conserved among species. Knowledge of the cDNA and genomic DNA sequences for human VWF allowed us to predict the cDNA sequence for murine VWF in silico and amplify its entire coding region by RT-PCR. The murine VWF cDNA has an open reading frame of 8,442 bp, encoding a protein of 2,813 amino acid residues with 83% identity to human pre-pro-VWF. The same strategy was used to predict in silico the cDNA sequence for the ortholog of VWF in a further six species. Many of these predictions diverged substantially from the putative Reference Sequences derived by ab initio methods. Our predicted sequences indicated that the VWF gene has a conserved structure of 52 exons in all seven mammalian species examined, as well as in the chicken. There is a minor structural variation in the pufferfish Takifugu rubripes insofar as the VWF gene in this species has 53 exons. Comparison of the translated amino acid sequences also revealed a high degree of conservation. In particular, the cysteine residues are conserved precisely throughout both the pro-peptide and the mature VWF sequence in all species, with a minor exception in the pufferfish VWF ortholog where two adjacent cysteine residues are omitted. The marked conservation of cysteine residues emphasizes the importance of the intricate pattern of disulfide bonds in governing the structure of pro-VWF and regulating the function of the mature VWF protein. It should also be emphasized that many of the conserved features of the VWF gene and protein were obscured when the comparison among species was based on the putative Reference Sequences instead of our predicted cDNA sequences.

  6. Influence of atrial fibrillation on plasma von willebrand factor, soluble E-selectin, and N-terminal pro B-type natriuretic peptide levels in systolic heart failure.

    Science.gov (United States)

    Freestone, Bethan; Gustafsson, Finn; Chong, Aun Yeong; Corell, Pernille; Kistorp, Caroline; Hildebrandt, Per; Lip, Gregory Y H

    2008-05-01

    Endothelial dysfunction is present in patients with heart failure (HF) due to left ventricular systolic dysfunction, as well as in patients with atrial fibrillation (AF) who have normal cardiac function. It is unknown whether AF influences the degree of endothelial dysfunction in patients with systolic HF. We measured levels of plasma von Willebrand factor (vWF) and E-selectin (as indexes of endothelial damage/dysfunction and endothelial activation, respectively; both enzyme-linked immunosorbent assay) in patients with AF and HF (AF-HF), who were compared to patients with sinus rhythm and HF (SR-HF), as well as in age-matched, healthy, control subjects. We also assessed the relationship of vWF and E-selectin to plasma N-terminal pro B-type natriuretic peptide (NTpro-BNP), a marker for HF severity and prognosis. One hundred ninety patients (73% men; mean age, 69.0 +/- 10.1 years [+/- SD]) with systolic HF were studied, who were compared to 117 healthy control subjects: 52 subjects (27%) were in AF, while 138 subjects (73%) were in sinus rhythm. AF-HF patients were older than SR-HF patients (p = 0.046), but left ventricular ejection fraction and New York Heart Association class were similar. There were significant differences in NT-proBNP (p NT-proBNP (p NT-proBNP levels (Spearman r = 0.139; p = 0.017). There is evidence of greater endothelial damage/dysfunction in AF-HF patients when compared to SR-HF patients. The clinical significance of this is unclear but may have prognostic value.

  7. 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.

  8. Clinical and laboratory diagnosis of von Willebrand disease: A synopsis of the 2008 NHLBI/NIH guidelines

    Science.gov (United States)

    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

    2017-01-01

    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 males and females, and reflects deficiency or defects of VWF that may also cause decreased FVIII. It may also occur less commonly as an acquired disorder (acquired von Willebrand syndrome). This article briefly summarizes selected features of the March 2008 evidence-based clinical and laboratory diagnostic recommendations from the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel for assessment for VWD or other bleeding disorders or risks. Management of VWD is also addressed in the NHLBI guidelines, but is not summarized here. The VWD guidelines are available at the NHLBI Web site (http://www.nhlbi.nih.gov/guidelines/vwd). PMID:19415721

  9. Relationship between ADAMTS13 activity, von Willebrand factor antigen levels and platelet function in the early and late phases after TIA or ischaemic stroke.

    Science.gov (United States)

    McCabe, Dominick J H; Murphy, Stephen J X; Starke, Richard; Harrison, Paul; Brown, Martin M; Sidhu, Paul S; Mackie, Ian J; Scully, Marie; Machin, Samuel J

    2015-01-15

    Reduced ADAMTS13 activity is seen in thrombotic thrombocytopenic purpura (TTP), and may lead to accumulation of prothrombotic ultra-large von Willebrand factor (ULVWF) multimers in vivo. ADAMTS13 activity and its relationship with VWF antigen (VWF:Ag) levels and platelet function in 'non-TTP related' TIA or ischaemic stroke has not been comprehensively studied. In this prospective pilot observational analytical case-control study, ADAMTS13 activity and VWF:Ag levels were quantified in platelet poor plasma in 53 patients in the early phase (≤ 4 weeks) and 34 of these patients in the late phase (≥ 3 months) after TIA or ischaemic stroke on aspirin. Data were compared with those from 22 controls not on aspirin. The impact of ADAMTS13 on platelet function in whole blood was quantified by measuring Collagen-ADP (C-ADP) and Collagen-Epinephrine closure times on a platelet function analyser (PFA-100(®)). Median ADAMTS13 activity was significantly reduced in the early phase (71.96% vs. 95.5%, P TIA or stroke compared with controls (86.3% vs. 95.5%, P=0.19). There was a significant inverse relationship between ADAMTS13 activity and VWF:Ag levels in the early phase (r=-0.31; P=0.024), but not in the late phase after TIA or stroke (P=0.74). There was a positive correlation between ADAMTS13 activity and C-ADP closure times in early phase patients only, likely mediated via VWF:Ag levels. ADAMTS13 activity is reduced and VWF:Ag expression is increased within 4 weeks of TIA or ischaemic stroke onset, and can promote enhanced platelet adhesion and aggregation in response to stimulation with collagen and ADP via VWF-mediated pathways. These data improve our understanding of the dynamic haemostatic and thrombotic profiles of ischaemic cerebrovascular disease (CVD) patients, and are important in view of the potential future role that ADAMTS13 may have to play as an anti-thrombotic agent in CVD. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Beneficial Effects of High-Density Lipoproteins on Acquired von Willebrand Syndrome in Aortic Valve Stenosis.

    Science.gov (United States)

    Gebhard, C; Maafi, F; Stähli, B E; Bonnefoy, A; Gebhard, C E; Nachar, W; de Oliveira Moraes, A Benjamim; Mecteau, M; Mihalache-Avram, T; Lavoie, V; Kernaleguen, A E; Shi, Y; Busseuil, D; Chabot-Blanchet, M; Perrault, L P; Rhainds, D; Rhéaume, E; Tardif, J C

    2018-02-01

     Infusions of apolipoprotein A-I (apoA-I), the major protein component of high-density lipoproteins (HDL), result in aortic valve stenosis (AVS) regression in experimental models. Severe AVS can be complicated by acquired von Willebrand syndrome, a haemorrhagic disorder associated with loss of high-molecular-weight von Willebrand factor (vWF) multimers (HMWM), the latter being a consequence of increased shear stress and enhanced vWF-cleaving protease (ADAMTS-13) activity. Although antithrombotic actions of HDL have been described, its effects on ADAMTS-13 and vWF in AVS are unknown.  We assessed ADAMTS-13 activity in plasma derived from a rabbit model of AVS ( n  = 29) as well as in plasma collected from 64 patients with severe AVS (age 65.0 ± 10.4 years, 44 males) undergoing aortic valve replacement (AVR). In both human and rabbit AVS plasma, ADAMTS-13 activity was higher than that in controls ( p  AVS patients had less HMWM than controls (66.3 ± 27.2% vs. 97.2 ± 24.1%, p  AVS rabbits as compared with the placebo group (2.0 ± 0.5 RFU/sec vs. 3.8 ± 0.4 RFU/sec, p  AVS ( r  = -0.3, p  = 0.045).  Our data indicate that HDL levels are associated with reduced ADAMTS-13 activity and increased HMWM. HDL-based therapies may reduce the haematologic abnormalities of the acquired von Willebrand syndrome in AVS. Schattauer GmbH Stuttgart.

  11. Diagnosis and management of von Willebrand disease: a developing country perspective.

    Science.gov (United States)

    Nair, Sukesh Chandran; Viswabandya, Auro; Srivastava, Alok

    2011-07-01

    Special challenges exist in the management of patients with von Willebrand disease (VWD) because of limitations in diagnostic facilities and therapeutic options. However, even within these limitations, it is possible to establish comprehensive services for this condition. Our data show that among 202 patients with VWD, 107 were type 3, 62 were type 1, and the others different categories of type 2. Basic tests such as bleeding time and activated partial thromboplastin time with factor (F)VIII coagulant are able to diagnose most of those with severe disease. We have been able to adapt the specific tests such as von Willebrand factor (VWF) ristocetin cofactor and VWF antigen from the tedious batched manual methods to cost-effective automated methods on advanced coagulometers. Discriminatory tests such as VWF collagen binding, VWF:FVIIIB, ristocetin-induced platelet agglutination (RIPA) are done in batches. Therapeutic options and for the treatment of bleeding include desmopressin, cryoprecipitate, and intermediate purity VWF-containing clotting factor concentrates. Tranexamic acid is also widely used as well as hormonal therapy for menorrhagia. We have also shown that modest doses of intermediate purity FVIII (Koate DVI; Talecris Biotherapeutics, Raleigh, NC, USA) at 35 IU/kg preoperatively and 10 to 20 IU/kg after that are sufficient for surgical hemostasis in these patients. © Thieme Medical Publishers.

  12. Towards personalised therapy for von Willebrand disease: a future role for recombinant products.

    Science.gov (United States)

    Favaloro, Emmanuel J

    2016-05-01

    von Willebrand disease (VWD) is reportedly the most common bleeding disorder and is caused by deficiencies and/or defects in the adhesive plasma protein von Willebrand factor (VWF). Functionally, normal VWF prevents bleeding by promoting both primary and secondary haemostasis. In respect to primary haemostasis, VWF binds to both platelets and sub-endothelial matrix components, especially collagen, to anchor platelets to damaged vascular tissue and promote thrombus formation. VWF also stabilises and protects factor VIII in the circulation, delivering FVIII to the site of injury, which then facilitates secondary haemostasis and fibrin formation/thrombus stabilisation. As a result of this, patients with VWD suffer a bleeding diathesis reflective of a primary defect caused by defective/deficient VWF, which in some patients is compounded by a reduction in FVIII. Management of VWD, therefore, chiefly entails replacement of VWF, and sometimes also FVIII, to protect against bleeding. The current report principally focuses on the future potential for "personalised" management of VWD, given the emerging options in recombinant therapies. Recombinant VWF has been developed and is undergoing clinical trials, and this promising therapy may soon change the way in which VWD is managed. In particular, we can envisage a personalised treatment approach using recombinant VWF, with or without recombinant FVIII, depending on the type of VWD, the extent of deficiencies, and the period and duration of treatment.

  13. Percutaneous coronary intervention and the management of acute coronary syndromes in patients with von Willebrand disease.

    Science.gov (United States)

    Rathore, Sulaiman; Deleon, Dexter; Akram, Hafsa; Sane, David; Ball, Timothy

    2013-04-01

    Von Willebrand disease (vWD) results from quantitative or qualitative deficiency of von Willebrand factor (vWF). The occurrence of myocardial infarction is very rare in patients with vWD. A few case reports of acute coronary syndrome (ACS) in vWD patients are present in the literature, but no definite management recommendations are available for such patients. We report a case of successful percutaneous coronary intervention (PCI) with bare-metal stent (BMS) implantation in a 46-year-old woman with type 1 vWD and history of coronary artery disease (CAD). She received periprocedural dual-antiplatelet therapy for 2 weeks and then continued aspirin without any bleeding complications. The optimal management of patients with vWD and ACS is complex and presents a therapeutic challenge. We propose that dual-antiplatelet therapy can be used safely in most vWD patients presenting with ACS as most of them are type 1 vWD. PCI with BMS can be done safely. Long-term management of these patients requires a systemic approach including hematological consultation, ascertaining vWF levels, as well as patient education and close outpatient follow-up.

  14. 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

  15. Hemophilia and von Willebrand's disease: 1. Diagnosis, comprehensive care and assessment. Association of Hemophilia Clinic Directors of Canada.

    Science.gov (United States)

    1995-07-01

    To present current strategies for the assessment and comprehensive care of patients with hemophilia and von Willebrand's disease. Hospital care, home care, single-provider care and multidisciplinary care. Morbidity and quality of life associated with bleeding and treatment. Relevant clinical studies and reports published from 1974 to 1994 were examined. A search was conducted of own reprint files, MEDLINE, citations in the articles reviewed and references provided by colleagues. In the MEDLINE search the following terms were used singly or in combination: "hemophilia," "von Willebrand's disease," "Factor VIII," "Factor IX," "von Willebrand factor," "diagnosis," "management," "home care," "comprehensive care," "inhibitor," "AIDS," "hepatitis," "life expectancy," "complications," "practice guidelines," "consensus statement" and "controlled trial." The in-depth review included only articles written in English from North America and Europe that were relevant to human disease and to a predetermined outline. The availability of treatment products in Canada was also considered. Minimizing morbidity and maximizing functional status and quality of life were given a high value. The optimal use of treatment procedures and home care offers patients the advantages of minimized disability, improved survival and financial benefit. It is also cost effective. Potential harm, including the risk of hepatitis B, hepatitis C and HIV infection, has now been minimized through viral inactivation of plasma-derived coagulation-factor concentrates and through the use of recombinant clotting factor concentrates and other non-plasma-derived hemostatic agents. Patients with hemophilia and severe von Willebrand's disease should be followed in comprehensive care centres that offer expertise in the diagnosis, assessment and management of bleeding and complications and that can meet the educational and counselling needs of patients, family members and health care providers. Eligible patients should

  16. Coats' disease, Turner syndrome, and von Willebrand disease in a patient with Wildtype Norrie disease pseudoglioma.

    Science.gov (United States)

    Desai, Rajen U; Saffra, Norman A; Krishna, Rati P; Rosenberg, Steven E

    2011-01-01

    The authors describe a girl diagnosed as having Coats' disease, Turner syndrome (45X karyotype), and type 1 von Willebrand disease. She tested negative for the Norrie disease pseudoglioma (NDP) gene located on the X-chromosome, which has been suspected of contributing to Coats' disease. Copyright 2010, SLACK Incorporated.

  17. A systematic review of the effects of hemophilia and von Willebrand disease on arterial trombosis

    NARCIS (Netherlands)

    Biere-Rafi, Sara; Zwiers, M.; Peters, Marjolein; Van Der Meer, Jan; Rosendaal, Frits R; Buller, Harry R; Kamphuisen, Pieter W

    Background: Patients with hemophilia and von Willebrand disease (VWD) may be protected against arterial thrombosis, through a hy-pocoagulable state or atherosclerosis. We performed a systematic review to assess the association between these clotting disorders, arterial thrombosis and the prevalence

  18. 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. © 2014 John Wiley & Sons Ltd.

  19. 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.

    Science.gov (United States)

    Jensen, Gitte S; Lenninger, Miki; Ero, Michael P; Benson, Kathleen F

    2016-01-01

    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. 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. 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 nattokinase, where the average diastolic BP dropped from 86 mmHg to 81 mmHg ( P nattokinase ( P nattokinase ( P nattokinase consumption in a North American population is associated with beneficial changes to BP in a hypertensive population, indicating sex-specific mechanisms of action of nattokinase's effect on vWF and hypertension.

  20. The metal-ion-dependent adhesion site in the Von Willebrand factor-A domain of α2δ subunits is key to trafficking voltage-gated Ca2+ channels

    Science.gov (United States)

    Cantí, C.; Nieto-Rostro, M.; Foucault, I.; Heblich, F.; Wratten, J.; Richards, M. W.; Hendrich, J.; Douglas, L.; Page, K. M.; Davies, A.; Dolphin, A. C.

    2005-01-01

    All auxiliary α2δ subunits of voltage-gated Ca2+ (CaV) channels contain an extracellular Von Willebrand factor-A (VWA) domain that, in α2δ-1 and -2, has a perfect metal-ion-dependent adhesion site (MIDAS). Modeling of the α2δ-2 VWA domain shows it to be highly likely to bind a divalent cation. Mutating the three key MIDAS residues responsible for divalent cation binding resulted in a MIDAS mutant α2δ-2 subunit that was still processed and trafficked normally when it was expressed alone. However, unlike WT α2δ-2, the MIDAS mutant α2δ-2 subunit did not enhance and, in some cases, further diminished CaV1.2, -2.1, and -2.2 currents coexpressed with β1b by using either Ba2+ or Na+ as a permeant ion. Furthermore, expression of the MIDAS mutant α2δ-2 reduced surface expression and strongly increased the perinuclear retention of CaVα1 subunits at the earliest time at which expression was observed in both Cos-7 and NG108–15 cells. Despite the presence of endogenous α2δ subunits, heterologous expression of α2δ-2 in differentiated NG108–15 cells further enhanced the endogenous high-threshold Ca2+ currents, whereas this enhancement was prevented by the MIDAS mutations. Our results indicate that α2δ subunits normally interact with the CaVα1 subunit early in their maturation, before the appearance of functional plasma membrane channels, and an intact MIDAS motif in the α2δ subunit is required to promote trafficking of the α1 subunit to the plasma membrane by an integrin-like switch. This finding provides evidence for a primary role of a VWA domain in intracellular trafficking of a multimeric complex, in contrast to the more usual roles in binding extracellular ligands in other exofacial VWA domains. PMID:16061813

  1. Frequency of von willebrand disease in patients of heavy menstrual bleeding

    International Nuclear Information System (INIS)

    Anjum, N.; Shaheen, Z.; Altaf, C.

    2016-01-01

    Objective: To determine the frequency of Von Willebrand disease (vWD) in patients of heavy menstrual bleeding (HMB). Study Design: Hospital based cross sectional study. Place and Duration of Study: Study was conducted at the Gynecology and Obstetrics department, Military Hospital, Rawalpindi in collaboration with Haematology Department of Armed Forces Institute of Pathology (AFIP) Rawalpindi, from Jul to Dec 2015. Material and Methods: Women presenting with HMB were enrolled in the study after informed consent. HMB was defined as cyclical bleeding at normal intervals but patient is using more than 5 pads per day or increase in duration 8/28 or more for at least last 06 months. Venous blood samples were taken and screened for the hemoglobin level (Hb), platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT) and Von Willebrand antigen (vWF:Ag) in addition to bleeding time (BT) at the Armed Forces Institute of Pathology (AFIP). The demographic details (age, age at menarche), clinical features (menstrual history, quantity of bleeding) and laboratory findings were recorded on the study proforma. Results: A total of 200 patients were enrolled in this study with mean age of 32.3 +- 8.5 years. Mean flow of menstrual blood was 9.8 +- 2.5 pads / day. Mean Hb percent was 8.1 +- 1.4 g/dl. Twenty nine (14.5 percent) patients were having low level of vWF:Ag. Conclusion: There is high frequency of von Willebrand disease among females presenting with heavy menstrual bleeding in our set up. Therefore all patients with heavy menstrual bleeding except those with obvious causes like multiple fibroid should be screened for von Willebrand disease. (author)

  2. Cesariana em paciente com doença de von Willebrand associada à infecção pelo HIV: relato de caso Cesárea en paciente con enfermedad de von Willebrand asociada a la infección por el HIV: relato de caso Anesthesia for cesarean section in patient with von Willebrand's disease and HIV infection: case report

    Directory of Open Access Journals (Sweden)

    Vanessa Rezende Balle

    2004-12-01

    Willebrand y HIV positiva sometida a cesárea. RELATO DEL CASO: Paciente de 24 años, portadora de anemia microcítica, enfermedad de von Willebrand y HIV, llegó a la emergencia obstétrica en inicio de trabajo de alumbramiento. No realizó prenatal. Fue indicada cesárea a fin de disminuir los riesgos de transmisión vertical en paciente con carga vírica de HIV desconocida. Presentaba hematomas por el cuerpo e historia de hematoma de pared abdominal en cesárea anterior. Los tests de coagulación estaban un poco alterados. Después de infusión de concentrado de factor VIII fue realizada anestesia general. Madre y recién nacido presentaron evolución satisfactoria. CONCLUSIONES: La evaluación de manifestaciones clínicas en pacientes con coagulopatia es fundamental en la decisión del tipo de anestesia que será indicada para cada paciente. La evaluación debe ser individualizada, considerando los riesgos y beneficios de la técnica escogida. En estas pacientes, se debe siempre restringir al máximo la indicación de interrupción de la gestación por vía alta, optándose siempre por los métodos menos invasivos. La terapia con concentrado de factor VIII es actualmente la mejor opción de tratamiento, corrigiendo la deficiencia específica y dismunuyendo los riesgos de transmisión vírica.BACKGROUND AND OBJECTIVES: Von Willebrand's disease is the most common hereditary coagulation disorder in young women. The incidence of HIV infection among women has been progressively increasing, and vertical transmission may account for 25% of cases. This report aimed at describing the case of an HIV-positive patient with von Willebrand's disease scheduled for cesarean section. CASE REPORT: Female HIV-positive patient, 24 years old, with microcytic anemia and von Willebrand's disease, admitted to the emergency room in early labor. She had no pre-natal care. Cesarean section was indicated to lower vertical transmission risks since HIV viral count was unknown. Patient had hematomas

  3. Paciente portadora de doença de von Willebrand submetida a cirurgia da valva mitral: uma estratégia para o controle da coagulopatia Patient with von Willebrand disease undergoing mitral valve repair: a strategy for the control of the coagulopathy

    Directory of Open Access Journals (Sweden)

    Ally Nader Roquetti Saroute

    2007-01-01

    Full Text Available Relatamos o caso de uma mulher de 60 anos portadora da doença de von Willebrand tipo I, submetida a cirurgia da valva mitral. A paciente necessitou de cuidados especiais em razão da coagulopatia e foi necessária a utilização de concentrado de fator VIII (VIIIf e fator de von Willebrand (vWf antes, durante e depois da cirurgia. Não houve complicações durante e após a cirurgia. Nove meses depois, a paciente encontra-se assintomática. A correção para valores adequados de VIIIf e vWf permitiu a realização da cirurgia com segurança.We report a case of a 60 year-old woman with von Willebrand disease type I that was submitted to a mitral valve repair. The patient needed special care due coagulopathy and needed VIII factor (VIIIf and von Willebrand factor (vWf, before, during and after surgery. There was no complication during or after surgery. Patient is asymptomatic nine months postoperatively. The correction of VIIIf and vWf allowed the realization of a safety surgery.

  4. Successful Ultrasound-Guided Femoral Nerve Blockade and Catheterization in a Patient with Von Willebrand Disease

    Directory of Open Access Journals (Sweden)

    Youmna E. DiStefano

    2015-01-01

    Full Text Available Peripheral nerve blockade (PNB is superior to neuraxial anesthesia and/or opioid therapy for perioperative analgesia in total knee replacement (TKR. Evidence on the safety of PNB in patients with coagulopathy is lacking. We describe the first documented account of continuous femoral PNB for perioperative analgesia in a patient with Von Willebrand Disease (vWD. Given her history of opioid tolerance and after an informative discussion, a continuous femoral PNB was planned for in this 34-year-old female undergoing TKR. A Humate-P intravenous infusion was started and the patient was positioned supinely. Using sterile technique with ultrasound guidance, a Contiplex 18 Gauge Tuohy needle was advanced in plane through the fascia iliaca towards the femoral nerve. A nerve catheter was threaded through the needle and secured without complications. Postoperatively, a levobupivacaine femoral catheter infusion was maintained, and twice daily Humate-P intravenous infusions were administered for 48 hours; enoxaparin thromboprophylaxis was initiated thereafter. The patient was discharged uneventfully on postoperative day 4. Given documentation of delayed, unheralded bleeding from PNB in coagulopathic patients, we recommend individualized PNB in vWD patients. Multidisciplinary team involvement is required to guide factor supplementation and thromboprophylaxis, as is close follow-up to elicit signs of bleeding throughout the delayed postoperative period.

  5. N1421K mutation in the glycoprotein Ib binding domain impairs ristocetin- and botrocetin-mediated binding of von Willebrand factor to platelets

    DEFF Research Database (Denmark)

    Lanke, E.; Kristoffersson, A.C.; Isaksson, C.

    2008-01-01

    , moderately decreased plasma factor VIII (FVIII) and VWF levels, and disproportionately low-plasma VWF:RCo levels. The patients were found to be heterozygous for the novel N1421K mutation, caused by a 4263C > G transversion in exon 28 of the VWF gene coding for the A1 domain. Botrocetin- and ristocetin-mediated...... binding of plasma VWF to GPIb were reduced in the patients. In vitro mutagenesis and expression in COS-7 cells confirmed the impairment of the mutant in botrocetin- and ristocetin-mediated VWF binding to GPIb. VWF collagen binding capacity was unaffected in plasma from the heterozygous individuals as well...

  6. 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...

  7. Bleeding spectrum in children with moderate or severe von Willebrand disease: Relevance of pediatric-specific bleeding

    NARCIS (Netherlands)

    Sanders, Yvonne V.; Fijnvandraat, Karin; Boender, Johan; Mauser-Bunschoten, Evelien P.; van der Bom, Johanna G.; de Meris, Joke; Smiers, Frans J.; Granzen, Bernd; Brons, Paul; Tamminga, Rienk Y. J.; Cnossen, Marjon H.; Leebeek, Frank W. G.

    2015-01-01

    The bleeding phenotype of children with von Willebrand disease (VWD) needs to be characterized in detail to facilitate diagnosis during childhood and aid in the planning and assessment of treatment strategies. The objective was to evaluate the occurrence, type, and severity of bleeding in a large

  8. Joint assessment in von Willebrand disease : Validation of the Haemophilia Joint Health score and Haemophilia Activities List

    NARCIS (Netherlands)

    van Galen, Karin P. M.; Timmer, Merel A.; de Kleijn, Piet; Fischer, Kathelijn; Foppen, Wouter; Schutgens, Roger E. G.; Eikenboom, Jeroen; Meijer, Karina; Cnossen, Marjon H.; Fijnvandraat, Karin; van der Bom, Johanna G.; Laros-van Gorkom, Britta A. P.; Leebeek, Frank W. G.; Mauser-Bunschoten, Eveline P.

    Assessment of clinical outcome after joint bleeding is essential to identify joint damage and optimise treatment, to prevent disability. However, disease-specific tools to assess the musculoskeletal status in patients with von Willebrand disease (VWD) are lacking. We aimed to determine validity and

  9. A 12.3-kb Duplication Within the VWF Gene in Pigs Affected by Von Willebrand Disease Type 3

    Directory of Open Access Journals (Sweden)

    Stefanie Lehner

    2018-02-01

    Full Text Available Von Willebrand Disease (VWD type 3 is a serious and sometimes fatal hereditary bleeding disorder. In pigs, the disease has been known for decades, and affected animals are used as models for the human disease. Due to the recessive mode of inheritance of VWD type 3, severe bleeding is typically seen in homozygous individuals. We sequenced the complete porcine VWF (Von Willebrand Factor complementary DNA (cDNA and detected a tandem duplication of exons 17 and 18, causing a frameshift and a premature termination codon (p.Val814LeufsTer3 in the affected pig. Subsequent next generation sequencing on genomic DNA proved the existence of a 12.3-kb tandem duplication associated with VWD. This duplication putatively originates from porcine Short Interspersed Nuclear Elements (SINEs located within VWF introns 16 and 18 with high identity. The premature termination truncates the VWF open reading frame by a large part, resulting in an almost entire loss of the mature peptide. It is therefore supposed to account for the severe VWD type 3. Our results further indicate the presence of strong, nonsense-mediated decay in VWF messenger RNA (mRNA containing the duplication, which was supported by the almost complete absence of the complete VWF protein in immunohistochemistry analysis of the VWD-affected pig. In the past, differentiation of wild-type and heterozygous pigs in this VWD colony had to rely on clinical examinations and additional laboratory methods. The present study provides the basis to distinguish both genotypes by performing a rapid and simple genetic analysis.

  10. Epidemiologic features of von Willebrand's disease in Doberman pinschers, Scottish terriers, and Shetland sheepdogs: 260 cases (1984-1988)

    Science.gov (United States)

    Brooks, M; Dodds, W J; Raymond, S L

    1992-04-15

    During a study period from 1985 through 1988, plasma von Willebrand's factor antigen (vWF:Ag) concentration was measured as a marker for prevalence of the von Willebrand's disease (vWD) trait in Doberman Pinschers (doberman, n = 5,554), Scottish Terriers (scottie, n = 1,363), and Shetland Sheepdogs (sheltie, n = 4,279). Significant increase in prevalence of the trait was seen in scotties and shelties during this period. In 1988, 73% of dobermans, 30% of scotties, and 28% of shelties tested had abnormal vWF:Ag concentration (less than 50% vWF:Ag). We found significant differences between breeds with respect to age and vWF:Ag concentration of clinically affected dogs at time of diagnosis. The affected dobermans were older (doberman mean age, 4.6 years; scottie mean age, 1.7 years; sheltie mean age, 1.9 years) and had higher concentration of plasma vWF:Ag (doberman mean vWF:Ag, 15%; scottie mean vWF:Ag, 0%; sheltie mean vWF:Ag, 8%). Bleeding in affected dogs of all 3 breeds was observed predominantly from mucosal surfaces and from cutaneous sites of surgery or trauma. The most common site of mucosal bleeding in scotties and shelties was oral or nasal cavity, and in dobermans was the urogenital tract. Differences in clinical manifestations of vWD in purebred dogs may reflect heterogeneous defects within the vWF gene, causing a variety of abnormalities in production, structure, and function of vWF protein. Analogous to vWD in human beings, acquired deficiencies of vWF may also contribute to the clinical variability of vWD in dogs.

  11. The Carmat Bioprosthetic Total Artificial Heart Is Associated With Early Hemostatic Recovery and no Acquired von Willebrand Syndrome in Calves.

    Science.gov (United States)

    Smadja, David M; Susen, Sophie; Rauch, Antoine; Cholley, Bernard; Latrémouille, Christian; Duveau, Daniel; Zilberstein, Luca; Méléard, Denis; Boughenou, Marie-Fazia; Belle, Eric Van; Gaussem, Pascale; Capel, Antoine; Jansen, Piet; Carpentier, Alain

    2017-10-01

    To determine hemostasis perturbations, including von Willebrand factor (VWF) multimers, after implantation of a new bioprosthetic and pulsatile total artificial heart (TAH). Preclinical study SETTING: Single-center biosurgical research laboratory. Female Charolais calves, 2-to-6 months old, weighing 102-to-122 kg. Surgical implantation of TAH through a mid-sternotomy approach. Four of 12 calves had a support duration of several days (4, 4, 8, and 10 days), allowing for the exploration of early steps of hemostasis parameters, including prothrombin time; coagulation factor levels (II, V, VII+X, and fibrinogen); and platelet count. Multimeric analysis of VWF was performed to detect a potential loss of high-molecular weight (HMW) multimers, as previously described for continuous flow rotary blood pumps. Despite the absence of anticoagulant treatment administered in the postoperative phase, no signs of coagulation activation were detected. Indeed, after an immediate postsurgery decrease of prothrombin time, platelet count, and coagulation factor levels, most parameters returned to baseline values. HMW multimers of VWF remained stable either after initiation or during days of support. Coagulation parameters and platelet count recovery in the postoperative phase of the Carmat TAH (Camat SA, Velizy Villacoublay Cedex, France) implantation in calves, in the absence of anticoagulant treatment and associated with the absence of decrease in HMW multimers of VWF, is in line with early hemocompatibility that is currently being validated in human clinical studies. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Thalidomide for treatment of gastrointestinal bleedings due to angiodysplasia : a case report in acquired von Willebrand syndrome and review of the literature

    NARCIS (Netherlands)

    Engelen, E T; van Galen, K P M; Schutgens, R E G

    INTRODUCTION: Acquired von Willebrand syndrome is a rare bleeding disorder and treatment of the associated gastrointestinal (GI) bleeding due to angiodysplasia is challenging. AIM: The aim of this study was to present a new case on the successful use of thalidomide in a patient with acquired von

  13. A case of von Willebrand disease discovered during treatment of a sacral pressure ulcer.

    Science.gov (United States)

    Murakami, Masahiro; Fukaya, Sumiko; Furuya, Masaichi; Hyakusoku, Hiko

    2010-12-01

    A sacral pressure ulcer developed in a patient hospitalized for cerebral infarction. Each time necrotic tissue was debrided from the ulcer, pressure hemostasis was necessary to stop the bleeding. As treatment continued, the pressure required to stop the bleeding caused the ulcer to worsen, leading to a downward spiral in the patient's condition. While trying to determine the cause of this problem, we discovered that the patient had von Willebrand disease. Medication controlled the bleeding, and the pressure ulcer began to heal at the same time. It was clear to us that conservative treatment would lead to a complete cure but that the healing process would take a long time and require continued administration of an expensive drug. We decided, therefore, to close the wound with a fasciocutaneous flap so that the patient could be quickly transferred to a rehabilitation hospital. About 1 month after surgery, epithelialization was complete, we were able to discontinue medication, and the patient was discharged. This experience demonstrates the importance of determining the cause of any deviation from the normal course of healing in pressure ulcers. It also indicates that the use of fasciocutaneous flaps, which involve little intraoperative bleeding in short surgeries, is appropriate in cases like this one.

  14. Generation and validation of the Condensed MCMDM-1VWD Bleeding Questionnaire for von Willebrand disease.

    Science.gov (United States)

    Bowman, M; Mundell, G; Grabell, J; Hopman, W M; Rapson, D; Lillicrap, D; James, P

    2008-12-01

    Given the challenges involved in obtaining accurate bleeding histories, attempts at standardization have occurred and the value of quantifying hemorrhagic symptoms has been recognized. An extensive validated bleeding questionnaire (MCMDM-1VWD) was condensed by eliminating all details that did not directly affect the bleeding score (BS) and the correlation between the two versions was tested. Additionally, the diagnostic utility of the condensed version was prospectively tested. Data on 259 individuals who were administered the questionnaire are presented here; 217 being prospectively investigated for von Willebrand disease (VWD) (group 1) and 42 previously known to have type 1, 2 or 3 VWD (group 2). Of the 217 prospectively investigated, 35 had positive BS (> or =4) and 182 had negative scores. Seven individuals (all with positive BS) had laboratory results consistent with type 1 VWD. This results in a sensitivity of 100% and a specificity of 87%. The positive predictive value is 0.20 and the negative predictive value is 1. The correlation between the full MCMDM-1VWD and condensed versions is excellent (Spearman's 0.97, P type 2 > type 1 VWD (anova P < 0.001). There is a strong inverse relationship between VWF:Ag level and BS (Spearman's -0.411, P < 0.001). The Condensed MCMDM-1VWD Bleeding Questionnaire is an efficient, effective tool in the evaluation of patients for VWD.

  15. Labor management in a patient with on willebrand

    International Nuclear Information System (INIS)

    Saaqib, S.

    2007-01-01

    von Willebrand disease (VWD) is an inherited bleeding disorder involving a deficiency or abnormal function of a blood clotting protein called von Willebrand factor (VWF). Deficiency of VWF, therefore, shows primarily in organs with small blood vessels such as the skin, the gastrointestinal tract and the uterus. This case report describes management of a patient presenting with type II von Willebrand disease in labor. She had history of lifethreatening hemorrhage from an operation for deviated nasal septum and had a risk of severe postpartum hemorrhage (PPH) within 48 hours of delivery, which was avoided by appropriate planning and timely management. (author)

  16. 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.

  17. Molecular and clinical profile of von Willebrand disease in Spain (PCM-EVW-ES): comprehensive genetic analysis by next-generation sequencing of 480 patients.

    Science.gov (United States)

    Borràs, Nina; Batlle, Javier; Pérez-Rodríguez, Almudena; López-Fernández, María Fernanda; Rodríguez-Trillo, Ángela; Lourés, Esther; Cid, Ana Rosa; Bonanad, Santiago; Cabrera, Noelia; Moret, Andrés; Parra, Rafael; Mingot-Castellano, María Eva; Balda, Ignacia; Altisent, Carme; Pérez-Montes, Rocío; Fisac, Rosa María; Iruín, Gemma; Herrero, Sonia; Soto, Inmaculada; de Rueda, Beatriz; Jiménez-Yuste, Víctor; Alonso, Nieves; Vilariño, Dolores; Arija, Olga; Campos, Rosa; Paloma, María José; Bermejo, Nuria; Berrueco, Rubén; Mateo, José; Arribalzaga, Karmele; Marco, Pascual; Palomo, Ángeles; Sarmiento, Lizheidy; Iñigo, Belén; Nieto, María Del Mar; Vidal, Rosa; Martínez, María Paz; Aguinaco, Reyes; César, Jesús María; Ferreiro, María; García-Frade, Javier; Rodríguez-Huerta, Ana María; Cuesta, Jorge; Rodríguez-González, Ramón; García-Candel, Faustino; Cornudella, Rosa; Aguilar, Carlos; Vidal, Francisco; Corrales, Irene

    2017-12-01

    Molecular diagnosis of patients with von Willebrand disease is pending in most populations due to the complexity and high cost of conventional molecular analyses. The need for molecular and clinical characterization of von Willebrand disease in Spain prompted the creation of a multicenter project (PCM-EVW-ES) that resulted in the largest prospective cohort study of patients with all types of von Willebrand disease. Molecular analysis of relevant regions of the VWF , including intronic and promoter regions, was achieved in the 556 individuals recruited via the development of a simple, innovative, relatively low-cost protocol based on microfluidic technology and next-generation sequencing. A total of 704 variants (237 different) were identified along VWF , 155 of which had not been previously recorded in the international mutation database. The potential pathogenic effect of these variants was assessed by in silico analysis. Furthermore, four short tandem repeats were analyzed in order to evaluate the ancestral origin of recurrent mutations. The outcome of genetic analysis allowed for the reclassification of 110 patients, identification of 37 asymptomatic carriers (important for genetic counseling) and re-inclusion of 43 patients previously excluded by phenotyping results. In total, 480 patients were definitively diagnosed. Candidate mutations were identified in all patients except 13 type 1 von Willebrand disease, yielding a high genotype-phenotype correlation. Our data reinforce the capital importance and usefulness of genetics in von Willebrand disease diagnostics. The progressive implementation of molecular study as the first-line test for routine diagnosis of this condition will lead to increasingly more personalized and effective care for this patient population. Copyright© 2017 Ferrata Storti Foundation.

  18. Acquired von Willebrand Syndrome Associated to Secondary IgM MGUS Emerging after Autologous Stem Cell Transplantation for AL Amyloidosis.

    Science.gov (United States)

    Qamar, Hina; Lee, Adrienne; Valentine, Karen; Skeith, Leslie; Jimenez-Zepeda, Victor H

    2017-01-01

    Acquired von Willebrand syndrome (AVWS) is a rare hemorrhagic disorder that occurs in patients with no prior personal or family history of bleeding. Here, we describe a case of AVWS occurring after autologous stem cell transplantation (ASCT). Interestingly, AVWS developed after bortezomib-based induction and conditioning regimens. Recent evidence suggests that the proximity of the bortezomib therapy to the collection of stem cells with consequent depletion of regulatory T cells after the conditioning regimen could explain some of the unusual autoimmune complications reported in patients receiving bortezomib prior to ASCT. In addition, this patient developed a secondary MGUS post-ASCT, which may have also contributed to the AVWS. To the best of our knowledge, this is the first case of post-ASCT AVWS reported. Prospective data is needed to better elucidate the mechanisms by which these unusual complications occur in patients receiving bortezomib prior to ASCT.

  19. Acquired von Willebrand Syndrome associated to secondary IgM MGUS emerging after Autologous Stem Cell Transplantation for AL Amyloidosis

    Directory of Open Access Journals (Sweden)

    Victor H Jimenez-Zepeda

    2017-05-01

    Full Text Available Acquired von Willebrand syndrome (AVWS is a rare hemorrhagic disorder that occurs in patients with no prior personal or family history of bleeding. Here, we describe a case of AVWS occurring after autologous stem cell transplantation (ASCT. Interestingly, AVWS developed after bortezomib-based induction and conditioning regimens. Recent evidence suggests that the proximity of the bortezomib therapy to the collection of stem cells with consequent depletion of regulatory T cells after the conditioning regimen could explain some of the unusual autoimmune complications reported in patients receiving bortezomib prior to ASCT. In addition, this patient developed a secondary MGUS post-ASCT, which may have also contributed to the AVWS. To the best of our knowledge, this is the first case of post-ASCT AVWS reported. Prospective data is needed to better elucidate the mechanisms by which these unusual complications occur in patients receiving bortezomib prior to ASCT.

  20. Platelet-type von Willebrand Disease: Diagnostic Challenges. Flaws and Pitfalls Experienced in the THROMKID Quality Project.

    Science.gov (United States)

    Maurer, M; Mesters, R; Schneppenheim, R; Knoefler, R; Streif, W

    2015-05-01

    Primary haemostasis defects comprise von Willebrand disease (VWD) and platelet disorders (PD). Although presenting with mild to moderate bleeding tendency in most cases, severe bleeding and blood loss may occur unexpectedly in trauma and surgery. Diagnosis of VWD and PD often remains difficult owing to the wide spectrum of clinical and laboratory manifestations. Platelet-type von Willebrand disease (PT-VWD) is frequently misdiagnosed as type 2B VWD. Discrimination between type 2B VWD and PT-VWD is crucial as treatment differs. A literature review revealed difficulties in diagnostic work-up and choice of optimal treatment of PT-VWD. Guidelines favour the therapeutic use of platelet concentrates. A telephone survey of diagnostic practice with regard to type 2B VWD/PT-VWD was conducted. The prevalence and incidence of type 2B and PT-VWD remained unclear, but PT-VWD may be underestimated. An international study estimated that PT-VWD constitutes up to 15% of the total number of patients diagnosed with type 2B VWD. Our survey confirmed difficulties with diagnosis and showed that some centres did not exclude PT-VWD in type 2B patients. Some authors emphasize that genetic testing is the gold standard for diagnosis, but functional testing allows immediate diagnosis. Due to the important therapeutic implications we suggest that type 2B VWD be confirmed by genetic testing and that in case of a negative result PT-VWD should be excluded. PT-VWD should be excluded in all suspected cases of type 2B. PT-VWD should be treated with platelet concentrates. © Georg Thieme Verlag KG Stuttgart · New York.

  1. Cyclical thrombocytosis, acquired von Willebrand syndrome and aggressive non-melanoma skin cancers are common in patients with Philadelphia-negative myeloproliferative neoplasms treated with hydroxyurea.

    Science.gov (United States)

    Verner, Emma; Forsyth, Cecily; Grigg, Andrew

    2014-05-01

    Abstract Cyclical thrombocytosis, acquired von Willebrand syndrome, aggressive non-melanoma skin cancers and other hydroxyurea complications have been reported in Philadelphia-negative myeloproliferative neoplasms (MPNs), but their incidence and clinical consequences have not been defined in a large cohort of patients. We conducted a retrospective analysis of 188 consecutive patients with MPNs specifically addressing the incidence of these complications. Cyclical thrombocytosis was documented in 29 patients (15%), the majority of whom were receiving hydroxyurea. Acquired von Willebrand syndrome was identified in 17 of the 84 screened patients (20%), but was not associated with any major bleeding complications. Non-melanoma skin cancers were reported in 51 patients (27%). Hydroxyurea-related fever occurred in nine of 149 patients (6%) who received hydroxyurea. Seventy-three patients (39%) experienced a total of 98 major thrombotic events, with the majority of these occurring prior to or within 3 months of the diagnosis. Cyclical thrombocytosis, acquired von Willebrand syndrome, aggressive non-melanoma skin cancers and other hydroxyurea-related complications are not infrequent in MPNs and have important clinical consequences for management.

  2. Identification and Characterization of Novel Variations in Platelet G-Protein Coupled Receptor (GPCR Genes in Patients Historically Diagnosed with Type 1 von Willebrand Disease.

    Directory of Open Access Journals (Sweden)

    Jacqueline Stockley

    Full Text Available The clinical expression of type 1 von Willebrand disease may be modified by co-inheritance of other mild bleeding diatheses. We previously showed that mutations in the platelet P2Y12 ADP receptor gene (P2RY12 could contribute to the bleeding phenotype in patients with type 1 von Willebrand disease. Here we investigated whether variations in platelet G protein-coupled receptor genes other than P2RY12 also contributed to the bleeding phenotype. Platelet G protein-coupled receptor genes P2RY1, F2R, F2RL3, TBXA2R and PTGIR were sequenced in 146 index cases with type 1 von Willebrand disease and the potential effects of identified single nucleotide variations were assessed using in silico methods and heterologous expression analysis. Seven heterozygous single nucleotide variations were identified in 8 index cases. Two single nucleotide variations were detected in F2R; a novel c.-67G>C transversion which reduced F2R transcriptional activity and a rare c.1063C>T transition predicting a p.L355F substitution which did not interfere with PAR1 expression or signalling. Two synonymous single nucleotide variations were identified in F2RL3 (c.402C>G, p.A134 =; c.1029 G>C p.V343 =, both of which introduced less commonly used codons and were predicted to be deleterious, though neither of them affected PAR4 receptor expression. A third single nucleotide variation in F2RL3 (c.65 C>A; p.T22N was co-inherited with a synonymous single nucleotide variation in TBXA2R (c.6680 C>T, p.S218 =. Expression and signalling of the p.T22N PAR4 variant was similar to wild-type, while the TBXA2R variation introduced a cryptic splice site that was predicted to cause premature termination of protein translation. The enrichment of single nucleotide variations in G protein-coupled receptor genes among type 1 von Willebrand disease patients supports the view of type 1 von Willebrand disease as a polygenic disorder.

  3. Identification and Characterization of Novel Variations in Platelet G-Protein Coupled Receptor (GPCR) Genes in Patients Historically Diagnosed with Type 1 von Willebrand Disease.

    Science.gov (United States)

    Stockley, Jacqueline; Nisar, Shaista P; Leo, Vincenzo C; Sabi, Essa; Cunningham, Margaret R; Eikenboom, Jeroen C; Lethagen, Stefan; Schneppenheim, Reinhard; Goodeve, Anne C; Watson, Steve P; Mundell, Stuart J; Daly, Martina E

    2015-01-01

    The clinical expression of type 1 von Willebrand disease may be modified by co-inheritance of other mild bleeding diatheses. We previously showed that mutations in the platelet P2Y12 ADP receptor gene (P2RY12) could contribute to the bleeding phenotype in patients with type 1 von Willebrand disease. Here we investigated whether variations in platelet G protein-coupled receptor genes other than P2RY12 also contributed to the bleeding phenotype. Platelet G protein-coupled receptor genes P2RY1, F2R, F2RL3, TBXA2R and PTGIR were sequenced in 146 index cases with type 1 von Willebrand disease and the potential effects of identified single nucleotide variations were assessed using in silico methods and heterologous expression analysis. Seven heterozygous single nucleotide variations were identified in 8 index cases. Two single nucleotide variations were detected in F2R; a novel c.-67G>C transversion which reduced F2R transcriptional activity and a rare c.1063C>T transition predicting a p.L355F substitution which did not interfere with PAR1 expression or signalling. Two synonymous single nucleotide variations were identified in F2RL3 (c.402C>G, p.A134 =; c.1029 G>C p.V343 =), both of which introduced less commonly used codons and were predicted to be deleterious, though neither of them affected PAR4 receptor expression. A third single nucleotide variation in F2RL3 (c.65 C>A; p.T22N) was co-inherited with a synonymous single nucleotide variation in TBXA2R (c.6680 C>T, p.S218 =). Expression and signalling of the p.T22N PAR4 variant was similar to wild-type, while the TBXA2R variation introduced a cryptic splice site that was predicted to cause premature termination of protein translation. The enrichment of single nucleotide variations in G protein-coupled receptor genes among type 1 von Willebrand disease patients supports the view of type 1 von Willebrand disease as a polygenic disorder.

  4. Erythrocytes and von Willebrand factor in venous thrombosis

    NARCIS (Netherlands)

    Smeets, M.W.J.

    2018-01-01

    Venous thromboembolism represents the third leading vascular disease after myocardial infarction and stroke. Erythrocytes, the most abundant cells in venous thrombi, were thought to be innocent bystanders that become tangled up in the fibrin mesh of venous thrombi. However, this thesis describes

  5. Molecular characterization of exon 28 of von Willebrand's factor ...

    African Journals Online (AJOL)

    2016-05-12

    May 12, 2016 ... were mostly among individuals with Arab ancestry.[3] In. Zimbabwe ... bleeding symptoms are epistaxis, menorrhagia (in women), easy bruising, oral cavity ... North American, British, and Japanese populations. rs1800383 ...

  6. Cuidados nos pacientes com hemofilia e doença de von Willebrand na cirurgia eletiva otorrinolaringológica

    Directory of Open Access Journals (Sweden)

    Marques Marise P. C.

    2003-01-01

    Full Text Available FORMA DE ESTUDO Clínico prospectivo. MATERIAL E MÉTODO: Foi realizado um estudo prospectivo de 10 anos de 20 pacientes com hemofilias ou doença de von Willebrand (DvW com indicação de cirurgia otorrinolaringológica. Os pacientes foram submetidos a um total de 25 cirurgias otorrinolaringológicas eletivas. A idade média foi de 23,75 anos (2 a 62 anos. O grupo de estudo consistiu em 14 hemofílicos, 11 com hemofilia A grave (1 do sexo feminino, uma portadora com 30% de atividade de fator VIII (FVIII, um hemofílico B leve e uma com deficiência grave de fator X; 6 com DvW, 4 tinham o tipo 1 (3 mulheres, um o tipo 2A e um o tipo 3. Treze hemofílicos tinham síndrome de imunodeficiência adquirida. A duração média do procedimento foi de 1 hora e 37 minutos (15 minutos a 12 horas. O defeito da coagulação foi corrigido com desmopressina (DDAVP, com concentrado de FVIII de pureza intermediária 8Y, com criopreciptado ou com complexo protrombínico não ativado (PPSB, de acordo com os níveis plasmáticos do fator e da severidade da cirurgia. O ácido épsilon aminocapróico também foi usado em associação. Em 1 hemofílico A grave houve sangramento pós-operatório que se resolveu com a elevação do nível mínimo de FVIII para 80% e em 1 paciente com DvW do Tipo 3 houve sangramento pós-operatório pela dificuldade de identificação do melhor concentrado a ser reposto. Após o uso do concentrado de pureza intermediária 8Y, houve controle do sangramento. RESULTADO: Todos os outros pacientes apresentaram a hemostasia considerada normal ou excelente. CONCLUSÃO: Concluiu-se que pacientes com hemofilias ou DvW não apresentam um risco cirúrgico aumentado se for realizada uma terapia adequada.

  7. Clinical Significance of von Willebrand Factor and Antithrombin in Diabetes Mellitus with Retinopathy%血管性血友病因子与抗凝血酶在糖尿病视网膜病变中的临床意义

    Institute of Scientific and Technical Information of China (English)

    张鹏; 汤荣华

    2012-01-01

    目的 探讨糖尿病微血管视网膜病变患者血管性血友病因子(vWF)、抗凝血酶(AT)的变化及临床意义.方法 将100例2型糖尿病患者分为两组,糖尿病无微血管视网膜病变并发症组53例,糖尿病微血管视网膜病变并发症组47例,设健康人群对照组50例.所有人群入院或体检时即采集静脉血,进行vWF:Ag、AT:A检测.结果 2型糖尿病无微血管视网膜病变并发症组患者血浆vWF:Ag含量较正常对照组增高(P<0.05),2型糖尿病微血管视网膜病变并发症组患者血浆vWF:Ag含量与2型糖尿病无微血管视网膜病变并发症组及正常对照组相比有显著性差异(P<0.05);且2型糖尿病微血管视网膜病变并发症组中背景性病变和增殖性病变患者血浆vWF:Ag含量比较有显著性差异(P<0.05).2型糖尿病无微血管视网膜病变并发症组患者血浆AT活性与正常对照组相比无显著性差异(P>0.05),2型糖尿病微血管视网膜病变并发症组患者血浆AT活性与2型糖尿病无微血管视网膜病变并发症组及正常对照组相比有显著性差异(P<0.05);且2型糖尿病微血管视网膜病变并发症组中背景性病变和增殖性病变患者血浆AT活性比较有显著性差异(P<0.05).结论 血浆vWF:Ag、AT:A的变化与糖尿病微血管视网膜病变的发生、发展有密切关系,监测其水平与活性对糖尿病微血管并发症的治疗和预防有重要的临床意义.%Objective To explore the changes of von Willebrand factor(vWF) and antithrombin(AT) in diabetic patients with retinopathy and its clinical implications. Methods 100 type 2 diabetes mellitus (T2DM) patients were divided into 2 groups,one group included 53 T2DM patients without retinopathy,another group included 47 T2DM patients with retinopathy, 50 healthy peoples were enrolled as control group. Venous blood was collected from all groups and vWF:Ag, AT; A were determined. Results The level of vWF;Ag in T2DM

  8. Functional characterisation of the type 1 von Willebrand disease candidate VWF gene variants: p.M771I, p.L881R and p.P1413L.

    Science.gov (United States)

    Berber, Ergul; Ozbil, Mehmet; Brown, Christine; Baslar, Zafer; Caglayan, S Hande; Lillicrap, David

    2017-10-01

    Abnormalities in the biosynthetic pathway or increased clearance of plasma von Willebrand factor (VWF) are likely to contribute to decreased plasma VWF levels in inherited type 1 von Willebrand disease (VWD). Recent studies demonstrated that 65% of type 1 VWD patients have candidate VWF mutations, the majority of which are missense variants. The purpose of this study was to explore the effects of three VWF missense mutations (p.M771I, p.L881R and p.P1413L) located in different functional domains of VWF, reported as candidate mutations in type 1 VWD patients in the course of the MCMDM-1VWD study. The focus of these studies was on the intracellular biosynthetic processing and localisation of VWF in a heterologous cell system. Molecular dynamic simulation for p.M771I and p.P1413L was also performed to analyse the conformational effects of the changes. As determined by immunofluorescence antibody staining and confocal microscopy of HEK293 cells, the intracellular localisation of recombinant VWF with the p.M771I variation was impaired. Transient transfection studies and phorbol myristate acetate stimulation in COS-7 cells revealed significant intracellular retention. In addition, major loss of VWF multimers was observed for only the p.M771I mutation. Molecular dynamic simulations on p.M771I mutant VWF revealed distinct structural rearrangements including a large deviation in the E' domain, and significant loss of β-sheet secondary structure. The pathogenic effects of candidate VWF gene mutations were explored in this study. In vitro expression studies in heterologous cell systems revealed impaired secretion of VWF and a dominant negative effect on the processing of the wild-type protein for only the p.M771I mutation and none of the mutations affected the regulated secretion.

  9. von Willebrand Disease

    Science.gov (United States)

    ... results from a physical exam and tests. Medical History Your doctor will likely ask questions about your ... a medical center that specializes in high-risk obstetrics and has a hematologist on staff for prenatal ...

  10. The classification problem for von Neumann factors

    DEFF Research Database (Denmark)

    Sasyk, R.; Törnquist, Asger Dag

    2009-01-01

    We prove that it is not possible to classify separable von Neumann factors of types II, II or III, 0 ≤ λ ≤ 1, up to isomorphism by a Borel measurable assignment of "countable structures" as invariants. In particular the isomorphism relation of type II factors is not smooth. We also prove...... that the isomorphism relation for von Neumann II factors is analytic, but is not Borel....

  11. Identification and characterization of a novel P2Y 12 variant in a patient diagnosed with type 1 von Willebrand disease in the European MCMDM-1VWD study.

    Science.gov (United States)

    Daly, Martina E; Dawood, Ban B; Lester, William A; Peake, Ian R; Rodeghiero, Francesco; Goodeve, Anne C; Makris, Michael; Wilde, Jonathan T; Mumford, Andrew D; Watson, Stephen P; Mundell, Stuart J

    2009-04-23

    We investigated whether defects in the P2Y(12) ADP receptor gene (P2RY12) contribute to the bleeding tendency in 92 index cases enrolled in the European MCMDM-1VWD study. A heterozygous mutation, predicting a lysine to glutamate (K174E) substitution in P2Y(12), was identified in one case with mild type 1 von Willebrand disease (VWD) and a VWF defect. Platelets from the index case and relatives carrying the K174E defect changed shape in response to ADP, but showed reduced and reversible aggregation in response to 10 muM ADP, unlike the maximal, sustained aggregation observed in controls. The reduced response was associated with an approximate 50% reduction in binding of [(3)H]2MeS-ADP to P2Y(12), whereas binding to the P2Y(1) receptor was normal. A hemagglutinin-tagged K174E P2Y(12) variant showed surface expression in CHO cells, markedly reduced binding to [(3)H]2MeS-ADP, and minimal ADP-mediated inhibition of forskolin-induced adenylyl cyclase activity. Our results provide further evidence for locus heterogeneity in type 1 VWD.

  12. J-GLOBAL MeSH Dictionary: von Willebrand病 [MeCab user dictionary for science technology term[Archive

    Lifescience Database Archive (English)

    Full Text Available MeCab user dictionary for science technology term von Willebrand病 名詞 一般 * * * * von Willebrand...病 ... MeSH D014842 200906053707829497 C LS51 UNKNOWN_2 von Willebrand

  13. von Willebrand Disease (For Parents)

    Science.gov (United States)

    [Skip to Content] for Parents Parents site Sitio para padres General Health Growth & Development Infections Diseases & Conditions Pregnancy & Baby Nutrition & Fitness Emotions & Behavior School & Family ...

  14. Exercise induced hypercoagulability, increased von Willebrand factor and decreased thyroid hormone concentrations in sled dogs

    DEFF Research Database (Denmark)

    Krogh, Anne Kirstine Havnsøe; Legind, Pernille; Kjelgaard-Hansen, Mads

    2014-01-01

    Sled dogs performing endurance races have been reported to have a high incidence of gastric erosions or ulcerations and an increased risk of gastro intestinal bleeding leading to death in some cases. In addition, these dogs also become hypothyroid during training and exercise. Canine hypothyroidi...

  15. Mutation analysis and clinical implications of von Willebrand factor-cleaving protease deficiency.

    NARCIS (Netherlands)

    Assink, K.F.H.; Schiphorst, R.H.M.; Allford, S.; Karpman, D.; Etzioni, A.; Brichard, B.; Kar, N.C.A.J. van de; Monnens, L.A.H.; Heuvel, L.P.W.J. van den

    2003-01-01

    BACKGROUND: The pentad of thrombocytopenia, hemolytic anemia, mild renal dysfunction, neurologic signs, and fever, classically characterizes the syndrome of thrombotic thrombocytopenic purpura (TTP). TTP usually occurs in adults as an acquired form but a congenital form in children has also been

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

    African Journals Online (AJOL)

    Jane

    2011-08-15

    Aug 15, 2011 ... potassium channels; RBECs, rat brain capillary endothelial cells. and transport of ... addition, adenine nucleotides modulate the release of endothelial-derive ..... A cellular model of endothelial cell ischemia. J Surg Res. 44(5): ...

  17. Structural studies on B2-glycoprotein I and von Willebrand factor A3 domain

    NARCIS (Netherlands)

    Bouma, B.

    2000-01-01

    The integrity of blood circulation is a prerequisite for life; its malfunctioning is a leading cause of morbidity and mortality in developed countries. For that reason the haemostatic system is a critical component of homeostasis. In Chapter I an overview is given of the biophysical and biochemical

  18. 可吸收镁合金支架植入后犬冠状动脉C-反应蛋白、基质金属蛋白酶9和血管性血友病因子的表达%Effect of absorbable magnesium alloy stenting on expression of C-reactive protein, matrix metalloproteinase-9 and von Willebrand factor in dogs

    Institute of Scientific and Technical Information of China (English)

    王汝朋; 杨水祥

    2015-01-01

    BACKGROUND:Our previous study have verified the biosafety of absorbable magnesium aloy stents from a macro perspective. OBJECTIVE:To study the expressions of C-reactive protein, matrix metaloproteinase-9 and von Wilebrand factor in local vascular tissue after magnesium aloy stenting, and to explore the histocompatibility and safety of magnesium aloy stents at the molecular expression level. METHODS:Twenty-five absorbable magnesium aloy stents were implanted into the left anterior descending artery or circumflex artery of 25 epidemic prevention mongrel dogs. Five dogs with no stenting served as control group. Five dogs were sacrificed respectively at 24 hours, 3 days, 5 days, 1 week, 1 month after stenting, and vascular specimens were taken for preparation of pathological sections. The expressions of C-reactive protein, matrix metaloproteinase-9 and von Wilebrand factor within the coronary artery wal were determined by immunohistochemical staining method. RESULTS AND CONCLUSION: Compared with the control group, the number of cels positive for C-reactive protein, matrix metaloproteinase-9 and von Wilebrand factor was significantly increased at different times after stenting (P 0.01). The inflammatory reactions induced by absorbable magnesium aloy stents are slight and last for short time, which suggests that the absorbable magnesium aloy stents have good histocompatibility and safety.%背景:课题组前期研究从宏观角度验证了可吸收镁合金支架的生物安全性。目的:观察可吸收镁合金支架植入后局部血管组织C-反应蛋白、基质金属蛋白酶9及血管性血友病因子的表达情况,从分子表达水平深层次探讨镁合金支架的组织相容性及安全性。方法:将25枚可吸收镁合金支架植入25只防疫杂种犬冠状动脉前降支或左回旋支,未植入支架的5只犬冠状动脉作为正常对照组,支架植入后24 h、3 d、5 d、1周、1个月各处死动物5只,取支架植入后的

  19. Expressão imunoistoquímica da endoglina (CD105 e do fator de von Willebrand em carcinoma epidermoide oral e sua relação com parâmetros clinicopatológicos

    Directory of Open Access Journals (Sweden)

    Rodrigo Porpino Mafra

    2016-03-01

    Full Text Available Resumo Contexto A angiogênese tem sido associada à progressão de neoplasias malignas e, embora haja estudos acerca de marcadores angiogênicos no carcinoma epidermoide oral (CEO, existem resultados conflitantes na literatura. Objetivos Avaliar a expressão imunoistoquímica do CD105 e do fator de von Willebrand (FvW em CEO e sua relação com parâmetros clínicos do tumor. Métodos A imunoexpressão dos referidos biomarcadores foi analisada em 30 casos de CEO e correlacionada a parâmetros clínicos do tumor (idade e sexo dos pacientes, localização anatômica e estadiamento clínico Tumor, Nodo e Metástase, TNM. Resultados A imunomarcação com o anticorpo anti-FvW foi mais efetiva que a do CD105 no CEO. No que concerne à localização anatômica, o assoalho bucal e a região retromolar apresentaram diferenças estatisticamente significativas quanto aos índices angiogênicos (p = 0,004, determinados pela técnica de contagem microvascular (MVC. Não houve relação estatisticamente significativa entre o estadiamento clínico TNM e os índices angiogênicos, com os dois biomarcadores. Conclusões Com base nos achados deste estudo, sugere-se um envolvimento da neoformação vascular na carcinogênese oral, embora não tenha sido evidenciada associação significativa com o estágio clínico da lesão.

  20. Early intraoperative blood collection does not affect complete blood counts, von Willebrand factor or factor VIII levels in normal children.

    Science.gov (United States)

    Darwish, Hanni; Mundell, Gillianne; Engen, Dale; Lillicrap, David; Silva, Mariana; James, Paula

    2011-01-01

    Obtaining blood from children for research studies can be difficult, particularly for controls. One solution is to obtain samples during elective surgery; however, consideration must be given to the potential effects of the timing of phlebotomy. Ten children were recruited and phlebotomy was carried out during a preoperative clinic visit and intraoperatively immediately after the induction of anesthesia but before the start of surgery. CBCs, VWF, and FVIII levels were measured at both time points and no significant differences were seen. This negative result may be beneficial to pediatric research by suggesting that early intraoperative blood collection for controls does not affect the results.

  1. Acquired Von Willebrand’s Syndrome in Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Sara Taveras Alam

    2014-01-01

    Full Text Available Acquired von Willebrand syndrome (AVWS is an uncommon, underdiagnosed, and heterogeneous disease which is increasingly recognized as a cause of bleeding diatheses. Systemic lupus erythematosus (SLE is an infrequent cause of AVWS. Herein, we report a case of AVWS diagnosed during the initial presentation of SLE in a previously healthy young man with no family history of bleeding diathesis who presented with worsening epistaxis, gastrointestinal bleeding, and anasarca. He was found to have severe anemia and prolonged activated partial thromboplastin time (aPTT with severely decreased levels of von Willebrand factor (VWF measurements in addition to markedly decreased factor VIII levels. Further evaluation revealed nephrotic syndrome and interstitial lung disease due to SLE. He initially received combination therapy with intravenous immunoglobulin (IVIG and von Willebrand factor/factor VIII concentrates without significant improvement. Treatment with steroids, cyclophosphamide, and rituximab was followed by clinical improvement evidenced by cessation of bleeding. The short follow-up did not allow us to definitely prove the therapeutic effect of immunosuppressive treatment on AVWS in SLE patients. This case adds to the literature supporting the relationship between AVWS and SLE and highlights the importance of combination therapy in the treatment of severe AVWS as well as the role of IVIG, cyclophosphamide, and rituximab in AVWS associated with SLE.

  2. Genetics Home Reference: von Willebrand disease

    Science.gov (United States)

    ... mildest and most common of the three types, accounting for 75 percent of affected individuals. Type 3 ... diseases that affect bone marrow or immune cell function. This rare form of the condition is characterized ...

  3. Ultralarge von Willebrand Factor Fibers Mediate Luminal Staphylococcus aureus Adhesion to an Intact Endothelial Cell Layer Under Shear Stress

    NARCIS (Netherlands)

    Pappelbaum, Karin I.; Gorzelanny, Christian; Graessle, Sandra; Suckau, Jan; Laschke, Matthias W.; Bischoff, Markus; Bauer, Corinne; Schorpp-Kistner, Marina; Weidenmaier, Christopher; Schneppenheim, Reinhard; Obser, Tobias; Sinha, Bhanu; Schneider, Stefan W.

    2013-01-01

    Background During pathogenesis of infective endocarditis, Staphylococcus aureus adherence often occurs without identifiable preexisting heart disease. However, molecular mechanisms mediating initial bacterial adhesion to morphologically intact endocardium are largely unknown. Methods and Results

  4. Data on the purification and crystallization of the loss-of-function von Willebrand disease variant (p.Gly1324Ser of the von Willebrand factor A1 domain

    Directory of Open Access Journals (Sweden)

    James C. Cambell

    2016-06-01

    In this data article we describe the production, quality control and crystallization of the p.Gly1324Ser vWD variant of the A1 domain of VWF. p.Gly1324Ser A1 was expressed in Escherichia coli as insoluble inclusion bodies. After the preparation of the inclusion bodies, the protein was solubilized, refolded, purified by affinity chromatography and crystallized. The crystal structure of the p.Gly1324Ser mutant of the A1 domain is deposited at the Protein Data Bank PDB: 5BV8

  5. Effects of coagulation factors and inflammatory cytokines on ...

    African Journals Online (AJOL)

    Tropical Journal of Pharmaceutical Research April 2016; 15 (4): 827-831. ISSN: 1596-5996 (print); ... fibrinogen (Fg) and von Willebrand factor (vWF) in plasma were analyzed by enzyme-linked ... determined by Western blot analysis. Inflammatory ... Currently, coronary heart disease (CHD) has become one .... membrane.

  6. 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

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

    NARCIS (Netherlands)

    van den Biggelaar, Maartje; Bouwens, Eveline A. M.; Kootstra, Neeltje A.; Hebbel, Robert P.; Voorberg, Jan; Mertens, Koen

    2009-01-01

    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 study, we

  8. Vascular endothelial cell function and cardiovascular risk factors in patients with chronic renal failure

    DEFF Research Database (Denmark)

    Haaber, A B; Eidemak, I; Jensen, T

    1995-01-01

    Cardiovascular risk factors and markers of endothelial cell function were studied in nondiabetic patients with mild to moderate chronic renal failure. The transcapillary escape rate of albumin and the plasma concentrations of von Willebrand factor, fibrinogen, and plasma lipids were measured in 29...

  9. Protéolyse du facteur Willebrand et cardiopathies à forces de cisaillement élevées : nouvelles approches diagnostiques et thérapeutiques

    OpenAIRE

    Rauch , Antoine

    2014-01-01

    In the first part of the thesis, we describe a novel approach based on antibody-based therapy to prevent the acquired von Willebrand factor (VWF) degradation observed in continuous-flow mechanical circulatory assist device therapy. Via a murine monoclonal antibody directed against VWF D4 domain and thus interfering with VWF-ADAMTS13 binding, a partial inhibition of VWF degradation is observed in whole blood using an ex vivo circulatory assist device model. In the second part of the thesis, we...

  10. Decrease of hemostatic cardiovascular risk factors by aggressive vs. conventional atorvastatin treatment in patients with Type 2 diabetes mellitus.

    NARCIS (Netherlands)

    Ree, M.A. van de; Maat, M.P. de; Kluft, C.; Meinders, A.E.; Princen, H.M.; Huisman, M.V.

    2003-01-01

    BACKGROUND: Patients with Type 2 diabetes mellitus have increased levels of hemostatic risk variables for cardiovascular disease, such as fibrinogen, von Willebrand factor (VWF), factor (F)VIIa, d-dimer and plasminogen activator inhibitor-1 (PAI-1). OBJECTIVES: To evaluate the effect of aggressive

  11. Clinical experience with Optivate®, high-purity factor VIII (FVIII) product with von Willebrand factor (VWF) in young children with haemophilia A.

    Science.gov (United States)

    Matysiak, M; Bobrowska, H; Balwierz, W; Chybicka, A; Kowalczyk, J R; Shaikh-Zaidi, R; Gillanders, K; Dash, C H

    2011-09-01

    Optivate® is a high-purity FVIII/VWF product. Its safety, tolerability and efficacy in subjects ≥ 12 years have been demonstrated. This study was undertaken to assess Optivate® in children with haemophilia A. Twenty-five children, including one PUP (previously untreated patient), aged 1-6 years (mean 4.67 years) were treated with Optivate® for 26 weeks. Inhibitors were assessed every 3 months and viral status at the study start and end. Prophylaxis was used by five boys and on demand by twenty. The mean number of bleeds in the study was lower compared to the same period pre-study (12.0/child vs. 16.2/child), with fewer bleeds (P related events (5%), all were mild and non-serious. There were no clinically significant changes in vital signs, viral transmissions or inhibitors. In young children Optivate® was well tolerated, safe and efficacious. © 2011 Blackwell Publishing Ltd.

  12. High serum interleukin-8 levels in Afro-Caribbean women with pre-eclampsia. Relations with tumor necrosis factor-alpha, Duffy negative phenotype and von Willebrand factor

    NARCIS (Netherlands)

    Velzing-Aarts, FV; Muskiet, FAJ; van der Dijs, FPL; Duits, AJ

    PROBLEM: Pre-eclampsia is characterized by neutrophil activation. Interleukin-8 (IL-8) is a strong neutrophil chemo-attractant and activator. METHOD OF STUDY: We measured serum IL-8 in 13 pre-eclamptic Afro-Caribbean women and 13 gestational age-, race- and parity-matched normotensive and

  13. Factorization and dilation problems for completely positive maps on von Neumann algebras

    DEFF Research Database (Denmark)

    Haagerup, Uffe; Musat, Magdalena

    2011-01-01

    We study factorization and dilation properties of Markov maps between von Neumann algebras equipped with normal faithful states, i.e., completely positive unital maps which preserve the given states and also intertwine their automorphism groups. The starting point for our investigation has been...

  14. Influence of atrial fibrillation on plasma von Willebrand factor, soluble E-selectin, and N-terminal pro B-type natriuretic peptide levels in systolic heart failure

    DEFF Research Database (Denmark)

    Freestone, B.; Gustasson, F.; Chong, A.Y.

    2008-01-01

    Background: Endothelial dysfunction is present in patients with heart failure (HF) due to left ventricular systolic dysfunction, as well as in patients with atrial fibrillation (AF) who have normal cardiac function. it is unknown whether AF influences the degree of endothelial dysfunction in pati...

  15. 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

    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....... 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...

  16. Von Willebrand's disease: case report and review of literature ...

    African Journals Online (AJOL)

    By taking a clinical history of bleeding (mucocutaneous bleeding symptoms suggestive of a primary haemostatic disorder, a quantitative or qualitative abnormality of VWF is possible) it is important to think about VWD and to make the appropriate diagnosis. If the VWD is suspected diagnostic tests should include an activated ...

  17. Patient with von Willebrand Disease for Gynaecologic Surgery - Perianaesthetic Concerns

    Directory of Open Access Journals (Sweden)

    Rakesh Garg

    2008-01-01

    Patients with vWD do not carry an increased operative risk during elective procedures if appropriate prophylac-tic and corrective therapy is administered. Although the administration of cryoprecipitate and other blood products has traditionally been the cornerstone of treatment for vWD, the recent development of desmopressin(DDAVP for clinical use may provide an effective alternative to replacement therapy with blood products. Further laparaoscopic procedures, taking care during ryle′s tube and foley′s catheter insertion, in such patients are the safer alternative for all kind of gynecologic surgeries.

  18. Treatment factors influencing survival in pancreatic carcinoma; Der Einfluss der Therapie auf das Ueberleben von Patienten mit Pankreaskarzinom. Eine Analyse von Einzelfaktoren

    Energy Technology Data Exchange (ETDEWEB)

    Warszawski, N.; Warszawski, A.; Schneider, B.M.; Roettinger, E.M. [Ulm Univ. (Germany). Abt. Radiologie 2 (Strahlentherapie); Link, K.H.; Gansauge, F. [Ulm Univ. (Germany). Abt. fuer Allgemeinchirurgie; Lutz, M.P. [Ulm Univ. (Germany). Abt. Innere Medizin 1

    1999-07-01

    Purpose: To identify the impact of treatment factors on overall survival in patients with pancreatic carcinoma. Patients and methods: We performed a follow-up study on 38 patients with adenocarcinoma of the pancreas treated from 1984 to 1998. 18/38 patients were resected. Irradiated volume included the primary tumor (or tumor bed) and regional lymph nodes. Thirty-seven patients received in addition chemotherapy consisting of mitoxantrone, 5-fluorouracil and cis-platin, either i.v. (14/38) or i.a. (23/38). The influence of treatment related factors on the overall survival was tested. Biologically effective dose was calculated by the linear-quadratic model ({alpha}/{beta}=25 Gy) and by losing 0.85 Gy per day starting accelerated repopulation at day 28. Results: Treatment factors influencing overall survival were resection (p=0.02), overall treatment time (p=0.03) and biologically effective dose (p<0.002). Total dose and kind of chemotherapy had no significant influence. Treatment volume had a negative correlation (r=-0.5, p=0.06) with overall survival, without any correlation between tumor size, tumor stage, and treatment volume. In multivariate analysis only biologically effective dose remained significant (p=0.02). Conclusions: Among with surgery, biologically effective dose strongly influences overall survival in patients treated for pancreatic carcinoma. Treatment volume should be kept as small as possible and all efforts should be made to avoid treatments splits in radiation therapy. (orig.) [Deutsch] Ziel: Behandlungsfaktoren zu identifizieren, die einen Einfluss auf das Ueberleben von Patienten mit Pankreaskarzinom haben. Patienten und Methode: In einer nichtrandomisierten Studie wurden 38 Patienten ausgewertet, die von 1984 bis 1998 wegen eines Adenokarzinoms des Pankreas behandelt worden waren. Bei 18/38 Patienten war eine Resektion vorgenommen worden. Das Bestrahlungsvolumen beinhaltete den Primaertumor bzw. das Tumorbett und die regionaeren Lymphknoten

  19. Patient-specific factors influence somatic variation patterns in von Hippel?Lindau disease renal tumours

    OpenAIRE

    Fei, Suzanne S.; Mitchell, Asia D.; Heskett, Michael B.; Vocke, Cathy D.; Ricketts, Christopher J.; Peto, Myron; Wang, Nicholas J.; S?nmez, Kemal; Linehan, W. Marston; Spellman, Paul T.

    2016-01-01

    Cancer development is presumed to be an evolutionary process that is influenced by genetic background and environment. In laboratory animals, genetics and environment are variables that can largely be held constant. In humans, it is possible to compare independent tumours that have developed in the same patient, effectively constraining genetic and environmental variation and leaving only stochastic processes. Patients affected with von Hippel?Lindau disease are at risk of developing multiple...

  20. 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.

  1. Haemodynamic responses and changes of haemostatic risk factors in cold-adapted humans.

    Science.gov (United States)

    De Lorenzo, F; Kadziola, Z; Mukherjee, M; Saba, N; Kakkar, V V

    1999-09-01

    Epidemiological studies have shown an increase in acute myocardial infarctions or deaths due to myocardial infarction in colder weather; the mechanisms most likely involve increased blood levels of haemostatic risk factors, and increases in arterial blood pressure and heart rate. We studied the relationship between cold adaptation, haemostatic risk factors and haemodynamic variables. Cold adaptation was obtained by a programme of immersion of the whole body up to the neck in a water-filled bath, the temperature of which was gradually decreased from 22 degrees C to 14 degrees C, time of exposure being increased from 5 to 20 min over a period of 90 days. We studied 428 patients (44% men) and measured blood levels of fibrinogen, plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator antigen (t-PA), plasma viscosity, von Willebrand factor, D-dimer and platelet count, both at baseline and after 90 days of daily immersion. There were significant reductions in von Willebrand factor (-3%; p cold adaptation (-310; p = 0.004). Cold adaptation, compared with exposure to cold weather, induces different haemodynamic responses and changes of blood levels of haemostatic risk factors.

  2. Bleeding score in Type 1 von Willebrand disease patients using the ISTH-BAT questionnaire.

    Science.gov (United States)

    Pathare, A; Al Omrani, S; Al Hajri, F; Al Obaidani, N; Al Balushi, B; Al Falahi, K

    2018-04-01

    Bleeding assessment tools have evolved in the last decade to standardize the assessment of the severity of bleeding symptom in a consistent way. In 2010, the International Society on Thrombosis and Hemostasis-Bleeding Assessment Tool (ISTH-BAT) was developed and validated. Our aim was to administer ISTH-BAT questionnaire to the Omani patients with type 1 VWD and obtain the bleeding score (BS). We also studied the severity of their bleeding symptoms and correlated it with the BS as well as with the laboratory parameters. Forty-eight type I VWD index cases and 52 normal subjects were interviewed and the ISTH-BAT questionnaire administered. The BS was calculated based on a history of bleeding symptoms from 12 different sites according to the standard ISTH-BAT questionnaire. Laboratory parameters were obtained from patient's medical records. The mean age of this cohort was 27 years (range, 6-49) with 60% being females. The median time to administer this questionnaire was 10 minutes with an interquartile range (IQR) from 8 to 17 minutes. Overall, the median BS was 7 (IQR; 2,11) although individual scores ranged between 0 and 36. The BS was negatively correlated with VWF: Ag, VWF: RCo, and VWF: CB and the Spearman's correlation coefficient "rho" was, respectively, -0.15, -0.08, and -0.22. The ISTH-BAT BS is designed to reflect the severity of bleeding. Our results demonstrate the inherent variability of this bleeding pattern. We also found that the ISTH-BAT BS significantly correlated with VWF: Ag and VWF: CB. © 2017 John Wiley & Sons Ltd.

  3. Van Willebrand's disease in the Western Cape

    African Journals Online (AJOL)

    agglutinate normal platelets but does not have an effect on platelets from patients with VWD. The ristocetin co-factor. (RiCo~ assay measures the ability of plasma to agglutinate fixed platelets and is therefore regarded as an indirect measure of VWF activity. Qualitative analysis of VWF antigen. 0JWF-Ag) is required for ...

  4. von Neumann Morgenstern Preferences

    DEFF Research Database (Denmark)

    Vind, Karl

    von Neumann Morgenstern utility is generalized to von Neumann Morgenstern preferences. The proof is an application of simple hyperplane theorems......von Neumann Morgenstern utility is generalized to von Neumann Morgenstern preferences. The proof is an application of simple hyperplane theorems...

  5. von Neumann Morgenstern Preferences

    DEFF Research Database (Denmark)

    Vind, Karl

    2000-01-01

    von Neumann Morgenstern utility is generalized to von Neumann Morgenstern preferences. The proof is an application of simple hyperplane theorems......von Neumann Morgenstern utility is generalized to von Neumann Morgenstern preferences. The proof is an application of simple hyperplane theorems...

  6. JST Thesaurus Headwords and Synonyms: von Willebrand病 [MeCab user dictionary for science technology term[Archive

    Lifescience Database Archive (English)

    Full Text Available MeCab user dictionary for science technology term von Willebrand病 名詞 一般 * * * * von... Willebrand病 von Willebrandビョウ ブイオーエヌ ダブリューアイエルエルイービーアールエイエヌディービョー Thesaurus2015 200906053707829497 C LS51 UNKNOWN_2 von Willebrand

  7. JST Thesaurus Headwords and Synonyms: Von Willebrand病 [MeCab user dictionary for science technology term[Archive

    Lifescience Database Archive (English)

    Full Text Available MeCab user dictionary for science technology term Von Willebrand病 名詞 一般 * * * * von... Willebrand病 von Willebrandビョウ ブイオーエヌ ダブリューアイエルエルイービーアールエイエヌディービョー Thesaurus2015 200906053707829497 C LS51 UNKNOWN_2 Von Willebrand

  8. JST Thesaurus Headwords and Synonyms: von Willebrand因子 [MeCab user dictionary for science technology term[Archive

    Lifescience Database Archive (English)

    Full Text Available MeCab user dictionary for science technology term von Willebrand因子 名詞 一般 * * * * vo...n Willebrand因子 von Willebrandインシ ブイオーエヌ ダブリューアイエルエルイービーアールエイエヌディーインシ Thesaurus2015 200906033515671406 C LS15/LS33 UNKNOWN_2 von Willebrand 因子

  9. The von Hippel-Lindau tumor suppressor gene inhibits hepatocyte growth factor/scatter factor-induced invasion and branching morphogenesis in renal carcinoma cells.

    Science.gov (United States)

    Koochekpour, S; Jeffers, M; Wang, P H; Gong, C; Taylor, G A; Roessler, L M; Stearman, R; Vasselli, J R; Stetler-Stevenson, W G; Kaelin, W G; Linehan, W M; Klausner, R D; Gnarra, J R; Vande Woude, G F

    1999-09-01

    Loss of function in the von Hippel-Lindau (VHL) tumor suppressor gene occurs in familial and most sporadic renal cell carcinomas (RCCs). VHL has been linked to the regulation of cell cycle cessation (G(0)) and to control of expression of various mRNAs such as for vascular endothelial growth factor. RCC cells express the Met receptor tyrosine kinase, and Met mediates invasion and branching morphogenesis in many cell types in response to hepatocyte growth factor/scatter factor (HGF/SF). We examined the HGF/SF responsiveness of RCC cells containing endogenous mutated (mut) forms of the VHL protein (VHL-negative RCC) with that of isogenic cells expressing exogenous wild-type (wt) VHL (VHL-positive RCC). We found that VHL-negative 786-0 and UOK-101 RCC cells were highly invasive through growth factor-reduced (GFR) Matrigel-coated filters and exhibited an extensive branching morphogenesis phenotype in response to HGF/SF in the three-dimensional (3D) GFR Matrigel cultures. In contrast, the phenotypes of A498 VHL-negative RCC cells were weaker, and isogenic RCC cells ectopically expressing wt VHL did not respond at all. We found that all VHL-negative RCC cells expressed reduced levels of tissue inhibitor of metalloproteinase 2 (TIMP-2) relative to the wt VHL-positive cells, implicating VHL in the regulation of this molecule. However, consistent with the more invasive phenotype of the 786-0 and UOK-101 VHL-negative RCC cells, the levels of TIMP-1 and TIMP-2 were reduced and levels of the matrix metalloproteinases 2 and 9 were elevated compared to the noninvasive VHL-positive RCC cells. Moreover, recombinant TIMPs completely blocked HGF/SF-mediated branching morphogenesis, while neutralizing antibodies to the TIMPs stimulated HGF/SF-mediated invasion in vitro. Thus, the loss of the VHL tumor suppressor gene is central to changes that control tissue invasiveness, and a more invasive phenotype requires additional genetic changes seen in some but not all RCC lines. These

  10. Molecular modelling of the Norrie disease protein predicts a cystine knot growth factor tertiary structure.

    Science.gov (United States)

    Meitinger, T; Meindl, A; Bork, P; Rost, B; Sander, C; Haasemann, M; Murken, J

    1993-12-01

    The X-lined gene for Norrie disease, which is characterized by blindness, deafness and mental retardation has been cloned recently. This gene has been thought to code for a putative extracellular factor; its predicted amino acid sequence is homologous to the C-terminal domain of diverse extracellular proteins. Sequence pattern searches and three-dimensional modelling now suggest that the Norrie disease protein (NDP) has a tertiary structure similar to that of transforming growth factor beta (TGF beta). Our model identifies NDP as a member of an emerging family of growth factors containing a cystine knot motif, with direct implications for the physiological role of NDP. The model also sheds light on sequence related domains such as the C-terminal domain of mucins and of von Willebrand factor.

  11. Immunoexpression of vascular endothelial growth factor in periapical granulomas, radicular cysts, and residual radicular cysts.

    Science.gov (United States)

    Nonaka, Cassiano Francisco Weege; Maia, Alexandre Pinto; Nascimento, George João Ferreira do; de Almeida Freitas, Roseana; Batista de Souza, Lélia; Galvão, Hébel Cavalcanti

    2008-12-01

    Our aim was to assess and compare the immunoexpression of vascular endothelial growth factor (VEGF) in periapical granulomas (PGs), radicular cysts (RCs), and residual radicular cysts (RRCs), relating it to the angiogenic index and the intensity of the inflammatory infiltrate. Twenty PGs, 20 RCs, and 10 RRCs were evaluated by immunohistochemistry using anti-VEGF antibody. Angiogenic index was determined by microvessel count (MVC) using anti-von Willebrand factor antibody. The PGs and RCs showed higher expression of VEGF than the RRCs. Lesions presenting few inflammatory infiltrate revealed the lowest immunoexpression of VEGF (P .05). VEGF is present in periapical inflammatory lesions but at a lower level in RRCs. The expression of this proangiogenic factor is closely related to the intensity of the inflammatory infiltrate in these lesions.

  12. A note on derivations of Murray–von Neumann algebras

    Science.gov (United States)

    Kadison, Richard V.; Liu, Zhe

    2014-01-01

    A Murray–von Neumann algebra is the algebra of operators affiliated with a finite von Neumann algebra. In this article, we first present a brief introduction to the theory of derivations of operator algebras from both the physical and mathematical points of view. We then describe our recent work on derivations of Murray–von Neumann algebras. We show that the “extended derivations” of a Murray–von Neumann algebra, those that map the associated finite von Neumann algebra into itself, are inner. In particular, we prove that the only derivation that maps a Murray–von Neumann algebra associated with a factor of type II1 into that factor is 0. Those results are extensions of Singer’s seminal result answering a question of Kaplansky, as applied to von Neumann algebras: The algebra may be noncommutative and may even contain unbounded elements. PMID:24469831

  13. A note on derivations of Murray-von Neumann algebras.

    Science.gov (United States)

    Kadison, Richard V; Liu, Zhe

    2014-02-11

    A Murray-von Neumann algebra is the algebra of operators affiliated with a finite von Neumann algebra. In this article, we first present a brief introduction to the theory of derivations of operator algebras from both the physical and mathematical points of view. We then describe our recent work on derivations of Murray-von Neumann algebras. We show that the "extended derivations" of a Murray-von Neumann algebra, those that map the associated finite von Neumann algebra into itself, are inner. In particular, we prove that the only derivation that maps a Murray-von Neumann algebra associated with a factor of type II1 into that factor is 0. Those results are extensions of Singer's seminal result answering a question of Kaplansky, as applied to von Neumann algebras: The algebra may be noncommutative and may even contain unbounded elements.

  14. JST Thesaurus Headwords and Synonyms: Von Willebrand症候群 [MeCab user dictionary for science technology term[Archive

    Lifescience Database Archive (English)

    Full Text Available MeCab user dictionary for science technology term Von Willebrand症候群 名詞 一般 * * * * v...on Willebrand病 von Willebrandビョウ ブイオーエヌ ダブリューアイエルエルイービーアールエイエヌディービョー Thesaurus2015 200906053707829497 C LS51 UNKNOWN_2 Von Willebrand 症候群

  15. JST Thesaurus Headwords and Synonyms: Von Willebrand因子欠乏 [MeCab user dictionary for science technology term[Archive

    Lifescience Database Archive (English)

    Full Text Available MeCab user dictionary for science technology term Von Willebrand因子欠乏 名詞 サ変接続 * * * ...* von Willebrand病 von Willebrandビョウ ブイオーエヌ ダブリューアイエルエルイービーアールエイエヌディービョー Thesaurus2015 200906053707829497 C LS51 UNKNOWN_2 Von Willebrand 因子 欠乏

  16. Incidence and risk factors of bleeding-related adverse events in patients with chronic lymphocytic leukemia treated with ibrutinib

    Science.gov (United States)

    Lipsky, Andrew H.; Farooqui, Mohammed Z.H.; Tian, Xin; Martyr, Sabrina; Cullinane, Ann M.; Nghiem, Khanh; Sun, Clare; Valdez, Janet; Niemann, Carsten U.; Herman, Sarah E. M.; Saba, Nakhle; Soto, Susan; Marti, Gerald; Uzel, Gulbu; Holland, Steve M.; Lozier, Jay N.; Wiestner, Adrian

    2015-01-01

    Ibrutinib is associated with bleeding-related adverse events of grade ≤2 in severity, and infrequently with grade ≥3 events. To investigate the mechanisms of bleeding and identify patients at risk, we prospectively assessed platelet function and coagulation factors in our investigator-initiated trial of single-agent ibrutinib for chronic lymphocytic leukemia. At a median follow-up of 24 months we recorded grade ≤2 bleeding-related adverse events in 55% of 85 patients. No grade ≥3 events occurred. Median time to event was 49 days. The cumulative incidence of an event plateaued by 6 months, suggesting that the risk of bleeding decreases with continued therapy. At baseline, von Willebrand factor and factor VIII levels were often high and normalized on treatment. Platelet function measured via the platelet function analyzer (PFA-100™) was impaired in 22 patients at baseline and in an additional 19 patients on ibrutinib (often transiently). Collagen and adenosine diphosphate induced platelet aggregation was tested using whole blood aggregometry. Compared to normal controls, response to both agonists was decreased in all patients with chronic lymphocytic leukemia, whether on ibrutinib or not. Compared to untreated chronic lymphocytic leukemia patients, response to collagen showed a mild further decrement on ibrutinib, while response to adenosine diphosphate improved. All parameters associated with a significantly increased risk of bleeding-related events were present at baseline, including prolonged epinephrine closure time (HR 2.74, P=0.012), lower levels of von Willebrand factor activity (HR 2.73, P=0.009) and factor VIII (HR 3.73, P=0.0004). In conclusion, both disease and treatment-related factors influence the risk of bleeding. Patients at greater risk for bleeding of grade ≤2 can be identified by clinical laboratory tests and counseled to avoid aspirin, non-steroidal anti-inflammatory drugs and fish oils. ClinicalTrials.gov identifier NCT01500733 PMID

  17. The antioxidative system of Norway spruce: Effects of different stress factors. Das antioxidative System der Fichte: Einfluss von verschiedenen Stressfaktoren

    Energy Technology Data Exchange (ETDEWEB)

    Schittenhelm, J. (Freiburg Univ., Inst. fuer Biologie 2, Abt. Botanik (Germany)); Westphal, S. (Freiburg Univ., Inst. fuer Biologie 2, Abt. Botanik (Germany)); Toder, S. (Freiburg Univ., Inst. fuer Biologie 2, Abt. Botanik (Germany)); Wagner, E. (Freiburg Univ., Inst. fuer Biologie 2, Abt. Botanik (Germany))

    1993-08-01

    The effects of different stress factors on the antioxidative system of 6-year-old Norway spruces of the same clone were examined. Flooding and permanent darkness had only minor effects. On the other hand drought, chilling, intense light, and very high ozone concentrations showed strong but distinct consequences. This indicates that the damages by these stress factors are due to different toxic oxygen species, and that the stress factors could produce synergistic damages under natural field conditions. (orig.)

  18. Von Hippel-Lindau (VHL inactivation in sporadic clear cell renal cancer: associations with germline VHL polymorphisms and etiologic risk factors.

    Directory of Open Access Journals (Sweden)

    Lee E Moore

    2011-10-01

    Full Text Available Renal tumor heterogeneity studies have utilized the von Hippel-Lindau VHL gene to classify disease into molecularly defined subtypes to examine associations with etiologic risk factors and prognosis. The aim of this study was to provide a comprehensive analysis of VHL inactivation in clear cell renal tumors (ccRCC and to evaluate relationships between VHL inactivation subgroups with renal cancer risk factors and VHL germline single nucleotide polymorphisms (SNPs. VHL genetic and epigenetic inactivation was examined among 507 sporadic RCC/470 ccRCC cases using endonuclease scanning and using bisulfite treatment and Sanger sequencing across 11 CpG sites within the VHL promoter. Case-only multivariate analyses were conducted to identify associations between alteration subtypes and risk factors. VHL inactivation, either through sequence alterations or promoter methylation in tumor DNA, was observed among 86.6% of ccRCC cases. Germline VHL SNPs and a haplotype were associated with promoter hypermethylation in tumor tissue (OR = 6.10; 95% CI: 2.28-16.35, p = 3.76E-4, p-global = 8E-5. Risk of having genetic VHL inactivation was inversely associated with smoking due to a higher proportion of wild-type ccRCC tumors [former: OR = 0.70 (0.20-1.31 and current: OR = 0.56 (0.32-0.99; P-trend = 0.04]. Alteration prevalence did not differ by histopathologic characteristics or occupational exposure to trichloroethylene. ccRCC cases with particular VHL germline polymorphisms were more likely to have VHL inactivation through promoter hypermethylation than through sequence alterations in tumor DNA, suggesting that the presence of these SNPs may represent an example of facilitated epigenetic variation (an inherited propensity towards epigenetic variation in renal tissue. A proportion of tumors from current smokers lacked VHL alterations and may represent a biologically distinct clinical entity from inactivated cases.

  19. Von Hippel-Lindau tumor suppressor gene loss in renal cell carcinoma promotes oncogenic epidermal growth factor receptor signaling via Akt-1 and MEK-1.

    Science.gov (United States)

    Lee, S Justin; Lattouf, Jean-Baptiste; Xanthopoulos, Julie; Linehan, W Marston; Bottaro, Donald P; Vasselli, James R

    2008-10-01

    Clear-cell renal cell carcinoma (RCC) is the most prevalent form of kidney cancer and is frequently associated with loss of von Hippel-Lindau (VHL) gene function, resulting in the aberrant transcriptional activation of genes that contribute to tumor growth and metastasis, including transforming growth factor-alpha (TGF-alpha), a ligand of the epidermal growth factor receptor (EGFR) tyrosine kinase. To determine the functional impact of EGFR activation on RCC, we suppressed critical components of this pathway: EGFR, Akt-1, and MEK-1. Stable transfection of RCC cells with plasmids bearing shRNA directed against each of these genes was used to individually suppress their expression. Transfectants were characterized for growth and invasiveness in vitro and tumorigenesis in vivo. RCC cell transfectants displayed significantly reduced growth rate and matrix invasion in vitro and RCC tumor xenograft growth rate in vivo. Analysis of tumor cells that emerged after extended periods in each model showed that significant EGFR suppression was sustained, whereas Akt-1 and MEK-1 knock-down cells had escaped shRNA suppression. EGFR, Akt-1, and MEK-1 are individually critical for RCC cell invasiveness in vitro and tumorigenicity in vivo, and even partial suppression of each can have a significant impact on tumor progression. The emergence of transfectants that had escaped Akt-1 and MEK-1 suppression during tumorigenicity experiments suggests that these effectors may each be more critical than EGFR for RCC tumorigenesis, consistent with results from clinical trials of EGFR inhibitors for RCC, where durable clinical responses have not been seen.

  20. Von Hippel-Lindau Tumor Suppressor Gene Loss in Renal Cell Carcinoma Promotes Oncogenic Epidermal Growth Factor Receptor Signaling via Akt-1 and MEK1

    Science.gov (United States)

    Lee, S. Justin; Lattouf, Jean-Baptiste; Xanthopoulos, Julie; Linehan, W. Marston; Bottaro, Donald P.; Vasselli, James R.

    2008-01-01

    Objectives Clear-cell renal cell carcinoma (RCC) is the most prevalent form of kidney cancer and is frequently associated with loss of von Hippel-Lindau (VHL) gene function, resulting in the aberrant transcriptional activation of genes that contribute to tumor growth and metastasis, including transforming growth factor-α (TGF-α), a ligand of the epidermal growth factor receptor (EGFR) tyrosine kinase. To determine the functional impact of EGFR activation on RCC, we suppressed critical components of this pathway: EGFR, Akt-1, and MEK-1. Methods Stable transfection of RCC cells with plasmids bearing shRNA directed against each of these genes was used to individually suppress their expression. Transfectants were characterized for growth and invasiveness in vitro and tumorigenesis in vivo. Results RCC cell transfectants displayed significantly reduced growth rate and matrix invasion in vitro and RCC tumor xenograft growth rate in vivo. Analysis of tumor cells that emerged after extended periods in each model showed that significant EGFR suppression was sustained, whereas Akt-1 and MEK-1 knockdown cells had escaped shRNA suppression. Conclusions EGFR, Akt-1, and MEK-1 are individually critical for RCC cell invasiveness in vitro and tumorigenicity in vivo, and even partial suppression of each can have a significant impact on tumor progression. The emergence of transfectants that had escaped Akt-1 and MEK-1 suppression during tumorigenicity experiments suggests that these effectors may each be more critical than EGFR for RCC tumorigenesis, consistent with results from clinical trials of EGFR inhibitors for RCC, where durable clinical responses have not been seen. PMID:18243508

  1. Success factors for the acceptance of renewable energy production plants; Erfolgsfaktoren fuer die Akzeptanz von Erneuerbare-Energie-Anlagen

    Energy Technology Data Exchange (ETDEWEB)

    Walter, Goetz [Zuerich Univ. (Switzerland). Lehrstuhl Sozialpsychologie; Krauter, Sven; Schwenzer, Andreas [The Advisory House GmbH, Muenchen (Germany)

    2011-03-15

    The majority of the German population is in support of the expansion of renewable energies. However, when it comes to construction work, project developers often meet with fierce opposition from the local population. One success factor in raising local acceptance of renewable energy production plants lies in planning projects such that citizens' interests and concerns are taken into account and well-conceived means of public participation are provided. Moreover, municipalities themselves can take on a pivotal role by becoming actively involved in the planning and development process and advertising renewable energy as a way towards municipal emancipation. This gives citizens less reasons to make a stand against such projects.

  2. Von Neumann algebras as complemented subspaces of B(H)

    DEFF Research Database (Denmark)

    Christensen, Erik; Wang, Liguang

    2014-01-01

    Let M be a von Neumann algebra of type II1 which is also a complemented subspace of B( H). We establish an algebraic criterion, which ensures that M is an injective von Neumann algebra. As a corollary we show that if M is a complemented factor of type II1 on a Hilbert space H, then M is injective...

  3. Experimental data for insulin-like growth factor-1 (IGF-1) and basic fibroblast growth factor (bFGF) in prevention of radiation myelopathy; Experimentelle Daten zum Einsatz von Insulin-Like Growth Factor-1 (IGF-1) und Basic Fibroblast Growth Factor (bFGF) zur Praevention einer Strahlenmyelopathie

    Energy Technology Data Exchange (ETDEWEB)

    Nieder, C. [Technische Univ. Muenchen (Germany). Klinik und Poliklinik fuer Strahlentherapie und Radiologische Onkologie; Price, R.E.; Rivera, B. [The Univ. of Texas, M. D. Anderson Cancer Center, Houston, TX (United States). Dept. of Veterinary Medicine and Surgery; Andratschke, N.; Kian Ang, K. [The Univ. of Texas, M. D. Anderson Cancer Center, Houston, TX (United States). Dept. of Experimental Radiation Oncology

    2002-03-01

    Background: Current models of radiation myelopathy provide a rationale for growth factor-based prevention strategies. Thus, we tested whether insulin-like growth factor-1 (IGF-1) and basic fibroblast growth factor (bFGF) alone or in combination modulate radiation tolerance of the rat cervical spinal cord. Materials and Methods: The cervical spinal cord of 68 adult Fisher F344 rats received a total dose of 30-36 Gy, given as a single fraction of 16 Gy followed by a second radiation dose of 14-20 Gy. Continuous intrathecal infusion of bFGF (44 rats) or saline (24 rats) into the cisterna magna was given concomitantly. A further experiment included 14 additional rats which were treated with subcutaneous injection of IGF-1 parallel to irradiation with a total dose of 34 Gy or 36 Gy. 20 rats received combined treatment, i.e. intrathecal infusion of bFGF plus subcutaneous injection of IGF-1, starting 24 hours before irradiation (total dose 33 Gy or 36 Gy) for a total of 4 days. Animals were followed until myelopathy developed or for a maximum of 12 months. Histopathologic examinations were performed post mortem. Results: Treatment with bFGF alone or IGF-1 alone increased the median time to myelopathy significantly. In the 36-Gy group, after combination treatment a comparable prolongation of latency was seen. Moreover, rats treated with 33 Gy and combined bFGF plus IGF-1 showed a significantly reduced risk of myelopathy, too (p = 0.0015). (orig.) [German] Hintergrund: Aktuelle Modelle zur Pathogenese der Strahlenmyelopathie lassen den praeventiven Einsatz von Wachstumsfaktoren sinnvoll erscheinen. Daher sollte ueberprueft werden, ob Insulin-Like Growth Factor-1 (IGF-1) und Basic Fibroblast Growth Factor (bFGF) als Einzelsubstanzen oder in Kombination die Strahlentoleranz des zervikalen Rueckenmarks von Ratten beeinflussen. Material und Methoden: Das Zervikalmark von 68 erwachsenen Fisher-F344-Ratten wurde mit zwei Einzelfraktionen bis insgesamt 30-36 Gy bestrahlt (16 Gy

  4. Ellis Von Creveld Syndrome

    Directory of Open Access Journals (Sweden)

    Afshar H

    1999-01-01

    Full Text Available One patient with Ellis Von Creveld syndrome contains: dwarfism, congenital heart"ndisease, ectodermal dysplasia, polyductyly, an abnormally wide labial frenum and maxillary"nmolars with single root.

  5. Lars von Triers film

    DEFF Research Database (Denmark)

    Nielsen, Lisbeth Overgaard

    2007-01-01

    Afhandlingen undersøger Lars von Triers filmæstetik, som den kommer til udtryk i spillefilmene fra perioden 1984-2007. Afhandlingen analyserer de enkelte films stil, virkningsstrategi og betydningsdannelse.......Afhandlingen undersøger Lars von Triers filmæstetik, som den kommer til udtryk i spillefilmene fra perioden 1984-2007. Afhandlingen analyserer de enkelte films stil, virkningsstrategi og betydningsdannelse....

  6. Cell genetic processes under space flight conditions: Analysis of two-factor crosses between spore color mutants of Sordaria macrospora. Final report; Zellgenetische Prozesse unter Weltraumbedingungen: Analyse von Zweifaktorenkreuzungen zwischen Sporenfarbenmutanten von Sordaria macrospora. Abschlussbericht

    Energy Technology Data Exchange (ETDEWEB)

    Hock, B.; Hahn, A.

    2001-07-01

    hervorgerufen. In Bodenreferenzexperimenten wurde ein dosisabhaengiger Effekt von Schwerionenpartikelstrahlung auf die Postreduktionsfrequenz und die dadurch errechenbaren Genabstaende festgestellt. Eine Erhoehung der Bestrahlungsdosis hat eine Erhoehung der Postreduktionsfrequenz zur Folge. Es konnten Dosis-Effektkurven fuer den Vergleich mit Roentgenstrahlen erstellt werden und die relative biologische Wirksamkeit der Schwerionenstrahlung bezueglich des errechneten Genabstands der Gene lu und r{sub 2} bestimmt werden. Das Myzel der geflogenen Pilzproben wurde auf molekularer Ebene mit Hilfe eines Einzelzellgelektrophorese-Assays auf DNA-Strangbrueche untersucht. Es ergaben sich in den Raumflugproben keine messbaren Genschaeden. Versuche zur DNA-Reparatur in S. macrospora belegen, dass die meisten Schaeden bereits nach wenigen Stunden repariert werden koennen. Es wurden maximale Wirkungsdosen von ionisierender und nichtionisierender Strahlung festgestellt, bei denen DNA-Reparatur noch moeglich ist. (orig./MG)

  7. Von Willebrand disease and other bleeding disorders in women: consensus on diagnosis and management from an international expert panel

    NARCIS (Netherlands)

    James, Andra H.; Kouides, Peter A.; Abdul-Kadir, Rezan; Edlund, Mans; Federici, Augusto B.; Halimeh, Susan; Kamphuisen, Pieter W.; Konkle, Barbara A.; Martínez-Perez, Oscar; McLintock, Claire; Peyvandi, Flora; Winikoff, Rochelle

    2009-01-01

    Reproductive tract bleeding in women is a naturally occurring event during menstruation and childbirth. In women with menorrhagia, however, congenital bleeding disorders historically have been underdiagnosed. This consensus is intended to allow physicians to better recognize bleeding disorders as a

  8. Von Hippel-Lindau Disease

    Directory of Open Access Journals (Sweden)

    Hes Frederik J

    2005-11-01

    Full Text Available Abstract A germline mutation in the Von-Hippel Lindau (VHL gene predisposes carriers to development of abundantly vascularised tumours in the retina, cerebellum, spine, kidney, adrenal gland and pancreas. Most VHL patients die from the consequences of cerebellar haemangioblastoma or renal cell carcinoma. The VHL gene is a tumour suppressor gene and is involved in angiogenesis by regulation of the activity of hypoxia-inducible factor 1-α (HIF1-α. Clinical diagnosis of VHL can be confirmed by molecular genetic analysis of the VHL gene, which is informative in virtually all VHL families. A patient with (suspicion for VHL is an indication for genetic counselling and periodical examination.

  9. Rohlin flows on Von Neumann algebras

    CERN Document Server

    Masuda, Toshihiko

    2016-01-01

    The authors will classify Rohlin flows on von Neumann algebras up to strong cocycle conjugacy. This result provides alternative approaches to some preceding results such as Kawahigashi's classification of flows on the injective type II_1 factor, the classification of injective type III factors due to Connes, Krieger and Haagerup and the non-fullness of type III_0 factors. Several concrete examples are also studied.

  10. Rhizostomeen von Manila

    NARCIS (Netherlands)

    Stiasny, G.

    1924-01-01

    Die hier beschriebene kleine Scyphomedusen-Sammlung wurde von Herrn Director P. B. Sivickis, Dept. of Zoology, University of Philippines, Manila, dem Rijksmuseum van Natuurlijke Historie in Leiden überwiesen. Das Material wurde im December 1922 in Manila-bay gefischt und befindet sich in bestem

  11. Schmetterlinge von Madeira

    NARCIS (Netherlands)

    Martin, K.

    1941-01-01

    Wer auf einer ozeanischen Insel Schmetterlinge sammeln will, darf seine Erwartungen nicht zu hoch spannen; aber dennoch waren meine Frau und ich sehr enttäuscht, als uns auf einer Reise nach Madeira von einer dort angesessenen, gebildeten Dame gesagt wurde, sie habe auf der Insel niemals einen

  12. Biologischer Anbau von Strauchbeeren

    OpenAIRE

    Schmid, Andi

    2004-01-01

    Das Merkblatt enthält auf Österreich angepasste, praxisnahe Informationen zur Produktion von hochwertigen Strauchbeeren wie Himbeeren, Brombeeren, Johannisbeeren, Stachelbeeren und Heidelbeeren. Weiterhin: übersichtliche Hinweise zur Planung, Standortwahl, Sortenauswahl, Bodenvorbereitung und Pflanzung, Bewässerung, Nährstoffversorgung, Witterungsschutz, Beikrautregulierung, Ernte und Lagerung. (Diese Publikation enthält spezifische Informationen für Österreich)

  13. Die Rolle von RANK-Ligand und Osteoprotegerin bei Osteoporose

    Directory of Open Access Journals (Sweden)

    Hofbauer LC

    2004-01-01

    Full Text Available Receptor activator of nuclear factor (NF- κB ligand (RANKL, sein zellulärer Rezeptor RANK und der Decoy-Rezeptor Osteoprotegerin (OPG stellen ein essentielles Zytokinsystem für die Zellbiologie von Osteoklasten dar. Verschiedene Untersuchungen belegen die Bedeutung von Störungen des OPG/RANKL/RANK-Systems bei der Pathogenese metabolischer Knochenerkrankungen. In dieser Arbeit werden die wichtigsten Störungen des OPG/RANKL/RANK-Systems bei verschiedenen Osteoporoseformen dargestellt. Östrogenrezeptor- (ER- Agonisten wie 17 β-Östradiol, Raloxifen und Genistein stimulieren die osteoblastäre Produktion von OPG durch Aktivierung von ER- α in vitro, während Lymphozyten von Patientinnen mit Östrogenmangel RANKL überexprimieren. Die parenterale Gabe von OPG vermag den mit Östrogenmangel assoziierten Knochenverlust im Tiermodell und in einer kleineren klinischen Studie zu verhindern. Glukokortikoide und Immunsuppressiva steigern gleichzeitig die RANKL-Expression und hemmen die OPG-Produktion in osteoblastären Zellen in vitro. Glukokortikoide sind auch in vivo imstande, die OPG-Serumspiegel deutlich zu reduzieren. Dagegen hemmen biomechanische Reize in vitro die RANKL-Produktion und steigern die OPG-Produktion. Ein Fehlen dieser biomechanischen Reize bei längerer Immobilisierung kann daher den RANKL/OPG-Quotienten steigern, während die tierexperimentelle Immobilisierungs-Osteoporose durch die parenterale Gabe von OPG gemildert werden kann.

  14. Industrial production of clotting factors: Challenges of expression, and choice of host cells.

    Science.gov (United States)

    Kumar, Sampath R

    2015-07-01

    The development of recombinant forms of blood coagulation factors as safer alternatives to plasma derived factors marked a major advance in the treatment of common coagulation disorders. These are complex proteins, mostly enzymes or co-enzymes, involving multiple post-translational modifications, and therefore are difficult to express. This article reviews the nature of the expression challenges for the industrial production of these factors, vis-à-vis the translational and post-translational bottlenecks, as well as the choice of host cell lines for high-fidelity production. For achieving high productivities of vitamin K dependent proteins, which include factors II (prothrombin), VII, IX and X, and protein C, host cell limitation of γ-glutamyl carboxylation is a major bottleneck. Despite progress in addressing this, involvement of yet unidentified protein(s) impedes a complete cell engineering solution. Human factor VIII expresses at very low levels due to limitations at several steps in the protein secretion pathway. Protein and cell engineering, vector improvement and alternate host cells promise improvement in the productivity. Production of Von Willebrand factor is constrained by its large size, complex structure, and the need for extensive glycosylation and disulfide-bonded oligomerization. All the licensed therapeutic factors are produced in CHO, BHK or HEK293 cells. While HEK293 is a recent adoption, BHK cells appear to be disfavored. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Nutzerorientiertes Management von materiellen und immateriellen Informationsobjekten

    OpenAIRE

    Hübsch, Chris

    2001-01-01

    Schaffung einer stabilen, erweiterbaren und skalierbaren Infrastruktur für die Bereitstellung von Diensten im Umfeld von Bibliotheken und ähnlichen wissensanbietenden Einrichtungen unter Verwendung von XML-RPC und Python.

  16. Determination of uranium transfer factors from soils contaminated with natural uranium along the Vereinigten Mulde in Zwickau; Bestimmung von Transferfaktoren von Uran aus natuerlich belasteten Boeden entlang der Zwickauer und Vereinigten Mulde

    Energy Technology Data Exchange (ETDEWEB)

    Brand, Andreas

    2011-07-01

    According to IAEA the food chain soil-plants-human is the predominant radionuclide ingestion path. The consumption of contaminated vegetarian food causes a continuous radiation exposure. In this context the problem of contaminated meadows in the Zwickauer and Vereinigten Mulde that is used for agriculture is of predominant interest. In this area intensive uranium mining has caused severe environmental contamination. The agricultural crop land and the grass land were studied with respect to the radionuclides U-238 and U-234. Following the radiochemical separation using ion chromatography the samples were analyzed by alpha-spectrometry. Compared to non-contaminated areas significant specific activities were measured. The transfer factors of the radionuclides U-238 and U-234 were determined for different plant parts. The transfer factors decrease with increasing radioactive contamination of the soils.

  17. Inattentional blindness and the von Restorff effect.

    Science.gov (United States)

    Schmidt, Stephen R; Schmidt, Constance R

    2015-02-01

    Sometimes we fail to notice distinctive or unusual items (inattentional blindness), while other times we remember distinctive items more than expected items (the von Restorff effect). A three-factor framework is presented and tested in two experiments in an attempt to reconcile these seemingly contradictory phenomena. Memory for different types of unexpected stimuli was tested after an easy or difficult Stroop color-naming task. Highly arousing taboo words were well remembered even when the difficult Stroop task limited attentional resources. However, a conceptual isolation effect was only observed when the nature of the category change was highlighted by the Stroop task, the Stroop task was easy, and/or the isolated targets enjoyed a retrieval advantage relative to comparison targets. As proposed in the three-factor framework, the arousing qualities of the stimuli, the attentional demands of the primary task, and the relevance of isolated features at encoding and retrieval combine to produce inattentional blindness and the von Restorff effect.

  18. Pure Jauch-Piron states on von Neumann algebras

    International Nuclear Information System (INIS)

    Hamhalter, J.

    1993-01-01

    We study Jauch-Piron states and two-valued measures on von Neumann algebra. We prove as the main result that, under some set-theoretical assumption, a pure state of a von Neumann algebra A not containing a central abelian portion is Jauch-Piron if and only if it is σ-additive. Moreover, we show that this result holds for type I factor indenpendently on the set-theoretical axiomatics. As a consequence we obtain a lucid characterization of pure Jauch-Piron states on von Neumann algebras acting on a Hilbert space with real-nonmeasurable dimension (this can be viewed as a generalization of the paper). We also characterize the von Neumann algebras whose logic of projections is Jauch-Piron. Finally, we prove that every two-valued measure on the projection logic of A, where A contains no type I 2 central portion, has to be concentrated at an abelian direct summand of A. (orig.)

  19. Renal Cell Carcinoma Programmed Death-ligand 1, a New Direct Target of Hypoxia-inducible Factor-2 Alpha, is Regulated by von Hippel-Lindau Gene Mutation Status.

    Science.gov (United States)

    Messai, Yosra; Gad, Sophie; Noman, Muhammad Zaeem; Le Teuff, Gwenael; Couve, Sophie; Janji, Bassam; Kammerer, Solenne Florence; Rioux-Leclerc, Nathalie; Hasmim, Meriem; Ferlicot, Sophie; Baud, Véronique; Mejean, Arnaud; Mole, David Robert; Richard, Stéphane; Eggermont, Alexander M M; Albiges, Laurence; Mami-Chouaib, Fathia; Escudier, Bernard; Chouaib, Salem

    2016-10-01

    Clear cell renal cell carcinomas (ccRCC) frequently display a loss of function of the von Hippel-Lindau (VHL) gene. To elucidate the putative relationship between VHL mutation status and immune checkpoint ligand programmed death-ligand 1 (PD-L1) expression. A series of 32 renal tumors composed of 11 VHL tumor-associated and 21 sporadic RCCs were used to evaluate PD-L1 expression levels after sequencing of the three exons and exon-intron junctions of the VHL gene. The 786-O, A498, and RCC4 cell lines were used to investigate the mechanisms of PD-L1 regulation. Fisher's exact test was used for VHL mutation and Kruskal-Wallis test for PD-L1 expression. If no covariate accounted for the association of VHL and PD-L1, then a Kruskal-Wallis test was used; otherwise Cochran-Mantel-Haenzsel test was used. We also used the Fligner-Policello test to compare two medians when the distributions had different dispersions. We demonstrated that tumors from ccRCC patients with VHL biallelic inactivation (ie, loss of function) display a significant increase in PD-L1 expression compared with ccRCC tumors carrying one VHL wild-type allele. Using the inducible VHL 786-O-derived cell lines with varying hypoxia-inducible factor-2 alpha (HIF-2α) stabilization levels, we showed that PD-L1 expression levels positively correlate with VHL mutation and HIF-2α expression. Targeting HIF-2α decreased PD-L1, while HIF-2α overexpression increased PD-L1 mRNA and protein levels in ccRCC cells. Interestingly, chromatin immunoprecipitation and luciferase assays revealed a direct binding of HIF-2α to a transcriptionally active hypoxia-response element in the human PD-L1 proximal promoter in 786-O cells. Our work provides the first evidence that VHL mutations positively correlate with PD-L1 expression in ccRCC and may influence the response to ccRCC anti-PD-L1/PD-1 immunotherapy. We investigated the relationship between von Hippel-Lindau mutations and programmed death-ligand 1 expression. We

  20. Regulation of FoxO transcription factors by environmental NO(x). Influence of metal ions and polycyclic aromatic hydrocarbons; Regulation von FoxO-Transkriptionsfaktoren durch Umweltnoxen. Einfluss von Metallionen und polyzyklischen aromatischen Kohlenwasserstoffen

    Energy Technology Data Exchange (ETDEWEB)

    Eckers, Anna

    2009-12-15

    FoxO transcription factors are crucial modulators of various cellular processes, controlling the expression of target genes such as those coding for manganese superoxide dismutase (MnSOD) and selenoprotein P (SeP), thereby supporting defense against oxidative stress. Environmental stimuli such as heavy metal ions and polycyclic aromatic hydrocarbons (PAH) modulate signaling pathways both by interaction with proteins or by inducing the generation of reactive oxygen species (ROS). Exposure of hepatoma cells to nickel ions at subcytotoxic doses did not translate into modulation of FoxO activity despite an activation of the Ser/Thr-kinase Akt. The cellular response to nickel ions under these conditions is most likely independent of the formation of ROS, since there were no increased levels of glutathione disulfide detectable. FoxO activity was then found to be modulated in response to exposure of cells to PAH or the tryptophan photoproduct FICZ. Both PAH and FICZ caused an increased activity of a FoxO-responsive promoter construct as well as of glucose 6-phosphatase promoter activity. In contrast, the activities of promoters of genes coding for MnSOD or SeP were decreased in response to exposure to the PAH 3-methylcholanthrene (3-MC). In line with the promoter effects, 3-MC also decreased steady-state levels of SeP mRNA. The response of the SeP promoter to 3-MC was abrogated by point mutations introduced at the two identified FoxO binding elements of the SeP promoter, implying that interaction of FoxO proteins with these sites is essential for the downregulation of promoter activity. In addition to FoxO activity being modulated by xenobiotics, it was then demonstrated that FoxO expression was also modulated by exposure of cells to PAH or FICZ. FoxO4 mRNA levels were downregulated in hepatoma cells exposed to 3-MC or FICZ. Similarly, insulin treatment caused a downregulation of mRNA levels of FoxO 1a, 3a and 4 in hepatoma cells. (orig.)

  1. Risk Factors for and Management of MPN-Associated Bleeding and Thrombosis.

    Science.gov (United States)

    Martin, Karlyn

    2017-10-01

    The Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) are characterized by both thrombotic and bleeding complications. The purpose of this review is to describe the risk factors associated with bleeding and thrombosis in MPN, as well as to review prevention strategies and management of these complications. Well-described risk factors for thrombotic complications include older age and history of prior thrombosis, along with traditional cardiovascular and venous thromboembolic risk factors. More recently, JAK2 V617F mutation has been found to carry an increased risk of thrombotic complications, whereas CALR has a lower risk than JAK2 mutation. Factors associated with an increased risk of bleeding in MPN include a prior history of bleeding, acquired von Willebrand syndrome, and primary myelofibrosis. Recent findings suggest that thrombocytosis carries a higher risk of bleeding than thrombosis in MPN, and aspirin may exacerbate this risk of bleeding, particularly in CALR-mutated ET. Much of the management of MPN focuses on predicting risk of bleeding and thrombosis and initiating prophylaxis to prevent complications in those at high risk of thrombosis. Emerging evidence suggests that sub-populations may have bleeding risk that outweighs thrombotic risk, particularly in setting of antiplatelet therapy. Future work is needed to better characterize this balance. At present, a thorough assessment of the risks of bleeding and thrombosis should be undertaken for each patient, and herein, we review risk factors for and management of these complications.

  2. Growth differentiation factor-15 (GDF-15) suppresses in vitro angiogenesis through a novel interaction with connective tissue growth factor (CCN2).

    Science.gov (United States)

    Whitson, Ramon J; Lucia, Marshall Scott; Lambert, James R

    2013-06-01

    Growth differentiation factor-15 (GDF-15) and the CCN family member, connective tissue growth factor (CCN2), are associated with cardiac disease, inflammation, and cancer. The precise role and signaling mechanism for these factors in normal and diseased tissues remains elusive. Here we demonstrate an interaction between GDF-15 and CCN2 using yeast two-hybrid assays and have mapped the domain of interaction to the von Willebrand factor type C domain of CCN2. Biochemical pull down assays using secreted GDF-15 and His-tagged CCN2 produced in PC-3 prostate cancer cells confirmed a direct interaction between these proteins. To investigate the functional consequences of this interaction, in vitro angiogenesis assays were performed. We demonstrate that GDF-15 blocks CCN2-mediated tube formation in human umbilical vein endothelial (HUVEC) cells. To examine the molecular mechanism whereby GDF-15 inhibits CCN2-mediated angiogenesis, activation of αV β3 integrins and focal adhesion kinase (FAK) was examined. CCN2-mediated FAK activation was inhibited by GDF-15 and was accompanied by a decrease in αV β3 integrin clustering in HUVEC cells. These results demonstrate, for the first time, a novel signaling pathway for GDF-15 through interaction with the matricellular signaling molecule CCN2. Furthermore, antagonism of CCN2 mediated angiogenesis by GDF-15 may provide insight into the functional role of GDF-15 in disease states. Copyright © 2012 Wiley Periodicals, Inc.

  3. Venom Concentrations and Clotting Factor Levels in a Prospective Cohort of Russell's Viper Bites with Coagulopathy.

    Directory of Open Access Journals (Sweden)

    Geoffrey K Isbister

    Full Text Available Russell's viper envenoming is a major problem in South Asia and causes venom induced consumption coagulopathy. This study aimed to investigate the kinetics and dynamics of venom and clotting function in Russell's viper envenoming.In a prospective cohort of 146 patients with Russell's viper envenoming, we measured venom concentrations, international normalised ratio [INR], prothrombin time (PT, activated partial thromboplastin time (aPTT, coagulation factors I, II, V, VII, VIII, IX and X, and von Willebrand factor antigen. The median age was 39 y (16-82 y and 111 were male. The median peak INR was 6.8 (interquartile range [IQR]: 3.7 to >13, associated with low fibrinogen [median,3 at 6 h post-antivenom but had reduced to <2, by 24 h. The aPTT had also returned to close to normal (<50 sec at 24 h. Factor VII, VIII and IX levels were unusually high pre-antivenom, median peak concentrations of 393%, 307% and 468% respectively. Pre-antivenom venom concentrations and the INR (r = 0.20, p = 0.02 and aPTT (r = 0.19, p = 0.03 were correlated (non-parametric Spearman analysis.Russell's viper coagulopathy results in prolonged aPTT, INR, low fibrinogen, factors V, VIII and X which recover over 48 h. Severity of clotting abnormalities was associated with venom concentrations.

  4. Von der Vielfalt einer Institution

    OpenAIRE

    Kabaum, Marcel; Buck, Marc Fabian

    2013-01-01

    Von der Vielfalt von Universitäten bzw. higher education institutions (HEIs) zu sprechen heißt, sich dem Dickicht an Komplexität zu stellen, das sich zwischen ihren Ideen und Realitäten ausbreitet. Der Text führt in den Sammelband "Ideen und Realitäten von Universitäten" ein und hebt die verschiedenen disziplinären Sichtweisen sowie die internationale Breite - Deutschland, Südamerika, USA, Afghanistan und China - der Beiträge hervor. (DIPF/Orig.)

  5. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... interferes with the body’s ability to make hemoglobin. Family history and genetics Von Willebrand disease is an ... deficiency anemia. Return to Risk Factors to review family history, lifestyle, unhealthy environments, or other factors that ...

  6. Alejandro Von Humboldt

    Directory of Open Access Journals (Sweden)

    Gerardo Paz Otero

    1965-09-01

    Full Text Available Diverso fue y sigue siéndolo, el destino de los dos hermanos Humboldt, Guillermo y Alejandro. Sino que se inicia con el nacimiento: Guillermo, el mayor, nace el 22 de junio de 1767 en Potsdam, residencia de los emperadores prusianos, la ciudad de los palacios imperiales, el imperio del militarismo germano; su cuna se meció cerca al palacete de Sans-Soussi, donde Federico el Grande forja ba el poderío de Prusia, cultivaba las ciencias y las artes, anfitrionaba a los intelectuales de Europa, y era "vasallo espiritual de Volta ire", según la aguda frase de Goethe. Alejandro viene al mundo dos años después (14 de septiembre de 1769 en Berlín, en la casa burguesa de la Jagerstrasse (calle del cazador que su madre Elizabeth von Humboldt heredara de su primer esposo.

  7. Polycystic ovary syndrome: cardiovascular risk factors according to specific phenotypes.

    Science.gov (United States)

    Aziz, Mubeena; Sidelmann, Johannes J; Faber, Jens; Wissing, Marie-Louise M; Naver, Klara V; Mikkelsen, Anne-Lis; Nilas, Lisbeth; Skouby, Sven O

    2015-10-01

    Polycystic ovary syndrome (PCOS) is associated with obesity and insulin resistance. The objective of this cross-sectional study was to investigate the impact of insulin resistance and body mass index (BMI) on inflammatory and hemostatic variables associated with long-term risk of cardiovascular disease in women with PCOS. 149 premenopausal women with PCOS were recruited consecutively from April 2010 to February 2012 at three Danish University Hospitals. The study was conducted at the Department of Gynecology and Obstetrics, Herlev University Hospital, Denmark. PCOS was diagnosed in accordance with the Rotterdam criteria and the women were classified into four phenotypes according to BMI and insulin resistance measured by the homeostasis model assessment of insulin resistance index. Body composition was determined by dual-energy X-ray absorptiometry. Main outcome measures were the biomarkers C-reactive protein (CRP), plasminogen activator inhibitor-1 (PAI-1), and von Willebrand factor antigen. Normal weight insulin-resistant PCOS women were characterized by abdominal obesity and elevated levels of plasma PAI-1. Overweight/obese insulin-resistant PCOS women had increased levels of both PAI-1 and CRP. Of the three Rotterdam criteria, only hyperandrogenemia was significantly associated with the hemostatic risk marker of long-term cardiovascular disease risk. Surrogate risk markers for cardiovascular disease are elevated in women with PCOS, especially insulin-resistant and overweight/obese women. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology.

  8. Kleben von Kunststoff mit Metall

    CERN Document Server

    Brockmann, W; Käufer, H

    1989-01-01

    Das Buch behandelt das Kleben von Kunststoffen mit Metallen in einer fur den Praktiker verstandlichen und umsetzbaren Form. Es leitet zu Klebeverfahren an, die optimale Ergebnisse hinsichtlich Qualitat, Dauerhaftigkeit und Wirtschaftlichkeit liefern.

  9. Emission factors and chemical characterisation of fine particulate emissions from modern and old residential biomass heating systems determined for typical load cycles; Emissionsfaktoren und chemische Charakterisierung von Feinstaubemissionen moderner und alter Biomasse-Kleinfeuerungen ueber typische Tageslastverlaeufe

    Energy Technology Data Exchange (ETDEWEB)

    Kelz, Joachim [BIOENERGY 2020+ GmbH, Graz (Austria); Brunner, Thomas; Obernberger, Ingwald [BIOENERGY 2020+ GmbH, Graz (Austria); Technische Universitaet Graz, Institut fuer Prozess- und Partikeltechnik, Graz (Austria); BIOS BIOENERGIESYSTEME GmbH, Graz (Austria)

    2012-12-15

    It is already well known that there are significant differences regarding the emissions, especially particulate matter (PM) emissions, of old and modern as well as automatically and not automatically controlled biomass based residential heating systems. This concerns their magnitude as well as their chemical composition. In order to investigate emission factors for particulate emissions and the chemical compositions of the PM emissions over typical whole day operation cycles, a project on the determination and characterisation of PM emissions from the most relevant small-scale biomass combustion systems was performed at the BIOENERGY 2020+ GmbH, Graz, Austria, in cooperation with the Institute for Process and Particle Engineering, Graz University of Technology. The project was based on test stand measurements, during which relevant operation parameters (gaseous emissions, boiler load, flue gas temperature, combustion chamber temperature etc.) as well as PM emissions have been measured and PM samples have been taken and forwarded to chemical analyses. Firstly, typical whole day operation cycles for residential biomass combustion systems were specified for the test runs. Thereby automatically fed and automatically controlled boilers, manually fed and automatically controlled boilers as well as manually fed stoves were distinguished. The results show a clear correlation between the gaseous emissions (CO and OGC) and the PM{sub 1} emissions. It is indicated that modern biomass combustion systems emit significantly less gaseous and PM emissions than older technologies (up to a factor of 100). Moreover, automatically fed systems emit much less gaseous and PM emissions than manually fed batch-combustion systems. PM emissions from modern and automatically controlled systems mainly consist of alkaline metal salts, while organic aerosols and soot dominate the composition of aerosols from old and not automatically controlled systems. As an important result comprehensive data

  10. Hypoxia-induced mitogenic factor enhances angiogenesis by promoting proliferation and migration of endothelial cells

    International Nuclear Information System (INIS)

    Tong Qiangsong; Zheng Liduan; Li Bo; Wang Danming; Huang Chuanshu; Matuschak, George M.; Li Dechun

    2006-01-01

    Our previous studies have indicated that hypoxia-induced mitogenic factor (HIMF) has angiogenic properties in an in vivo matrigel plug model and HIMF upregulates expression of vascular endothelial growth factor (VEGF) in mouse lungs and cultured lung epithelial cells. However, whether HIMF exerts angiogenic effects through modulating endothelial cell function remains unknown. In this study, mouse aortic rings cultured with recombinant HIMF protein resulted in enhanced vascular sprouting and increased endothelial cell spreading as confirmed by Dil-Ac-LDL uptake, von Willebrand factor and CD31 staining. In cultured mouse endothelial cell line SVEC 4-10, HIMF dose-dependently enhanced cell proliferation, in vitro migration and tubulogenesis, which was not attenuated by SU1498, a VEGFR2/Flk-1 receptor tyrosine kinase inhibitor. Moreover, HIMF stimulation resulted in phosphorylation of Akt, p38 and ERK1/2 kinases in SVEC 4-10 cells. Treatment of mouse aortic rings and SVEC 4-10 cells with LY294002, but not SB203580, PD098059 or U0126, abolished HIMF-induced vascular sprouting and angiogenic responses. In addition, transfection of a dominant-negative mutant of phosphatidylinositol 3-kinase (PI-3K), Δp85, blocked HIMF-induced phosphorylation of Akt, endothelial activation and tubulogenesis. These results indicate that HIMF enhances angiogenesis by promoting proliferation and migration of endothelial cells via activation of the PI-3K/Akt pathways

  11. Iodine ingestion dose factors for the thyroid exposure of infants. Technical instructions 7. Jod-Ingestionsdosisfaktor fuer die Strahlenexposition der Schilddruese von Kleinkindern. Weisungsbeschluss 7

    Energy Technology Data Exchange (ETDEWEB)

    1976-01-01

    For calculations of the thyroid exposure of infants via the pasture-cow-milk pathway, the dose factor = 8.8 x 10/sup 5/ rem x m/sup 3/ / Ci x s should be used for elementary iodine during the vegetation period. For the components of other chemical-physical forms of /sup 131/I, the above value should be multiplied by the following factors: 1) For iodine aerosols, by the factor 0.1; 2) for organic iodine, by the factor 0.01. The mean vegetation period in the Federal Republic of Germany is 6 months.

  12. Assessment of the safety factor of the new EC-specified test gas for intrinsically safe electric circuits of mining equipment; Ermittlung des Sicherheitsfaktors des neuen in der EG festgelegten Pruefgases fuer eigensichere Stromkreise von Bergbau-Betriebsmitteln

    Energy Technology Data Exchange (ETDEWEB)

    Hauke, R. [Fachstelle fuer Sicherheit Elektrischer Betriebsmittel, Dortmund (Germany). Bergbauversuchsstrecke

    2001-07-01

    The real safety factor of the new gas (52 % by volume H{sub '}'/air mixture) was compared to the earlier gas mixture (ethylene) for group I (methane) was investigated. Further, it was investigated whether more or less intrinsically safe systems can be connected to a single supply source. Extensive experiments were carried out in two test sites, supplemented by evaluations of earlier BVS experiments and a literature search. [German] Im Rahmen des Vorhabens sollte die Hoehe des realen Sicherheitsfaktors der neuen Wasserstoffmischung (52 Vol.-% H{sub 2}/Luft-Gemisch) im Vergleich zu der frueher verwandten Pruefgasmischung (Ethylen) fuer die Gruppe I (Methan) untersucht werden. Ebenfalls sollte eine Antwort auf die Frage gesucht werden, ob das neue Pruefgasgemisch eine Erleichterung fuer die Bescheinigungspraxis von eigensicheren Systemen fuer den Steinkohlenbergbau mit sich bringt (mehr Verbraucher an eine speisende Quelle moeglich) oder ob eine Beschraenkung (wesentlich weniger Verbraucher an eine speisende Quelle) zu erwarten ist. Beide Fragestellungen konnte durch ein umfangreiches Versuchsprogramm, das an zwei aufgebauten Pruefplaetzen innerhalb der verlaengerten Projektlaufzeit durchgefuehrt wurde, in Verbindung mit der Neuauswertung aelterer Versuche der BVS und der recherchierten Literatur beantwortet werden. (orig.)

  13. Richard von Volkmann

    Science.gov (United States)

    Willy, Christian; Schneider, Peter; Engelhardt, Michael; Hargens, Alan R.

    2008-01-01

    Richard von Volkmann (1830–1889), one of the most important surgeons of the 19th century, is regarded as one of the fathers of orthopaedic surgery. He was a contemporary of Langenbeck, Esmarch, Lister, Billroth, Kocher, and Trendelenburg. He was head of the Department of Surgery at the University of Halle, Germany (1867–1889). His popularity attracted doctors and patients from all over the world. He was the lead physician for the German military during two wars. From this experience, he compared the mortality of civilian and war injuries and investigated the general poor hygienic conditions in civilian hospitals. This led him to introduce the “antiseptic technique” to Germany that was developed by Lister. His powers of observation and creativity led him to findings and achievements that to this day bear his name: Volkmann’s contracture and the Hueter-Volkmann law. Additionally, he was a gifted writer; he published not only scientific literature but also books of children’s fairy tales and poems under the pen name of Richard Leander, assuring him a permanent place in the world of literature as well as orthopaedics. PMID:18196438

  14. Hepatocellular hypoxia-induced vascular endothelial growth factor expression and angiogenesis in experimental biliary cirrhosis.

    Science.gov (United States)

    Rosmorduc, O; Wendum, D; Corpechot, C; Galy, B; Sebbagh, N; Raleigh, J; Housset, C; Poupon, R

    1999-10-01

    We tested the potential role of vascular endothelial growth factor (VEGF) and of fibroblast growth factor-2 (FGF-2) in the angiogenesis associated with experimental liver fibrogenesis induced by common bile duct ligation in Sprague-Dawley rats. In normal rats, VEGF and FGF-2 immunoreactivities were restricted to less than 3% of hepatocytes. One week after bile duct ligation, hypoxia was demonstrated by the immunodetection of pimonidazole adducts unevenly distributed throughout the lobule. After 2 weeks, hypoxia and VEGF expression were detected in >95% of hepatocytes and coexisted with an increase in periportal vascular endothelial cell proliferation, as ascertained by Ki67 immunolabeling. Subsequently, at 3 weeks the density of von Willebrand-labeled vascular section in fibrotic areas significantly increased. Semiquantitative reverse transcription polymerase chain reaction showed that VEGF(120) and VEGF(164) transcripts, that correspond to secreted isoforms, increased within 2 weeks, while VEGF(188) transcripts remained unchanged. FGF-2 mainly consisting of a 22-kd isoform, according to Western blot, was identified by immunohistochemistry in 49% and 100% of hepatocytes at 3 and 7 weeks, respectively. Our data provide evidence that in biliary-type liver fibrogenesis, angiogenesis is stimulated primarily by VEGF in response to hepatocellular hypoxia while FGF-2 likely contributes to the maintenance of angiogenesis at later stages.

  15. Aggregation und Management von Metadaten im Kontext von Europeana

    Directory of Open Access Journals (Sweden)

    Gerda Koch

    2017-09-01

    Full Text Available Mit dem In-Beziehung-Setzen und Verlinken von Daten im Internet wird der Weg zur Umsetzung des semantischen Webs geebnet. Erst die semantische Verbindung von heterogenen Datenbeständen ermöglicht übergreifende Suchvorgänge und späteres „Machine Learning“. Im Artikel werden die Aktivitäten der Europäischen Digitalen Bibliothek im Bereich des Metadatenmanagements und der semantischen Verlinkung von Daten skizziert. Dabei wird einerseits ein kurzer Überblick zu aktuellen Forschungsschwerpunkten und Umsetzungsstrategien gegeben, und darüber hinaus werden einzelne Projekte und maßgeschneiderte Serviceangebote für naturhistorische Daten, regionale Kultureinrichtungen und Audiosammlungen beschrieben.

  16. Diagnosis and Treatment of Thrombotic Thrombocytopenic Purpura

    African Journals Online (AJOL)

    Abe Olugbenga

    historical pentad of clinical features once thought to be needed to make the diagnosis include fever .... bond in the central A2 subunit of Von Willebrand Factor .... there were some catheter related and plasma ... and venous thrombosis (9).

  17. Treatment of reperfusion injury with recombinant ADAMTS13 in a porcine model of acute myocardial infarction

    NARCIS (Netherlands)

    Eerenberg, E.S.; Teunissen, P.F.A.; Van Den Born, B.J.; Meijers, J.C.; Hollander, M.; Aly, M.; Niessen, H.W.M.; Kamphuisen, P.W.; Levi, M.; Van Royen, N.

    Background: No reflow and decreased microvascular perfusion after percutaneous coronary intervention increase morbidity and mortality in ST-elevation myocardial infarction (STEMI) patients. No reflow may be mediated by platelet vessel wall interaction that is governed by von Willebrand factor.

  18. Disease: H00225 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ID:18574040 ... AUTHORS ... Sadler JE ... TITLE ... Von Willebrand factor, ADAMTS13, and thrombotic thrombocytopen...MID:17124092 ... AUTHORS ... Sadler JE ... TITLE ... Thrombotic thrombocytopenic purpura: a moving target. ... JOURN

  19. Hypothermia and Platelet Dysfunction

    National Research Council Canada - National Science Library

    Michelson, Alan

    1993-01-01

    ... (the OPlib-Illa complex).3 Circulating platelets are normally in a resting state and, despite the presence of platelet surface GPTh-IX and OPlib-Illa complexes, they bind neither plasma von Willebrand factor nor plasma fibrinogen...

  20. Hypothermia and Platelet Dysfunction

    National Research Council Canada - National Science Library

    Michelson, A

    1994-01-01

    ... (the GPIIb-IIIa complex). Circulating platelets are normally in a resting state and, despite the presence of platelet surface GPIb-IX and GPIIb-IIIa complexes, they bind neither plasma von Willebrand factor nor plasma fibrinogen...

  1. The effect of hyperthyroidism on procoagulant, anticoagulant and fibrinolytic factors: a systematic review and meta-analysis.

    Science.gov (United States)

    Stuijver, Danka J F; van Zaane, Bregje; Romualdi, Erica; Brandjes, Dees P M; Gerdes, Victor E A; Squizzato, Alessandro

    2012-12-01

    Several coagulation and fibrinolytic parameters appear to be affected by thyroid hormone excess; however, the net effect on the haemostatic system remains unclear. We aimed to update our previous review and systematically summarise and meta-analyse the data by assessing the effects of thyrotoxicosis on the coagulation and fibrinolytic system in vivo . Data sources included MEDLINE (2006-2012), EMBASE (2006-2012), and reference lists. The sources were combined with our previous search containing studies from 1980-2006. Eligible studies were all observational or experimental studies. Two investigators independently extracted data and rated study quality. Weighted mean proportion and 95% confidence intervals were calculated and pooled using a fixed and a random-effects model. A total of 29 articles consisting of 51 studies were included, as in several articles more than one study was described. We included four intervention (before and after treatment in hyperthyroid patients), five cross-sectional (hyperthyroid subjects and euthyroid controls), and four experimental (before and after use of thyroid hormone in euthyroid subjects) medium/high quality studies for meta-analysis. We found that thyrotoxicosis shifts the haemostatic balance towards a hypercoagulable and hypofibrinolytic state with a rise in factors VIII and IX, fibrinogen, von Willebrand factor, and plasminogen activator inhibitor-1. This was observed in endogenous and exogenous thyrotoxicosis, and in subclinical as well as overt hyperthyroidism. We conclude that both subclinical and overt hyperthyroidism induce a prothrombotic state, which is therefore likely to be a risk factor for venous thrombosis.

  2. A von Neumann type inequality for certain domains in Cn

    Czech Academy of Sciences Publication Activity Database

    Ambrozie, Calin-Grigore; Timotin, D.

    2002-01-01

    Roč. 131, č. 3 (2002), s. 859-869 ISSN 0002-9939 R&D Projects: GA ČR GA201/03/0041 Institutional research plan: CEZ:AV0Z1019905 Keywords : von Neumann inequality * multioperators * Nevanlinna-Pick problem Subject RIV: BA - General Mathematics Impact factor: 0.334, year: 2002

  3. John von Neumann selected letters

    CERN Document Server

    2005-01-01

    John von Neuman was perhaps the most influential mathematician of the twentieth century, especially if his broad influence outside mathematics is included. Not only did he contribute to almost all branches of mathematics and created new fields, but he also changed post-World War II history with his work on the design of computers and with being a sought-after technical advisor to many figures in the U.S. military-political establishment in the 1940s and 1950s. The present volume is the first substantial collection of (previously mainly unpublished) letters written by von Neumann to colleagues, friends, government officials, and others. The letters give us a glimpse of the thinking of John von Neumann about mathematics, physics, computer science, science management, education, consulting, politics, and war. Readers of quite diverse backgrounds will find much of interest in this fascinating first-hand look at one of the towering figures of twentieth century science.

  4. Automatisierung von HiL Tests

    OpenAIRE

    Asbach, Lennart; Ebrecht, Lars

    2010-01-01

    Automatisierung von HiL Tests. Darstellung und Bewertung einer praktischen Umsetzung. Das Poster zeigt die Motivation, die Durchführung, einen aktuellen Stand und einen Ausblick der Testautomatisierung im Bahnlabor RailSiTe. Als Beispiel dient der Konformitätstest von ETCS-Onboard Zugrechnern, um die Einführung von ETCS zu unterstützen.

  5. Trp[superscript 2313]-His[superscript 2315] of Factor VIII C2 Domain Is Involved in Membrane Binding Structure of a Complex Between the C[subscript 2] Domain and an Inhibitor of Membrane Binding

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Zhuo; Lin, Lin; Yuan, Cai; Nicolaes, Gerry A.F.; Chen, Liqing; Meehan, Edward J.; Furie, Bruce; Furie, Barbara; Huang, Mingdong (Harvard-Med); (UAH); (Maastricht); (Chinese Aca. Sci.)

    2010-11-03

    Factor VIII (FVIII) plays a critical role in blood coagulation by forming the tenase complex with factor IXa and calcium ions on a membrane surface containing negatively charged phospholipids. The tenase complex activates factor X during blood coagulation. The carboxyl-terminal C2 domain of FVIII is the main membrane-binding and von Willebrand factor-binding region of the protein. Mutations of FVIII cause hemophilia A, whereas elevation of FVIII activity is a risk factor for thromboembolic diseases. The C2 domain-membrane interaction has been proposed as a target of intervention for regulation of blood coagulation. A number of molecules that interrupt FVIII or factor V (FV) binding to cell membranes have been identified through high throughput screening or structure-based design. We report crystal structures of the FVIII C2 domain under three new crystallization conditions, and a high resolution (1.15 {angstrom}) crystal structure of the FVIII C2 domain bound to a small molecular inhibitor. The latter structure shows that the inhibitor binds to the surface of an exposed {beta}-strand of the C2 domain, Trp{sup 2313}-His{sup 2315}. This result indicates that the Trp{sup 2313}-His{sup 2315} segment is an important constituent of the membrane-binding motif and provides a model to understand the molecular mechanism of the C2 domain membrane interaction.

  6. Idiopathic combined, autoantibody-mediated ADAMTS-13/factor H deficiency in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome in a 17-year-old woman: a case report

    Directory of Open Access Journals (Sweden)

    Patschan Daniel

    2011-12-01

    Full Text Available Abstract Introduction Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome is a life-threatening condition with various etiopathogeneses. Without therapy approximately 90% of all patients die from the disease. Case presentation We report the case of a 17-year-old Caucasian woman with widespread hematomas and headache. Due to hemolytic anemia, thrombocytopenia, and schistocytosis, thrombotic thrombocytopenic purpura-hemolytic uremic syndrome was suspected and plasma exchange therapy was initiated immediately. Since her thrombocyte level did not increase during the first week of therapy, plasma treatment had to be intensified to a twice-daily schedule. Further diagnostics showed markedly reduced activities of both ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 - also known as von Willebrand factor-cleaving protease and factor H. Test results for antibodies against both proteins were positive. While plasma exchange therapy was continued, rituximab was given once weekly for four consecutive weeks. After the last dose, thrombocytes and activities of ADAMTS-13 and factor H increased into the normal range. Our patient improved and was discharged from the hospital. Conclusions Since no clinical symptoms/laboratory findings indicated a malignant or specific autoimmune-mediated disorder, the diagnosis made was thrombotic thrombocytopenic purpura-hemolytic uremic syndrome due to idiopathic combined, autoantibody-mediated ADAMTS-13/factor H deficiency.

  7. Expression of connective tissue growth factor (CTGF/CCN2) in breast cancer cells is associated with increased migration and angiogenesis.

    Science.gov (United States)

    Chien, Wenwen; O'Kelly, James; Lu, Daning; Leiter, Amanda; Sohn, Julia; Yin, Dong; Karlan, Beth; Vadgama, Jay; Lyons, Karen M; Koeffler, H Phillip

    2011-06-01

    Connective tissue growth factor (CTGF/CCN2) belongs to the CCN family of matricellular proteins, comprising Cyr61, CTGF, NovH and WISP1-3. The CCN proteins contain an N-terminal signal peptide followed by four conserved domains sharing sequence similarities with the insulin-like growth factor binding proteins, von Willebrand factor type C repeat, thrombospondin type 1 repeat, and a C-terminal growth factor cysteine knot domain. To investigate the role of CCN2 in breast cancer, we transfected MCF-7 cells with full-length CCN2, and with four mutant constructs in which one of the domains had been deleted. MCF-7 cells stably expressing full-length CCN2 demonstrated reduced cell proliferation, increased migration in Boyden chamber assays and promoted angiogenesis in chorioallantoic membrane assays compared to control cells. Deletion of the C-terminal cysteine knot domain, but not of any other domain-deleted mutants, abolished activities mediated by full-length CCN2. We have dissected the role of CCN2 in breast tumorigenesis on a structural basis.

  8. Homopteren von Java, gesammelt von Herrn Edw. Jacobson

    NARCIS (Netherlands)

    Melichar, L.

    1914-01-01

    Herr Edw. Jacobson hat auf Java in den Jahren 1908— 1910 Homopteren gesammelt und mir die Bearbeitung des gesammelten Materiales übertragen. Die Jacobson’sche Ausbeute ist insoferne bemerkenswert, als dieselbe viele Mikrohomopteren enthält, welche von nichtfachkundigen Sammlern gewöhnlich nicht

  9. Intra-plaque production of platelet-activating factor correlates with neoangiogenesis in human carotid atherosclerotic lesions.

    Science.gov (United States)

    Lupia, Enrico; Pucci, Angela; Peasso, Paolo; Merlo, Maurizio; Baron, Paolo; Zanini, Cristina; Del Sorbo, Lorenzo; Rizea-Savu, Simona; Silvestro, Luigi; Forni, Marco; Emanuelli, Giorgio; Camussi, Giovanni; Montrucchio, Giuseppe

    2003-09-01

    Platelet-activating factor (PAF) is a phospholipid mediator synthesized by activated inflammatory and endothelial cells. Recently PAF has been shown to contribute to neoangiogenesis in several experimental models. Here we evaluated the presence of PAF and its potential role in neovascularization within human atherosclerotic plaques. The amount of PAF extracted from 18 carotid plaques (266.65+/-40.07 pg/100 mg dry tissue; mean +/- SE) was significantly higher than that extracted from 18 normal arterial specimens (6 from carotid artery and 12 from aorta) (4.72+/-2.31 pg/100 mg dry tissue; mean +/- SE). The levels of PAF significantly correlated with the infiltration of CD68-positive monocytes and the extent of neovascularization, detected as von Willebrand Factor-positive cells. The amount of PAF also correlated with the area occupied by TNF-alpha-expressing cells. The absence of enhanced level of PAF in the circulation of atherosclerotic patients suggests a local production of this mediator within the plaque. The lipid extracts of atherosclerotic plaques containing high levels of PAF-bioactivity, but not those of control arteries, were angiogenic in a murine Matrigel model. WEB 2170, a specific PAF receptor antagonist, significantly prevented angiogenesis induced by the lipid extracts of atherosclerotic plaques. Our results indicate a local production of PAF within the atherosclerotic plaques and suggest that it may contribute to intra-plaque neoangiogenesis.

  10. Properties of von Neumann entropy

    Indian Academy of Sciences (India)

    disentangled) as seen by moving observers, is used to investigate the properties of von Neumann entropy, as a measure of spin–momentum entanglement. To do so, we partition the total Hilbert space into momentum and spin subspaces so that the ...

  11. von Hippel-Lindau disease

    DEFF Research Database (Denmark)

    Binderup, Marie Louise Mølgaard; Gimsing, Steen; Kosteljanetz, Michael

    2013-01-01

    Endolymphatic sac tumours (ELSTs) of the inner ear occur in 16% of patients with the hereditary tumor syndrome von Hippel-Lindau disease (vHL). ELSTs of all sizes can cause irreversible hearing loss which can, however, be prevented through early diagnosis and treatment. We aim to emphasize the ch...

  12. [Friedrich Ludwig von Maydelli pildid Baltimaade ajaloost = Friedrich Ludwig von Maydells Baltische Geschichte in Bildern = Friedrich Ludwig von Maydell ́s Baltic history in images] / Ulrike Plath

    Index Scriptorium Estoniae

    Plath, Ulrike, 1972-

    2014-01-01

    Arvustus: Friedrich Ludwig von Maydelli pildid Baltimaade ajaloost = Friedrich Ludwig von Maydells Baltische Geschichte in Bildern = Friedrich Ludwig von Maydell ́s Baltic history in images. Eesti kunstimuuseum, Kadrioru kunstimuuseum. Tallinn 2013

  13. Pigment epithelium derived factor inhibits the growth of human endometrial implants in nude mice and of ovarian endometriotic stromal cells in vitro.

    Directory of Open Access Journals (Sweden)

    Yanmei Sun

    Full Text Available Angiogenesis is a prerequisite for the formation and development of endometriosis. Pigment epithelium derived factor (PEDF is a natural inhibitor of angiogenesis. We previously demonstrated a reduction of PEDF in the peritoneal fluid, serum and endometriotic lesions from women with endometriosis compared with women without endometriosis. Here, we aim to investigate the inhibitory effect of PEDF on human endometriotic cells in vivo and in vitro. We found that PEDF markedly inhibited the growth of human endometrial implants in nude mice and of ovarian endometriotic stromal cells in vitro by up-regulating PEDF expression and down-regulating vascular endothelial growth factor (VEGF expression. Moreover, apoptotic index was significantly increased in endometriotic lesions in vivo and endometriotic stromal cells in vitro when treated with PEDF. In mice treated with PEDF, decreased microvessel density labeled by Von Willebrand factor but not by α-Smooth Muscle Actin was observed in endometriotic lesions. And it showed no increase in PEDF expression of the ovary and uterus tissues. These findings suggest that PEDF gene therapy may be a new treatment for endometriosis.

  14. Effect of Puumala hantavirus infection on Human Umbilical Vein Endothelial Cell hemostatic function: platelet interactions, increased tissue factor expression and fibrinolysis regulator release

    Directory of Open Access Journals (Sweden)

    Marco Goeijenbier

    2015-03-01

    Full Text Available Puumala virus (PUUV infection causes over 5000 cases of hemorrhagic fever in Europe annually and can influence the hemostatic balance extensively. Infection might lead to hemorrhage, while a recent study showed an increased risk of myocardial infarction during or shortly after PUUV infection. The mechanism by which this hantavirus influences the coagulation system remains unknown. Therefore we aimed to elucidate mechanisms explaining alterations seen in primary and secondary hemostasis during PUUV infection. By using low passage PUUV isolates to infect primary human umbilical vein endothelial cells (HUVECs we were able to show alterations in the regulation of primary- and secondary hemostasis and in the release of fibrinolysis regulators. Our main finding was an activation of secondary hemostasis due to increased tissue factor expression leading to increased thrombin generation in a functional assay. Furthermore, we showed that during infection platelets adhered to HUVECs and subsequently specifically to PUUV virus particles. Infection of HUVECs with PUUV did not result in increased von Willebrand factor while they produced more plasminogen activator inhibitor type-1 (PAI-1 compared to controls. The PAI-1 produced in this model formed complexes with vitronectin. This is the first report that reveals a potential mechanism behind the pro-coagulant changes in PUUV patients, which could be the result of increased thrombin generation due to an increased tissue factor expression on endothelial cells during infection. Furthermore, we provide insight into the contribution of endothelial cell responses regarding hemostasis in PUUV pathogenesis.

  15. Examination of influencing factors on cyclic crack growth behaviour of cracked components. Final report; Untersuchung von Einflussfaktoren auf das zyklische Risswachstum angerissener Bauteile. Abschlussbericht

    Energy Technology Data Exchange (ETDEWEB)

    Soppa, Ewa Anna; Silcher, Horst

    2015-01-31

    Fatigue crack growth of short and long cracks was investigated for both materials: the Nb-stabilized austenitic stainless steel X6 CrNiNb 18-10 and the ferritic-bainitic steel 22 NiMoCr 3-7. These both steels belong to the materials in the primary circuit of german power plants. For a reliable estimation of the lifetime of components subject to cyclic fatigue a detailed knowledge of the phenomena accompanying fatigue processes and which cause both - initiation and growth of fatigue cracks is essential. The deformation induced transformation of austenite into α'-martensite at room temperature is thus very important in the initiation and growth of fatigue cracks. Because these processes are manifest at first at the microlevel, the use of methods which reveal information at high resolution is of significant importance. In order to study the initiation and growth of short cracks, cylindrical smooth specimens, compact tension C(T)- and modified C(T)-specimens have been used. Cyclic crack propagation of long cracks was investigated on compact tension C(T)-specimens with W=50 mm and B=10 mm. The SEM, TEM and EBSD technique are powerful methods for determining crystallographic orientation, for the identification of individual phases and for recealing plastic deformation. They were used for analyses of microcracks in combination with interrupted cyclic tests. The impact of crack closure on the threshold parameter ΔK{sub th} and the crack growth rate da/dN was investigated experimentally for the growth of long cracks under cyclic loading for different R-values at room temperature. Additional tests were performed at T=288 C in order to investigate the role of temperature on crack growth rates. The effect of overloads in tension and compression as another factor influencing the crack growth was also studied. Measured crack growth curves were fitted using Paris and Erdogan-Ratwani law as well as the NASGRO-equation. Fracture surfaces of selected specimens for both steels

  16. Die Rolle von Osteoklasten bei der arthritischen Knochenerosion

    Directory of Open Access Journals (Sweden)

    Schett G

    2003-01-01

    Full Text Available Knöcherne Erosionen stellen eine wesentliche Ursache für die funktionelle Einschränkung von Patienten mit rheumatoider Arthritis dar. Bis vor kurzem war über den Pathomechanismus dieser Veränderungen nur wenig bekannt. Dieser Review faßt die letzten Erkenntnisse über die Ausbildung einer Knochenschädigung bei entzündlichen Gelenkerkrankungen zusammen und fokussiert insbesondere die Rolle von Osteoklasten. Es wird ein Überblickzu den Hinweisen für eine Präsenz von Osteoklasten im entzündlich veränderten Gelenk gegeben. Weiters werden die Faktoren diskutiert, die die Osteoklastogenese im Rahmen einer Gelenkentzündung aktivieren können. Hier wird im besonderen auf die Rolle von Receptor-Activator of Nuclear Factor Kappa B Ligand (RANKL eingegangen. Im weiteren werden die Auswirkungen einer Osteoklastenhemmung in den verschiedenen Arthritismodellen zusammengefaßt und Möglichkeiten einer therapeutischen Nutzung bei rheumatoider Arthritis diskutiert.

  17. Shock, diaschisis and von Monakow

    Directory of Open Access Journals (Sweden)

    Eliasz Engelhardt

    2013-07-01

    Full Text Available The concept of shock apparently emerged in the middle of the 18th century (Whyett as an occurrence observed experimentally after spinal cord transection, and identified as "shock" phenomenon one century later (Hall. The concept was extended (Brown-Séquard and it was suggested that brain lesions caused functional rupture in regions distant from the injured one ("action à distance". The term "diaschisis" (von Monakow, proposed as a new modality of shock, had its concept broadened, underpinned by observations of patients, aiming at distinguishing between symptoms of focal brain lesions and transitory effects they produced, attributable to depression of distant parts of the brain connected to the injured area. Presently, diaschisis is related mainly to cerebrovascular lesions and classified according to the connection fibers involved, as proposed by von Monakow. Depression of metabolism and blood flow in regions anatomically separated, but related by connections with the lesion, allows observing diaschisis with neuroimaging.

  18. Bleeding complications in BCR-ABL negative myeloproliferative neoplasms: prevalence, type, and risk factors in a single-center cohort.

    Science.gov (United States)

    Kander, Elizabeth M; Raza, Sania; Zhou, Zheng; Gao, Juehua; Zakarija, Anaadriana; McMahon, Brandon J; Stein, Brady L

    2015-11-01

    The BCR-ABL1-negative myeloproliferative neoplasms (MPN) share an increased risk of thrombotic and hemorrhagic complications. Risk factors for hemorrhage are less well defined than those for thrombosis. Because patients with CALR mutations have higher platelet counts compared to JAK2 V617F-mutated patients, bleeding rates may be increased in this group. Our aim was to retrospectively evaluate whether acquired von Willebrand disease (AvWD), thrombocytosis, mutational status, or treatment history are associated with bleeding in a cohort of MPN patients. Using an electronic database, MPN patients seen between 2005 and 2013 were retrospectively identified using ICD-9 codes and billing records. A bleeding event was defined as one that was identified in the medical record and graded based on the Common Terminology Criteria for Adverse Event (CTCAE) version 4.0. Among 351 MPN patients, 15.6 % experienced 64 bleeding event types. There was no association of bleeding with mutational status, gender, MPN subtype, aspirin use, prior thrombosis, or platelet count at presentation. There was an association between bleeding and older age at diagnosis. aVWD was identified in six patients. In this single-center retrospective study, bleeding events were identified in 15 % of patients, and associated with older age at diagnosis. aVWD was rarely tested for in this cohort.

  19. Von Hippel–Lindau disease

    Directory of Open Access Journals (Sweden)

    Juhara Haron

    2017-04-01

    Full Text Available Von Hippel–Lindau (VHL disease is a rare autosomal dominantly inherited multisystem disorder characterised by the development of a variety of benign and malignant tumours. We report a case of VHL disease that was inherited by a daughter from her father, who both presented at a young age with progressive headache and were found to have a posterior fossa haemangioblastoma (HB on magnetic resonance imaging (MRI. Multiple benign pancreatic and renal cysts were also noted in both patients.

  20. Microfinance als Geflecht von Anreizproblemen

    OpenAIRE

    Schmidt, Reinhard H.; Tschach, Ingo E.

    2001-01-01

    Während sich die Entwicklungsfinanzierung in Theorie und Praxis generell mit dem Finanzwesen in Entwicklungs- und Transformationsländern befasst, steht im Teilgebiet der Microfinance die Frage im Vordergrund, wie in diesen Ländern der Zugang ärmerer Bevölkerungsgruppen und speziell von Klein- und Kleinstunternehmer(innen), Kleinbauern und sonstigen wirtschaftlich Selbständigen aus eher niedrigen sozialen Schichten zu Kredit und anderen Finanzdiensleistungen verbessert werden kann. Obwohl es e...

  1. Moose von Inselbergen in Benin

    OpenAIRE

    Frahm, Jan-Peter; Porembski, Stefan

    1998-01-01

    Acht Leber- und zehn Laubmoosarten werden von Inselbergen aus Benin angegeben. Fünf der Lebermoose (Acrolejeunea emergens, Riccia atropurpurea, R. congoana, R. discolor, R. moenkemeyeri) und alle Laubmoose (Archidium ohioense, Brachymenium acuminatum, B. exile, Bryum arachnoideum, B. argenteum, Bryum deperssum, Garckea moenkemeyeri, Hyophila involuta, Philonotis mniobryoides und Weissia cf. edentula) werden neu für Benin angegeben. Eight liverworts and ten mosses are reported from inselber...

  2. Entwicklung und Anwendung von Methoden zur Bestimmung von Selen-Spezies in human-biologischem Material

    OpenAIRE

    Jäger, Thomas

    2014-01-01

    Selen ist essentieller Bestandteil von mehr als 25 physiologisch wichtigen menschlichen Enzymen. Der tägliche Bedarf wird überwiegend in Form von organischen Selenverbindungen wie Selenmethionin oder Selenocystein aus der Nahrung aufgenommen. Weitere Expositionswege sind die Einnahme von Nahrungsergänzungsmitteln zur Selensupplementation sowie die inhalative oder dermale Aufnahme von in erster Linie anorganischen Selenverbindungen oder elementarem Selen an Arbeitsplätzen der Selen-verarbeiten...

  3. Dr. von Braun Briefing Walt Disney

    Science.gov (United States)

    1965-01-01

    Dr. von Braun began his association with Walt Disney in the 1950s when the rocket scientist appeared in three Disney television productions related to the exploration of space. Years later, Dr. von Braun invited Disney and his associates to tour the Marshall Space Flight Center (MSFC) in Huntsville, Alabama. This photograph is dated April 13, 1965. From left are R.J. Schwinghamer from the MSFC, Disney, B.J. Bernight, and Dr. von Braun.

  4. Wohnquartiersbeschreibung: ein Instrument zur Regionalisierung von Nachbarschaften

    OpenAIRE

    Hoffmeyer-Zlotnik, Jürgen H. P.

    2001-01-01

    'Ausgehend von der Annahme, daß soziale Differenzierung sich in räumlicher Differenzierung niederschlägt, bietet eine Beschreibung der Struktur des näheren Wohnumfeldes die Möglichkeit, das Wohnquartier als Handlungsraum und Sozialisationsinstanz zur Interpretation von Umfragedaten zu nutzen. Das vorliegende Instrumentarium erlaubt es, das Wohnquartier unabhängig von Zensusdaten über Merkmale, die in der eigenen Umfrage erhoben werden, zu charakterisieren.' (Autorenreferat) 'The general hy...

  5. Untersuchungen zur Entwicklung von Satellitengalaxien

    Science.gov (United States)

    Seidel, Björn

    2002-01-01

    Gleichgewichtsmodelle ein- und zweikomponentiger Satellitengalaxien werden erzeugt und die Gezeiteneinwirkungen der als starres äußeres Potential angenommenen Milchstraße auf sie betrachtet. Eine erste Reihe von Simulationen mit anfänglich kugelsymmetrischen einkomponentigen Satelliten zeigt, daß sich nach elliptischer Deformation ein Balken und Schweife ungleicher Länge ausbilden, deren Aussehen sich periodisch ändert. Mithilfe von Vergleichssimulationen wurden folgende Phänomene am Satelliten entdeckt: (1) Hochdichtebereiche in den Schweifen, (2) Niedrigdichtebereiche um den Kern bzw. Balken und (3) ein oft verdeckter Balken. Analysiert wird das Erscheinungsbild in Zeitabhängigkeit. Die Teilchen gehen dem Kern über den Balken verloren und bewegen sich entlang gewisser stets gleich aussehender charakteristischer Strukturen in die Schweife. Nach einer Herleitung allgemeiner Größen des mehrkomponentigen Kingprofils werden drei stabile Standardmodelle zweikomponentiger Satellitengalaxien mit Massenverhältnis 1:10 (baryonische zu dunkle Materie) und unterschiedlicher Verteilung der dunklen und sichtbaren Materie gefunden. Ohne die Allgemeinheit der Ergebnisse zu beeinträchtigen, wurde dabei die Große Magellanische Wolke als Grundlage der Modelle genommen. Nach geeigneter Wahl der Bahn, zu der der Gezeitenradius des verwendeten dreikomponentigen Milchstraßenpotentials sowohl analytisch als auch numerisch berechnet wird, werden Simulationen der Modelle analysiert. Hauptaugenmerk ist das unterschiedliche Verhalten der Komponenten. Hauptergebnisse: (1) Es ist möglich, große Anteile dunkler, jedoch nur geringe sichtbarer Materie abzulösen. Dunkle und sichtbare Materie können unterschiedliche morphologische Strukturen bilden. (2) Je nach Konzentration der Komponenten ist die Eigengravitation der Teilchen mehr oder weniger für das Aussehen bestimmend. (3) Die Kernauflösung des Satelliten findet im Perigalaktikum (PG), sein Zerfall aber erst im

  6. Research, design and education, Von Humboldt revisited

    NARCIS (Netherlands)

    Bax, M.F.T.; Doevendans, C.H.; Trum, H.M.G.J.; Langenhuizen, Anja; Ouwerkerk, Marieke van; Rosemann, Jurgen

    2001-01-01

    This paper is a result of reflection on the interrelation design-research-cultivation, and on the interpretation of Von Humboldt's maxim: 'Einheit von Forschung und Lehre', which governed the academic world in the past two centuries. It is argued that 'Forschung' should be interpreted as 'Research

  7. Diffusion von Leerstelleninseln auf Cu(111)

    NARCIS (Netherlands)

    Verheij, Laurens K.; Schlößer, Dietmar; Rosenfeld, Georg

    1998-01-01

    Die zufällige Bewegung von Leerstelleninseln wurde bisher vorwiegend in einem Bild beschrieben, das von der Diffusion einzelner Atome ausgeht. In diesem Bild kann man Inseldiffusion durch die Einstein-Beziehung für Brownsche Bewegung ((Δ r)2 = 4 D Δ t) beschreiben. Für die Diffusionskonstante D wird

  8. Optimizing customer contact management to bolster loyalty and profitability. Optimizing specifically quality of service and cost; Loyalitaet und Profitabilitaet von Privat- und Gewerbekunden durch optimiertes Kundenkontaktmanagement steigern. Servicequalitaet und Kosten zielgerichtet optimieren

    Energy Technology Data Exchange (ETDEWEB)

    Hillebrand, S.; Fratzke-Weiss, B.; Handschuh, M.; Muench, U.; Kreuz, W. [A.T. Kearney Management Consultants, Frankfurt/Main (Germany)

    2003-09-08

    Building on the sales strategy, the customer care center's processes, systems, and organization can be optimized in a focused way. Based on the set of success factors described by the authors private and commercial customers' value can be increased significantly. (orig.) [German] Eine klar definierte Vertriebsstrategie ist von elementarer Bedeutung, um das Kundenkontaktmanagement so auszurichten, dass es maximalen Wert fuer das Unternehmen generiert. Ausgehend von der Vertriebsstrategie koennen die Prozesse, die Systeme und die Organisation von Customer Care Centern zielgerichtet optimiert werden. Durch die Beruecksichtigung der von den Verfassern beschriebenen Erfolgsfaktoren kann der Wert von Privat- und Gewerbekunden dabei signifikant gesteigert werden. (orig.)

  9. Prevalence of nucleic acid sequences specific for human parvoviruses, hepatitis A and hepatitis E viruses in coagulation factor concentrates.

    Science.gov (United States)

    Modrow, S; Wenzel, J J; Schimanski, S; Schwarzbeck, J; Rothe, U; Oldenburg, J; Jilg, W; Eis-Hübinger, A M

    2011-05-01

    Due to their high resistance to inactivation procedures, nonenveloped viruses such as parvovirus B19, human bocavirus (HBoV), human parvovirus 4 (PARV4), hepatitis A (HAV) and hepatitis E virus (HEV) pose a particular threat to blood products. Virus transmission to patients treated with blood products presents an additional burden to disease. We determined the frequency and the amount of nucleic acid specific for nonenveloped viruses in recently manufactured preparations of commercial coagulation factor concentrates. At least three different batches of each of 13 different plasma-derived and recombinant coagulation factor products were tested for the presence and the amount of nucleic acid for parvovirus B19, HBoV, human parvovirus 4, hepatitis A virus and HEV by using quantitative polymerase chain reaction. Whereas none of the recombinant products tested positive for any of these viruses, parvovirus B19 DNA with amounts ranging between 2×10(1) and 1.3×10(3) genome equivalents/ml was detected in five plasma-derived products. In addition to parvovirus B19 genotype 1, genotypes 2 and 3 were observed in two batches of a factor VIII/von-Willebrand factor product. In two products (one factor VIII concentrate and one activated prothrombin complex concentrate), a combination of both genotypes 1 and 2 of parvovirus B19 was detected. The data show that nucleic acids from several relevant nonenveloped viruses are not found at detectable levels in coagulation factor concentrates. In some cases, parvovirus B19 DNA was detectable at low levels. Testing of the plasma pools for the full range of parvovirus genotypes is advocated for ensuring product safety. © 2010 The Author(s). Vox Sanguinis © 2010 International Society of Blood Transfusion.

  10. Jacob Stael von Holstein ja palladionism eesti arhitektuuris / Ants Hein

    Index Scriptorium Estoniae

    Hein, Ants, 1952-

    2005-01-01

    Sõjaväeinsenerist ja arhitektist Jacob Stael von Holsteinist (1628, Pärnu-1679), tema kavandatud hoonetest ja rollist 17. sajandi II poole arhitektuuris. Fabian von Ferseni Toompeal Lossiplatsil asunud elamust (lammutati 1894) ja Maardu mõisahoonest, Hans von Ferseni Mäo mõisahoonest Järvamaal, Otto Wilhelm von Ferseni majast Toompeal, Axel von Roseni majast Tallinnas Pikk t. 28 (1670-74), Otto Reinhold von Taube majast Tartus (hävinud), J. S. von Holsteini enda hoonetest: majast Tallinnas Toompea 1, Anija mõisahoonest, elamust Riias jm. Bibliograafia lk. 452

  11. The von Meyenburg complex; Der von Meyenburg Komplex

    Energy Technology Data Exchange (ETDEWEB)

    Schwab, S.A.; Bautz, W.; Uder, M.; Kuefner, M.A. [Erlangen-Nuernberg Univ., Erlangen (Germany). Inst. fuer Radiologie

    2008-07-01

    The von Meyenburg complex (VMC) describes bile duct hamartomas and presents a rare, benign incidental finding in liver imaging. We report on a 61-year-old man, who was referred for a follow up study 14 years after remission of Hodgkin's disease. Computed tomography (CT) revealed multiple hypodense lesions throughout the liver, primary suggesting recurrent Hodgkin's disease. Previous CT-examinations, which were obtained at a later date, showed those lesions in identical distribution and morphology over the years, leading to diagnosis of multiple bile duct hamartomas (VMC). Making imaging-based diagnosis of VMC including ultrasound, CT and magnetic resonance imaging is a challenging task for the radiologist. Based on literature research findings, the impact of different modalities in the diagnostic work-up of VMC is discussed. (orig.)

  12. Neues über das Tertiär von Java und die mesozoischen Schichten von West-Borneo

    NARCIS (Netherlands)

    Martin, K.

    1888-01-01

    Die Monographie, welche unter dem Titel Die Fossilien von Java herausgegeben wird ¹), ist so weit fortgeschritten, dass sich aus den in ihr beschriebenen Gastropoden bereits eine Anzahl von Schlussfolgerungen ableiten lässt, welche für die in Bearbeitung begriffene, geologische Karte von Java von

  13. Eine Analyse des Zusammenhangs zwischen dem Konsum von Alkopops und dem Problemverhalten von Jugendlichen

    OpenAIRE

    Metzner, Cornelia Beate Isabel

    2007-01-01

    Zielsetzung: In dieser Arbeit wird untersucht, ob bei Jugendlichen ein Zusammenhang zwischen dem Konsum von Alkopops einerseits und dem sonstigen Alkoholtrinkverhalten, dem Konsum von Zigaretten und illegalen Drogen sowie weiteren Risikoverhaltensweisen andererseits besteht, ferner ob sich Unterschiede im Verhalten von Jungen und Mädchen ergeben. Theoretischer und empirischer Hintergrund: �Alkopops�, d. h. Mischgetränke diverser Hersteller aus Likör bzw. Schnaps und Limonade sowie wein- ...

  14. Analytik von Minorlipiden: Ferulasäureester von Phytosterolen (gamma-Oryzanol) in Reis

    OpenAIRE

    Miller, Andreas

    2005-01-01

    Ferulasäureestern von Phytosterolen (γ-Oryzanol) werden antioxidative und cholesterinsenkende Eigenschaften zugeschrieben. Bisher beschriebene Methoden zur Analytik von γ-Oryzanol in Reis erforderten eine aufwendige Aufreinigung des Probenextrakts. In dieser Arbeit wurde basierend auf der on-line LC-GC eine Methode entwickelt, die die simultane Bestimmung von γ-Oryzanol-Gehalt und Sterylferulat-Verteilung ohne Aufreinigung des Probenextrakts erlaubt. Mit Hilfe der Technik wurden die natürlich...

  15. Redoxspeziation von endlagerrelevanten Elementen mit Hilfe von Trennmethoden gekoppelt an ein Massenspektrometer mit induktiv gekoppeltem Plasma

    OpenAIRE

    Graser, Carl-Heinrich

    2015-01-01

    Im Rahmen dieser Arbeit wurden Redoxspeziationsanalysen von Eisen, Neptunium und Plutonium per CE-SF-ICP-MS durchgeführt. Durch Optimierung der Trennparameter konnten Trennungen der Pu Oxidationsstufen III bis VI und Trennungen der Np Oxidationsstufen IV bis VI binnen 15 Minuten mit einer Nachweisgrenze von 10-12 M durchgeführt werden. Die Trennung der Fe Oxidationsstufen II und III gelang in weniger als 5 Minuten mit einer Nachweisgrenze von 5-10-8 M.

  16. 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....

  17. Practical event analysis; Durchfuehrung von Ereignisanalysen in der Praxis

    Energy Technology Data Exchange (ETDEWEB)

    Scheuring, R. [Bayernwerk Kernenergie GmbH - Kernkraftwerk Grafenrheinfeld (Germany)

    1999-04-01

    The paper explains the systematic approaches and practical aspects of evaluation of NPP operating reports and implementation of identified remedial action for enhancing the safety in terms of human, organisational, and technology factors. The procedures adopted for the Grafenrheinfeld nuclear power station (KKG) serve as an example. (orig./CB) [German] Ein wichtiger Bestandteil zur Erhaltung und Fortentwicklung des Sicherheitsniveaus ist das Lernen aus der Erfahrung. Hierzu wiederum ist ein systematisches Vorgehen zur Vermeidung von Fehlern und Behebung von Schwachstellen menschlicher, technischer und organisatorischer Natur unabdingbare Voraussetzung. Die Anwendung einer umfassenden Auswertemethodik beinhaltet - die Erfassung und Informationsweitergabe externer und interner Vorkommnisse und Erfahrungen - eine systematische Analyse/Auswertung - eine konsequente Umsetzung der Abhilfemassnahmen unter Einbeziehen aller betroffenen Organisationseinheiten. Wie erfolgt die Umsetzung dieser Vorgaben in die Praxis? Im Kernkraftwerk Grafenrheinfeld (KKG) ist die Auswertung von externen und internen Betriebserfahrungen als Aufgabe im Betriebshandbuch (BHB) 'Personelle Betriebsorganisation' vorgegeben und im Detail im Sinne der Ablauforganisation im Qualitaetssicherungshandbuch in Qualitaetssicherungsanweisungen (QSA) beschrieben. (orig.)

  18. Purification and characterization of factor VIII 1,689-Cys: a nonfunctional cofactor occurring in a patient with severe hemophilia A.

    Science.gov (United States)

    O'Brien, D P; Tuddenham, E G

    1989-06-01

    We have purified the factor VIII from a CRM+ Hemophilia A plasma (90 U/dL VIII:Ag but 0 U/dL VIII:C) and analyzed the protein before and after thrombin activation by Western blotting with monoclonal antibodies (MoAbs). Normal or patient citrated plasma was ultracentrifuged, cryo-ethanol-precipitated and chromatographed on Sepharose 6B. The void volume fractions were reduced and subjected to ion exchange chromatography yielding material of specific activity approximately 1,000 U/mg protein (VIII:C or VIII:Ag). Factor VIII purified in this way from normal plasma is fully activatable by thrombin with proteolytic fragmentation as previously described by F. Rotblat et al (Biochemistry 24: 4294, 1985). Factor VIII 1,689-Cys has the normal distribution of factor VIII light and heavy chains prior to thrombin activation. After exposure to thrombin the heavy chain polypeptides were fully proteolysed but the light chain was totally resistant to cleavage. This is consistent with the demonstration in the patient's leucocyte DNA of a C to T transition in codon 1,689 converting Arg to Cys at the light chain thrombin cleavage site as previously described by J. Gitschier et al (Blood 72:1022, 1988). Uncleaved light chain of Factor VIII 1,689-Cys is not released from von Willebrand factor (vWF) by thrombin, but this is not the sole cause of the functional defect since the protein purified free of vWF has no coagulant activity. We conclude that the functional defect in factor VIII 1,689-Cys is a consequence of failure to release the acidic peptide from the light chain upon thrombin activation.

  19. THE DIGITAL VON FAHRENHEID PYRAMID

    Directory of Open Access Journals (Sweden)

    M. Bura

    2017-08-01

    Full Text Available 3D Scanners Lab from Digital Humanities Laboratory at the University of Warsaw initiated the scientific project, the purpose of which was to call attention to systematically penetrated and devastated pyramid-shaped tomb from the XVIII/XIX century, of family von Fahrenheid in Rapa in Banie Mazurskie commune (NE Poland. By conducting a series of non-invasive studies, such as 3D inventory using terrestrial laser scanning (TLS, thermal imaging, georadar measurements (around and inside the tomb and anthropological research of mummified remains as well - the complete dataset was collected. Through the integration of terrestrial (TLS and airborne laser scanning (ALS authors managed to analyse the surroundings of Fahrenheid pyriamid and influence of some objects (like trees on the condition and visibility of the Pyramids in the landscape.

  20. Die Wirkung von Desacetylcefotaxin, einem Metaboliten von Cefotaxim, in vitro und auf die experimentelle Infektion mit Escherichia coli

    OpenAIRE

    Wirbelauer, J.; Hof, H.; Hacker, Jörg

    2009-01-01

    Die MHK-Werte von Desacetylcefotaxim gegen verschiedene, z. T. ampicillinresistente Stämme von Escherichia coH, die mit Hilfe einer Agardilutionsmethode erhoben wurden, waren höher als die von Cefotaxim und Ceftriaxon, jedoch niedriger als die von Cefoxitin. In einem Modell der systemischen Infektion der Maus mit einem plasmidtragenden, betalactamaseproduzierenden Stamm von E. coli führte die Therapie mit Desacetylcefotaxim zu einer starken Reduktion der Keime pro Leber. Im Vergleich zur Ther...

  1. VON WISPR Family Processors: Volume 1

    National Research Council Canada - National Science Library

    Wagstaff, Ronald

    1997-01-01

    ...) and the background noise they are embedded in. Processors utilizing those fluctuations such as the von WISPR Family Processors discussed herein, are methods or algorithms that preferentially attenuate the fluctuating signals and noise...

  2. Von Onlineplattformen und mittelalterlichen Märkten

    Directory of Open Access Journals (Sweden)

    Claudius Gräbner

    2017-12-01

    Full Text Available Mit der zunehmenden Digitalisierung und Vernetzung ökonomischer Systeme haben plattformbasierte Interaktionsbeziehungen stark an Bedeutung gewonnen. Hier werden zwei oder mehr Nutzungsgruppen durch eine dritte Seite, die Plattform, zusammengebracht. Die Interaktion wird in solchen zweiseitigen Märkten von den Plattformbetreibern kontrolliert. Kreditkartensysteme, Softwaremärkte oder werbefinanzierte Online-Communities stellen typische Beispiele dar. Da die Analyse von zweiseitigen Märkten mit Gleichgewichtsmodellen aufgrund der algebraischen Struktur des Problems in der Regel nicht praktikabel ist, präsentieren wir im vorliegenden Beitrag ein agentenbasiertes Modell, welches in einem kürzlich erschienenen Artikel ausführlicher diskutiert wird. Anhand von illustrativen Beispielen verdeutlichen wir die Implikationen eines agentenbasierten Ansatzes für die Innovationsökonomik im Allgemeinen und das Studium von Technologieentwicklung im Besonderen.

  3. Johann Friedrich Wilhelm Adolf von Baeyer

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 19; Issue 6. Johann Friedrich Wilhelm Adolf von Baeyer: A Pioneer of Synthetic Organic Chemistry. Gopalpur Nagendrappa. General Article Volume 19 Issue 6 June 2014 pp 489-522 ...

  4. Titanisierung von Implantatoberflächen

    Science.gov (United States)

    Zimmermann, Hanngörg; Heinlein, Markus; Guldner, Norbert W.

    Titan gilt seit Jahrzehnten als einer der wichtigsten Implantatwerkstoffe in der Medizin. Neben den guten mechanischen Eigenschaften (Leichtigkeit, hohe Festigkeit etc.), besitzen Titanimplantate vor allem eine hervorragende Körperverträglichkeit, so dass die Implantate optimal in den humanen Organismus integriert werden [1]. Ist jedoch aufgrund der Anforderungen an das Implantat eine hohe Flexibilität und/ oder Elastizität gefragt, so scheidet der Werkstoff Titan aufgrund seiner spröden und unflexiblen Materialeigenschaften aus. Die Folge ist der Einsatz von Implantatmaterialien, sowohl künstlichen als auch biologischen Ursprungs, welche nicht selten eine unzureichende Biokompatibilität aufweisen und somit zu Fremdköper- und immunologischen Reaktionen und Einkapselung des Implantates führen können. Die Erhöhung der Körperverträglichkeit, eine Adaption an das biologische Umfeld und eine hohe Biokompatibilität sind demzufolge die wichtigsten Eigenschaften bei der bedarfsgerechten Herstellung von Implantaten und Implantatoberflächen. Zur Gestaltung von innovativen, biokompatiblen Oberflächen stehen unterschiedliche technische Lösungsansätze zur Verfügung. Zum einen besteht die Möglichkeit, geeignete Oberflächeneigenschaften aus dem Grundmaterial selbst zu optimieren. Dies geschieht unter anderem durch Modifikation der Werkstoffoberflächen in Form von Texturierungen und Oberflächenrauhigkeiten. Zum anderen können die Oberflächeneigenschaften unabhängig von denen des Trägermaterials gestaltet werden. Durch Funktionalisierung der Oberflächen mit geeigneten Beschichtungen oder der Zugabe von Medikamenten (Drug Eluting) werden die Kunststoffimplantate dahingehend verändert, dass eine Steigerung der Körperakzeptanz erreicht wird. Die Titanbeschichtung von Implantatoberflächen kombiniert die positiven Materialeigenschaften von Titan und Polymer.

  5. 50th birthday of Christian von Ferber

    Directory of Open Access Journals (Sweden)

    2011-06-01

    Full Text Available On May 15, 2011 Christian von Ferber - member of the Editorial Board of "Condensed Matter Physics" and renowned expert in the fields of soft matter physics and complex systems - celebrated his 50th birthday. The Editorial board of CMP, colleagues and friends warmy congratulate Christian von Ferber and wish him and his family continuing good health and to enjoy many adventures and discoveries in his future scientific travels!

  6. Hullud päevad von Krahlis

    Index Scriptorium Estoniae

    2006-01-01

    Von Krahli Teatris mängitakse neil päevi neli korda Peeter Jalaka lavastuses Tõnu Kõrvitsa kammeroopereid "Tuliaed" ja "Mu luiged, mu mõtted", mille aluseks on luuletaja Marie Heibergi saatus. Libreto autor on Maarja Kangro. Kammerooperid tulevad lavale Von Krahli Teatri ja Nargen Opera koostöös. Esitavad Kädy Plaas, Helen Lokuta, Nargen Opera koor ja Tallinna Kammerorkester, dirigent Tõnu Kaljuste

  7. Bedeutung von Umwelt- und Organismusfaktoren bei Autoaggressionen

    OpenAIRE

    Rohmann, Ulrich H.; Elbing, Ulrich; Hartmann, Hellmut

    1988-01-01

    In der vorliegenden Arbeit werden übergeordnete Hypothesen zu autoaggressiven Verhaltensweisen formuliert, wobei prozeßhafte Abläufe von umweltbezogenen und organischen Variablen angenommen werden. Eine solche dynamische Beziehung hat ihre Bedeutung sowohl für verursachende als auch aufrechterhaltende Faktoren. In einer Querschnittuntersuchung lassen sich Korrelationen von Tageszeit- und Tätigkeitscharakteristiken (umweltbezogene Variablen) zur Autoaggressionshäufigkeit und Pulsfrequenz (Orga...

  8. Visualisierung von typisierten Links in Linked Data

    Directory of Open Access Journals (Sweden)

    Georg Neubauer

    2017-09-01

    Full Text Available Das Themengebiet der Arbeit behandelt Visualisierungen von typisierten Links in Linked Data. Die wissenschaftlichen Gebiete, die im Allgemeinen den Inhalt des Beitrags abgrenzen, sind das Semantic Web, das Web of Data und Informationsvisualisierung. Das Semantic Web, das von Tim Berners Lee 2001 erfunden wurde, stellt eine Erweiterung zum World Wide Web (Web 2.0 dar. Aktuelle Forschungen beziehen sich auf die Verknüpfbarkeit von Informationen im World Wide Web. Um es zu ermöglichen, solche Verbindungen wahrnehmen und verarbeiten zu können sind Visualisierungen die wichtigsten Anforderungen als Hauptteil der Datenverarbeitung. Im Zusammenhang mit dem Sematic Web werden Repräsentationen von zuhammenhängenden Informationen anhand von Graphen gehandhabt. Der Grund des Entstehens dieser Arbeit ist in erster Linie die Beschreibung der Gestaltung von Linked Data-Visualisierungskonzepten, deren Prinzipien im Rahmen einer theoretischen Annäherung eingeführt werden. Anhand des Kontexts führt eine schrittweise Erweiterung der Informationen mit dem Ziel, praktische Richtlinien anzubieten, zur Vernetzung dieser ausgearbeiteten Gestaltungsrichtlinien. Indem die Entwürfe zweier alternativer Visualisierungen einer standardisierten Webapplikation beschrieben werden, die Linked Data als Netzwerk visualisiert, konnte ein Test durchgeführt werden, der deren Kompatibilität zum Inhalt hatte. Der praktische Teil behandelt daher die Designphase, die Resultate, und zukünftige Anforderungen des Projektes, die durch die Testung ausgearbeitet wurden.

  9. von Neumann entropy associated with the haldane exclusion statistics

    International Nuclear Information System (INIS)

    Rajagopal, A.K.

    1995-01-01

    We obtain the von Neumann entropy per state of the Haldane exclusion statistics with parameter g in terms of the mean occupation number bar n{wlnw-(1+w)ln(1+w)}, where w=(1-bar n). This reduces correctly to the well known expressions in the limiting cases of Bose (g=0) and Fermi (g=1) statistics. We have derived the second and third order fluctuations in the occupation numbers for arbitrary g. An elegant general duality relationship between the w factor associated with the particle and that associated with the hole at the reciprocal g is deduced along with the attendant relationship between the two respective entropies

  10. Von Bertalanffy's dynamics under a polynomial correction: Allee effect and big bang bifurcation

    Science.gov (United States)

    Leonel Rocha, J.; Taha, A. K.; Fournier-Prunaret, D.

    2016-02-01

    In this work we consider new one-dimensional populational discrete dynamical systems in which the growth of the population is described by a family of von Bertalanffy's functions, as a dynamical approach to von Bertalanffy's growth equation. The purpose of introducing Allee effect in those models is satisfied under a correction factor of polynomial type. We study classes of von Bertalanffy's functions with different types of Allee effect: strong and weak Allee's functions. Dependent on the variation of four parameters, von Bertalanffy's functions also includes another class of important functions: functions with no Allee effect. The complex bifurcation structures of these von Bertalanffy's functions is investigated in detail. We verified that this family of functions has particular bifurcation structures: the big bang bifurcation of the so-called “box-within-a-box” type. The big bang bifurcation is associated to the asymptotic weight or carrying capacity. This work is a contribution to the study of the big bang bifurcation analysis for continuous maps and their relationship with explosion birth and extinction phenomena.

  11. ˝FLUMINENSIA˝ VON FRAN KURELAC

    Directory of Open Access Journals (Sweden)

    Leopoldina Veronika Banaš

    1990-01-01

    Full Text Available Das Buch "Fluminensia" (1862 von Fran Kurelac enthält die für die Schulfestlichkeiten geschriebenen Reden, Gelegenheitsgedichte - Ehrengedichte den bedeutenden und verdienstvollen Zeitgenossen gewidmet: dem Bischof von Senj und Modrus" Mirko Ožegović, Bartol Zmajic von Bakar, dem kroatischen Ban Josip Jelačić u.a. Danach folgen Aufrufe ("Proglasi" aus stürmischem 1848, gerichtet auf die Granzlandbewohner, Deutscher, ungarische Kroaten, Rumänen und Slawonier. Die Aufrufe wurden von Kurelac im Namen der Banalregierung beschrieben. Am Ende des Buches steht eine sprachwissenschaftliche Abhandlung über die ubstantivbiegung. Die für die Schulfestlichkeiten geschreibenen Reden sind wissenschaftliche Inhalte, essaystisch-didaktisch gestalltet, mit der Meldung über die Bedeutung der Wisenschaft, über die Bedeutung und Rolle der Sprache und des Buches für den Fortschritt des Volkes. Der Verfasser widmete dieses Buch seinen ehemaligen Schülern. "Fluminensia" nimmt eine wichtige Stelle in literarischer und sprachwissenschaftlicher Schöpfung auf dem Gebiet von Rijeka und Kroatien im 19. Jahrhundert ein.

  12. Privatiserung von Geschichte. Probleme einer differenzierten Aufarbeitung

    Directory of Open Access Journals (Sweden)

    Birthe Kundrus

    2000-11-01

    Full Text Available Ausgangspunkt der Untersuchung von Vera Neumann ist die These, daß im Krieg Erlebtes und Erlittenes in den Wiederaufbau- und Wirtschaftswunderjahren Westdeutschlands einem Thematisierungstabu unterlegen sei. Anhand von 50 Interviews, die in den 80er Jahren im Rahmen des von Lutz Niethammer geleiteten Projekts „Lebensgeschichte und Sozialgeschichte im Ruhrgebiet 1930–1960“ (LUSIR entstanden sind und die sie jetzt anhand der Tonbandprotokolle und Abschriften ein zweites Mal auswertet, möchte die Historikerin diese Verschüttungen aufspüren. Im Anschluß an Niethammers These der „Privatisierung von Geschichte“ will sie zeigen, daß seelische und körperliche Kriegsfolgen wie Deprivations- und Überlastungsgefühle, der Verlust von Angehörigen und Kriegsbeschädigungen „privatisiert“, d.h. an die Familien übertragen wurden. Dort seien dann in erster Linie die weiblichen Familienmitglieder mit der Versorgungs- und Pflegearbeit konfrontiert worden. An vier Fallbeispiele schließt sich eine detaillierte Auswertung des gesamten Interviewmaterials an. Diesen Teilen folgt ein Abschnitt zur staatlichen Kriegsopferversorgung in der frühen Bundesrepublik.

  13. A new von Mises probabilistic formula for quartet invariants

    International Nuclear Information System (INIS)

    Giacovazzo, C.; Camalli, M.; Spagna, R.

    1989-01-01

    Von Mises formulas for quartet invariants, even is useful in most cases of practical interest, suffer from some systematic errors. A new von Mises formula is suggested with better theoretical features. (orig.)

  14. Kerttu Wagner. Die historischen romane von Jaan Kross / Wolfgang Drechsler

    Index Scriptorium Estoniae

    Drechsler, Wolfgang, 1963-

    2001-01-01

    Arvustus: Wagner, Kerttu. Die historischen Romane von Jaan Kross : am Beispiel einer Untersuchung der deutschen und englischen Übersetzungen von "Professor Martensi ärasõit" (1984). Frankfurt am Main [etc.] : P. Lang, 2001.

  15. IAS 25, Bilanzierung von Finanzinvestitionen (Accounting for Investments)

    OpenAIRE

    Steiner, Manfred

    1997-01-01

    IAS 25, Bilanzierung von Finanzinvestitionen (Accounting for Investments). - In: Rechnungslegung nach International Accounting Standards (IAS) / hrsg. von Jörg Baetge ... - Stuttgart : Schäffer-Poeschel, 1997. - S. 923-953

  16. Borel reductibility and classification of von neumann algebras

    DEFF Research Database (Denmark)

    Sasyk, R.; Törnquist, Asger Dag

    2009-01-01

    We announce some new results regarding the classification problem for separable von Neumann algebras. Our results are obtained by applying the notion of Borel reducibility and Hjorth's theory of turbulence to the isomorphism relation for separable von Neumann algebras....

  17. Zr-89-Bevacizumab PET Visualizes Disease Manifestations in Patients with von Hippel-Lindau Disease

    NARCIS (Netherlands)

    Oosting, Sjoukje F.; van Asselt, Sophie J.; Brouwers, Adrienne H.; Bongaerts, Alfons H. H.; Steinberg, Julia D. J.; de Jong, Johan; Lub-de Hooge, Marjolijn N.; Horst-Schrivers, van der Anouk N. A.; Walenkamp, Annemiek M. E.; Hoving, Eelco W.; Sluiter, Wim J.; Zonnenberg, Bernard A.; de Vries, Elisabeth G. E.; Links, Thera P.

    2016-01-01

    Patients with von Hippel-Lindau disease (VHL) are at risk to develop multiple tumors. The growth of lesions is unpredictable, and regular surveillance is critical for early treatment to control local damage. Vascular endothelial growth factor A (VEGF-A) produced locally is supposed to play an

  18. Medien und Berufsvorstellungen von Kindern: eine experimentelle Studie zum Einfluss von Kinderbüchern auf das Berufsspektrum von Kindergartenkindern

    OpenAIRE

    Brüggemann, Tim; Gehrau, Volker; Handrup, Jutta

    2015-01-01

    "Der Beitrag thematisiert zunächst den Stand der beruflichen Orientierung von Jugendlichen sowie die pädagogischen Bemühungen beim Übergang Schule-Beruf, insbesondere im Hinblick auf eine Erweiterung des häufig engen Spektrums von Berufen, die bei der Berufswahl berücksichtig werden. Dabei richten sich die Bestrebungen, diesem Problem entgegenzuwirken, bislang vor allem auf Jugendliche. Anschließend wird anhand vorliegender Ergebnisse aus der Medienforschung diskutiert, in welcher Weise Masse...

  19. Gemeinsam hilfreich oder einsam lästig? Beurteilung von praktikumsbegleitenden Weblogs von angehenden Lehrpersonen

    Directory of Open Access Journals (Sweden)

    Nives Egger

    2017-02-01

    Full Text Available Weblogs werden an Hochschulen vermehrt zur Unterstützung von Lern- und Reflexionsprozessen eingesetzt, in der Lehrer/innenbildung auch zunehmend während der berufspraktischen Ausbildung. Die Studierenden beurteilen den Einsatz von Weblogs jedoch unterschiedlich. Dabei ist wenig bekannt, welchen Einfluss die Vergabe und das Erhalten von Peerfeedback auf den Beurteilungsprozess von praktikumsbegleitenden Weblogs sowie auf den Umfang von Blogpostings haben. Im folgenden Beitrag wird dieser Frage mittels einer Befragung von 74 angehenden Lehrpersonen nachgegangen, die praktikumsbegleitende Weblogs mit oder ohne Peerfeedback nutzten, um über herausfordernde Ereignisse im Praktikum zu reflektieren. Die Ergebnisse zeigen, dass Studierende, die Peerfeedback erhielten und andere Blogbeiträge kommentierten, den Weblogeinsatz nützlicher einschätzen sowie eine höhere Motivation und positivere Einstellung gegenüber den Einsatz von Weblogs aufweisen als Studierende, die ohne Peerfeedback bloggen. Keinen Einfluss hat Peerfeedback auf den Umfang der Blogbeiträge und auf die dafür aufgewendete Zeit.

  20. [Anja Wilhelmi. Lebensweltlen von Frauen der deutschen Oberschicht im Baltikum (1800-1939). Eine Untersuchung anhand von Autobiographien] / Alexander Ewig

    Index Scriptorium Estoniae

    Ewig, Alexander, 1980-

    2011-01-01

    Arvustus: Wilhelmi, Anja. Lebenswelten von Frauen der deutschen Oberschicht im Baltikum (1800-1939). Eine Untersuchung anhand von Autobiographien. (Veröffentlichungen des Nordost-Instituts, 10.) (Wiesbaden : HArrassowitz 2008)

  1. Gasification of liquid manure; Vergasung von Guelle

    Energy Technology Data Exchange (ETDEWEB)

    Gudenau, H.W.; Hoberg, H.; Hirsch, U. [Technische Hochschule Aachen (Germany). Inst. fuer Eisenhuettenkunde

    1996-12-31

    The potential of thermal use of liquid manure is investigated. It is recommended to separate the liquid and solid fraction. While the liquid fraction can be used as fertilizer, the solid fraction can be used for generating a fuel gas for combined heat and power generation. (orig) [Deutsch] Die Untersuchungen haben ergeben, dass in der thermischen Verwertung von Guelle ein bisher nur wenig genutztes Potential vorliegt. Die zum Anbau von Getreide notwendige Duengung kann durch Separation von Guelle in Fest- und Duennfraktion effektiver und kostenguenstiger durchgefuehrt werden. Der Naehrstoffgehalt des Guellefeststoffs sollte durch thermische Aufbereitung aufkonzentriert werden, so dass eine Vermarktung auch mit laengeren Transpoertwegen darstellbar ist. Die bei der thermischen Behandlung gewonnene Waerme kann prozessintern genutzt und ueberschuessige Waerme an Abnehmer in der naeheren Umgebung geliefert werden. Genauso besteht die Moeglichkeit, ein Brenngas zu erzeugen und die Energie mit Kraft-Waerme-Kopplung zu nutzen. (orig)

  2. Gasification of liquid manure; Vergasung von Guelle

    Energy Technology Data Exchange (ETDEWEB)

    Gudenau, H W; Hoberg, H; Hirsch, U [Technische Hochschule Aachen (Germany). Inst. fuer Eisenhuettenkunde

    1997-12-31

    The potential of thermal use of liquid manure is investigated. It is recommended to separate the liquid and solid fraction. While the liquid fraction can be used as fertilizer, the solid fraction can be used for generating a fuel gas for combined heat and power generation. (orig) [Deutsch] Die Untersuchungen haben ergeben, dass in der thermischen Verwertung von Guelle ein bisher nur wenig genutztes Potential vorliegt. Die zum Anbau von Getreide notwendige Duengung kann durch Separation von Guelle in Fest- und Duennfraktion effektiver und kostenguenstiger durchgefuehrt werden. Der Naehrstoffgehalt des Guellefeststoffs sollte durch thermische Aufbereitung aufkonzentriert werden, so dass eine Vermarktung auch mit laengeren Transpoertwegen darstellbar ist. Die bei der thermischen Behandlung gewonnene Waerme kann prozessintern genutzt und ueberschuessige Waerme an Abnehmer in der naeheren Umgebung geliefert werden. Genauso besteht die Moeglichkeit, ein Brenngas zu erzeugen und die Energie mit Kraft-Waerme-Kopplung zu nutzen. (orig)

  3. Spectral theory and quotients in Von Neumann algebras | West ...

    African Journals Online (AJOL)

    In this note we consider to what extent the functional calculus and the spectral theory in von Neumann algebras are preserved by the taking of quotients relative to two-sided ideals of the von Neumann algebra. Keywords:von Neumann algebra, functional calculus, spectral theory, quotient algebras. Quaestiones ...

  4. Extension of Tissue Plasminogen Activator Treatment Window by Granulocyte-Colony Stimulating Factor in a Thromboembolic Rat Model of Stroke

    Directory of Open Access Journals (Sweden)

    Ike C. dela Peña

    2018-05-01

    Full Text Available When given beyond 4.5 h of stroke onset, tissue plasminogen activator (tPA induces deleterious side effects in the ischemic brain, notably, hemorrhagic transformation (HT. We examined the efficacy of granulocyte-colony stimulating factor (G-CSF in reducing delayed tPA-induced HT, cerebral infarction, and neurological deficits in a thromboembolic (TE stroke model, and whether the effects of G-CSF were sustained for longer periods of recovery. After stroke induction, rats were given intravenous saline (control, tPA (10 mg/kg, or G-CSF (300 μg/kg + tPA 6 h after stroke. We found that G-CSF reduced delayed tPA-associated HT by 47%, decreased infarct volumes by 33%, and improved motor and neurological deficits by 15% and 25%, respectively. It also prevented delayed tPA treatment-induced mortality by 46%. Immunohistochemistry showed 1.5- and 1.8-fold enrichment of the endothelial progenitor cell (EPC markers CD34+ and VEGFR2 in the ischemic cortex and striatum, respectively, and 1.7- and 2.8-fold increases in the expression of the vasculogenesis marker von Willebrand factor (vWF in the ischemic cortex and striatum, respectively, in G-CSF-treated rats compared with tPA-treated animals. Flow cytometry revealed increased mobilization of CD34+ cells in the peripheral blood of rats given G-CSF. These results corroborate the efficacy of G-CSF in enhancing the therapeutic time window of tPA for stroke treatment via EPC mobilization and enhancement of vasculogenesis.

  5. Der Einfluss von sozialer Ungleichheit und kulturellen Unterschieden auf die Wahrnehmung von finanziellen und Arbeitsplatzrisiken: Überlegungen zur Risikogesellschaft

    OpenAIRE

    Abbott, David; Quilgars, Deborah; Jones, Anwen

    2006-01-01

    Der vorliegende Artikel beruht auf Daten einer Studie, die sich mit der Frage beschäftigt, wie verschiedene soziale und kulturelle Gruppen die Risiken von Einkommens- und Arbeitsplatzverlust wahrnehmen und darauf reagieren. Autoren wie LASH, DOUGLAS und LUPTON betonten die Bedeutung von Gruppenzugehörigkeit und sozialen Kategorien für die Strukturierung der Reaktionsweisen auf verschiedene Risikoarten. Sie sprechen daher lieber von Risikokulturen als von der Risikogesellschaft. Trotzdem erken...

  6. Bewertung von Fahrzeuggeräuschen

    Science.gov (United States)

    Genuit, Klaus; Schulte-Fortkamp, Brigitte; Fiebig, André; Haverkamp, Michael

    Bei der Wahrnehmung und Beurteilung eines Automobils sind unzählige Merkmale und Eigenschaften von Bedeutung. Dabei können Merkmale objektiv-technisch beschrieben werden, wie Angaben zur Motorisierung, Höchstgeschwindigkeit, Drehmoment, zulässige Zuladung, Verbrauch usw. Daneben sind weitere Eigenschaften von Bedeutung, die sich einer einfachen objektiv-technischen Beschreibung entziehen. Hier sind Begriffe zu nennen, wie Sicherheit, allgemeine Qualitätsanmutung, Design, Ergonomie, Komfort, Haptik, Fahrdynamik, Zuverlässigkeit, die deutlich schwieriger objektiv erfassbar und beschreibbar sind (Abb. 4.1).

  7. Asymptotic analysis of a von Koch beam

    International Nuclear Information System (INIS)

    Carpinteri, Alberto; Pugno, Nicola; Sapora, Alberto

    2009-01-01

    Fractal geometry is used in diverse research areas, being an useful tool in describing the mechanical behaviour of natural and man-made structures. In this paper, the structural behaviour of a von Koch cantilever beam is analyzed in the small deformations regime. Analytical recursive formulae for the strain energy scaling are derived, which have been found in good agreement with numerical simulations. Energy considerations suggest a peculiar scaling for the beam rigidity in order to prevent compliance divergence. The results are then extended to evaluate the stiffness matrix of a von Koch beam.

  8. Von Mumien, Cyborgs und Röntgenbildern

    Directory of Open Access Journals (Sweden)

    Regina Schleicher

    2004-03-01

    Full Text Available Unter dem Titel Techniken der Reproduktion liegt ein Sammelband vor, der die Beiträge einer Tagung an der Universität Paderborn vom Dezember 2001 enthält. In enger Verknüpfung verschiedener disziplinärer Perspektiven werden Schlaglichter auf eine Vielzahl von Themen geworfen, die sich mit dem Begriff „Reproduktion“ verbinden. Dabei wird deutlich, wie eng die Geschichte der Medien und die Entwicklung von Technologien der biologischen Fortpflanzung miteinander verzahnt sind.

  9. Measurement and analysis of environmental exposure factors in the Federal Republic of Germany 1985/86. 1. environmental survey. Vol. 3c. Indoor situation in homes: Indoor air. Description of VOC in the indoor air of the Federal Republic of Germany; Messung und Analyse von Umweltbelastungsfaktoren in der Bundesrepublik Deutschland 1985/86. 1. Umwelt-Survey. Bd. 3c. Wohn-Innenraum: Raumluft. Deskription fluechtiger organischer Verbindungen in der Raumluft der Bundesrepublik Deutschland

    Energy Technology Data Exchange (ETDEWEB)

    Krause, C.; Chutsch, M.; Henke, M.; Huber, M.; Kliem, C.; Leiske, M.; Mailahn, M.; Schulz, C.; Schwarz, E.; Seifert, B.; Ullrich, D.

    1992-05-01

    This volume is based upon the data of the research project ``Environment and Health - Measurement and Analysis of Environmental Exposure Factors in the Federal Republic of Germany 1985/86`` (1st Environment Survey). These data were established for a representative sample of n=2731 cases selected by age, sex, and community size. It constitutes part C of the third report volume and contains the description of the concentrations of a large number of volatile organic compounds (VOC) in indoor air from households of the general population of the Federal Republic of Germany (sub-sample). Function and objectives of this third part of evaluated data are to give, as far as possible, a precise assessment of the exposure to VOC in households among the general population of the Federal Republic of Germany in 1985/86. This is to gie interested persons an orientation and a classifying survey of laboratory results to be evaluatd. In this sense, the estimated distributions of the measured concentrations are presented for the entire population as well as for the below menioned subpopulations classified by outdoor temperatures, community size, type of region, number of persons in industrial jobs in the urban/rural area, building density, year of construction of the house, floor area of home, type of heating, type of fuel, number of persons in household, children (below 14 years) in household, smokers in household, age of floor covering, age of wall coating, age of furniture, new painting/wall-paper/furniture in recent months, presence of chipboard on walls/floor, furniture from chipboard (in the case of formaldehyde only), use of insecticides, room fresheners/deodorants in toilet and of cleansing agents/disinfectants. (orig.) [Deutsch] Der vorliegende Berichtsband basiert auf den Daten der Studie ``Messung und Analyse von Umweltbelastungsfaktoren in der Bundesrepublik Deutschland 1985/86 - Umwelt und Gesundheit`` (1. Umwelt-Survey), der eine nach Alter, Geschlecht und

  10. Die Verteilung und Eigenschaften von Bodenformen in der Deutschen Bucht, eine Rekonstruktion der Karten von Ulrich (1973)

    DEFF Research Database (Denmark)

    Winter, Christian; Lefebvre, Alice; Benninghoff, Markus

    2015-01-01

    Entstehung, Gestalt und Dynamik von Bodenformen in vergleichsweise kleinen Untersuchungsgebieten ist die Arbeit von ULRICH (1973) über die Verteilung von Bodenformen in der Deutschen Bucht bis heute die einzige verfügbare zusammenhängende Darstellung für die deutsche Nordseeküste. Die analogen Karten und die...

  11. Evaluation von Bildungssoftware im Spannungsfeld von Objektivität und praktischer Anwendung

    Directory of Open Access Journals (Sweden)

    Cornelia Biffi

    2002-05-01

    Full Text Available Das Angebot an Bildungs- bzw. Lernsoftware umfasst eine breite Palette von sehr unterschiedlichen Produkten. Eigentliche Unterrichtssoftware, die speziell für den Unterricht hergestellt und auf Lehrmittel und Curriculum abgestimmt ist, gibt es kaum. Im Projekt «Lernsoftware Evaluation» des Pestalozzianums Zürich ermitteln Lehrpersonen die Qualität von Bildungssoftware, indem sie diese im Unterricht einsetzen und anhand eines Kriterienrasters beurteilen. Eine Analyse der in der Evaluation generierten Daten belegt die Problematik des Anspruchs einer objektiven Qualitätsbeurteilung. Es werden die Probleme bei der Anwendung von Kriterienraster und Beurteilungsmodus aufgezeigt und ermittelt, worin die subjektiven Qualitätsmassstäbe der Evaluierenden begründet sind. Diese Ausführungen sind Teil eines Forschungsprojekts für die Weiterentwicklung einer theoretisch fundierten, aber dennoch praxisnahen Evaluation von Bildungssoftware.

  12. Von der Medienwirkungsbehauptung zur erziehungswissenschaftlichen Medienrezeptionsforschung. Vorschlag zur Analyse von Filmkommunikaten

    Directory of Open Access Journals (Sweden)

    Barbara Drinck

    2001-04-01

    Full Text Available Im Hinblick auf die Erforschung spezifischer Zusammenhänge von Medienkonsum und der Herausbildung von Einstellungen und Handlungen wird eine konstruktivistische Theorieorientierung plausibilisiert, indem zunächst auf den Stand der Medienwirkungsforschung eingegangen und vor dem Hintergrund einer begründeten Kritik des Wirkungsverständnisses auf die Notwendigkeit einer medienrezeptionswissenschaftlichen Forschungsalternative hingewiesen wird. Weiterhin wird der Stand der (erziehungswissenschaftlichen Medienrezeptionsforschung erörtert. Sodann werden Elemente einer konstruktivistischen Methodologie von Medienrezeptionsforschung beschrieben, die am Beispiel der Rezeption von Filmen konkretisiert werden. Dabei wird das Konzept des Kommunikates (S.J. Schmidt als Ausgangspunkt genommen, ein Vorschlag für eine Beschreibungssprache für (Film- Kommunikate entwickelt und eine Adaption des Ansatzes filmischer Narration zur Sprache gebracht.

  13. Erzeugung gleichverteilter Stichproben von Lozenge-Teilungen mittels Kopplung von Markovketten

    OpenAIRE

    Keller, Peter

    2011-01-01

    Aus dem Inhalt: 1 Einleitung 2 Eigenschaften der Lozengeteilungen 3 Coupling From The Past (CFTP) 4 Simulation von uniform verteilten Lozengeteilungen 5 Programmlisting und Diskussion der Implementierung 6 Ausblick A Anhang

  14. Der Briefwechsel zwischen Alexander von Humboldt und Karl Ernst von Baer

    Directory of Open Access Journals (Sweden)

    Thomas Schmuck

    2012-10-01

    Full Text Available Zusammenfassung Der kurze, nicht vollständig erhaltene Briefwechsel zwischen Alexander von Humboldt und Karl Ernst von Baer behandelt sehr verschiedene Themen: Politik, Kriegsgefahr, den Wissenschaftsbetrieb, Auszeichnungen und Tagungen, Embryologie und Cholera. Gemeinsam mit Briefen und Reden ergibt sich dabei ein differenziertes Bild der Beurteilung der beiden Wissenschaftler durch den jeweils anderen. Während Baer sich als Bewunderer Humboldts erweist, erscheint umgekehrt Humboldts Einschätzung Baers als ambivalent. Abstract The short, not completely preserved correspondence between Alexander von Humboldt and Karl Ernst von Baer deals with a wide range of subjects: politics and the danger of war, academic activities, scientific awards and conferences, aspects of embryology and the cholera. Letters to third persons and speeches, together with the correspondence between Humboldt and Baer show a differentiated pattern of mutual appraisal: While Baer always remained an admirer of the elder naturalist, Humboldt’s estimation was characterized by ambivalence.

  15. Jungen als Verlierer? Die Diskussion um die Benachteiligung von Jungen in der Schule

    Directory of Open Access Journals (Sweden)

    Hilde von Balluseck

    2009-03-01

    Full Text Available Die im Vergleich zu den Mädchen schlechteren Schulleistungen von Jungen werden in der öffentlichen Diskussion häufig dem weiblichen Geschlecht von pädagogischen Fachkräften angelastet. Das Leistungs- und Sozialverhalten der meisten Jungen ist jedoch weitaus stärker durch Männer- und Frauenbilder in ihrem sozialen Umfeld bedingt. Wenn diese sich an hegemonialen Vorstellungen von Männlichkeit – gerade auch in der gesellschaftlich ohnmächtigen Unterschicht – orientieren, geraten Jungen in der Schule in einen Konflikt. Dieser wird verstärkt, wenn sie – statistisch häufiger als Mädchen – zu Hause geschlagen werden. Der im Vergleich zu Mädchen weitaus intensivere Konsum von Gewalt verherrlichenden Medien ist ein weiterer Faktor für die größere Schuldistanz von Jungen. Die pauschalisierende Annahme, das weniger angepasste Leistungsverhalten von Jungen stehe im direkten Zusammenhang mit dem weiblichen Geschlecht der Lehrkräfte, geht somit an den eigentlichen Problemen vorbei.In the public discussions about the relatively poor school achievements of boys as compared to girls, the female gender of the pedagogical specialists is often blamed. Most of the boys’ social performance and attitude toward achievement is, however, conditioned through images of men and women in their immediate social surroundings. Boys often find themselves in conflict at school when these images are oriented toward hegemonic conceptions of masculinity, in particular when found in the socially powerless underclass. This conflict is heightened when the boys are abused at home, statistically more likely to happen than in the case of girls. Another factor for the boys’ greater distancing from schools is their higher consumption of media forms that glorify violence. The trivializing assumption that the poorer achievements of boys are directly related to the female gender of the teachers thus ignores the true problems.

  16. Soolopartiid Von Krahli katuse all / Kristi Eberhart

    Index Scriptorium Estoniae

    Eberhart, Kristi

    2007-01-01

    Von Krahli Teatri kolmest lavastusest: "Erki ja Tiina" (lavastaja Mart Kangro, tantsivad Erki Laur ja Tiina Tauraite), "Faust" (J. W. Goethe ainetel tekst ja lavastus Taavi Eelmaa, muusika ja laulud Chalice, osades Jarek Kasar ja Rein Pakk), "Hamletid" (William Shakespeare'i ainetel kontseptsiooni, lavastuse, koreograafia, kujunduse, valguse autor Sasha Pepeljajev, video- ja helikunstnik Taavet Jansen. Esitaja Juhan Ulfsak)

  17. Alexander von Humboldt and Coenraad Jacob Temminck

    NARCIS (Netherlands)

    Raat, A.J.P.

    1976-01-01

    INTRODUCTION In the archives of the Rijksmuseum van Natuurlijke Historie in Leiden there is a map with three letters written by Alexander von Humboldt (17691859) to the first director of the Museum, Coenraad Jacob Temminck (1778-1858). The map, the hard cover of John Gould's "Synopsis of the birds

  18. Differential functional von Foerster equations with renewal

    Directory of Open Access Journals (Sweden)

    H.Leszczyński

    2008-06-01

    Full Text Available Natural iterative methods converge to the exact solution of a differential-functional von Foerster-type equation which describes a single population dependent on its past time and state densities as well as on its total size. On the lateral boundary we impose a renewal condition.

  19. Wege zur Entdeckung von Communities in Folksonomies

    OpenAIRE

    Jäschke, Robert; Hotho, Andreas; Schmitz, Christoph; Stumme, Gerd

    2006-01-01

    Ein wichtiger Baustein des neu entdeckten World Wide Web - des "Web 2.0" - stellen Folksonomies dar. In diesen Systemen können Benutzer gemeinsam Ressourcen verwalten und mit Schlagwörtern versehen. Die dadurch entstehenden begrifflichen Strukturen stellen ein interessantes Forschungsfeld dar. Dieser Artikel untersucht Ansätze und Wege zur Entdeckung und Strukturierung von Nutzergruppen ("Communities") in Folksonomies.

  20. Hans von Engel and the ICPIG Conference

    International Nuclear Information System (INIS)

    Franklin, R.

    2000-01-01

    The history of the, organized by Hans von Engel, International Conference on Phenomena in Ionized Gases is presented: Oxford (1953), Delft (1955), Venice (1957), Uppsala (1959), Munich (1961), Oxford (1971) and Berlin (1977). Some organizational aspects, financial support and remarkable events like international prizes in field of plasma physics are given

  1. Guido von Pirquet: Austrian pioneer of astronautics

    Science.gov (United States)

    Sykora, F.

    1977-01-01

    The works of Guido von Pirquet, Austrian pioneer of rocketry, were assessed. Major emphasis was given to Pirquet's calculation of the route to Venus which in fact was followed by the first Russian rocket to Venus. Of interest also is Pirquet's valuable construction of a space station and his analysis of interstellar space flight.

  2. Ueberreste vorweltlicher Proboscidier von Java und Banka

    NARCIS (Netherlands)

    Martin, K.

    1884-01-01

    Junghuhn führte in seinem Werke über Java nur einen einzigen Wirbelthierrest, Carcharias megalodon, an (7, IV, pag. 97); es war ihm nicht gelungen bei seinem ersten Aufenthalte auf der Insel Reste von Säugethieren zu finden, so eifrig er auch darnach in den Höhlen des Tertiaergebirges suchte (7, IV,

  3. Ueber eine Anomalie von Acromitus flagellatus (Stiasny)

    NARCIS (Netherlands)

    Stiasny, G.

    1934-01-01

    Bei erneuter Durchsicht des reichhaltigen Materiales von Acromitus flagellatus (Stiasny) in der Scyphomedusen-Sammlung des Rijksmuseum van Natuurlijke Historie in Leiden (vergl. meine Mitteilungen daruber, 1920, Uebersichtstabelle III und 1921, p. 131/136) fand ich ein Exemplar, das eine

  4. Von Kalifornien nach Taxham / Katri Soe

    Index Scriptorium Estoniae

    Soe, Katri, 1971-

    2005-01-01

    Neljas osa magistritööst "Von Kalifornien nach Taxham: Formen und Strukturen der Kommunikation in Peter Handkes Romanen "Der kurze Brief zum langen Abschied" und "In einer dunklen Nacht ging ich aus meinem stillen Haus"" (Tartu, 2000. Juhendaja: Claus Sommerhage)

  5. Von der lernenden Region zur "Smart Region“

    OpenAIRE

    Poschwatta, Wolfgang

    2004-01-01

    Von der lernenden Region zur "Smart Region“ / M. Hilpert, W. Poschwatta. - In: Nabizadeh-Araghi, Nima : Auf dem Weg zur "Smart Region" : regionale Entwicklung am Beispiel der Pistazienproduktion im Iran. - Augsburg : Müllerdruck, 2004. - S. 5-9. - (Terra facta ; 2)

  6. Factors promoting development of renal tubulointerstitial lesions in patients with diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Minara Shamkhalovna Shamkhalova

    2010-09-01

    Full Text Available Aim. To identify profibrogenic mediators, markers of endothelial dysfunction and hemostasis in patients with diabetes mellitus (DM and chronickidney disease (CKD. Materials and methods. The study included 120 patients with DM and 20 age-matched normotensive subjects without DM showing the glomerularfiltration rate (GFR > 60 ml/min/1.73 m3. Four groups of patients were distinguished: 1 - DM2 patients without renal pathology (n=33, 2 - DM2 patients with diabetic nephropathy (n=24, 3 - DM2 patients with ischemic nephropathy (IN (n=33 verified by contrast visualization techniques(multispiral CM of abdominal aorta and renal arteries, abdominal angiography of renal arteries or MR angiography of renal arteries and abdominal aorta, 4 - DM1 patients with DN (n=30. Clinical examination included assessment of complaints, analysis of medical history of the main diseaseand concomitant disorders, determination of the main clinical and biochemical characteristics of blood and urine, measurement of НbА1с and 24-hralbuminuria (AU by standard methods, estimation of GFR by the MDRD formula, ECG, echocardiography, 24-hr AP monitoring, counseling bycardiologist and ophthalmologist (fundal examination by ophthalmoscopy. Standard kits were used to detect profibrogenic mediators and markersof endothelial dysfunction including transforming growth factor-beta (TGF-b, angiotensin II (AT II, monocyte chemoattractant protein (MCP-1,regulated on activation normal T cell expressed and secreted (RANTES, adhesion factors (intracellular adhesion molecule (ICAM-1, vascular celladhesion molecule (VCAM-1 vascular endothelial growth factor (VEGF, interleukin-6 (IL-6, asymmetric dimethylargnine (ADMA, homocysteine(HCYST, metalloproteinases (MMP, von Willebrand factor (vWF, plasminogen activator inhibitor (PAI-I. Results. DM patients with CKD had elevated blood profibrogenic cytokine (MCP-1, TGF-1b, IL-6 and extracellular matrix degradation factor(MMP-9 levels compared with

  7. Defibrotide prevents the activation of macrovascular and microvascular endothelia caused by soluble factors released to blood by autologous hematopoietic stem cell transplantation.

    Science.gov (United States)

    Palomo, Marta; Diaz-Ricart, Maribel; Rovira, Montserrat; Escolar, Ginés; Carreras, Enric

    2011-04-01

    Endothelial activation and damage occur in association with autologous hematopoietic stem cell transplantation (HSCT). Several of the early complications associated with HSCT seem to have a microvascular location. Through the present study, we have characterized the activation and damage of endothelial cells of both macro (HUVEC) and microvascular (HMEC) origin, occurring early after autologous HSCT, and the potential protective effect of defibrotide (DF). Sera samples from patients were collected before conditioning (Pre), at the time of transplantation (day 0), and at days 7, 14, and 21 after autologous HSCT. Changes in the expression of endothelial cell receptors at the surface, presence and reactivity of extracellular adhesive proteins, and the signaling pathways involved were analyzed. The expression of ICAM-1 at the cell surface increased progressively in both HUVEC and HMEC. However, a more prothrombotic profile was denoted for HMEC, in particular at the time of transplantation (day 0), reflecting the deleterious effect of the conditioning treatment on the endothelium, especially at a microvascular location. Interestingly, this observation correlated with a higher increase in the expression of both tissue factor and von Willebrand factor on the extracellular matrix, together with activation of intracellular p38 MAPK and Akt. Previous exposure and continuous incubation of cells with DF prevented the signs of activation and damage induced by the autologous sera. These observations corroborate that conditioning treatment in autologous HSCT induces a proinflammatory and a prothrombotic phenotype, especially at a microvascular location, and indicate that DF has protective antiinflammatory and antithrombotic effects in this setting. Copyright © 2011 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  8. 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.

  9. Measurements of emission rates of hydrocarbons from sunflower as a function of temperature, light intensity and stress (ozone levels); Bestimmung von Emissionsraten pflanzlicher Kohlenwasserstoffe bei Sonnenblumen in Abhaengigkeit von Temperatur, Lichtintensitaet und Stress, insbesondere von der Belastung mit Ozon

    Energy Technology Data Exchange (ETDEWEB)

    Schuh, G.; Wildt, J.; Kley, D.

    1996-08-01

    The emission rates of isoprene, mono- and sesquiterpenes from sunflower (Helianthus annuus L. cv. giganteus) were determined in an environmental chamber, a continuously stirred tank reactor. {alpha}-pinene, {beta}-caryophyllene and two oxygenated compounds were emitted. The emission rates of all terpenes increased exponentially with temperature. Substance specific differences of the rate of increase of the emission rates were observed. For all substances the dependence of their emission rates on temperature increased with increasing light intensity. Increasing lightflux resulted in an increase of the emission rates for all substances. The raise of emission rates with lightflux was dependent on temperature and increased with increasing temperature. During periods without plant stress the emission rates exhibited a good correlation with the rate of transpiration as well as with the rate of net photosynthesis. Sunflowers emitted higher amounts of terpenes when they were stressed by mechanical, wounding and ozone treatment as well as nutrient- or water deficiency. The emission rates increased by a factor of 5-300. Exposure with ozone had an effect on hydrocarbon emission rates with a delay-time. 3-4 h after exposure with 25-120 ppb ozone the emission rates increased by factor of 5-100. This increase was only observed on the first day of exposure. Nutrient deficiency resulted in an increase of emission rates by a factor of 10-300. In situations of mechanical, wounding and ozone stress, substance specific changes in the emission spectrum were observed. A model was developed to explain the observed phenomena. The main pathway of ozone loss in the chamber is caused by the uptake through the stomata of the plants. However, up to 50% of the ozone loss must be explained by other processes indirectly caused by the plants. (orig./MG) [Deutsch] In Laborversuchen wurden Emissionsraten biogener Kohlenwasserstoffe von Sonnenblumen gemessen. Die groessten Emissionsraten wiesen die

  10. Wir zeigen andere Bilder von Frauen ...

    Directory of Open Access Journals (Sweden)

    Bettina Rulofs

    2010-03-01

    Full Text Available Der vorliegende Beitrag beleuchtet die Bedeutung der Geschlechterordnung im Prozess der sportmedialen Kommunikation. Im Kern geht es um die Frage, inwiefern im Prozess der medialen Vermittlung von Sport traditionelle Geschlechterstereotype aufrechterhalten werden oder Möglichkeiten der Irritation solcher Stereotype bestehen. Dazu werden verschiedene Ebenen des massenmedialen Kommunikationsprozesses in den Blick genommen: die Medienprodukte, die Öffentlichkeitsarbeit und Selbst-Präsentation der Sportler/innen, die Medienrezeption und die Herstellungsprozesse von Medien in den Sportredaktionen. This article illustrates the relevance of gender in processes of sports media communication. The question in focus is in what way traditional gender stereotypes are perpetuated in the process of media communication in sport and how such stereotypes can be irritated. Therefore different levels of mass media communication are considered: the media products, the public relations of athletes and the presentation of themselves as athletes, the media-reception and the production processes in sport departments of media institutions.

  11. von Neumann's hypothesis concerning coherent states

    International Nuclear Information System (INIS)

    Zak, J

    2003-01-01

    An orthonormal basis of modified coherent states is constructed. Each member of the basis is an infinite sum of coherent states on a von Neumann lattice. A single state is assigned to each unit cell of area h (Planck constant) in the phase plane. The uncertainties of the coordinate x and the square of the momentum p 2 for these states are shown to be similar to those for the usual coherent states. Expansions in the newly established set are discussed and it is shown that any function in the kq-representation can be written as a sum of two fixed kq-functions. Approximate commuting operators for x and p 2 are defined on a lattice in phase plane according to von Neumann's prescription. (leeter to the editor)

  12. Theodor von Grotthuss’ Contribution to Electrochemistry

    International Nuclear Information System (INIS)

    Pauliukaite, Rasa; Juodkazytė, Jurga; Ramanauskas, Rimantas

    2017-01-01

    Freiherr Christian Johann Dietrich Theodor von Grotthuss (1785-1822) lived and worked in Lithuania. Inspired by Volta's pile he proposed the first theory of water electrolysis, which was published in 1805 in Rome. Michael Faraday acknowledged T. Grotthuss for this theory in his further investigations of electrolysis processes. Having studied in Germany and France Grotthuss brought science to province by establishing his laboratory in Gedučiai village in his mother's real estate. Lithuanian scientists are proud that life of Theodor von Grotthuss was related to this country. Many events to remember this prominent scientist are organised in Vilnius and other places. His works and example provided a good basis for further development of electrochemical science in Lithuania. Grotthuss insights into the mechanism of proton transport still are of great relevance to such areas of modern science as membrane biochemistry, energy conversion and storage.

  13. Verbesserung der Symmetrie von Hirnaufnahmen entlang der Sagittalebene

    Science.gov (United States)

    Ens, Konstantin; Wenzel, Fabian; Fischer, Bernd

    Die lokale Symmetrie von Hirnscans entlang der Sagittalebene zu ermitteln und zu modizifieren, ist für eine Reihe neurologischer Anwendungen interessant. Beispielsweise kann der voxelweise Vergleich von rechter und linker Hirnhälfte nur dann Aufschluss über die Lokalisierung von Läsionen geben, wenn durch Transformation ein Hirnscan eine möglichst hohe Symmetrie aufweist. Ein weiteres Anwendungsgebiet ist die Visualisierung von medialen Hirnschnitten, für die die Trennfläche beider Hirnhälfte möglichst eben sein sollte. Diese Arbeit stellt die Entwicklung eines Verfahrens vor, mit dessen Hilfe die Symmetrie von Hirnaufnahmen entlang der Sagittalebene verbessert werden kann. Dies geschieht unter Verwendung von aktiven Konturen, die mit Hilfe einer neuartigen Kostenfunktion gesteuert werden. Experimente am Ende der Arbeit mit strukturellen Kernspinaufnahmen demonstrieren die Leistungsfähigkeit des Verfahrens.

  14. Development and characterization of recombinant ovine coagulation factor VIII.

    Directory of Open Access Journals (Sweden)

    Philip M Zakas

    Full Text Available Animal models of the bleeding disorder, hemophilia A, have been an integral component of the biopharmaceutical development process and have facilitated the development of recombinant coagulation factor VIII (fVIII products capable of restoring median survival of persons with hemophilia A to that of the general population. However, there remain several limitations to recombinant fVIII as a biotherapeutic, including invasiveness of intravenous infusion, short half-life, immunogenicity, and lack of availability to the majority of the world's population. The recently described ovine model of hemophilia A is the largest and most accurate phenocopy. Affected sheep die prematurely due to bleeding-related pathogenesis and display robust adaptive humoral immunity to non-ovine fVIII. Herein, we describe the development and characterization of recombinant ovine fVIII (ofVIII to support further the utility of the ovine hemophilia A model. Full-length and B-domain deleted (BDD ofVIII cDNAs were generated and demonstrated to facilitate greater biosynthetic rates than their human fVIII counterparts while both BDD constructs showed greater expression rates than the same-species full-length versions. A top recombinant BDD ofVIII producing baby hamster kidney clone was identified and used to biosynthesize raw material for purification and biochemical characterization. Highly purified recombinant BDD ofVIII preparations possess a specific activity nearly 2-fold higher than recombinant BDD human fVIII and display a differential glycosylation pattern. However, binding to the carrier protein, von Willebrand factor, which is critical for stability of fVIII in circulation, is indistinguishable. Decay of thrombin-activated ofVIIIa is 2-fold slower than human fVIII indicating greater intrinsic stability. Furthermore, intravenous administration of ofVIII effectively reverses the bleeding phenotype in the murine model of hemophilia A. Recombinant ofVIII should facilitate

  15. Marktorientierte Vertriebs-Reorganisation von Energieversorgungsunternehmen

    OpenAIRE

    Beutin, Nikolas; Scholl, Michael; Fürst, Andreas

    2003-01-01

    Seit der Liberalisierung des Energiemarktes im Jahre 1998 sehen sich Energieversorgungsunternehmen (EVUs) einer veränderten Markt- und Wettbewerbssituation gegenüber. Neben Risiken, wie dem Eintritt von Wettbewerbern in das vormals geschützte Gebiet, eröffnete sich ihnen hierdurch aber auch die Chance, außerhalb des eigenen Netzbereiches neue Kunden zu gewinnen. Um sowohl dem Margenverfall als auch der direkten Vergleichbarkeit mit ...

  16. La Medea de Lars von Trier

    Directory of Open Access Journals (Sweden)

    Iratxe Fresneda Delgado

    2013-04-01

    Full Text Available El presente artículo analiza el modo en el que Lars von Trier recrea para el cine el estereotipo de Medea. Mediante el análisis fílmico de la película y apoyándose en los estudios culturales, el texto se interroga acerca de la importancia y el poder potencial del cine a la hora recuperar el antiguo mito y demostrar su vigencia. El análisis amplía horizontes para la compresión de los mecanismos que articulan el entramado de significados de la película, donde Von Trier aporta una nueva visión del arquetipo de Medea uniéndola, a la tradición pictórica del Romanticismo. Una influencia que habita en las posteriores obras del director danés, donde el paisaje, la naturaleza, se erige en elemento catalizador de las pulsiones humanas, en su cómplice y testigo.This paper explores the way that Lars von Trier’s film recreates the stereotype of Medea. Using film analysis and based on cultural studies the article asks about the importance and potential power of cinema to recover the ancient myth and show their effects. The analysis expands horizons for the understanding of the mechanisms that link the network of meanings of the film, where the author offers a new vision of Medea's archetype attaching it to the pictorial tradition tied to the Romanticism. An influence that can be seen in the later works of Lars von Trier, where the landscape, the nature, stands as a catalyst of human drives, as his accomplice and witness.

  17. Visuelle Analyse von E-mail-Verkehr

    OpenAIRE

    Mansmann, Florian

    2003-01-01

    Diese Arbeit beschreibt Methoden zur visuellen geographischen Analyse von E-mail Verkehr.Aus dem Header einer E-mail können Hostadressen und IP-Adressen herausgefiltert werden. Anhand einer Datenbank werden diesen Host- und IP-Adressen geographische Koordinaten zugeordnet.Durch eine Visualisierung werden in übersichtlicher Art und Weise mehrere tausend E-mail Routen dargestellt. Zusätzlich dazu wurden interktive Manipulationsmöglichkeiten vorgestellt, welche eine visuelle Exploration der Date...

  18. Zur Kenntnis von Gnetum neglectum Bl

    NARCIS (Netherlands)

    Markgraf, F.

    1960-01-01

    Gnetum neglectum war nicht nur, wie der Name andeutet, bis zu Blumes Zeit übersehen worden, sondern es wurde von Späteren wiederum verkannt, wie ich in Bull. J. B. Buitenzorg 3. Ser. 10 (1930) 474 näher ausgeführt habe. Die echte Art taucht verhältnismässig selten in den Herbarien auf. Sie ist eine

  19. Von Medien, Übertragungen und Automaten

    Directory of Open Access Journals (Sweden)

    Alessandro Barberi

    2013-12-01

    Full Text Available Im Zuge der Debatten zum Medialen Habitus wurde vielfach betont, dass die >Theorie der Praxispraxeologischen Medientheorie< des Medialen Habitus avant la lettre gesprochen werden kann. Dieser Artikel untersucht – ausgehend von den Debatten zur "Medienkompetenz" – wie Bourdieu Sprache, Sprechen und Diskurs, sowie Akteure, Felder und Habitus als Medien begreift und betont dabei die Nützlichkeit der Bourdieuschen Bildungssoziologie im Rahmen einer sozialwissenschaftlichen Grundlegung der Medienpädagogik.

  20. Ultraproducts of von Neumann algebras

    DEFF Research Database (Denmark)

    Ando, Hiroshi; Haagerup, Uffe

    2014-01-01

    this connection, we show that the ultraproduct action of the modular automorphism group of a normal faithful state φ of M   on the Ocneanu ultraproduct is the modular automorphism group of the ultrapower state (... that the ultrapower MωMω of a Type III0 factor is never a factor. Moreover we settle in the affirmative a recent problem by Ueda about the connection between the relative commutant of M   in MωMω and Connes' asymptotic centralizer algebra MωMω....

  1. Portrait of Dr. Von Braun with Walt Disney, 1954.

    Science.gov (United States)

    1954-01-01

    Marshall Center Director Dr. Wernher Von Braun is pictured with Walt Disney during a visit to the Marshall Space Flight Center in 1954. In the 1950s, Dr. Von Braun while working in California on the Saturn project, also worked with Disney studios as a technical director in making three films about Space Exploration for television. Disney's tour of Marshall in 1965 was Von Braun's hope for a renewed public interest in the future of the Space Program at NASA.

  2. Gespiegelte Planeten – Die Anordnung der Pyramiden von Gizeh

    OpenAIRE

    Jelitto, Hans

    2000-01-01

    Antike Bauwerke wurden wiederholt auf astronomische Zusammenhänge hin untersucht, so z. B. ihre Ausrichtung in Bezug auf die Bewegung von Sonne oder Sternen. Vor diesem Hintergrund wurden für die Pyramiden von Gizeh drei ungewöhnliche Gleichungen entdeckt, die die Pyramidengrößen mit einer Genauigkeit von ca. 0,1 % festlegen. Gleichzeitig legen diese drei Gleichungen nahe, die drei Pyramiden in der Reihenfolge Mykerinos-, Chefren- und Cheopspyramide den inneren drei Planeten unseres Sonnensys...

  3. Saage tuttavaks : Elisabeth ja Karl von Hoerschelmann / Mai Levin

    Index Scriptorium Estoniae

    Levin, Mai, 1942-

    2004-01-01

    Kuraator M. Levin kuni 10. X 2004 Adamson-Ericu muuseumis avatud näitusest "Tuntud ja tundmatud Elisabeth von Rosendorff-Hoerschelmann ja Karl von Hoerschelmann". Enamik töid on kunstnike laste Konstantin Hoerschelmanni ja Anna Röder-Hoerschelmanni omand. Elisabeth Rosendorff (1898-1984) sündis Virumaal Maidlas eesti perekonnas, Karl von Hoerschelmann (1899-1951) Sevastoopolis saksa perekonnas

  4. Arbeitszeiten von Professorinnen und Professoren in Deutschland 2016

    OpenAIRE

    Weihs, Claus; Hernández Rodríguez, Tanja; Doeckel, Maximilian; Marty, Christoph; Wormer, Holger

    2018-01-01

    In dieser Studie werden belastbare Prognoseintervalle der wöchentlichen Gesamtarbeitszeit von Universitätsprofessorinnen und -professoren aus Daten einer Umfrage aus dem Jahre 2016 und a-priori Informationen aus früheren Studien bestimmt. Neben der Gesamtarbeitszeit werden auch Teilarbeitszeiten zum Beispiel für Lehre und Forschung ermittelt. Die Ergebnisse von frequentistischer und Bayesianischer Analyse werden verglichen. Aus den gültigen Fragebögen von aktiven Vollzeit arbeitenden Universi...

  5. Estudo de fatores pró-trombóticos e pró-inflamatórios na cardiomiopatia chagásica Study of pro-thrombotic and pro-inflammatory factors in chagas cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Leila Maria Magalhães Pessoa de Melo

    2010-10-01

    Full Text Available FUNDAMENTO: A relação entre atividade inflamatória e pró-trombótica na cardiomiopatia chagásica e em outras etiologias é obscura. OBJETIVO: Estudar o perfil de marcadores pró-trombóticos e pró-inflamatórios em pacientes com insuficiência cardíaca chagásica e compará-los com os de etiologia não chagásica. MÉTODOS: Coorte transversal. Critérios de inclusão: fração de ejeção do VE (FEVE um mês. Os pacientes foram divididos em dois grupos: grupo 1 (G1 - sorologias positivas para Chagas - e grupo 2 (G2 - sorologias negativas para Chagas. Fator pró-inflamatório: PCR ultrassensível. Fatores pró-trombóticos: fator trombina-antitrombina, fibrinogênio, antígeno do fator de von Willebrand, P-selectina plasmática e tromboelastograma. Amostra calculada para poder de 80%, assumindo-se diferença de 1/3 de desvio-padrão; p significativo se BACKGROUND: The relationship between inflammatory and prothrombotic activity in chagas cardiomyopathy and in other etiologies is unclear. OBJECTIVE: To study the profile of pro-thrombotic and pro-inflammatory markers in patients with Chagas' heart failure and compare them with patients of non-chagas etiology. METHODS: Cross-sectional cohort. Inclusion criteria: left ventricle ejection fraction (LVEF one month. The patients were divided into two groups: group 1 (G1 - seropositive for Chagas - and group 2 (G2 - seronegative for Chagas. Pro-inflammatory factor: Ultra-sensitive CRP. Pro-thrombotic factors: thrombin-antithrombin factor, fibrinogen, von Willebrand factor antigen, plasma P-selectin and thromboelastography. Sample calculated for 80% power, assuming a standard deviation difference of 1/3; significant p if it is < 0.05. Statistical analysis: Fisher's exact test for categorical variables; unpaired Student's t-test for parametric continuous variables and Mann-Whitney test for nonparametric continuous variables. RESULTS: Between January and June 2008, 150 patients were included, 80 in G1

  6. Influence of region and site-specific factors on the degree of general validity of ecological and primary-energy-related assessments of biogas; Einfluss regionaler und standortspezifischer Faktoren auf die Allgemeingueltigkeit oekologischer und primaerenergetischer Bewertungen von Biogas

    Energy Technology Data Exchange (ETDEWEB)

    Dressler, Daniela

    2015-11-01

    As described in this publication, since the early 1990s numerous studies based on the life cycle assessment methodology have been dedicated to assessments of different kinds of bioenergy in comparison with fossil energy resources in terms of their energy balance and environmental impact. On reviewing the results of these studies one finds a strikingly wide range of variation. One major factor of influence on the results of life cycle assessments, besides methodological factors such as the choice of allocation method, is the representativeness of the data used. Thus, widely varying results are also obtained when balance calculations and assessments are performed on energy crops with due consideration to regional and site-specific factors. To address this problem the present study endeavoured to identify region and site-specific factors and assess them in terms of their influence on the life cycle assessment of the cultivation and conversion to biogas of different kinds of energy crops. For this purpose the following questions were explored: What influence do region, site and equipment-specific factors have on the results of ecological and primary-energy-related assessments; and how large are the differences in results between region and site-specific assessments on the one hand and assessments based on general assumptions on the other? It transpires that the results of region and site-specific assessments differ from one another in terms of both the assessment of energy cropping and the assessment of the entire process chain of biogas production and conversion to electricity.

  7. Untersuchungen zur Farbreaktion von Amilorid, Chlorhexidin und Proguanil mit Hypobromit

    OpenAIRE

    Huth, Silke

    2004-01-01

    Bei der Reaktion von Amiloridhydrochlorid (1· HCl) mit Brom in alkalischer Lösung wird ein gelbbraunes Dehydrierungsprodukt erhalten, daß als 3-(3-Amino-1,2,4-oxadiazol-5-yl)-5-chlor-2,6-pyrazindiamin (6) identifiziert werden konnte. Durch Vergleich von Massen- und NMR-Spektren der Verbindung 6 mit Spektren von 1· HCl und Referenzsubstanzen I-III konnte auf die verbindung 6 geschlossen werden. Die Struktur wurde durch eine Röntgenstrukturanalyse abgesichert. Erhitzen von Amiloridhydrochlorid ...

  8. Chancen und Gefahren von Global-Marketing-Konzepten

    OpenAIRE

    Berndt, Ulrike

    1990-01-01

    Chancen und Gefahren von Global-Marketing-Konzepten. - Augsburg : Förderges. Marketing, 1990. - 57, XII S. - Zugl: Augsburg, Univ., Diplomarb. - (Arbeitspapiere zur Schriftenreihe Schwerpunkt Marketing ; 29)

  9. A bicategorical approach to Morita equivalence for von Neumann algebras

    International Nuclear Information System (INIS)

    Brouwer, R. M.

    2003-01-01

    We relate Morita equivalence for von Neumann algebras to the ''Connes fusion'' tensor product between correspondences. In the purely algebraic setting, it is well known that rings are Morita equivalent if they are equivalent objects in a bicategory whose 1-cells are bimodules. We present a similar result for von Neumann algebras. We show that von Neumann algebras form a bicategory, having Connes's correspondences as 1-morphisms, and (bounded) intertwiners as 2-morphisms. Further, we prove that two von Neumann algebras are Morita equivalent iff they are equivalent objects in the bicategory. The proofs make extensive use of the Tomita-Takesaki modular theory

  10. Optimized detection and characterization of liver metastases. The role of current MRI contrast agents; Optimierte Detektion und Charakterisierung von Lebermetastasen. Leistungsvermoegen aktueller MRT-Kontrastmittel

    Energy Technology Data Exchange (ETDEWEB)

    Weinrich, J.M.; Well, L.; Bannas, P. [Universitaetsklinikum Hamburg-Eppendorf, Zentrum fuer Radiologie und Endoskopie, Klinik und Poliklinik fuer diagnostische und interventionelle Radiologie und Nuklearmedizin, Hamburg (Germany)

    2017-05-15

    Metastases are the most common malignant lesions of the liver. The presence of liver metastases is an important prognostic factor and is decisive for the further management, especially in patients with colorectal cancer. Detection and characterization of liver metastases as well as differentiation from benign lesions are of high importance and a daily challenge in clinical radiology. Contrast-enhanced magnetic resonance imaging (MRI) has the highest sensitivity in detecting liver metastases. The sensitivity of MRI has been further increased due to the development of liver-specific contrast agents. This article describes the role of extracellular and hepatobiliary contrast agents for the detection and characterization of liver metastases. Moreover, the current knowledge on safety, sequence optimization, transient severe dyspnea and the combination of hepatobiliary with intravascular contrast agents for liver imaging is discussed. (orig.) [German] Metastasen sind die haeufigsten malignen Leberlaesionen. Das Vorhandensein von Lebermetastasen ist entscheidend fuer die Prognose und weitere Therapieplanung von Tumorpatienten, insbesondere von Patienten mit kolorektalen Karzinomen. Die Detektion von Lebermetastasen sowie deren Unterscheidung von anderen Leberlaesionen sind daher von hoechster Bedeutung und stellen eine alltaegliche Herausforderung fuer den Radiologen dar. Die Bildgebung mit der hoechsten Sensitivitaet fuer die Detektion von Lebermetastasen stellt die dynamische kontrastmittelgestuetzte Magnetresonanztomographie (MRT) dar. Die bereits hohe Sensitivitaet der MRT wird durch den Einsatz leberspezifischer Kontrastmittel noch weiter gesteigert. Dieser Artikel beleuchtet die Rolle der aktuellen unspezifischen und leberspezifischen MRT-Kontrastmittel fuer die Detektion und Charakterisierung von Lebermetastasen. Weiterhin werden Erkenntnisse zur Sicherheit, Sequenzoptimierung, zu transienten Atemartefakten und zur Kombination von MRT-Kontrastmitteln fuer die

  11. Water quality objectives for priority substances aiming at the protection of the aquatic community. Final report; Ableitung von Zielvorgaben fuer prioritaere Stoffe zum Schutz von Oberflaechengewaessern. Endbericht

    Energy Technology Data Exchange (ETDEWEB)

    Herrchen, M.; Mueller, M.; Storm, A.

    2000-03-15

    Beside the emission principle operationalized as best available technology (BAT) the derivation of water quality criteria is a main approach to protect surface waters. Water quality criteria are defined as not legally binding objectives of protection and are no limit values. The quality objectives are derived for pre-defined objectives namely the aquatic community, fishery, sediments and drinking water. It was aim of the project to derive quality objectives for the aquatic community. In principle, the lowest NOEC-value for the most sensitive species out of four trophic levels of the biocenose was used as the basis. In case the entire data set was not available factors were applied with their figures depending on test duration, biological endpoint and size of the data ensemble. The current report mainly presents water quality objectives for plant protection products, but also gives some figures for halogenated compounds as well as the currently discussed nonylphenols and tributyltin compounds. The acquired data allows for a derivation of quality objectives for 11 out of 27 compounds/groups of compounds. Results of the data acquistion as well as of the evaluation are documented in both, an electronic data base with a link to the oekotoxikologische Schnellauskunft (OESA)' and data reports. (orig.) [German] Neben dem Emissionsansatz ist das Prinzip der Formulierung von Gewaessergueteanforderungen - im Sinne eines Immissionsminimierungsprinzips - ein wesentlicher Bestandteil des Schutzes der Oberflaechengewaesser. Waehrend die Gewaessergueteanforderungen zunaechst als Qualitaetsziele beschrieben wurden, wurde dieser Terminus zur Vermeidung des Eindrucks einer rechtlichen Verbindlichkeit - im Sinne von Grenzwerten - in Zielvorgaben umformuliert. Die Zielvorgaben werden schutzzielbezogen abgeleitet, wobei es sich um die Schutzgueter aquatische Lebensgemeinschaft, Berufs- und Sportfischerei und Sedimente sowie Trinkwasserversorgung handelt. Zur Ableitung der

  12. Influence of S, P, C on grain boundary diffusion and creep properties of Alloy 800; Einfluss von S, P, C auf die Korngrenzendiffusion und Kriecheigenschaften von Alloy 800

    Energy Technology Data Exchange (ETDEWEB)

    Lindemann, J.; Hannesen, K.; Mast, R.; Viefhaus, H. [Max-Planck-Institut fuer Eisenforschung GmbH, Duesseldorf (Germany); Grabke, H.J.

    1998-12-31

    The paper reports examinations of Alloy 800 and specific commercially available variants known under the names of 800H, 800HT, and 800LC, differing in their concentrations of C, Al, and Ti. In addition, melts also containing phosphorus (0.09 wt-%) or sulfur (0.04 wt-%) as additional alloying materials have been prepared for the experiments. The volume diffusion and the grain boundary diffusion of {sup 59}Fe in those alloys was measured at temperatures between 800 and 1000 C by means of a radioactive tracer method combined with residual activity measurements. It was found that accompanying elements like phosphorus and sulfur increase the activation energy of the grain boundary diffusion of the iron and thus delay the grain boundary self-diffusion in Alloy 800. Creep curves were measured of the same materials after age-hardening treatment for 100 hours at 800 C, measurements performed at constant temperature but at three different, constant creep stress loads. The results showed that addition of phosphorus markedly increases the lifetime of Alloy 800, and reduces the creep rupture strain. The minimum strain rate in Alloy 800 containing 0.09 wt-% of phosphorus was found to be lower by a factor of 100, as compared to the other Alloy 800 materials used. (orig./CB) [Deutsch] Alloy 800 ist ein austenitischer Fe-Ni-Cr Stahl, der relativ geringe, aber wichtige Konzentrationen von Kohlenstoff, Aluminium und Titan enthaelt. Besondere Varianten von Alloy 800, bekannt als 800H, 800HT und 800LC, unterscheiden sich in den Konzentrationen dieser Elemente. Diese kommerziellen Legierungen wurden untersucht, und zusaetzlich wurden Schmelzen mit zulegiertem Phosphor (0,09 Gew-%) bzw. Schwefel (0,04 Gew-%) hergestellt. Mittels einer radioaktiven Tracermethode in Verbindung mit Restaktivitaetsmessungen wurde die Volumen- und Korngrenzendiffusion von {sup 59}Fe in diesen Legierungen im Temperaturbereich 800-1000 C gemessen. Es wurde gefunden, dass Begleitelemente wie Phosphor und

  13. Intracranial Hemorrhage: A Devastating Outcome of Congenital Bleeding Disorders-Prevalence, Diagnosis, and Management, with a Special Focus on Congenital Factor XIII Deficiency.

    Science.gov (United States)

    Alavi, Seyed Ezatolla Rafiee; Jalalvand, Masumeh; Assadollahi, Vahideh; Tabibian, Shadi; Dorgalaleh, Akbar

    2018-04-01

    Intracranial hemorrhage (ICH) is a medical emergency. In congenital bleeding disorders, ICH is a devastating presentation accompanied with a high rate of morbidity and mortality. The prevalence of ICH is highly variable among congenital bleeding disorders, with the highest incidence observed in factor (F) XIII deficiency (FXIIID) (∼30%). This life-threatening presentation is less common in afibrinogenemia, FVIII, FIX, FVII, and FX deficiencies, and is rare in severe FV and FII deficiencies, type 3 von Willebrand disease and inherited platelet function disorders (IPFDs). In FXIIID, this diathesis most often occurs after trauma in children, whereas spontaneous ICH is more frequent in adults. About 15% of patients with FXIIID and ICH die; the bleeding causes 80% of deaths in this coagulopathy. Although in FXIIID, the bleed most commonly is intraparenchymal (> 90%), epidural, subdural, and subarachnoid hemorrhages also have been reported, albeit rarely. As this life-threatening bleeding causes neurological complications, early diagnosis can prevent further expansion of the hematoma and secondary damage. Neuroimaging plays a crucial role in the diagnosis of ICH, but signs and symptoms in patients with severe FXIIID should trigger replacement therapy even before establishment of the diagnosis. Although a high dose of FXIII concentrate can reduce the rate of morbidity and mortality of ICH in FXIIID, it may occasionally trigger inhibitor development, thus complicating ICH management and future prophylaxis. Nevertheless, replacement therapy is the mainstay of treatment for ICH in FXIIID. Neurosurgery is performed in patients with FXIIID and epidural hematoma and a hemorrhage diameter exceeding 2 cm or a volume of ICH is more than 30 cm 3 . Contact sports are not recommended in people with FXIIID as they can elicit ICH. However, a considerable number of safe sports and activities have been suggested to have more benefits than dangers for patients with congenital bleeding

  14. Behaviour of metals during the thermal conversion of Chinese reed; Verhalten von Metallen bei der thermischen Nutzung von Schilfgras

    Energy Technology Data Exchange (ETDEWEB)

    Klensch, S.; Reimert, R. [Karlsruhe Univ. (T.H.) (Germany). Engler-Bunte-Institut Bereich 1 - Gas, Erdoel und Kohle

    1998-12-31

    During thermal conversion (gasification and combustion) of biomasses solid residues (ashes) are produced which should be returned to the forests and the agricultural areas respectively as fertilizers. This aims for avoiding the use of synthetic fertilizers and the necessity of deposition of such ashes. However, to do so the heavy metal concentrations of ashes may not exceed specific limited values. To investigate in the heavy metal behaviour during biomass conversion a bench scale plant was erected. With this plant the influences of the conversion temperature (1000-1300 C), of the gas atmosphere (reducing, oxidising) and of the dedusting temperature (300-750 C) during gasification and combustion of Chinese reed are determined. In essence the plant consists of an entrained flow reactor (length of reaction zone: 2500 mm; inner diameter: 70 mm) and a candle barrier filter with 6 rigid filter elements (DIA-Schumalith 10-20). The biomass flow rate is 6 kg/h and the operating pressure is about 1,2 bar. The test results for the gasification of Chinese reed are presented in form of metal concentrations of Chinese reed original ash, slag, fly ash and product gas concerning the elements Si, Al, Ca, Fe, Mg, Na, K, Pb, Zn, Cr, Cu and Ni. The data represent average values for a range of temperatures from 1000 to 1160 C with a constant filter temperature of 550 C. In order to better illustrate the behaviour of the metals during thermal processing enrichment (concerning the fly ash) and deficiency (concerning the slag) factors for the elements are introduced. The concentrations of the non or hardly volatile elements like Si, Al, Ca, Fe, Mg and K are nearly similar in the original ash, the slag and the fly ash. The concentrations of the environmentally relevant heavy metals like Cr, Pb and Zn in the slag are significantly lower than in the original ash. These heavy metals are enriched in the fly ash. A comparison between the measured fly ash concentrations and the corresponding

  15. Der Einfluß der Ablauforganisation auf die Effizienz von Entscheidungen: Eine empirische Untersuchung am Beispiel von Bilanzanalysen

    OpenAIRE

    Gemünden, Hans Georg

    1987-01-01

    Der vorliegende Beitrag widmet sich einem in der Organisationstheorie stark vernachlässigten Problem: der Ablauforganisation von Entscheidungen. Am Beispiel von Bilanzanalysen wird empirisch geprüft, in welcher Weise eine Gliederung des Prozesses nach Verrichtungen oder Objekten die Qualität der Analyse beeinflußt. Hierzu wird ein validiertes Konzept zur Messung der Qualität von Bilanzanalysen entwickelt. Es wird gezeigt, wie man mittels prozeßbegleitender experimenteller Organisationsforschu...

  16. Beeinflussung der Wirkung von Ernährungsinformation durch Framing: Analyse am Beispiel von Folsäure

    OpenAIRE

    Lensch, Kathrin; Hartmann, Monika; Simons, Johannes

    2011-01-01

    Die Bereitstellung und verbrauchergerechte Aufbereitung von Informationen stellt eine Möglichkeit dar, Konsumenten darin zu unterstützen, Gesundheitsaspekte vermehrt in das Kauf- und Essverhalten zu integrieren. In der Verhaltensökonomik gelten Framing-Effekte als wichtige Bestimmungsfaktoren für die Wahrnehmung von Informationen. Im Rahmen des vorliegenden Beitrags werden Framing-Effekte am Beispiel von Ernährungsinformationen über Folsäure mit Hilfe eines Experiments untersucht. Die Ergebni...

  17. Investigation of mass transfer phenomena in biofilm systems; Untersuchung von Stoffuebergangsphaenomenen in Biofilmsystemen

    Energy Technology Data Exchange (ETDEWEB)

    Waesche, S.; Hempel, D.C. [Technische Univ. Braunschweig (Germany). Inst. fuer Bioverfahrenstechnik; Horn, H. [Fachhochschule Magdeburg (Germany). Hydro- und Abfallchemie

    1999-07-01

    Substance transfer in the boundary layer bulk/biofilm can be only inadequately described by conventional model concepts. In such cases where the surface structure of a biofilm adapts to given hydraulic conditions, the substance transfer phenomena need to be studied in depth. In addition, the entire biofilm structure is much influenced both by substrate conditions and by hydrodynamic conditions during growth. With a view to quantifying these factors, biofilms were cultured under various substrate and hydrodynamic conditions in tube reactors with a diameter of 2.6 cm. For characterizing the cultured biofilms, biofilm density and substrate turnover measured as maximum mass transfer density were determined in each test series. Biofilm density (dry biomass/biofilm volume) was determined by gravimetry. Maximum mass transfer densities in biofilm were established in batch experiments with excess substrate. By means of oxygen microelectrodes, oxygen profiles in the biofilm were measured directly in the reactor. These measurements concerned biofilms of thicknesses ranging from 400 to 2000 {mu}m, where the biofilms did not yet exhibit erosion. (orig.) [German] Der Stoffuebergang in der Grenzschicht Bulk/Biofilm ist mit herkoemmlichen Modellvorstellungen nur ungenuegend beschreibbar. Eine sich an die aktuellen hydraulischen Bedingungen anpassende Oberflaechenstruktur des Biofilms erfordert eine intensive Untersuchung der Stoffuebergangsphaenomene in derartigen Systemen. Darueber hinaus wird die gesamte Biofilmstruktur sowohl von den Substratbedingungen als auch von den hydrodynamischen Bedingungen waehrend des Wachstums stark beeinflusst. Um diese Faktoren quantifizieren zu koennen, wurden Biofilme bei verschiedenen Substrat- und hydrodynamischen Bedingungen in Rohrreaktoren mit einem Durchmesser von 2,6 cm kultiviert. Zur Charakterisierung der kultivierten Biofilme wurde die Biofilmdichte und der Substratumsatz, gemessen als maximale Massestromdichte, bei jeder Versuchsreihe

  18. [Prevalence and risk factors of extra-coronary artery disease in patients with diabetes which confirmed atherosclerosis of coronary arteries].

    Science.gov (United States)

    Gracheva, S A; Biragova, M S; Glazunova, A M; Klefortova, I I; Melkozerov, K V; Shamkhalova, M Sh; Dzhavelidze, M I; Soldatova, T V; Il'in, A V; Deev, A D; Shestakova, M V; Tugeeva, E F; Buziashvili, Iu I

    2014-01-01

    To assess prevalence and risk factors of extra-coronary artery disease (peripheral artery (PA) disease (D) of lower extremities (LE), brachiocephalic arterial (BCA) stenosis (S), renal arterial (RA) S in type 1 and 2 (T1 and T2) diabetes (D) patients (P) with confirmed atherosclerosis of coronary arteries (CA). 100 P (48 with T2D, 18 with T1D, 34 without diabetes - PWD), with hemodynamically significant atherosclerosis of CA confirmed by coronary angiography. All patients underwent duplex ultrasonography of PA LE, BCA, RA. Other studies included assessment of clinical characteristics and measurement of the following parameters: profibrogenic cytokines (transforming growth factor [TGF] beta1, matrix metalloproteinase 9 [MMP9], monocyte chemotactic protein-1 [MCP-1], regulated on activation normal T-cell expressed and secreted [RANTES), markers of endothelial dysfunction (von Willebrand factor [VWF], homocystein [HCYST], plasminogen activator inhibitor-1 [PAI-1], vascular cell adhesion molecule [VCAM], soluble intercellular adhesion molecules-1 [sICAM], vascular endothelial growth factor [VEGF], asymmetric dimethylarginine [ADMAD, N-terminal fragment of pro-brain natriuretic peptide (NT-pro BNP), fibroblast growth factor 23 (FGF-23), and fibrinogen. Portions of P with multivessel CA disease were similar in all three groups (T1D - 88.9, T2D - 85.5, WD - 82.3%). Coexistence of atherosclerosis in 2 or more vascular beds was identified in 85.3% of T2D and in 50% of WD P (p = 0.005). In T1D group 61.1 and 11.1% of P had atherosclerosis in 2 and 3 vascular beds, respectively. Levels of profibrogenic cytokines and factors of endothelial activation (RANTES, MMP-9, PAI-I, VCAM, sICAM, ADMA) were significantly higher in P with diabetes vs P WD. P with diabetes and multifocal atherosclerosis demonstrated significant increases of CRP, fibrinogen, NT-proBNP, VWF, PAI-1, ADMA, sICAM, and decrease of GFR compared with P with atherosclerosis in 1 vascular bed. Logistic regression

  19. Philologie im Horizont der Geschichtlichkeit von Sprache und Text: zum Tagungsband von Wulf Oesterreicher und Maria Selig

    Directory of Open Access Journals (Sweden)

    Olaf Müller

    2016-03-01

    Full Text Available Wulf Oesterreicher und Maria Selig, Hrsg., Geschichtlichkeit von Sprache und Text: Philologien – Disziplingenese – Wissenschaftshistoriographie (Paderborn: Wilhelm Fink, 2014, 332 S.

  20. TLX controls angiogenesis through interaction with the von Hippel-Lindau protein

    OpenAIRE

    Zhao-jun Zeng; Erik Johansson; Amiko Hayashi; Pavithra L. Chavali; Nina Akrap; Takeshi Yoshida; Kimitoshi Kohno; Hiroto Izumi; Keiko Funa

    2012-01-01

    Summary TLX is known as the orphan nuclear receptor indispensable for maintaining neural stem cells in adult neurogenesis. We report here that neuroblastoma cell lines express high levels of TLX, which further increase in hypoxia to enhance the angiogenic capacity of these cells. The proangiogenetic activity of TLX appears to be induced by its direct binding to the von Hippel-Lindau protein (pVHL), which stabilizes TLX. In turn, TLX competes with hydroxylated hypoxia-inducible factor (HIF-α) ...

  1. Von den Liven von Oesel / August Ludwig Schlözer

    Index Scriptorium Estoniae

    Schlözer, August Ludwig

    2008-01-01

    Avaldatud Eberhard Winkleri initsiatiivil A. L. Schlözeri teose põhjal: Gesammelte Nachrichten von den Ueberresten der Liven, in Livland und Kurland. (1770), mis moodustab osa teosest: Schlözer, August Ludwig. M. Johann Joseph Haigold's Beylagen zum Neuveränderten Russland. Zweiter Theil. Riga und Leipzig, 1770

  2. Aino Lepik von Wiren / Aino Lepik von Wiren ; interv. Kadi Alatalu

    Index Scriptorium Estoniae

    Lepik von Wirén, Aino, 1961-

    2007-01-01

    Heinrich Marga eksiilvalitsuse (20.06.1990-7.10.1992) kohtuminister Aino Lepik von Wiren pagulaslapse elust Rootsis, haridusest ja elukutse valikust, tööst eksiilvalitsuses, tööleasumisest Eestisse 1992. aastal, seadusandlikust tegevusest ning aluse panekust välismaalaste- ja kodakondsuspoliitikale, naiste võimalustest poliitilisse tippu tõusmiseks, kodu- ja väliseestlaste vastandamisest

  3. Ööklubi Club von Überlingen = Club von Überlingen

    Index Scriptorium Estoniae

    2008-01-01

    Ööklubi Club von Überlingen (Madara 22A, Tallinn) sisekujundusest. Sisearhitekt: Taavi Aunre (Boom.ee OÜ). Taavi Aunrest, tema tähtsamad tööd. I-II korruse plaan, 11 värv. vaadet, foto T. Aunrest

  4. Case report

    African Journals Online (AJOL)

    abp

    2017-06-29

    Jun 29, 2017 ... described by the Finish physician Erik von Willebrand in 1926. VWD ... on day 4 and showed normal factor IX level but factor VIII level was low at 16.6%. ... and hemophilia A or between VWD 2B and a platelet disorder.

  5. Vasa vasorum in the tunica media and tunica adventitia of the porcine aorta

    Czech Academy of Sciences Publication Activity Database

    Tonar, Z.; Tomášek, P.; Loskot, P.; Janáček, Jiří; Králíčková, M.; Witter, K.

    2016-01-01

    Roč. 205, č. 2016 (2016), s. 22-36 ISSN 0940-9602 Institutional support: RVO:67985823 Keywords : artery * microvessels * pig * stereology * vascular wall * von Willebrand factor Subject RIV: EA - Cell Biology Impact factor: 1.864, year: 2016

  6. Polychaeten aus den Zoologischen Museen von Leiden und Amsterdam I

    NARCIS (Netherlands)

    Augener, H.

    1933-01-01

    In der vorliegenden Arbeit ist die Untersuchung eines sehr umfangreichen Polychaeten-Materials niedergelegt, das mir von Herrn Prof. Dr. E. D. van Oort in Leiden und Herrn Prof. Dr. L. F. de Beaufort in Amsterdam zur Bearbeitung übergeben wurde. Von diesem Material ist der dem Museum in Leiden

  7. [Hans Jakob Christoffel von Grimmelshausen. Saksa Simplicissimuse seiklused] / Meelis Friedenthal

    Index Scriptorium Estoniae

    Friedenthal, Meelis, 1973-

    2011-01-01

    Tutvustus: Grimmelshausen, Hans Jakob Christoffel von. Saksa Simplicissimuse seiklused, teisisõnu: ühe veidra vagabundi elulugu, kel Melchior Sternfels von Fuchshaim nimeks, et kus ja mis moel ta siia ilma sündis ning mida siin nägi, õppis, oma nahal tunda sai ja kannatas, nagu sellestki, miks ta siinsest ilmast vabatahtlikult loobub. [Tallinn] : Pegasus, c2010

  8. An accurate von Neumann's law for three-dimensional foams

    NARCIS (Netherlands)

    Hilgenfeldt, Sascha; Kraynik, Andrew M.; Koehler, Stephan A.; Stone, Howard A.

    2001-01-01

    The diffusive coarsening of 2D soap froths is governed by von Neumann's law. A statistical version of this law for dry 3D foams has long been conjectured. A new derivation, based on a theorem by Minkowski, yields an explicit analytical von Neumann's law in 3D which is in very good agreement with

  9. Erfahrungen an der Schnittstelle von Medienarbeit und Praxisforschung

    Directory of Open Access Journals (Sweden)

    Peter Holzwarth

    2007-11-01

    Full Text Available Der Beitrag reflektiert die Verbindung von praktischer Medienarbeit und Forschung am Beispiel eines internationalen EU-Forschungsprojekts zum Thema Medien und Migration. Neben didaktischen Prinzipien und Konzepten für die aktive Medienarbeit im Forschungskontext geht es um die Kooperation von medienpädagogischer Begleitung (MB und wissenschaftlicher Begleitung (WB sowie um deren spezifische Kompetenzen.

  10. Die baltischen Kapitulationen von 1710 : Kontext, Wirkungen, Interpretationen / Marten Seppel

    Index Scriptorium Estoniae

    Seppel, Marten, 1979-

    2015-01-01

    Arvustus: Die baltischen Kapitulationen von 1710 : Kontext, Wirkungen, Interpretationen, hrsg. von Karsten Brüggemann, Mati Laur und Pärtel Piirimäe, Queleln und Studien zur baltischen Geschichte, Bd 23 (Köln u.a: Böhlau Verlag, 2014)

  11. [Precocious puberty and von Recklinghausen's disease].

    Science.gov (United States)

    Barg, Ewa; Wikiera, Beata; Basiak, Aleksander; Głab, Ewa

    2006-01-01

    Von Recklinghausen's disease belongs to a group of neurocutaneous syndromes and is characterised by skin, nerve and bone abnormalities. We present a case of von Recklinghausen's disease and precocious puberty in 7-year-old boy. At the age of three café au lait spots on the skin and an incranial tumour situated near the optic chiasm--qualified as inoperable--were discovered. At the age of 7 first signs of precocious puberty appeared (pubic hair P3 and enlargement of the testes (15 ml) and penis). Laboratory measurements included: LH 7.5 mIU/ml, FSH 1.1 mIU/ml, testosterone 183 ng/ml, assessment of bone age: 9 years. The response to LHRH stimulation was characteristic for true precocious puberty (LH 15.9 mIU/ml and FSH 1.5 mIU/ml after 30 minutes). The MRI of the brain showed a tumour of the suprasellar region with compression of pituitary stalk. True precocious puberty was diagnosed. Treatment with Diphereline was introduced. At present the boy is 9 years old and has been treated with Diphereline for 16 months. The volume of the testicles has decreased to 7 ml and loss of pubic hair was noted. The MRI does not show any progression in tumour growth. The authors would like to underline the need of close observation of children with von Reclinghausen disease with regard to possibility of uncovering true precocious puberty which is critical for rapid diagnosis and introduction of correct treatment.

  12. Unlawfulness of environmental zones; Rechtswidrigkeit von Umweltzonen

    Energy Technology Data Exchange (ETDEWEB)

    Balbach, Jan

    2016-07-01

    The author examines the new findings on the effectiveness of the environmental zones and, in this context, questions their legitimacy. In addition, the efforts of the European and German legislators are analyzed in order to reduce the particulate matter pollution. In addition, legal protection against the exceeding of limits for particulate matter is critically appreciated. [German] Der Autor beleuchtet die neuen Erkenntnisse zur Wirksamkeit der Umweltzonen und hinterfragt vor diesem Hintergrund deren Rechtmaessigkeit. Darueber hinaus werden die Bemuehungen des europaeischen und deutschen Gesetzgebers analysiert, um die Feinstaubbelastung zu senken. Zudem wird der Rechtsschutz gegen die Ueberschreitung von Feinstaubgrenzwerten kritisch gewuerdigt.

  13. A Metabiography of Alexander von Humboldt

    Directory of Open Access Journals (Sweden)

    Nicolaas A. Rupke

    2006-04-01

    Full Text Available Article in English.The author's recently published monograph on Alexander von Humboldt describes the multiple images of this great cultural icon. The book is a metabiographical study that shows how from the middle of the nineteenth century to the present day Humboldt has served as a nucleus of crystallisation for a variety of successive socio-political ideologies, each producing its own distinctive representation of him. The historiographical implications of this biographical diversity are profound and support current attempts to understand historical scholarship in terms of memory cultures.

  14. Die Biopsie von Knochen- und Weichteiltumoren

    OpenAIRE

    Fuchs, B

    2008-01-01

    Technisch stellt die Biopsie von Knochen- und Weichteiltumoren einen simplen Akt dar, intellektuell aber ist die Planung einer Biopsie höchst anspruchsvoll. Zu häufig werden heutzutage immer noch Biopsien unsachgemäss durchgeführt, so dass die Behandlung - im besten Fall - erschwert wird. Eine unsachgemäss durchgeführte Biopsie führt häufig zu negativen funktionellen Konsequenzen für den Patienten, im schlimmsten Fall kann es die Prognose direkt beeinträchtigen. Aus diesem Grund soll...

  15. Die Altäre von Selinunt

    OpenAIRE

    Voigts, Clemens

    2014-01-01

    In der Dissertation wurden die Altäre von Selinunt, einer griechischen Kolonie auf Sizilien, mit den Methoden der Bauforschung untersucht. Die neun behandelten Brandopferaltäre sind monumentale Quaderbauten, die bis zu 20 m Länge erreichen. Sie stammen aus der Blütezeit Selinunts, dem 6. und 5. Jh. v. Chr. Die Bauten waren bereits im 19. und 20. Jh. freigelegt worden und wurden nun in Bauaufnahmen dokumentiert, zeichnerisch rekonstruiert und zeitlich eingeordnet. Dabei ließ sich an ihnen eine...

  16. Alexander von Humboldt’s footnotes

    OpenAIRE

    Werner, Anja

    2015-01-01

    Alexander von Humboldts Fußnoten waren ihrer Zeit weit voraus, obwohl sie kaum den heutigen akademischen Standards entsprechen. Dieser Artikel untersucht die Fußnoten in Humboldts Essai politique sur l‘île de Cuba (1826). Zwar ist es nicht immer leicht, die manchmal recht geheimnisvollen Verweise zu entschlüsseln, dennoch lohnt sich der Versuch: Humboldts Fußnoten geben nicht nur Auskunft über seine umfassenden Netzwerke des Wissens. Sie verweisen auch auf Auseinandersetzungen verschiedener G...

  17. [Heinz von zur Mühlen. Das Bürgertum Fordert Blut. Ein Bolschewistiches Flugblatt von 1918] / Paul Kaegbein

    Index Scriptorium Estoniae

    Kaegbein, Paul

    2007-01-01

    Arvustus: Heinz von zur Mühlen. Das Bürgertum Fordert Blut. Ein Bolschewistiches Flugblatt von 1918. In : Ostseeprovinzen, baltische Staaten und das Nationale. Münster : LIT, 2005, lk. 403-414. 1918. aastast pärit lendlehest, mille käekirja järgi otsustades on kirjutanud Viktor Kingissepp

  18. Negative regulation of hypoxia-inducible genes by the von Hippel-Lindau protein.

    OpenAIRE

    Iliopoulos, O; Levy, A P; Jiang, C; Kaelin, W G; Goldberg, M A

    1996-01-01

    Inactivation of the von Hippel-Lindau protein (pVHL) has been implicated in the pathogenesis of renal carcinomas and central nervous system hemangioblastomas. These are highly vascular tumors which overproduce angiogenic peptides such as vascular endothelial growth factor/vascular permeability factor (VEGF/VPF). Renal carcinoma cells lacking wild-type pVHL were found to produce mRNAs encoding VEGF/VPF, the glucose transporter GLUT1, and the platelet-derived growth factor B chain under both no...

  19. Guy von Dardel 1919-2009

    CERN Multimedia

    2009-01-01

    Guy von Dardel, a well-known figure at CERN and in the international particle physics community, passed away on 28 August. Guy von Dardel came to CERN when it was founded in 1954 and was a full-time staff member until 1964, performing several experiments and working on technical developments. These included the first measurement of the neutral pion’s life-time. Called to Lund University in 1964, he became professor there in 1965 and director of the 1.2 GeV electron accelerator. In the late 1960s, he performed an experiment at CERN’s PS that measured the decays of the Λ. Then, in the early 1970s, he involved the Lund group in a series of experiments at the Intersecting Storage Rings (ISR), where he measured the production of various types of particles. In particular, he participated in a series of experiments that observed the production of a high abundance of particles with large transverse momenta. This required an explanation...

  20. Die Krakauer Kirche von Karmeliten und Karmelitaninnen

    Directory of Open Access Journals (Sweden)

    Józef Szymon Wronski

    2004-12-01

    Full Text Available 1. Die Klosterkirche der unbeschuhten Karmelitinnen Zum Heiligen Josef. Ein glücklicher Auftakt und somit die charakteristische Einführung in das 20. Jh. für den Kirchenbau von Krakau war die Errichtung der Karmeliterinnen St. Josephs-Kirche an der Lobzowska-Straße 40, in der die Architekten (Tadeusz Stryjeński (1849-1943 - Projektant der Kirche und Franciszek Mączyński (1874-1947 - Ausführer des Bauprojektes mit eigenen Verbesserungen die historisch- eklektizistischen Formen d.h. die mittelalterlichen Formen vor allem des sog. Übergangsstils vereinfachten. Die Kirche, die in den Jahren 1903-1905 errichtet wurde, steht inmitten vom Baukomplex des Klosters, dessen Grundriss das Quadrat ist49. Der Kirchenbau ist ein dem Gesamtbau des Klosters eingefügter Längsraum. Hinter dem Chor liegt das Oratorium des Konvents. Das Material Backstein (mit Verwendung von Stein erinnert an die Baukunst eines der besten Architekten jener Zeit, nämlich Teodor Talowskis (1857-1910, der viele Kirchen in Südpolen, aber auch viele Bürgerhäuser nicht nur in Krakau im ausgehenden 19. Jh. baute. Die Architektur der Karmeliterinnen St. Josephs-Kirche ist immer noch im Malerischen begriffen. Aber die Vereinfachung der historischen Formen führt zu ihrer „Beruhigung” und dadurch zur Wuchtigkeit des Ausdrucks. Bemerkenswert ist die in dieser Zeit (in der Anlage noch seltene ausgewogene Proportionierung des Baukörpers. Das methodische Prinzip jener Zeit ist der Kontrast. Im Kontrast zu den gedrungenen und wuchtigen Formen des Baukörpers stehen z.B. die sich verjüngenden obeliskenförmigen und pylonenartigen Türmchen, die nicht nur die Eingangsfassade der Kirche flankieren, sondern auch an den Ecken des Querhauses der Kirche stehen. Die ingravierten weißen Steine an der Fassade in der Zahl von Zehn erinnern an das Gebot des Karmelterinnenordens: Bete täglich den Rosenkranz und sind zugleich ein Vanitativmotiv. 2. Die Klosterkirche der unbeschuhten

  1. Suitability of tracers; Eignung von Tracern

    Energy Technology Data Exchange (ETDEWEB)

    Klotz, D. [GSF - Forschungszentrum fuer Umwelt und Gesundheit GmbH, Neuherberg (Germany). Inst. fuer Hydrologie

    1999-02-01

    Hydrological tracer techniques are a means of making statements on the direction and speed of underground water. One of the simpler tasks is to find out whether there is hydrological communication between two given points. This requires a determination of the direction of flow, which places less exacting demands on the properties of the tracer than does the task of determining the flow velocity of underground water. Tracer methods can serve to infer from flow velocity the distance (flow) velocity, which is defined as the ratio between the distance between two points located in flow direction and the actual time it takes water to flow from one to the other. [Deutsch] Mit Hilfe der hydrologischen Markierungstechniken koennen Aussagen ueber die Richtung und die Geschwindigkeit von Bewegungen des unterirdischen Wassers gemacht werden. Der einfachere Fall liegt vor, wenn festgestellt werden soll, ob zwischen zwei Punkten eine hydrologische Verbindung besteht. Bei dieser Fliessrichtungsbestimmung sind die Forderungen an die Eigenschaften der einzusetzenden Tracer geringer als bei der Bestimmung der Geschwindigkeit des unterirdischen Wassers. Von den Geschwindigkeiten des unterirdischen Wassers ist die Abstands-(Fliess)geschwindigkeit, die definiert ist durch das Verhaeltnis aus dem Abstand und der wahren Fliesszeit zwischen zwei in Bewegungsrichtung gelegenen Punkten, durch Tracermethoden zu bestimmen. (orig.)

  2. Kontextualisierung von Queer Theory Contextualizing Queer Theory

    Directory of Open Access Journals (Sweden)

    Anna Voigt

    2008-03-01

    Full Text Available Christine M. Klapeer legt in diesem Einführungsband dar, aus welchen politischen und theoretischen Kontexten heraus sich ‚queer‘ zu einem Begriff mit besonderem politischem und theoretischem Gehalt entwickelt hat. Wesentlich zielt sie dabei auf eine kritische Kontextualisierung von „queer theory”. Die Autorin geht zunächst auf das Gay Liberation Movement ein, grenzt die Queer Theory vom Poststrukturalismus, von feministischen Theorien und den Lesbian and Gay Studies ab, beleuchtet Eckpunkte queeren Denkens und zeichnet schließlich die Entwicklungen in Österreich sowohl politisch-rechtlich als auch bewegungsgeschichtlich und in der Wissenschaftslandschaft nach.Christine M. Klapeer’s introductory volume demonstrates the manner in which ‘queer’ grew out of various political and theoretical contexts to become a term with special political and theoretical content. She focuses primarily on a critical contextualization of “queer theory.” The author begins by approaching the Gay Liberation Movement and then distinguishes Queer Theory from poststructuralism, from feminist theories, and from Lesbian and Gay Studies. She continues on to illuminate the key aspects of queer thought and concludes by sketching the development in Austria in terms of politics and the law, the history of movements, and within the landscape of knowledge.

  3. Ludwig Leichhardt und Alexander von Humboldt

    Directory of Open Access Journals (Sweden)

    Aliya-Katarina Südfels

    2012-10-01

    Full Text Available Zusammenfassung Im Juli des Jahres 1841 kommt es zu einem Treffen zwischen zwei Männern, das zunächst belanglos erscheint, sich aber Jahre später als wichtige historische Begebenheit herausstellen wird. In seinem Pariser Büro empfängt der 71jährige Naturforscher Alexander von Humboldt den jungen Preußen Ludwig Leichhardt. Der angehende Naturwissenschaftler erhofft sich Zuspruch und Empfehlung des berühmten Alexander von Humboldts. Die Unterredung ist kurz und verläuft für Leichhardt ergebnislos. Es wird das einzige Treffen der beiden Naturwissenschaftler bleiben. Aus heutiger Sicht unverständlich, da Ludwig Leichhardt und Alexander von Humboldt mehr verband, als ihre Leidenschaft für die Naturwissenschaften. Viel zu wenig ist sich bis jetzt den biographischen Analogien und den vergleichbaren geographischen Leistungen der beiden Preußen gewidmet worden. Abstract During July 1841 a meeting between two men takes place, which seems to have been extraneous, but turns out to be a significant historical incident. 71 year old natural scientist Alexander von Humboldt welcomes young Ludwig Leichhardt from Prussia in his office in Paris. The prospective young scientist expects help and references from famous Alexander von Humboldt. The conversation is short and ends from Leichhardt’s point of view without results. Unfortunately this is going to be the only meeting between the two scientists even though the two Prussians have more in common than their passion for the natural sciences. Way too seldomly have biographical analogy and geographical productivity of the two men been compared. Résumé En juillet 1841 une rencontre entre deux hommes a lieu, qui au premier abord semble sans importance, mais qui des années plus tard est considéré comme un événement historique majeur. Dans son bureau parisien, le naturaliste Alexandre de Humboldt, alors âgé de 71 ans, reçoit le jeune Prussien Ludwig Leichhardt. Le jeune scientifique en devenir

  4. Techniques for quantification of liver fat in risk stratification of diabetics; Techniken zur Leberfettquantifizierung bei der Risikostratifikation von Diabetikern

    Energy Technology Data Exchange (ETDEWEB)

    Kuehn, J.P.; Spoerl, M.C.; Mahlke, C.; Hegenscheid, K. [Universitaetsmedizin Greifswald, Abteilung Experimentelle Radiologie, Institut fuer Diagnostische Radiologie und Neuroradiologie, Greifswald (Germany)

    2015-04-01

    Fatty liver disease plays an important role in the development of type 2 diabetes. Accurate techniques for detection and quantification of liver fat are essential for clinical diagnostics. Chemical shift-encoded magnetic resonance imaging (MRI) is a simple approach to quantify liver fat content. Liver fat quantification using chemical shift-encoded MRI is influenced by several bias factors, such as T2* decay, T1 recovery and the multispectral complexity of fat. The confounder corrected proton density fat fraction is a simple approach to quantify liver fat with comparable results independent of the software and hardware used. The proton density fat fraction is an accurate biomarker for assessment of liver fat. An accurate and reproducible quantification of liver fat using chemical shift-encoded MRI requires a calculation of the proton density fat fraction. (orig.) [German] Die Fettleber scheint einen unmittelbaren Einfluss auf die Pathophysiologie des Diabetes mellitus Typ 2 zu besitzen. Zur Detektion und Quantifizierung des Leberfetts werden in der klinischen Diagnostik akkurate Verfahren gebraucht. Ein einfaches Verfahren ist die Chemical-shift-kodierte Magnetresonanztomographie (MRT). Eine suffiziente Quantifizierung von Leberfett mithilfe der Chemical-shift-kodierten MRT erfordert eine Beruecksichtigung von Stoervariablen, wie den T2*-Zerfall, den T1-Wiederaufbau und die multispektrale Komplexitaet von Fett. Eine Korrektur aller Stoervariablen wird als Proton-density-Fettfraktion bezeichnet. Diese liefert unabhaengig von der verwendeten Einstellung und Hardware reproduzierbare Ergebnisse. Die korrigierte Proton-density-Fettfraktion ist ein akkurater Biomarker zur Quantifizierung von Leberfett. Die akkurate und reproduzierbare Quantifizierung von Leberfett in der MRT erfordert eine Berechnung der Proton-density-Fettfraktion. (orig.)

  5. Sucralfate for the treatment of radiation induced mucositis; Einsatz von Sucralfat in der Radioonkologie

    Energy Technology Data Exchange (ETDEWEB)

    Belka, C. [Univ. Tuebingen (Germany). Abt. fuer Strahlentherapie; Hoffmann, W. [Univ. Tuebingen (Germany). Abt. fuer Strahlentherapie; Paulsen, F. [Univ. Tuebingen (Germany). Abt. fuer Strahlentherapie; Bamberg, M. [Univ. Tuebingen (Germany). Abt. fuer Strahlentherapie

    1997-05-01

    Purpose: Radiotherapy, a cornerstone in the management of head and neck cancer, pelvic cancer, and esophageal cancer is associated with a marked mucosal toxicity. Pain, malnutrition and diarrhea are the most prevalent clinical symptoms of radiation induced mucosal damage. Because there is no known way to obviate radiation mucositis all efforts to prevent aggravation and accelerate healing of mucosal changes are of great importance. Numerous agents including antimicrobials, local and systemic analgesics, antiinflammatory drugs, antidiarrheal drugs, in combination with intensive dietetic care are used to relieve symptoms. Recently coating agents like the polyaluminum-sucrose complex sucralfate were suggested for the prevention and treatment of mucosal reactions. Since sucralfate protects ulcerated epithelium by coating, liberates protective prostaglandins and increases the local availability of protective factors this drug might directly interact with the pathogenesis of mucositis. Patients and Method: The results of available studies are analysed and discussed. Results: The results of several studies indicate that sucralfate treatment especially during radiotherapy for pelvic cancer leads to a significant amelioration of clinical symptoms and morphological changes. An application of sucralfate during radiotherapy of head and neck cancer reveals only limited benefits in most studies performed. Conclusion: Nevertheless sucralfate is a save, cheap and active drug for the prevention and treatment of radiation mucositis especially in patients with pelvic irradiation. (orig.) [Deutsch] Hintergrund: Schleimhautreaktionen stellen eine wesentliche akute und chronische Nebenwirkung radioonkologischer Therapieverfahren dar. Klinisch im Vordergrund stehen Schmerzen, Ernaeherungsprobleme und Durchfaelle. Da bislang keine kausalen Therapie- oder Prophylaxemassnahmen bekannt sind, erfolgt die Behandlung symptomorientiert. Hierbei kommen insbesondere lokale und systemische

  6. CD31-Expression am Primärtumor und Nachweis hämatogen disseminierter Tumorzellen im Knochenmark von Brustkrebspatientinnen

    OpenAIRE

    Eisenmann, Petra

    2005-01-01

    Der Nachweis von disseminierten Tumorzellen im Knochenmark von Patientinnen mit primärem Mammakarzinom ist ein wichtiger prognostischer Parameter. In der vorliegenden Arbeit wurde der Nachweis von CD31 am Primärtumor Mammakarzinom mit dem Auftreten von Mikrometastasen im Knochenmark korreliert. Ferner wurde die prognostische Bedeutung von disseminierten Tumorzellen im Knochenmark und die prognostische Bedeutung von CD31 evaluiert. Bei 50 Patientinnen des Gesamtkollektivs von 195 (25,6%) wu...

  7. Clarifying the link between von Neumann and thermodynamic entropies

    Science.gov (United States)

    Deville, Alain; Deville, Yannick

    2013-01-01

    The state of a quantum system being described by a density operator ρ, quantum statistical mechanics calls the quantity - kTr( ρln ρ), introduced by von Neumann, its von Neumann or statistical entropy. A 1999 Shenker's paper initiated a debate about its link with the entropy of phenomenological thermodynamics. Referring to Gibbs's and von Neumann's founding texts, we replace von Neumann's 1932 contribution in its historical context, after Gibbs's 1902 treatise and before the creation of the information entropy concept, which places boundaries into the debate. Reexamining von Neumann's reasoning, we stress that the part of his reasoning implied in the debate mainly uses thermodynamics, not quantum mechanics, and identify two implicit postulates. We thoroughly examine Shenker's and ensuing papers, insisting upon the presence of open thermodynamical subsystems, imposing us the use of the chemical potential concept. We briefly mention Landau's approach to the quantum entropy. On the whole, it is shown that von Neumann's viewpoint is right, and why Shenker's claim that von Neumann entropy "is not the quantum-mechanical correlate of thermodynamic entropy" can't be retained.

  8. Das Geschäftsmodell von Retail Banken im Wandel der Digitalisierung

    OpenAIRE

    Messikommer, Cédric

    2016-01-01

    Der Prozess der Digitalisierung führt in unterschiedlichen Branchen zu tiefgreifenden Veränderungen. Dazu gehört auch der Finanzsektor, dessen Umfeld von erodierenden Margen und Tiefstzinsen geprägt ist. Die Digitalisierung hat weitreichende Auswirkungen auf die Geschäftsmodelle von Banken und speziell von Retail Banken. Deren Basisdienstleistungen werden zunehmend von neuen Mitbewerbern mit modernster Internet-Technologie angeboten. Damit sind wesentliche Teile der Wertschöpfungskette von Re...

  9. Strukturbasierte Entwicklung von Assaysystemen und Charakterisierung von orthosterischen und allosterischen Kinaseinhibitoren

    OpenAIRE

    Klüter, Sabine

    2010-01-01

    Die Proteinkinasen stellen eine wichtige Enzymklasse für die Regulation der Signaltransduktion dar. Sie steuern diese diffizil regulierten, intrazellulären Signalkaskaden durch Übertragung der ?-Phosphatgruppe von ATP auf andere Proteine. Fehlregulationen dieser komplexen Stoffwechselwege können Krankheiten wie Krebs, Diabetes oder Autoimunkrankheiten verursachen. Somit gehören die Kinasen in den letzten Jahren zu den wichtigsten Zielproteinen der Pharmaindustrie. Die klassi...

  10. Der Effekt von Akupunktur in der Prävention von Prüfungsangst

    OpenAIRE

    Krüger, Peter

    2017-01-01

    Prüfungsangst ist ein weit verbreitetes gesellschaftliches Phänomen, das bisher in nur wenigen wissenschaftlichen Ansätzen untersucht wurde. Die Zahl der Studenten, die Gehirn - Doping zur Leistungssteigerung und zur Minimierung von Prüfungsangst nutzen, steigt stetig an. In bisherigen Studien wurde Akupunktur an Herz 7 als vielversprechende Behandlungsalternative dargestellt. Basierend auf diesen Ergebnissen, wurde in dieser Arbeit untersucht, ob eine Einzelpunktakupunktur an Herz 7 die ...

  11. [Albert Reder Ritter von Schellmann (1826-1904)].

    Science.gov (United States)

    Schmidt, G; Holubar, K

    1990-01-01

    Albert Reder von Schellmann (1826-1904) was an important syphilidologist of the Vienna Medical School in the second half of the nineteenth century. He went in for the dualistic concept of the origin of syphilis and ulcer caused by soft chancre. In 1870 - Reder became head of a third dermato-syphilidologic department in the "Josephinum" in Vienna, where military surgeons got their medical education. At the same time the two full professorships of dermatosyphilidology in the Vienna General Hospital were held by Ferdinand von Hebra (1816-1880) and Carl Ludwig Sigmund von Ilanor (1810-1883).

  12. Speziation von Gadolinium-MRT-Kontrastmitteln in Umweltmatrizes

    OpenAIRE

    Lindner, Uwe

    2017-01-01

    Gd-Kontrastmittel werden in der Medizin für die Magnetresonanztomographie (MRT) benötigt, um einen besseren Bildkontrast zu erzielen. Nach der Anwendung gelangen diese Arzneimittel über das Abwasser in die Klärwerke und von dort in die jeweiligen anliegenden Oberflächengewässer. Somit wird es notwendig, den Verbleib der Gd-MRT-Kontrastmittel in der Umwelt zu verfolgen und aufzuklären. In dieser Arbeit werden für die Analyse von Umweltproben Methoden zur Speziesanalytik von Gd-Kontrastmitteln ...

  13. Decreased plasma ADAMTS-13 activity as a predictor of postoperative bleeding in cyanotic congenital heart disease

    Directory of Open Access Journals (Sweden)

    Rosangela P.S. Soares

    2013-04-01

    Full Text Available OBJECTIVE: To analyze the preoperative plasma antigenic concentration and activity of von Willebrand factor and its main cleaving protease ADAMTS-13 in pediatric patients with cyanotic congenital heart disease undergoing surgical treatment and investigate possible correlations with postoperative bleeding. METHODS: Plasma antigenic concentrations (von Willebrand factor:Ag and ADAMTS-13:Ag were measured using enzyme-linked immunoassays. Collagen-binding assays were developed to measure biological activities (von Willebrand factor:collagen binding and ADAMTS-13 activity. The multimeric structure of von Willebrand factor was analyzed using Western immunoblotting. Demographic, diagnostic, and general and specific laboratory data and surgery-related variables were subjected to univariate, bivariate, and multivariate analysis for the prediction of postoperative bleeding. RESULTS: Forty-eight patients were enrolled, with ages ranging from 9 months to 7.6 years (median 2.5 years. The plasma concentrations of von Willebrand factor:Ag and ADAMTS-13:Ag were decreased by 65 and 82%, respectively, in the patients compared with the controls (p<0.001. An increased density of low-molecular-weight fractions of von Willebrand factor, which are suggestive of proteolytic degradation (p = 0.0081, was associated with decreased ADAMTS-13 activity, which was likely due to ADAMTS-13 consumption (71% of controls, p = 0.0029 and decreased von Willebrand factor:collagen binding (76% of controls, p = 0.0004. Significant postoperative bleeding occurred in 13 patients. The preoperative ADAMTS-13 activity of <64.6% (mean level for the group, preoperative activated partial thromboplastin time, and the need for cardiopulmonary bypass were characterized as independent risk factors for postoperative bleeding, with respective hazard ratios of 22.35 (95% CI 1.69 to 294.79, 1.096 (95% CI 1.016 to 1.183, and 37.43 (95% CI 1.79 to 782.73. CONCLUSION: Low plasma ADAMTS-13

  14. 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...

  15. NCBI nr-aa BLAST: CBRC-TTRU-01-0026 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-TTRU-01-0026 ref|YP_001642747.1| ATPase [Bacillus weihenstephanensis KBAB4] gb...|ABY46772.1| AAA ATPase containing von Willebrand factor type A (vWA)-like domain [Bacillus weihenstephanensis KBAB4] YP_001642747.1 5e-80 50% ...

  16. Effect of exercise on platelet activation during aspirin or clopidogrel intake in healthy men

    DEFF Research Database (Denmark)

    Hjorth Madsen, Esben; Christiansen, Morten Krogh; Schmidt, Erik Berg

    2009-01-01

    aggregometry. A significant increase in plasma von Willebrand Factor was also found in response to exercise. In conclusion, platelet activation occurs during exercise in healthy individuals. This activation is not prevented by use of aspirin or clopidogrel, and may partly be explained by an increase in plasma...

  17. Elevated urinary albumin excretion is associated with impaired arterial dilatory capacity in clinically healthy subjects

    DEFF Research Database (Denmark)

    Clausen, P; Jensen, J S; Jensen, G

    2001-01-01

    (endothelium-dependent, flow-associated dilation) and to nitroglycerin (endothelium-independent, nitroglycerin-induced dilation). Plasma concentrations of the endothelial markers nitrate/nitrite, thrombomodulin, and von Willebrand factor antigen were also measured. Both flow-associated and nitroglycerin...

  18. Biomarkers of endothelial dysfunction are elevated and related to prognosis in chronic heart failure patients with diabetes but not in those without diabetes

    DEFF Research Database (Denmark)

    Kistorp, C.; Chong, A.Y.; Gustafsson, F.

    2008-01-01

    Biomarkers of endothelial dysfunction, such as soluble E-selectin, and von Willebrand factor (vWf) are elevated in patients with chronic heart failure (CHF). The impact of diabetes mellitus (DM) on these biomarkers, and their relation to prognosis remains unknown....

  19. A case of refractory thrombotic thrombocytopenic purpura treated ...

    African Journals Online (AJOL)

    Background. Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threaten- ing disorder that occurs due to deficiency of ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member. 13), which is a von Willebrand factor (VWF) cleaving protein.[1]. The absent or severely reduced activity ...

  20. Renal arteriovenous fistula: A rare complication of electro-hydraulic ...

    African Journals Online (AJOL)

    A 62-year-old man with type 1 Von Willebrand's disease was electively admitted to a Northern Ireland district general hospital for endoscopic management of a 1 cm right lower pole calculus. After pre-operative administration of appropriate haematological factors, flexible ureteroscopic electro-hydraulic lithotripsy (EHL).

  1. Platelet-vessel wall interaction in health and disease

    NARCIS (Netherlands)

    Löwenberg, E. C.; Meijers, J. C. M.; Levi, M. [=Marcel M.

    2010-01-01

    Upon vessel wall injury platelets rapidly adhere to the exposed subendothelial matrix which is mediated by several cellular receptors present on platelets or endothelial cells and various adhesive proteins such as von Willebrand factor, collagen and fibrinogen. Subsequent platelet activation results

  2. Safety, tolerability, pharmacokinetics and pharmacodynamics of anti-VWF nanobody® ALX-0681 after single and multiple subcutaneous administrations to healthy volunteers

    NARCIS (Netherlands)

    Abd-Elaziz, Khalid; Kamphuisen, Pieter W; Lyssens, Christophe; Reuvers, Mariska; Den Daas, Izaak; Van Bockstaele, Femke; Vercruysse, Kristof; Ulrichts, Hans; Baumeister, Judith; Crabbe, Patricia; Compernolle, Veerle; Holz, Josefin-Beate

    2009-01-01

    ALX-0681 is a humanized bivalent Nanobody®, that binds to the A1 domain of von Willebrand factor (vWF) and hence blocks its interaction with platelet receptor GPIb-IX-V. Given its mode of action, ALX-0681 could provide an alternative treatment option for thrombotic thrombocytopenic purpura (TTP), a

  3. Endothelial dysfunction, ambulatory pulse pressure and albuminuria are associated in Type 2 diabetic subjects

    DEFF Research Database (Denmark)

    Knudsen, Søren Tang; Jeppesen, Peter; Frederiksen, Christian Alcaraz

    2007-01-01

    as three urinary albumin/creatinine ratios. Von Willebrand factor (vWF), fibrinogen, E-selectin and soluble intercellular adhesion molecule 1 (ICAM-1) were measured in plasma. RESULTS: Thirty-four patients had normoalbuminuria (group N) and 12 had micro- or macroalbuminuria (group A). PP levels increased...

  4. Interdisciplinary stratification of patients with myoma-related symptoms; Interdisziplinaere Stratifizierung von Patientinnen mit myombedingten Beschwerden

    Energy Technology Data Exchange (ETDEWEB)

    David, M. [Campus Virchow-Klinikum, Charite - Universitaetsmedizin Berlin, Klinik fuer Frauenheilkunde und Geburtshilfe, Berlin (Germany)

    2008-07-15

    With the establishment of uterine artery embolization (UAE), the individualization of treatment of the symptomatic myomatous uterus showed a general progression. The concrete therapy decision is made in an interactive process between doctor and patient. A series of factors influence the choice of a suitable, operative or non-operative, therapeutic procedure. In the weighting of therapeutic options between surgery or UAE, in addition to current results of studies which compare both techniques,recommendations made by expert committees and guidelines are helpful for a competent counseling of patients and additionally supportive in decision processes such as interdisciplinary stratification. (orig.) [German] Mit der Etablierung der Uterusarterienembolisation (UAE) wurde die Individualisierung der Behandlung beim symptomatischen Uterus myomatosus insgesamt weiter vorangetrieben. Die Therapieentscheidung wird individuell in einem interaktiven Prozess zwischen Arzt und Patientin getroffen. Eine Reihe von Faktoren beeinflusst die Auswahl eines geeigneten - operativen oder nichtoperativen - Therapieverfahrens. Bei der Abwaegung der Therapieoptionen Operation vs. UAE sind neben aktuellen Ergebnisse von Studien, die beide Verfahren vergleichen, fuer eine kompetente Beratung der Patientinnen Empfehlungen von Expertengremien bzw. Leitlinien hilfreich und in Entscheidungsprozessen wie der interdisziplinaeren Stratifizierung zusaetzlich unterstuetzend. (orig.)

  5. Modernisation of ventilation systems; Modernisierung von Lueftungsanlagen

    Energy Technology Data Exchange (ETDEWEB)

    Richter, W. [Technische Univ. Dresden (Germany). Inst. fuer Thermodynamik und Technische Gebaeudeausruestung

    1997-12-31

    When redeveloping buildings it is common to use window constructions with air-tight rabbets which obviate the inflow of fresh air almost entirely. This leads to the well-known structural-physics and hygienic consequences. As an added effect, the distinctly enhanced thermal insulation results in changes in dynamic heat loss. The paper focuses on the issues of how to safeguard the inflow of fresh air, and the heating capacity of radiators. (MSK) [Deutsch] Da die bei Gebaeudesanierungen eingesetzten fugendichten Fensterkonstruktionen die Nachstroemmoeglichkeiten fuer die Zuluft fast ganz unterbinden, fuehrt das zu den bekannten bauphysikalischen und hygienischen Konsequenzen. Dazu kommen veraenderte dynamische Waermverlustverhaeltnisse aufgrund der deutlich verbesserten Waermedaemmung. Im Folgenden wird schwerpunktmaessig auf die Probleme Zuluftsicherung und Waermeleistung von Heizkoerpern eingegangen.

  6. Ex-ante Evaluation von Investitionsalternativen

    Directory of Open Access Journals (Sweden)

    Matthias Müller

    2017-12-01

    Full Text Available Der Beitrag zeigt, wie mit Hilfe der Methode der agentenbasierten Modellierung und Simulation (ABMS ein Beitrag zur ex-ante Policy-Beratung geleistet werden kann. Anhand eines exemplarischen Anwendungsfalls, der VISIBLE Simulationsumgebung („Virtual Simulation Lab for the Analysis of Investments in Learning and Education“, diskutieren wir die Konsequenzen unterschiedlicher Kooperationsförderinstrumente für Wissensdiffusionsprozesse in Netzwerken am Beispiel der Region Heilbronn-Franken. Die Simulationsergebnisse zeigen, dass die strukturelle Konfiguration eines regionalen Innovationssystems eine zentrale Bedeutung für die Gestaltung von Kooperationsfördermaßnahmen hat und dass Interventionen, die darauf abzielen, Wissenstransfer zwischen den Akteuren anzuregen, genau die entgegengesetzten Wirkungen entfalten können.

  7. The driver workstation in commercial vehicles; Ergonomie und Design von Fahrerarbeitsplaetzen in Nutzfahrzeugen

    Energy Technology Data Exchange (ETDEWEB)

    Kraus, W. [HAW-Hamburg (Germany)

    2003-07-01

    Nowadays, ergonomics and design are quality factors and indispensable elements of commercial vehicle design and development. Whereas a vehicle's appearance, i.e. its outside design, produces fascination and image, the design of its passenger cell focuses entirely on drivers and their tasks. Today, passenger-cell design and the ergonomics of driver workstations in commercial vehicles are clearly becoming more and more important. This article concentrates above all on defining commercial vehicle drivers, which, within the scope of research projects on coach-driver workstations, has provided new insight into the design of driver workstations. In light of the deficits determined, the research project mainly focused on designing driver workstations which were in line with the latest findings in ergonomics and human engineering. References to the methodology of driver-workstation optimization seems important in this context. The afore-mentioned innovations in the passenger cells of commercial vehicles will be explained and described by means of topical and practical examples. (orig.) [German] Ergonomie und Design sind heute Qualitaetsfaktoren und unverzichtbarer Bestandteil bei der Entwicklung von Nutzfahrzeugen. Erzeugt das Erscheinungsbild, die Aussengestaltung des Fahrzeugs, die Faszination und das Image, so ist die Innengestaltung weitgehend ganz auf die Bedienpersonen und ihre Arbeitsaufgaben bezogen. Die Innenraumgestaltung und die Ergonomie von Fahrerarbeitsplaetzen in Nutzfahrzeugen sind heute in einer Phase der deutlichen Aufwertung zu sehen. Im Beitrag wird besonders auf die Definition der Bedienpersonen fuer Nutzfahrzeuge eingegangen, die im Rahmen des Forschungsprojekts Fahrerarbeitsplatz im Reisebus zu neuen Erkenntnissen bei der Auslegung von Arbeitsplaetzen fuehrte. Gemaess der ermittelten Defizite konzentriert sich die Studie im Kern auf das Gestaltungskonzept des Fahrerarbeitsplatzes nach ergonomischen und arbeitswissenschaftlichen Erkenntnissen

  8. Quality assurance for photovoltaic energy supply. Final report; Qualitaetssicherung von photovoltaischen Energieversorgungssystemen. Abschlussbericht

    Energy Technology Data Exchange (ETDEWEB)

    Bopp, G.; Gabler, H.; Hille, G.; Puls, G.; Rehm, M.; Sauer, U.; Schulz, M.; Schweizer-Ries, P.

    2000-07-01

    The availability of isolated PV systems was to be improved by an inspection agreement between operators, users and inspection organisations. The systems were to be inspected and serviced once a year. In all, 22 systems were inspected regularly between 1996 and 1999, and a failure statistics was drawn up on the basis of the records. On average, there were three failures per system and per year, one of which was caused by research activities. In a second detailed analysis after termination of the project, the failure rate had decreased to one every two years, i. e. a reduction by a factor of 6. [German] Ziel des Projektes war die Erhoehung der Betriebssicherheit und der Lebensdauer netzunabhaengiger Photovoltaikanlagen (Inselanlagen) durch Ermittlung und Reduzierung des Wartungsbedarfs sowie durch Komponentenoptimierung. Zu Projektbeginn war der technische und finanzielle Umfang von Wartungsarbeiten und somit den Betriebskosten dieser Anlagen nur sehr lueckenhaft bekannt und vorhersehbar. Um belastbare Erkenntnisse ueber den Wartungsbedarf und -kosten zu erhalten, fuehrten ortsansaessige Firmen mit Hilfe von Wartungshandbuechern auf Kosten der Betreiber in 22 ausgewaehlten Inselanlagen 4 Jahre lang 1 mal jaehrlich eine Fruehjahrskontrolle und eine Herbstinspektion durch. Das Fraunhofer ISE erstellte eine Fehlerstatistik, analysierte die Fehler und den Optimierungsbedarf. Durch die einmal jaehrliche Inspektion und durch den Einsatz optimierter Komponenten liess sich die anfaengliche Fehlerrate von 3 Fehlern pro Jahr und Anlage auf 1 Fehler innerhalb von 2 Jahren reduzieren. Die Anlagenfehler wurden ueberwiegend durch alterungsbedingte Bauteildefekte in Komponenten verursacht. Zusammen mit Herstellern wurde an Komponenten, wie Ladereglern und Wechselrichtern, Optimierungen durchgefuehrt. Die Optimierung der Anlagenbetriebsfuehrung erhoehte deutlich die Zufriedenheit des Nutzers und die Batterielebensdauer. Die Stromgestehungskosten in optimierten und regelmaessig

  9. Budke, Alexandra; Kanwischer, Detlef; Pott, Andreas (Hg.), Internetgeographien : Beobachtungen zum Verhältnis von Internet, Raum und Gesellschaft / [rezensiert von] Helmut Klüter

    OpenAIRE

    Klüter, Helmut

    2009-01-01

    Rezensiertes Werk: Internetgeographien : Beobachtungen zum Verhältnis von Internet, Raum und Gesellschaft / hrsg. von Alexandra Budke ... - Stuttgart : Steiner, 2004. - 192 S. : Ill., graph. Darst., Kt. - (Erdkundliches Wissen ; 136) ISBN 3-515-08506-8

  10. Entwicklung der Reglementierung von 10 MEM-Berufen im Kontext von Bildungsreformen und dem Wandel in der Arbeitswelt: Eine Kurzstudie im Auftrag von LIBS: Eine Kurzstudie im Auftrag von LIBS Industrielle Berufslehren Schweiz, Baden

    OpenAIRE

    Egg, Maria Esther; Renold, Ursula

    2015-01-01

    Im Auftrag der LIBS Industrielle Berufslehren Schweiz, hat die KOF die Entwicklung von 10 MEM1-Berufsbildern seit dem ersten Berufsbildungsgesetz dargestellt und diese eingebettet in eine kurze Zusammenfassung der wichtigsten Etappenschritte des Schweizer Berufsbildungssystems.

  11. Magnus Georg von Paucker (1787-1855) / Eckhard Spring

    Index Scriptorium Estoniae

    Spring, Eckhard

    2013-01-01

    Eestis sündinud ja Tartu Ülikoolis õppinud silmapaistvast baltisaksa teadlasest ja tema lapselapsest Alexandrine Pauckerist. 23. novembril 2012 Jelgavas/Mitaus toimunud Magnus Georg von Pauckerile pühendatud teaduskonverentsist

  12. Warum das Controlling den systematischen Einsatz von Simulationen vorantreiben sollte

    DEFF Research Database (Denmark)

    Spitzner, Jan; Schneider, Melanie L.

    2017-01-01

    Simulationen werden in der Unternehmenssteuerung heutzutage noch nicht systematisch eingesetzt. Dass sich jedoch die existierenden Hemmnisse durchaus überwinden lassen, legen die Antworten von Studienteilnehmern nahe, die Simulationen häufig einsetzen. Dabei kann Controlling eine Vorreiterrolle e...

  13. Pharmakobotanische Untersuchungen von Lavendelsorten auf dem Plattensee- Plateau

    Directory of Open Access Journals (Sweden)

    Tóth, Frida

    2014-09-01

    Full Text Available Auf dem Hof Dörgicsei Levendula Major GmbH wurden 9 Lavendelsorten (6 Sorten von Lavandula angustifolia und 3 Sorten von Lavandula x intermedia untersucht. Neben den morphologischen und Wachstumseigenschaften wurden auch Frisch- und Trockengewichte bewertet. Quantitative und qualitative Untersuchungen von den Blüten- und Ätherischöldrogen wurden auch durchgeführt. Die statistische Analyse zeigte signifikant höhere Erträge bei den Sorten L. angustifolia ’Essence Purple’ und L. x intermedia ’Edelweiss’. Gehalt und Zusammensetzung von ätherischem Öl war eindeutig bei der Sorte L. angustifolia ’Ellagance Purple’ am günstigsten.

  14. Von Krahli Teater toob Eestisse erakordse auhinna / Tiit Tuumalu

    Index Scriptorium Estoniae

    Tuumalu, Tiit, 1971-

    2004-01-01

    Bessie-auhinna puhul, millega New Yorgis pärjati Von Krahli Teatri lavastust "Luikede järv." Mõjukuselt on seda võrreldud Broadway teatriauhinna Tonyga. Lisatud lühiandmed P. Jalaka ja S. Pepeljajevi kohta

  15. Frobenius theory for positive maps of von Neumann algebras

    International Nuclear Information System (INIS)

    Albeverio, S.; Hoegh-Krohn, R.

    1978-01-01

    Frobenius theory about the cyclic structure of eigenvalues of irreducible non negative matrices is extended to the case of positive linear maps of von Neumann algebras. Semigroups of such maps and ergodic properties are also considered. (orig.) [de

  16. Optimized sampling of hydroperoxides and investigations of the water vapour dependence of hydroperoxide formation during ozonolysis of alkenes; Optimierung der Probenahme von Hydroperoxiden und Untersuchungen zur Wasserdampfabhaengigkeit der Bildung von Hydroperoxiden bei der Ozonolyse von Alkenen

    Energy Technology Data Exchange (ETDEWEB)

    Becker, K.H.; Plagens, H.

    1997-06-01

    There are several sampling methods for hydroperoxides none of which is particularly reliable. The authors therefore tested three new methods in order to optimize hydroperoxide sampling and, using the optimized sampling procedure, to investigate the water vapour dependence of hydroperoxide formation during ozonolysis of alkenes. (orig.) [Deutsch] Fuer die Probenahme von Hydroperoxiden existieren verschiedene Verfahren, von denen bisher keines als besonders zuverlaessig angesehen werden konnte. Daher wurden in dieser Arbeit drei Verfahren getestet, um die Probenahme von Hydroperoxiden zu optimieren und mit dem entsprechenden Verfahren die Wasserdampfabhaengigkeit der Bildung von Hydroperoxiden bei der Ozonolyse von Alkenen zu untersuchen. (orig.)

  17. Numerical Analysis Of Buckling Of Von Mises Planar Truss

    Directory of Open Access Journals (Sweden)

    Kalina Martin

    2015-12-01

    Full Text Available A computational algorithm of a discrete model of von Mises planar steel truss is presented. The structure deformation is evaluated by seeking the minimal potential energy. The critical force invented by mathematical solution was compared with solution by computer algorithm. Symmetric and asymmetric effects of initial shape of geometric imperfection of axis of struts are used in model. The shapes of buckling of von Mises planar truss of selected vertical displacement of top joint are shown.

  18. Analytische und Effektor-Studien von N-Acyl-Ethanolaminphosphaten

    OpenAIRE

    Ates, Ebru

    2011-01-01

    Bei N-Acyl-Ethanolaminphosphaten handelt es sich um eine bislang wenig untersuchte Klasse polarer Substanzen, deren Erforschung aufgrund ihrer strukturellen Analogie zu apolaren, physiologisch wirksamen N-Acyl-Ethanolaminen von Interesse ist. Zu bear-beiten waren analytische Fragestellungen, die auch synthetische Aufgaben beinhalteten, wie Methodenentwicklung und Versuche zur Erfassung von N-Acyl-Ethanolamin-phosphaten in ausgewählten Lebensmitteln sowie strukturelle Studien zur „Bioaktivität...

  19. Spurenstoffuntersuchungen zur Bildung und Ausbreitung von Wassermassen im subpolaren Nordatlantik

    OpenAIRE

    Hildebrandt, Hauke

    2001-01-01

    In der vorliegenden Arbeit wurde ein umfangreicher Spurenstoffdatensatz aus dem subpolaren Nordatlantik erstellt und ausgewertet, der Tritium-, Helium- und Neon- sowie O-18-Messungen umfaßt. Das Hauptaugenmerk galt dabei der Bildung und Ausbreitung der tiefen Wassermassen und deren Variabilität auf Zeitskalen von einigen Jahren. Anhand von Tracermittelwerten, die mit Hilfe eines optimierten Interpolationsverfahrens gewonnen wurden, konnte gezeigt werden, daß die konvektive Neubildung de...

  20. Nash y von Neumann: mundos posibles y juegos de lenguaje

    Directory of Open Access Journals (Sweden)

    Salazar , Boris

    2004-06-01

    Full Text Available Este ensayo emplea las nociones de juego de lenguaje y de equivalencia entre juegos para examinar la decisión de John Nash de no jugar el juego coalicional que propuso John von Neumann. El argumento central es que Nash concibió una clase de mundos posibles incompatible con la de von Neumann, y que en el origen de esa divergencia estarían sus distintas nociones de racionalidad.

  1. Von Neumann's impossibility proof: Mathematics in the service of rhetorics

    Science.gov (United States)

    Dieks, Dennis

    2017-11-01

    According to what has become a standard history of quantum mechanics, in 1932 von Neumann persuaded the physics community that hidden variables are impossible as a matter of principle, after which leading proponents of the Copenhagen interpretation put the situation to good use by arguing that the completeness of quantum mechanics was undeniable. This state of affairs lasted, so the story continues, until Bell in 1966 exposed von Neumann's proof as obviously wrong. The realization that von Neumann's proof was fallacious then rehabilitated hidden variables and made serious foundational research possible again. It is often added in recent accounts that von Neumann's error had been spotted almost immediately by Grete Hermann, but that her discovery was of no effect due to the dominant Copenhagen Zeitgeist. We shall attempt to tell a story that is more historically accurate and less ideologically charged. Most importantly, von Neumann never claimed to have shown the impossibility of hidden variables tout court, but argued that hidden-variable theories must possess a structure that deviates fundamentally from that of quantum mechanics. Both Hermann and Bell appear to have missed this point; moreover, both raised unjustified technical objections to the proof. Von Neumann's argument was basically that hidden-variables schemes must violate the ;quantum principle; that physical quantities are to be represented by operators in a Hilbert space. As a consequence, hidden-variables schemes, though possible in principle, necessarily exhibit a certain kind of contextuality. As we shall illustrate, early reactions to Bohm's theory are in agreement with this account. Leading physicists pointed out that Bohm's theory has the strange feature that pre-existing particle properties do not generally reveal themselves in measurements, in accordance with von Neumann's result. They did not conclude that the ;impossible was done; and that von Neumann had been shown wrong.

  2. Räumliche Aspekte von Transformationsproblemen aus systemtheoretischer Perspektive

    OpenAIRE

    Klüter, Helmut

    2000-01-01

    Der mit dem Topos "Transformation von Wirtschafts- und Gesellschaftssystemen" axiomatisch angenommene Unvereinbarkeit sozialistischer und marktwirtschaftlicher Strukturen ist aus raumwissenschaftlicher Sicht nicht nachvollziehbar. Zum einen gibt es in Wirtschaftsgeographie und Infrastrukturtheorie eine ganze Reihe von Gemeinsamkeiten und Berührungspunkten, die man für den konstruktiven Systemumbau nutzen kann. Zum andern benötigt der Umbau selbst eine räumliche Infrastruktur. Und zum dritten ...

  3. Integration von 3D-Kamerasystemen am Gabelstapler

    OpenAIRE

    Kleinert, Steffen; Overmeyer, Ludger

    2013-01-01

    Dieser Beitrag beschreibt die Integration von laufzeitmessenden 3D Kamerasystemen in die Gabelzinkenspitzen eines Flurförderzeugs. Mit Hilfe der integrierten Kameras und deren ausgewerteter Aufnahmen wurde ein Assistenzsystem für die Handhabung von Ladungsträgern realisiert, das dem Fahrer des Flurförderzeugs Verfahrempfehlungen für die Optimierung der Relativposition zwischen Gabelzinken und Ladungsträger bzw. Lagerplatz ausgibt. Neben der Vorstellung der verwendeten Kamera-Hardware und der ...

  4. Die Darstellung von guten und schlechten Beziehungen in Kinderzeichnungen

    OpenAIRE

    Gramel, Sabine

    2005-01-01

    Nach welchen Kriterien sich Bilder, auf denen Kinder eine positive Beziehung darstellen, von Bildern unterscheiden, auf denen negative Beziehungen dargestellt sind, wurde an einer Stichprobe von 45 Kindern zwischen 4;6 und 11;6 Jahren untersucht. Die Kinder fertigten jeweils ein positives und ein negatives Beziehungsbild an. Es zeigte sich, dass die Kinder in beiden Beziehungskategorien zum großen Teil Gleichaltrige darstellten. Sie benannten für ihre Bilder Kriterien, anhand derer man die po...

  5. Zur Dialektik von Soft Skills und fachlicher Kompetenz

    OpenAIRE

    Jendrowiak, Hans-Werner

    2010-01-01

    [Der Autor stellt folgende Thesen zur Dialektik von Soft Skills und fachlicher Bildung auf:] 1. Soft Skills sind normale Bildungskategorien und Teil einer Allgemeinen Bildung. […] 2. Soft Skills sind als personalgebundene Kriterien auch immer schon Gegenstand bildungstheoretischer Debatten. […] 3. Soft Skills ist eine trendorientierte Bezeichnung für Bildung. […] 4. Soft Skills sind Ausdruck von Vorstellungen, Ideen und Theorien (Schulkultur, Unternehmenskultur, Unternehmensphilosophie). 5. S...

  6. Politische Bildung im Kontext von Regierung, Unterricht und Zucht

    Directory of Open Access Journals (Sweden)

    Thomas Rucker

    2014-02-01

    Full Text Available Johann Friedrich Herbart (1776-1841 gilt als der Begründer der wissenschaftlichen Pädagogik. In diesem Beitrag wird zu zeigen versucht, dass Herbart die Unterstützung politischer Bildung als eine Aufgabe von Regierung, Unterricht und Zucht bestimmt und in seinem Werk wichtige „Bausteine“ für eine Theorie der politischen Bildung unter den Bedingungen von Erziehung vorlegt hat. Nach Herbart ist das politische Selbst- und Weltverhältnis auf Sachverhalte bezogen, die nicht nur die Lebensführung einzelner Menschen, sondern die Lebensführung einer Mehrzahl von Menschen betreffen. Nicht das Zusammenleben von Menschen generell ist jedoch Orientierungsgesichtspunkt des politischen Selbst- und Weltverhältnisses, sondern nur das problematisch gewordene Zusammenleben. Politik ergibt sich nach Herbart aus einem Konflikt hinsichtlich der Frage, wie das Zusammenleben von Menschen geregelt sein sollte. Während die Regierung lediglich mittelbar einen Beitrag zur politischen Bildung leistet, indem sie die Voraussetzungen für Unterricht und Zucht bereitstellt, fungieren die beiden zuletzt genannten Formen von Erziehung als die eigentlichen Medien, in denen die politische Bildung im Sinne Herbarts ihren Ort hat.

  7. Placental Growth Factor Contributes to Liver Inflammation, Angiogenesis, Fibrosis in Mice by Promoting Hepatic Macrophage Recruitment and Activation

    Directory of Open Access Journals (Sweden)

    Xi Li

    2017-07-01

    Full Text Available Placental growth factor (PlGF, a member of the vascular endothelial growth factor (VEGF family, mediates wound healing and inflammatory responses, exerting an effect on liver fibrosis and angiogenesis; however, the precise mechanism remains unclear. The aims of this study are to identify the role of PlGF in liver inflammation and fibrosis induced by bile duct ligation (BDL in mice and to reveal the underlying molecular mechanism. PlGF small interfering RNA (siRNA or non-targeting control siRNA was injected by tail vein starting 2 days after BDL. Liver inflammation, fibrosis, angiogenesis, macrophage infiltration, and hepatic stellate cells (HSCs activation were examined. Our results showed that PlGF was highly expressed in fibrotic livers and mainly distributed in activated HSCs and macrophages. Furthermore, PlGF silencing strongly reduced the severity of liver inflammation and fibrosis, and inhibited the activation of HSCs. Remarkably, PlGF silencing also attenuated BDL-induced hepatic angiogenesis, as evidenced by attenuated liver endothelial cell markers CD31 and von Willebrand factor immunostaining and genes or protein expression. Interestingly, these pathological ameliorations by PlGF silencing were due to a marked reduction in the numbers of intrahepatic F4/80+, CD68+, and Ly6C+ cell populations, which were reflected by a lower expression of these macrophage marker molecules in fibrotic livers. In addition, knockdown of PlGF by siRNA inhibited macrophages activation and substantially suppressed the expression of pro-inflammatory cytokines and chemokines in fibrotic livers. Mechanistically, evaluation of cultured RAW 264.7 cells revealed that VEGF receptor 1 (VEGFR1 mainly involved in mediating the role of PlGF in macrophages recruitment and activation, since using VEGFR1 neutralizing antibody blocking PlGF/VEGFR1 signaling axis significantly inhibited macrophages migration and inflammatory responses. Together, these findings indicate

  8. Entwicklung von Extraktions- und Absorptionssystemen auf Basis ionischer Flüssigkeiten für die Entschwefelung von Kohlenwasserstoffen

    OpenAIRE

    Kuhlmann, Esther

    2008-01-01

    Da die Anforderungen an den Schwefelgehalt der fossilen Brennstoffe - nicht zuletzt durch gesetzliche Richtlinien bezüglich der Schadstoffemissionen - im Laufe der Zeit ständig gestiegen sind, sind effektive Entschwefelungsverfahren für fossile Brennstoffe von hohem Interesse. Die derzeitige Entschwefelungstechnologie basiert auf dem HDS-Verfahren, alternative Verfahren sind aber wünschenswert, insbesondere wenn Anwendungen einen Schwefelgehalt von weit unter 10 ppm erforderlich machen. Daher...

  9. Molecular analysis of the von hippel-lindau disease gene.

    Science.gov (United States)

    Chernoff, A; Kasparcova, V; Linehan, W M; Stolle, C A

    2001-01-01

    Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder that predisposes the affected individual to develop characteristic tumors. These include CNS hemangioblastoma, retinal angiomas, endolymphatic sac tumors, pancreatic cysts and tumors, epididymal cystadenomas, pheochromocytomas, renal cysts, and clear-cell renal carcinoma. The VHL gene was localized to 3p25 and then isolated by Latif et al. (1). The gene contains three exons with an open reading frame of 852 nucleotides, which encode a predicted protein of 284 amino acids. The VHL protein is believed to have several functions. It is involved in transcription regulation through its inhibition of elongation by binding to the B and C subunits of elongin. Mutations of VHL allow the B and C subunits to bind with the A subunit. This complex then overcomes "pausing" of RNA polymerase during mRNA transcription (2,3). Several studies suggest that the VHL protein is also involved in regulation of hypoxia-inducible transcripts, particularly vascular endothelial growth factor (VEGF), by altering mRNA stability (4,5). Therefore, VHL gene mutations permit the overexpression of VEGF under normoxic conditions, which leads to the angiogenesis believed to be required for tumor growth. The VHL-elongin BC complex (VBC) also binds two other proteins-CUL2 and Rbx1-in a complex that has structural similarity to other E3 ubiquitin ligase complexes (6). Such complexes mediate the degradation of cell-cycle regulatory proteins.

  10. Electronic Resource Management System. Vernetzung von Lizenzinformationen

    Directory of Open Access Journals (Sweden)

    Michaela Selbach

    2014-12-01

    Full Text Available In den letzten zehn Jahren spielen elektronische Ressourcen im Bereich der Erwerbung eine zunehmend wichtige Rolle: Eindeutig lässt sich hier ein Wandel in den Bibliotheken (fort vom reinen Printbestand zu immer größeren E-Only-Beständen feststellen. Die stetig wachsende Menge an E-Ressourcen und deren Heterogenität stellt Bibliotheken vor die Herausforderung, die E-Ressourcen effizient zu verwalten. Nicht nur Bibliotheken, sondern auch verhandlungsführende Institutionen von Konsortial- und Allianzlizenzen benötigen ein geeignetes Instrument zur Verwaltung von Lizenzinformationen, welches den komplexen Anforderungen moderner E-Ressourcen gerecht wird. Die Deutsche Forschungsgemeinschaft (DFG unterstützt ein Projekt des Hochschulbibliothekszentrums des Landes Nordrhein-Westfalen (hbz, der Universitätsbibliothek Freiburg, der Verbundzentrale des Gemeinsamen Bibliotheksverbundes (GBV und der Universitätsbibliothek Frankfurt, in dem ein bundesweit verfügbares Electronic Ressource Managementsystem (ERMS aufgebaut werden soll. Ein solches ERMS soll auf Basis einer zentralen Knowledge Base eine einheitliche Nutzung von Daten zur Lizenzverwaltung elektronischer Ressourcen auf lokaler, regionaler und nationaler Ebene ermöglichen. Statistische Auswertungen, Rechteverwaltung für alle angeschlossenen Bibliotheken, kooperative Datenpflege sowie ein über standardisierte Schnittstellen geführter Datenaustausch stehen bei der Erarbeitung der Anforderungen ebenso im Fokus wie die Entwicklung eines Daten- und Funktionsmodells. In the last few years the importance of electronic resources in library acquisitions has increased significantly. There has been a shift from mere print holdings to both e- and print combinations and even e-only subscriptions. This shift poses a double challenge for libraries: On the one hand they have to provide their e-resource collections to library users in an appealing way, on the other hand they have to manage these

  11. Von Roll RCP method - first experiences; Von Roll RCP - Verfahren. Erste Erfahrungen

    Energy Technology Data Exchange (ETDEWEB)

    Capitaine, P.; Engweiler, J. [Roll Umwelttechnik AG, Zuerich (Switzerland)

    1998-09-01

    The RCP method was designed as a residue-optimised alternative to the thermally optimised grate firing of residual wastes. Its technical realisation and development to market maturity took no more than 5 years. In the first process stage the waste is converted to high-carbon pyrolysis charcoal and high-rank gas in the absence of oxygen. In the second stage these substances are oxidised by addition of oxygen. The resulting temperature causes the non-combustible constituents of the slag to melt. In a third, optional, stage this molten slag can be liberated of (heavy) metals to such an extent that it can subsequently be used directly as additive for grinding. Further exhaust gas treatment is facilitated by the use of a circulatory fluidised-bed secondary combustion chamber. Despite the reduced flue gas volume and resultant higher pollutant concentrations in the crude gas, overall emissions are lower than in conventional plants. [Deutsch] Das reststoffoptimierte RCP Verfahren ist als Alternative zur thermisch optimierten Rostverbrennung von Restabfaellen konzipiert. In nur fuenf Jahren wurde das Verfahren technisch umgesetzt und zur Marktreife entwickelt. In einer ersten Stufe des Verfahrens wird der Abfall unter Luftabschluss in einen kohlenstoffreichen Pyrolysekoks und eine heizwertreiches Gas umgesetzt. Im zweiten Schritt werden diese Stoffe unter Zugabe von Sauerstoff oxidiert. Dabei treten Temperaturen auf, bei denen die nichtbrennbaren Bestandteile der Schlacke schmelzen. Optional wird diese Schmelzschlacke in einem dritten Schritt derart von (Schwer-) Metallen befreit, dass sie anschliessend direkt als Zement-Zumahlstoff eingesetzt werden kann. Die Nutzung der zirkulierenden Wirbelschicht - Nachbrennkammer zur Abgasbehandlung vereinfacht die weitergehende Abgasbehandlung. Trotz verringertem Rauchgasvolumen und damit hoeheren Schadstoffkonzentrationen im Rohgas werden die Gesamtemissionen gegenueber konventionellen Anlagen verringert. (orig./SR)

  12. Investigations of time-dependent water pollution effects of overburden dumps - partial project 1. Final report; Untersuchungen gewaesserrelevanter Einfluesse von Bergbauhalden in Abhaengigkeit von der Standzeit - Teilprojekt 1. Abschlussbericht

    Energy Technology Data Exchange (ETDEWEB)

    Beuge, P.; Dunger, C.; Mibus, J.; Starke, R.

    1998-02-01

    Management of overburden dumps necessitates careful stocktaking and precise definitions of pollutant emissions so that, if necessary, conclusions can be drawn concerning sanitation concepts in consideration of emission limits and environmental balances. In view of the large number of overburden dumps in Saxony, Saxony-Anhalt and Thuringia caused the authors to restrict their investigations to ore mines and to select elements characteristic of the worked deposits and their potential environmental effects. The following problems were investigated: Are overburden dumps significant emitters of elements at all? Which elements are emitted in what concentrations, in what form and up to what distance from the dump? Are there really different patterns for gangue and impregnation types? How big is the real reaction space of the dump? Should the whole dump be assumed to be a reservoir of elements for emission or just parts of it? What are the factors that most strongly influence element mobilisation and/or retention? What measures should be recommended for emission reduction or prevention from the aspects of necessity, economic efficiency and long-term stability? (orig./SR) [Deutsch] Es ergibt sich fuer den Umgang mit Halden die Notwendigkeit einer gruendlichen Bilanzierung und schaerferen Definition von Schadstoffemission aus ihnen, um daraus Konsequenzen fuer eventuell erforderliche Sanierungskonzeptionen unter Beruecksichtigung von Grenzwerteinhaltung und Umweltbilanz abzuleiten. Der Umfang der einzelnen Fragestellungen und die Bedeutung der Halden in Sachsen, Sachsen-Anhalt und Thueringen sowie Anzahl und ihr Inhalt fuehrte zur Beschraenkung auf den Erzbergbau und auf die Kontrolle ausgewaehlter Elemente, die fuer den jeweils abgebauten Lagerstaetteninhalt charakteristisch und fuer die Wirkung auf die Umwelt von Bedeutung sind. Folgende konkrete Fragestellungen sollen verfolgt werden: - Sind Halden ueberhaupt nennenswerte Emittenten von Elementen? - Welche Elemente werden

  13. Einfluss von Informationskompetenz-Veranstaltungen auf die Qualität von Masterarbeiten

    Directory of Open Access Journals (Sweden)

    Gary Seitz

    2016-02-01

    Full Text Available Am Geographischen Institut der Universität Zürich haben die Studierenden, welche als erster Jahrgang die IK-Veranstaltung als Pflichtmodul absolvierten, ihre Masterarbeit abgeschlossen. Mit einer quantitativen Auswertung wird untersucht, ob sich die Qualität der Quellen in den Masterarbeiten verbessert hat. Dazu werden die Literaturverzeichnisse einer bibliometrischen Analyse unterzogen. Anschliessend werden die erhaltenen Werte mit denjenigen verglichen, welche von Arbeiten ohne IK-Schulung erhoben wurden. Diese Methodik könnte ein Werkzeug darstellen, um Informationskompetenz-Veranstaltungen bezüglich ihrer Relevanz für wissenschaftliches Arbeiten evaluieren zu können.

  14. "Die Toten reiten schnelle." Literarische Zitate in Briefen von und an Alexander von Humboldt

    Directory of Open Access Journals (Sweden)

    Ingo Schwarz

    2007-04-01

    Full Text Available Article in GermanAbstract in English and GermanAlexander von Humboldt and his correspondents liked to enrich or embellish their letters with quotations from classic works of ancient literature as well as from recent poems, plays, or novels. This paper tries to show that references to literature were very often used in order to express thoughts and feelings more clearly not so much for impressing the recipients of letters with high education. In educated circles a good knowledge of ancient and modern works of literature was a standard requirement, which often allowed the letter writers to use quotations in a playful manner.

  15. Richard von Volkmann: surgeon and Renaissance man.

    Science.gov (United States)

    Willy, Christian; Schneider, Peter; Engelhardt, Michael; Hargens, Alan R; Mubarak, Scott J

    2008-02-01

    Richard von Volkmann (1830-1889), one of the most important surgeons of the 19(th) century, is regarded as one of the fathers of orthopaedic surgery. He was a contemporary of Langenbeck, Esmarch, Lister, Billroth, Kocher, and Trendelenburg. He was head of the Department of Surgery at the University of Halle, Germany (1867-1889). His popularity attracted doctors and patients from all over the world. He was the lead physician for the German military during two wars. From this experience, he compared the mortality of civilian and war injuries and investigated the general poor hygienic conditions in civilian hospitals. This led him to introduce the "antiseptic technique" to Germany that was developed by Lister. His powers of observation and creativity led him to findings and achievements that to this day bear his name: Volkmann's contracture and the Hueter-Volkmann law. Additionally, he was a gifted writer; he published not only scientific literature but also books of children's fairy tales and poems under the pen name of Richard Leander, assuring him a permanent place in the world of literature as well as orthopaedics.

  16. Geschichte der Natur bei Alexander von Humboldt

    Directory of Open Access Journals (Sweden)

    Christian Helmreich

    2009-05-01

    Full Text Available Article in German, Abstracts in English, German and French.This article analyses the importance of an historical view of nature in the works of Alexander von Humboldt. In several of his first writings, Humboldt seems to outline the importance of what one may call history of nature. But even before his famous American travel, his position changed and he became reluctant to accept the seriousness of historical enquiry in the area of natural sciences: if we want to reconstruct the past state of nature, we cannot rely on empirical proofs; and history of nature is therefore necessarily based on uncertain hypotheses. Humboldt kept his sceptical attitude in the first decades of the 19th century, despite the positive results of the palaeontological researches of his scientific colleagues. However, he gradually convinced himself of the scientific interest of historical investigations in the natural sciences. The Cosmos paradoxally displays two apparently conflicting points of view: in his methodological remarks, Humboldt maintains that precise accounts of the past state of nature are out of reach of human knowledge, yet elsewhere in the same Cosmos he gives broad and rather vivid descriptions of the eventful history of nature.

  17. Hypercontractivity in group Von Neumann algebras

    CERN Document Server

    Junge, Marius; Parcet, Javier

    2017-01-01

    In this paper, the authors provide a combinatorial/numerical method to establish new hypercontractivity estimates in group von Neumann algebras. They illustrate their method with free groups, triangular groups and finite cyclic groups, for which they obtain optimal time hypercontractive L_2 \\to L_q inequalities with respect to the Markov process given by the word length and with q an even integer. Interpolation and differentiation also yield general L_p \\to L_q hypercontrativity for 1 < p \\le q < \\infty via logarithmic Sobolev inequalities. The authors' method admits further applications to other discrete groups without small loops as far as the numerical part-which varies from one group to another-is implemented and tested on a computer. The authors also develop another combinatorial method which does not rely on computational estimates and provides (non-optimal) L_p \\to L_q hypercontractive inequalities for a larger class of groups/lengths, including any finitely generated group equipped with a condit...

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

    Directory of Open Access Journals (Sweden)

    Dambrauskienė R

    2017-06-01

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

  19. Ecobalance of natural gas vehicles; Oekobilanz von Erdgasfahrzeugen

    Energy Technology Data Exchange (ETDEWEB)

    Nigge, K.M. [Simon, Kucher und Partners Strategy und Marketing Consultants GmbH, Bonn (Germany)

    2000-07-01

    The impacts on human health and the natural environment of using natural gas, Diesel and petrol as fuels for city buses and passenger cars are compared in a Life Cycle Assessment. In addition to the burning of the fuels in the engines, this assessment also comprises the upstream processes of the fuel supply chain. Despite the increased energy demand of the vehicles, natural gas is associated with the lowest impacts overall for both city buses and passenger cars. The health impacts that can be avoided through the use of natural gas instead of Diesel or petrol thereby differ only weakly between the use of the vehicles in cities of various sizes within Germany. From the perspective of environmental protection, the market introduction of natural gas vehicles therefore does not need remain limited to large cities within agglomerated regions. (orig.) [German] Die Auswirkungen der Verwendung von Erdgas, Diesel und Benzin als Kraftstoffe fuer Stadtbusse und Pkw auf die menschliche Gesundheit und die natuerliche Umwelt werden in einer Oekobilanz verglichen. Diese umfasst neben der motorischen Verbrennung der Kraftstoffe auch die vorgelagerten Prozessketten der Kraftstoffbereitstellung. Sowohl fuer Stadtbusse als auch fuer Pkw schneidet Erdgas trotz eines energetischen Mehrbedarfes der Fahrzeuge insgesamt am guenstigsten ab. Die durch den Einsatz von Erdgas anstelle von Diesel oder Benzin vermeidbaren Gesundheitsschaeden unterscheiden sich dabei zwischen einem Einsatz der Fahrzeuge in Staedten verschiedener Groesse innerhalb von Deutschland nur wenig. Die Markteinfuehrung von Erdgasfahrzeugen muss also aus Sicht des Umweltschutzes nicht auf grosse Staedte in Ballungsgebieten beschraenkt bleiben. (orig.)

  20. Proof of pipeline strength based on measurements of inspection pigs; Festigkeitsnachweis von Pipelines aufgrund der Messergebnisse von Pruefmolchen

    Energy Technology Data Exchange (ETDEWEB)

    De la Camp, H.J.; Feser, G.; Hofmann, A.; Wolf, B.; Schmidt, H. [TUeV Sueddeutschland Bau und Betrieb GmbH, Muenchen (Germany); Herforth, H.E.; Juengling, K.H.; Schmidt, W. [TUeV Anlagentechnik GmbH, Berlin-Schoeneberg (Germany). Unternehmensgruppe TUeV Rheinland/Berlin-Brandenburg

    2002-01-01

    The report is aimed at collecting and documenting the state of the art and the extensive know how of experts and pipeline operators with regard to judging the structural integrity of pipelines. In order to assess the actual mechanical strength of pipelines based on measurement results obtained by inspection pigs, guidance is given for future processing, which eventually can be used as a basis for an industry standard. A literature study of the commercially available types of inspection pigs describes and synoptically lists the respective pros and cons. In essence the report comprises besides check lists of operating data for the pipeline and the pig runs mainly the evaluation of defects and respective calculating procedures. Included are recommendations regarding maintenance planning, verification of defects as well as repetition of pig runs. (orig.) [German] Ziel des Berichtes ist die Erfassung und Dokumentation zum derzeitigen Stand der Technik und des vorhandenen umfangreichen Know-how von Sachverstaendigen und Pipelinebetreibern auf dem Gebiet der sicherheitstechnischen Beurteilung von Pipelines. Fuer den Festigkeitsnachweis von Pipelines aufgrund der Messergebnisse von Pruefmolchen wurde ein Leitfaden als Basis fuer die zukuenftige Vorgehensweise erstellt, der eventuell die Grundlage eines normativen Regelwerkes bilden kann. In einer Literaturstudie wurden die auf dem Markt befindlichen Pruefmolchtypen zusammenfassend beschrieben und ihre Vor- und Nachteile tabellarisch gegenuebergestellt und bewertet. Neben der Erstellung von Checklisten fuer notwendige Daten zum Betrieb der Pipeline und der Molchlaeufe bildet die Fehlerbewertung mit entsprechenden Berechnungsverfahren den Hauptteil dieses Berichtes. Hinweise zur Instandhaltungsplanung (Fehlerverifikation und Molchlaufwiederholung) werden gegeben. (orig.)

  1. Ein „neuer" javanischer Fundort von Phrynoglossus laevis laevis ( Gthr.)

    NARCIS (Netherlands)

    Brongersma, L.D.

    1935-01-01

    In der herpetologischen Sammlung, die dem Rijksmuseum van Natuurlijke Historie, Leiden, vor etwa hundert Jahre von Boie und Macklot übersandt wurde, befanden sich zwei Exemplare von Phrynoglossus laevis laevis (Gthr.). Diese Stücke wurden von Van Kampen (1923, p. 232 Fussnote: Oxyglossus laevis) in

  2. Neuro- und Gliotoxizität von Wolframcarbid-basierten Nanopartikeln in vitro

    OpenAIRE

    Bastian, Susanne

    2011-01-01

    Die Anzahl neurodegenerativer Erkrankungen nimmt in unserer Gesellschaft stetig zu. Obwohl inzwischen eine Reihe genetischer Ursachen identifiziert worden sind, wird auch der Einfluss von Umweltfaktoren bei der Pathogenese dieser Erkrankungen zunehmend in Betracht gezogen. Der Beitrag von ultrafeinen Partikeln aus Industrie und Umwelt auf neurodegenerative Erkrankungen steht daher zunehmend im Fokus der Forschung. Die Translokation von ultrafeinen Partikeln bzw. Nanopartikeln ins Gehirn ist b...

  3. Muuga / Mary von Grünewaldt ; tõlk. Mati Sirkel

    Index Scriptorium Estoniae

    Grünewaldt, Mary von

    2004-01-01

    Leo Zoegelt ostetud Muuga mõisahoone korrastamisest ja uue hoone ehitamisest C. T. von Neffi kunstikogu paigutamise tarbeks. Tütre mälestused. Tõlgitud raamatust: Skizzen und Bilder aus dem Leben Carl Timoleon von Neff / Mary von Grünewaldt. Darmstadt, 1887

  4. Die grossen Physiker und ihre Entdeckungen von den fallenden Körpern zu den Quarks

    CERN Document Server

    Segrè, Emilio

    1998-01-01

    Von Galileo Galilei bis zu Richard Feynman und Murray Gell-Mann - von den fallenden Körpern zu den Quarks: Der Physiknobelpreisträger Emilio Segre hat seine ganz persönliche Geschichte der Physik geschrieben. Er erzählt von den großen Gestalten und deren wichtigen Entdeckungen mit großer Anschaulichkeit und Lebendigkeit.

  5. Vergleich verschiedener Methoden zur Haftkraftmessung von Dentinadhäsiven

    OpenAIRE

    Schwertner, Katharina

    2010-01-01

    Zur Bestimmung der Haftkraft von Adhäsiven stehen verschiedene Methoden zur Verfügung. Ziel dieser Studie war es, vier gebräuchliche in vitro Haftkraftmessmethoden (Tensile Bond Strength Test, Shear Bond Strength Test, Microtensile Bond Strength Test, Push-out Bond Strength Test) an drei unterschiedlichen Adhäsivsystemen (Syntac, Clearfil SE Bond, Adper Scotchbond Multi Purpose) zu testen und die Ergebnisse zu vergleichen. Die Haftkräfte sind abhängig von der verwendeten Messmethode. Viele Pa...

  6. The smooth entropy formalism for von Neumann algebras

    International Nuclear Information System (INIS)

    Berta, Mario; Furrer, Fabian; Scholz, Volkher B.

    2016-01-01

    We discuss information-theoretic concepts on infinite-dimensional quantum systems. In particular, we lift the smooth entropy formalism as introduced by Renner and collaborators for finite-dimensional systems to von Neumann algebras. For the smooth conditional min- and max-entropy, we recover similar characterizing properties and information-theoretic operational interpretations as in the finite-dimensional case. We generalize the entropic uncertainty relation with quantum side information of Tomamichel and Renner and discuss applications to quantum cryptography. In particular, we prove the possibility to perform privacy amplification and classical data compression with quantum side information modeled by a von Neumann algebra

  7. Dr. Space the life of Wernher von Braun

    CERN Document Server

    Ward, Bob

    2013-01-01

    Written by veteran aerospace journalist Bob Ward, who spent years investigating his subject, this biography presents a revealing but even-handed portrait of the father of modern rocketry. As he chronicles Wernher von Braun's life, Ward explodes many myths and misconceptions about the controversial genius who was a hero to some, a villain to others. The picture of von Braun that emerges is of a brilliant scientist with limitless curiosity and a drive to achieve his goals at almost any price from, developing the world's first ballistic missile used against the Allies in World War II to help

  8. Die Bundesstatistik als Anbieter und Nutzer von raumbezogenen Daten

    Directory of Open Access Journals (Sweden)

    R. Humbel

    Einige konkrete und potentielle Anwendungen der vorhandenen Daten sollen das Potential und die Breite der Fragestellungen, die damit angegangen werden können, illustrieren. Eine besondere Stellung dürfte in Zukunft aber auch die Satellitenfernerkundung erhalten, deren Daten und Auswertungen eine willkommene Ergänzung für die eher traditionellen GIS-Datensätze bilden werden. Ein erster Pilotversuch wurde vor wenigen Monaten im BFS gestartet, der zum Ziel hat, die Machbarkeit einer gesamtschweizerischen Unterscheidung von Laub-, Nadel- und Mischwald als Ergänzung der auf der Grundlage von konventionellen Luftbildern erhobenen Arealstatistik nachzuweisen.

  9. The smooth entropy formalism for von Neumann algebras

    Energy Technology Data Exchange (ETDEWEB)

    Berta, Mario, E-mail: berta@caltech.edu [Institute for Quantum Information and Matter, California Institute of Technology, Pasadena, California 91125 (United States); Furrer, Fabian, E-mail: furrer@eve.phys.s.u-tokyo.ac.jp [Department of Physics, Graduate School of Science, University of Tokyo, Tokyo, Japan and Institute for Theoretical Physics, Leibniz University Hanover, Hanover (Germany); Scholz, Volkher B., E-mail: scholz@phys.ethz.ch [Institute for Theoretical Physics, ETH Zurich, Zurich (Switzerland)

    2016-01-15

    We discuss information-theoretic concepts on infinite-dimensional quantum systems. In particular, we lift the smooth entropy formalism as introduced by Renner and collaborators for finite-dimensional systems to von Neumann algebras. For the smooth conditional min- and max-entropy, we recover similar characterizing properties and information-theoretic operational interpretations as in the finite-dimensional case. We generalize the entropic uncertainty relation with quantum side information of Tomamichel and Renner and discuss applications to quantum cryptography. In particular, we prove the possibility to perform privacy amplification and classical data compression with quantum side information modeled by a von Neumann algebra.

  10. Kodierung von Metadaten digitaler Briefeditionen in TEI-XML

    OpenAIRE

    Dumont, Stefan

    2017-01-01

    Folien zu einem Vortrag im Rahmen des Digital-Humanities-Kolloquium an der BBAW am 7.7.2017. Der Vortrag erläutert, ausgehend von editionswissenschaftlichen Entwicklungen der 1980er und 1990er Jahre, wie die "Kopfdaten" eines Briefes nach den Richtlinien der Text Encoding Initiative (TEI) kodiert werden können. Insbesondere wird auf das TEI-Element correspDesc eingegangen und die Kodierung anhand eines Beispiels veranschaulicht. Darüber hinaus wird der Mehrwert von Briefmetadaten sowohl für d...

  11. Risk-centered calculation of network charges in the power transmission sector; Risikoorientierte Kalkulation von Netznutzungsentgelten in der Stromverteilungswirtschaft

    Energy Technology Data Exchange (ETDEWEB)

    Maennel, W. [Friedrich-Alexander-Univ., Erlangen-Nuernberg (Germany). Betriebswirtschafliches Inst.

    2004-04-01

    Utilities insist that contrary to the opinions of the Federal Cartel Office and network users, distribution network operation is a high-risk enterprise. The contribution starts by listing typical relevant risks in power distribution and then proceeds to discussing risk factors one by one. Empirical findings generated with the Capital Asset Pricing Mode (CAPM) prove that the conservative approach for calculating the risk-based surcharges laid down in the VV II plus agreement is appropriate. (orig./CB) [German] Entgegen der Auffassung von Bundeskartellbehoerden und Netznutzern ist das stark anlagenintensive Netzgeschaeft mit bedeutsamen Unternehmerrisiken behaftet, deren Ueberwaelzung nur begrenzt moeglich ist. Ausgehend von generell bedeutsamen und typischen Unternehmerrisiken im Stromverteilungssektor beschaeftigt sich der Artikel mit den direkt auf die Eigenkapitalverzinsung einwirkenden Risikofaktoren. Mit dem Capital Asset Pricing Mode (CAPM) genierierte empirische Befunde bestaetigen die konservativen Wagniszuschlaege in der VV II plus. (orig.)

  12. Novel targeted approaches to treating biliary tract cancer: the dual epidermal growth factor receptor and ErbB-2 tyrosine kinase inhibitor NVP-AEE788 is more efficient than the epidermal growth factor receptor inhibitors gefitinib and erlotinib.

    Science.gov (United States)

    Wiedmann, Marcus; Feisthammel, Jürgen; Blüthner, Thilo; Tannapfel, Andrea; Kamenz, Thomas; Kluge, Annett; Mössner, Joachim; Caca, Karel

    2006-08-01

    Aberrant activation of the epidermal growth factor receptor is frequently observed in neoplasia, notably in tumors of epithelial origin. Attempts to treat such tumors with epidermal growth factor receptor antagonists resulted in remarkable success in recent studies. Little is known, however, about the efficacy of this therapy in biliary tract cancer. Protein expression of epidermal growth factor receptor, ErbB-2, and vascular endothelial growth factor receptor-2 was assessed in seven human biliary tract cancer cell lines by immunoblotting. In addition, histological sections from 19 patients with extrahepatic cholangiocarcinoma were analyzed for epidermal growth factor receptor, ErbB-2 and vascular endothelial growth factor receptor-2 expression by immunohistochemistry. Moreover, we sequenced the cDNA products representing the entire epidermal growth factor receptor coding region of the seven cell lines, and searched for genomic epidermal growth factor receptor amplifications and polysomy by fluorescence in-situ hybridization. Cell growth inhibition by gefitinib erlotinib and NVP-AEE788 was studied in vitro by automated cell counting. In addition, the anti-tumoral effect of erlotinib and NVP-AEE788 was studied in a chimeric mouse model. The anti-tumoral drug mechanism in this model was assessed by MIB-1 antibody staining, terminal deoxynucleotidyl transfer-mediated dUTP nick end-labelling assay, von Willebrand factor staining, and immunoblotting for p-p42/44 (p-Erk1/2, p-MAPK) and p-AKT. Immunoblotting revealed expression of epidermal growth factor receptor, ErbB-2, and vascular endothelial growth factor receptor-2 in all biliary tract cancer cell lines. EGFR was detectable in six of 19 (32%) extrahepatic human cholangiocarcinoma tissue samples, ErbB-2 in 16 of 19 (84%), and vascular endothelial growth factor receptor-2 in nine of 19 (47%). Neither epidermal growth factor receptor mutations nor amplifications or polysomy were found in the seven biliary tract cancer

  13. Analyse der pharmazeutischen Versorgungssituation von Patienten mit Psoriasis-Arthritis auf Basis von Routinedaten der Gesetzlichen Krankenversicherung.

    Science.gov (United States)

    Sondermann, Wiebke; Ventzke, Julia; Matusiewicz, David; Körber, Andreas

    2018-03-01

    Die Psoriasis-Arthritis (PsA) gehört zu den chronisch entzündlichen Gelenkerkrankungen. Trotz zahlreicher versorgungswissenschaftlicher Studien in Deutschland liegen zur pharmazeutischen Versorgungssituation von PsA-Patienten bisher kaum aktuelle Ergebnisse vor. Mit Hilfe einer systematischen Literaturrecherche sowie anhand von Routinedaten der Allgemeinen Ortskrankenkasse (AOK) Rheinland/Hamburg wird ein aktueller Überblick über die pharmazeutische Versorgung von PsA-Patienten in Deutschland gegeben. Selektiert wurden Versicherte aus dem ambulanten und stationären Bereich, die im 1. und 2. Quartal des Jahres 2014 die gesicherte Abrechnungsdiagnose Psoriasis-Arthritis L40.5+ aufwiesen. Anschließend wurden auf Basis dieser "vorab definierten" Kohorte die Arzneimitteldaten für 5 Jahre (01.01.2010-31.12.2014) abgerufen. Es konnten insgesamt n  =  3205 Versicherte (45 % männlich, 55 % weiblich) der AOK Rheinland/Hamburg mit einer gesicherten PsA-Diagnose selektiert werden. Das Durchschnittsalter betrug 58,9 Jahre. 53,7 % der PsA-Patienten wurden mit systemischen PsA-relevanten Arzneimitteln versorgt. Nichtsteroidale Antirheumatika (NSAR) wurden am häufigsten verordnet, gefolgt von systemischen Glucocorticoiden. Von den selektierten PsA-Patienten, die eine Systemtherapie erhielten, wurden 72,1 % mittels einer Disease-modifying-antirheumatic-Drug (DMARD)-Monotherapie behandelt, gefolgt von der Kombinationstherapie aus DMARDs und Biologika (20,9 %). Die pharmakologische Therapie der PsA muss eine Gewährleistung zwischen adäquater Versorgung der PsA mit Verhinderung der Krankheitsprogression und ökonomischer Verantwortung darstellen. © 2018 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  14. Entwicklung von Antikörper-Mikroarray : von Biophysik der Mikrospot-Reaktion bis zur Hochdurchsatzanalyse der Proteine

    OpenAIRE

    Kusnezow, Wlad

    2007-01-01

    Obwohl Protein-Mikroarrays ursprünglich aus dem gut entwickelten und fest etablierten DNA-Pendant entstanden sind, repräsentierte jedoch die Umstellung der Mikroarray-Technik von der DNA- auf die Proteinanalyse aufgrund der enormen physikalisch-chemischen Variabilität der Proteine, deren relativ niedrigen Stabilität und der komplexen Mikrospot-Kinetik eine große technologische Herausforderung. Deshalb setzt das Vorhaben, die Technik der Antikörper–Mikroarrays von ihrem konzeptuellen Zustand a...

  15. Automatische Ableitung und Anwendung von Regeln für die Rekonstruktion von Fassaden aus heterogenen Sensordaten

    OpenAIRE

    Becker, Susanne

    2011-01-01

    3D-Stadtmodelle finden seit einigen Jahren in immer stärkerem Maß und in den verschiedensten Bereichen Verwendung. Sie bilden unter anderem die Grundlage bei Stadtplanungen, für virtuelle Stadtrundgänge oder für die Berechnung von Simulationen. Internetdiensten wie Google Earth oder Microsoft Bing Maps ist es zu verdanken, dass 3D-Darstellungen von Gebäuden mittlerweile auch für eine breite Öffentlichkeit allgegenwärtig sind. Die erhöhte Nachfrage nach 3D-Gebäudemodellen verlangt nach effizie...

  16. Von-Neumann and Beyond: Memristor Architectures

    KAUST Repository

    Naous, Rawan

    2017-05-01

    An extensive reliance on technology, an abundance of data, and increasing processing requirements have imposed severe challenges on computing and data processing. Moreover, the roadmap for scaling electronic components faces physical and reliability limits that hinder the utilization of the transistors in conventional systems and promotes the need for faster, energy-efficient, and compact nano-devices. This work thus capitalizes on emerging non-volatile memory technologies, particularly the memristor for steering novel design directives. Moreover, aside from the conventional deterministic operation, a temporal variability is encountered in the devices functioning. This inherent stochasticity is addressed as an enabler for endorsing the stochastic electronics field of study. We tackle this approach of design by proposing and verifying a statistical approach to modelling the stochastic memristors behaviour. This mode of operation allows for innovative computing designs within the approximate computing and beyond Von-Neumann domains. In the context of approximate computing, sacrificing functional accuracy for the sake of energy savings is proposed based on inherently stochastic electronic components. We introduce mathematical formulation and probabilistic analysis for Boolean logic operators and correspondingly incorporate them into arithmetic blocks. Gate- and system-level accuracy of operation is presented to convey configurability and the different effects that the unreliability of the underlying memristive components has on the intermediary and overall output. An image compression application is presented to reflect the efficiency attained along with the impact on the output caused by the relative precision quantification. In contrast, in neuromorphic structures the memristors variability is mapped onto abstract models of the noisy and unreliable brain components. In one approach, we propose using the stochastic memristor as an inherent source of variability in

  17. Evaluiertes Training von Führungskompetenzen in der medizinischen Aus- und Weiterbildung [Training of Leadership Skills in Medical Education

    Directory of Open Access Journals (Sweden)

    Fischer, Martin R.

    2013-11-01

    Full Text Available [english] Background: Effective team performance is essential in the delivery of high-quality health-care. Leadership skills therefore are an important part of physicians’ everyday clinical life. To date, the development of leadership skills are underrepresented in medical curricula. Appropriate training methods for equipping doctors with these leadership skills are highly desirable. Objective: The review aims to summarize the findings in the current literature regarding training in leadership skills in medicine and tries to integrate the findings to guide future research and training development. Method: The PubMED, ERIC, and PsycArticles, PsycINFO, PSYNDEX and Academic search complete of EBSCOhost were searched for in German and English. Relevant articles were identified and findings were integrated and consolidated regarding the leadership principles, target group of training and number of participants, temporal resources of the training, training content and methods, the evaluation design and trainings effects. Results: Eight studies met all inclusion criteria and no exclusion criteria. The range of training programs is very broad and leadership skill components are diverse. Training designs implied theoretical reflections of leadership phenomena as well as discussions of case studies from practice. The duration of training ranged from several hours to years. Reactions of participants to trainings were positive, yet no behavioral changes through training were examined. Conclusions: More research is needed to understand the factors critical to success in the development of leadership skills in medical education and to adapt goal-oriented training methods. Requirements analysis might help to gain knowledge about the nature of leadership skills in medicine. The authors propose a stronger focus on behavioral training methods like simulation-based training for leadership skills in medical education.[german] Hintergrund: Eine effektive

  18. Der Zusammenhang von Partnermarktopportunitäten aus dem Freundeskreis und der Stabilität von Paarbeziehungen : Eine Analyse mit den Daten des Partnermarktsurvey

    OpenAIRE

    Häring, Armando

    2014-01-01

    "Der Beitrag analysiert den Zusammenhang zwischen Partnermarktoportunitäten aus dem Freundeskreis und der Stabilität von Paarbeziehungen. Unter Verwendung des theoretischen Konzepts der Theorie der Interaktionsgelegenheiten sowie von Annahmen der Austauschtheorie und der Familienökonomie, werden mögliche Zusammenhänge zwischen gemeinsamen Freundeskreisen mit dem Partner, Partnermarktgelegenheiten aus dem Freundeskreis (sex ratio) und der Stabilität von Paarbeziehungen diskutiert. Der Beitrag ...

  19. Von Kármán between Aachen and Pasadena

    Science.gov (United States)

    Krause, Egon; Kalkmann, Ulrich

    2013-05-01

    In the Introduction the reader is referred back to the academic ceremonials held after Theodore von Kármán's death in Aachen in May 1963. His work as the first director of the Aerodynamisches Institut (Institute of Aerodynamics) of the RWTH Aachen University of Technology from 1913 on and his initiative to re-establish international cooperation after World War I, resulting in the International Union of Theoretical and Applied Mechanics (IUTAM), are commented on. The following chapter describes von Kármán's relation to his former teacher Ludwig Prandtl. Some of von Kármán's scientific contributions during his time in Aachen are briefly reviewed. Thereafter, his first contacts to the California Institute of Technology are covered. Finally, the scientific and political circumstances, which led to von Kármán's decision to leave Germany in the early thirties, are elucidated in some detail. The English translation of the titles of the Aachen papers is given in Appendix I.

  20. Wernher von Braun: Reflections on His Contributions to Space Exploration

    Science.gov (United States)

    Goldman, Arthur E.

    2012-01-01

    In 1950, Dr. Wernher von Braun and approximately 100 of his team members came to Huntsville, Alabama, to begin work with the Army on what would later become America's historic space program. He would later serve as the first director of the Marshall Space Flight Center and led the development of the Saturn V launch vehicle that launched seven crewed American mission to the moon, as well as America s first space station, Skylab. Von Braun is best known for his team s technical achievements. He realized his dream of exploring outer space by helping place humans on the moon. His engineering and managerial talent during the Apollo era had contributed to a technological revolution. He was by all accounts a good engineer, but he was only one among many. What set Von Braun apart were his charisma, his vision, and his leadership skills. He inspired loyalty and dedication in the people around him. He understood the importance of communicating his vision to his team, to political and business leaders and the public. Today, the Marshall Center continues his vision by pursuing engineering and scientific projects that will continue to open space to exploration. This presentation will discuss Von Braun's impact on Huntsville, the Marshall Center, the nation and the world and look at his contributions in context of where world space exploration is today.

  1. Nonlinear von Neumann equations for quantum dissipative systems

    International Nuclear Information System (INIS)

    Messer, J.; Baumgartner, B.

    1978-01-01

    For pure states nonlinear Schroedinger equations, the so-called Schroedinger-Langevin equations are well-known to model quantum dissipative systems of the Langevin type. For mixtures it is shown that these wave equations do not extend to master equations, but to corresponding nonlinear von Neumann equations. Solutions for the damped harmonic oscillator are discussed. (Auth.)

  2. Nonlinear von Neumann equations for quantum dissipative systems

    International Nuclear Information System (INIS)

    Messer, J.; Baumgartner, B.

    For pure states nonlinear Schroedinger equations, the so-called Schroedinger-Langevin equations are well-known to model quantum dissipative systems of the Langevin type. For mixtures it is shown that these wave equations do not extend to master equations, but to corresponding nonlinear von Neumann equations. Solutions for the damped harmonic oscillator are discussed. (Author)

  3. Dr. von Braun With a Model of a Launch Vehicle

    Science.gov (United States)

    1950-01-01

    Dr. von Braun stands beside a model of the upper stage (Earth-returnable stage) of the three-stage launch vehicle built for the series of the motion picture productions of space flight produced by Walt Disney in the mid-1950's.

  4. Ernst von Glasersfeld's Radical Constructivism and Truth as Disclosure

    Science.gov (United States)

    Joldersma, Clarence W.

    2011-01-01

    In this essay Clarence Joldersma explores radical constructivism through the work of its most well-known advocate, Ernst von Glasersfeld, who combines a sophisticated philosophical discussion of knowledge and truth with educational practices. Joldersma uses Joseph Rouse's work in philosophy of science to criticize the antirealism inherent in…

  5. Eritrea : Von der Befreiung zur Unterdrückung

    NARCIS (Netherlands)

    van Reisen, Mirjam; Buck, K.D.

    2015-01-01

    Über das heutige Eritrea ist nur wenig bekannt. Als das kleine Land am Horn von Afrika 1993 die Unabhängigkeit erlangte, waren nicht nur im Land selbst die Hoffnungen groß, dass nach dem dreißig Jahre dauernden Befreiungskampf gegen Äthiopien eine bessere und friedliche Zukunft für alle beginnen

  6. Sakslased tulevad! Ärevad ajad Tallinnas Von Krahli Teatris

    Index Scriptorium Estoniae

    2001-01-01

    Von Krahli Teater ja Showcase Beat Le Mot valmistuvad oma esimeseks koostööprojektiks - lavastuseks "Pirates", kus osalevad mõlema teatri näitlejad ja tehnikud. Ühisprojekti toetavad Goethe Instituut, Hamburgi Linnavalitsus ja Eesti Kultuurkapital

  7. Professor Oberth and Dr. von Braun at ARS Banquet

    Science.gov (United States)

    1961-01-01

    Dr. Wernher von Braun holds the coveted Hermarn Oberth award presented to him by Professor Oberth during the banquet hosted by the Alabama Section of the American Rocket Society (ARS), on October 19, 1961. The Oberth award was given for outstanding technical contributions to the field of astronautics or for the promotion and advancement of astronautical sciences.

  8. Semiparametric Bernstein–von Mises for the error standard deviation

    NARCIS (Netherlands)

    Jonge, de R.; Zanten, van J.H.

    2013-01-01

    We study Bayes procedures for nonparametric regression problems with Gaussian errors, giving conditions under which a Bernstein–von Mises result holds for the marginal posterior distribution of the error standard deviation. We apply our general results to show that a single Bayes procedure using a

  9. Semiparametric Bernstein-von Mises for the error standard deviation

    NARCIS (Netherlands)

    de Jonge, R.; van Zanten, H.

    2013-01-01

    We study Bayes procedures for nonparametric regression problems with Gaussian errors, giving conditions under which a Bernstein-von Mises result holds for the marginal posterior distribution of the error standard deviation. We apply our general results to show that a single Bayes procedure using a

  10. De identiteit van Portulaca advena Reichg. & Von Poellnitz

    NARCIS (Netherlands)

    Geesink, R.

    1969-01-01

    Portulaca advena Reichg. & Von Poellnitz (1939), based on adventive specimens collected near Erp, prov. N.-Brabant, Netherlands, and afterwards cultivated in a garden at Nijmegen, appears to be identical with the South American P. papulosa Schldl. (1853). The adventive species of Portulaca found in

  11. Alexander von Humboldt's invention of the natural landscape

    NARCIS (Netherlands)

    Kwa, C.

    2005-01-01

    Landscape took on a new meaning through the new science of plant geography of Alexander von Humboldt (1769-1857). In the seventeenth and eighteenth centuries, "landscape" was foremost a painterly genre. Slowly, painted landscapes came to bear on natural surroundings, but by 1800 it was still not

  12. KK -theory and spectral flow in von Neumann algebras

    DEFF Research Database (Denmark)

    Kaad, Jens; Nest, Ryszard; Rennie, Adam

    2012-01-01

    We present a definition of spectral flow for any norm closed ideal J in any von Neumann algebra N. Given a path of selfadjoint operators in N which are invertible in N/J, the spectral flow produces a class in Ko (J). Given a semifinite spectral triple (A, H, D) relative to (N, t) with A separable...

  13. Enfermedad de Von Gierke: Reporte de tres casos

    Directory of Open Access Journals (Sweden)

    E. Espinosa

    2001-07-01

    Full Text Available La enfermedad de Von Gierke es un defecto en la glucosa 6 fosfatasa, degrada el glucógeno en el hígado, riñón e intestino. Asociada con hipoglicemia, acidosis láctica e hiperuricemia.

  14. Characterizing ξ-Lie Multiplicative Isomorphisms on Von Neumann Algebras

    Directory of Open Access Journals (Sweden)

    Yamin Song

    2014-01-01

    Full Text Available Let ℳ and be von Neumann algebras without central summands of type I1. Assume that ξ∈ℂ with ξ≠1. In this paper, all maps Φ:ℳ→ satisfying ΦAB-ξBA=ΦAΦB-ξΦBΦ(A are characterized.

  15. A bicategorical approach to Morita equivalence for Von Neumann algebras

    NARCIS (Netherlands)

    R.M. Brouwer (Rachel)

    2003-01-01

    textabstractWe relate Morita equivalence for von Neumann algebras to the ``Connes fusion'' tensor product between correspondences. In the purely algebraic setting, it is well known that rings are Morita equivalent if and only if they are equivalent objects in a bicategory whose 1-cells are

  16. A paradox of rationality à la von Neumann-Morgenstern

    NARCIS (Netherlands)

    Ismail, M.S.

    2015-01-01

    We show that there are games and decision situations in which it is not possible for the decision maker to be rational a la von Neumann-Morgenstern in both situations simultaneously, which is the source of the paradox presented in this note. We provide an assumption which is the necessary and

  17. Extensions of von Neumann's method for generating random variables

    International Nuclear Information System (INIS)

    Monahan, J.F.

    1979-01-01

    Von Neumann's method of generating random variables with the exponential distribution and Forsythe's method for obtaining distributions with densities of the form e/sup -G//sup( x/) are generalized to apply to certain power series representations. The flexibility of the power series methods is illustrated by algorithms for the Cauchy and geometric distributions

  18. Computed tomography of von Meyenburg complex simulating micro-abscesses

    International Nuclear Information System (INIS)

    Sada, P.N.; Ramakrishna, B.

    1994-01-01

    A case is presented of a bile duct hamartoma in a 44 year old man being evaluated for abdominal pain. The computed tomography (CT) findings suggested micro-abscesses in the liver and a CT guided tru-cut biopsy showed von Meyenburg complex. 9 refs., 3 figs

  19. Ueber die arten und den Skelettbau von Culcita

    NARCIS (Netherlands)

    Hartlaub, Clemens

    1892-01-01

    Das Genus Culcita Agass. zählt durch die merkwürdige Form und die ansehnliche Grösse seiner Arten zu den interessantesten Asteriden, und gut conservirte Exemplare davon gehören zu den Zierden unsrer Museen. Um so bedauerlicher erschien es mir, als ich vor einiger Zeit den Versuch machte die von

  20. Mollusken aus posttertiären Schichten von Celebes

    NARCIS (Netherlands)

    Schepman, M.M.

    1912-01-01

    Die im Folgenden behandelten Mollusken stammen aus der Nähe von Kajoe ragi auf Celebes, woselbst sie durch R. FENNEMA aus denselben Schichten ausgelesen wurden, aus denen früher durch J. G. DE MAN einige brachyure Krebse beschrieben sind. Es darf deswegen betreffs näherer Angaben über die Herkunft

  1. Die Korallenfauna des Perm von Timor und die permische Vereisung

    NARCIS (Netherlands)

    Gerth, H.

    1926-01-01

    Bei den zahlreichen Rekonstruktionen der klimatologischen Verhältnisse, die man für das Ende des Palaeozoikums gemacht hat, ist man fast immer von der Kohlenbildung, der Florenverbreitung und den Vereisungserscheinungen ausgegangen. Der marinen Tierwelt hat man bei der Behandlung dieser Fragen meist

  2. Ueber einige Entwicklungsstadien von Rhopilema hispidum (Vanhoeffen) Maas

    NARCIS (Netherlands)

    Stiasny, G.

    1933-01-01

    Gelegentlich der Durchsicht einiger älterer Planktonfänge aus dem malayischen Archipel in den Sammlungen des Rijks Museum van Natuurlijke Historie in Leiden fanden sich zahlreiche Entwicklungsstadien von Rhopilema hispidum (VANH.) MAAS vor, über die ich hier kurz berichten will. Ueber die

  3. Fossile Säugethierreste von Java und Japan

    NARCIS (Netherlands)

    Martin, K.

    1884-01-01

    Die Beschreibung eines Stegodontenzahnes von Java in der vorhergehenden Abhandlung dieses Bandes ist die Veranlassung geworden, dass De Koninklijke Natuurkundige Vereeniging in Nederlandsch Indië eine grosse Sammlung fossiler Säugethierreste dem Geologischen Museum in Leiden übersandte. Es befinden

  4. Minimum Moduli in Von Neumann Algebras | Gopalraj | Quaestiones ...

    African Journals Online (AJOL)

    In this paper we answer a question raised in [12] in the affirmative, namely that the essential minimum modulus of an element in a von. Neumann algebra, relative to any norm closed two-sided ideal, is equal to the minimum modulus of the element perturbed by an element from the ideal. As a corollary of this result, we ...

  5. Die filmstilistische Darstellung von Klaras Gehbehinderung im Kinderfilm "Heidi"

    Directory of Open Access Journals (Sweden)

    Maria Ohrfandl

    2016-09-01

    Full Text Available Dieser Beitrag soll die Forschungslücke zur Darstellung von Behinderungen speziell im Kinderfilm im deutschsprachigen Raum füllen. Auf Basis einer neoformalistisch orientierten Filmanalyse nach Bordwell und Thompson (2008, wird anhand von drei Filmsequenzen eine mögliche Lesart des Kinderfilms "Heidi" (Marcus 2005 entwickelt, um die filmstilistische Darstellung der Gehbehinderung des Mädchens Klara zu untersuchen. Die Ergebnisse werden mit theoretischen Überlegungen zur Problematik der Begriffsbestimmung von Körperbehinderung sowie zur Mobilität und Selbstbestimmung von Menschen mit Körperbehinderungen in Bezug gesetzt. Dabei zeigt sich im Wesentlichen, dass im Kinderfilm "Heidi" (Marcus 2005 Klaras Gehbehinderung als 'heilbare Krankheit' und der Rollstuhl als Einschränkung von Mobilität begriffen wird. Außerdem unterliegt Klara aufgrund ihrer Körperbehinderung überwiegend der Fremdbestimmung von Erwachsenen. Zur Klärung wahrscheinlicher filmischer Bildungspotenziale werden die Ergebnisse schließlich anhand der von Jörissen und Marotzki (2009 entwickelten Orientierungsdimensionen "Wissens-, Handlungs-, Grenz- und Biographiebezug" diskutiert. This article aims to bridge a knowledge gap by showing ways of representing disabilities in the German children film genre. Using Bordwell and Thomson's (2008 neoformalistically orientated film analysis approach, the movie "Heidi" (Marcus 2005 is analysed. Bordwell and Thompson's (2008 method is applied to three sequences of "Heidi" in order to present an interpretation and to discuss the representation of Clara's walking impediment. The results are then associated with theoretical considerations regarding the mobility and self-determination of people with disabilities and problematic definitions of the term 'physical disability'. It is shown that characters in the children's film "Heidi" (Marcus 2005 regard Clara's walking impediment as a 'curable disease' and the wheelchair as a limitation

  6. Optimierung der Gesichtsklassifikation bei der Erkennung von Akromegalie

    Directory of Open Access Journals (Sweden)

    Frohner R

    2013-01-01

    Full Text Available In vorausgegangenen Studien konnte gezeigt werden, dass eine Gesichtsklassifikation mittels Gesichtsphotographien zur Diagnostik von Akromegalie mit guten Ergebnissen eingesetzt werden kann. In diesem Artikel werden die grundlegende Vorgehensweise der Klassifikation mittels der Software FIDA erläutert sowie Optimierungsansätze mit dem Ziel diskutiert, diese Methode näher an den klinischen Einsatz zu bringen. Die Gesichtsklassifikation basiert auf „Knotenpunkten“, die verteilt über die jeweilige Frontal- und/oder Seitenansicht des Gesichts platziert werden und den so genannten „Graphen“ bilden. Mittels mathematischer Verfahren erfolgt eine Analyse der zugrunde liegenden Textur des Bildes sowie die Auswertung geometrischer Informationen. Untersucht wird, wie sich die Reduktion von als irrelevant eingestuften Knoten auf das Klassifikationsergebnis auswirkt. Ebenso wird untersucht, wie sich neu definierte Knoten, die die typischen morphologischen Veränderungen der akromegalen Erkrankung im Gesicht berücksichtigen, auf die Klassifizierungsergebnisse auswirken. Die interne Validierung erfolgt an einem Datenset bestehend aus 57 an Akromegalie erkrankten Probanden (29 weiblich, 28 männlich sowie 59 Kontrollen (29 weiblich, 30 männlich. Die externe Validierung wird an einer weiteren Stichprobe gemessen, die zum Zeitpunkt der Präsentation auf der Tagung der European Neuroendocrine Association 2012 in Wien 13 akromegale Patienten (7 weiblich, 6 männlich sowie 45 Kontrollen (25 weiblich, 20 männlich umfasste. Die Datenbank wird ständig durch neue Probanden aus verschiedenen Quellen erweitert. Erste Ergebnisse zeigen, dass die Verwendung von Graphen mit reduzierten Knoten und von neuen Sets von Knoten unter Einbeziehung typischer morphologischer Veränderungen des Gesichts die Klassifizierung weiter verbessert. Diese Ergebnisse ermutigen zu weiteren Untersuchungen an einer erweiterten Datenbank.

  7. Eine selbstkonsistente Carleman Linearisierung zur Analyse von Oszillatoren

    Directory of Open Access Journals (Sweden)

    H. Weber

    2017-09-01

    Full Text Available Die Analyse nichtlinearer dynamischer Schaltungen ist bis heute eine herausfordernde Aufgabe, da nur selten analytische Lösungen angegeben werden können. Daher wurden eine Vielzahl von Methoden entwickelt, um eine qualitative oder quantitative Näherung für die Lösungen der Netzwerkgleichung zu erhalten. Oftmals wird beispielsweise eine Kleinsignalanalyse mit Hilfe einer Taylorreihe in einem Arbeitspunkt durchgeführt, die nach den Gliedern erster Ordnung abgebrochen wird. Allerdings ist diese Linearisierung nur in der Nähe des stabilen Arbeitspunktes für hyperbolische Systeme gültig. Besonders für die Analyse des dynamischen Verhaltens von Oszillatoren treten jedoch nicht-hyperbolische Systeme auf, sodass diese Methode nicht angewendet werden kann Mathis(2000. Carleman hat gezeigt, dass nichtlineare Differentialgleichungen mit polynomiellen Nichtlinearitäten in ein unendliches System von linearen Differentialgleichungen transformiert werden können Carleman(1932. Wird das unendlichdimensionale Gleichungssystem für numerische Zwecke abgebrochen, kann bei Oszillatoren der Übergang in eine stationäre Schwingung (Grenzzyklus nicht wiedergegeben werden.In diesem Beitrag wird eine selbstkonsistente Carleman Linearisierung zur Untersuchung von Oszillatoren vorgestellt, die auch dann anwendbar ist, wenn die Nichtlinearitäten keinen Polynomen entsprechen. Anstelle einer linearen Näherung um einen Arbeitspunkt, erfolgt mit Hilfe der Carleman Linearisierung eine Approximation auf einem vorgegebenen Gebiet. Da es jedoch mit der selbstkonsistenten Technik nicht möglich ist, das stationäre Verhalten von Oszillatoren zu beschreiben, wird die Berechnung einer Poincaré-Abbildung durchgeführt. Mit dieser ist eine anschließende Analyse des Oszillators möglich.

  8. Eine selbstkonsistente Carleman Linearisierung zur Analyse von Oszillatoren

    Science.gov (United States)

    Weber, Harry; Mathis, Wolfgang

    2017-09-01

    Die Analyse nichtlinearer dynamischer Schaltungen ist bis heute eine herausfordernde Aufgabe, da nur selten analytische Lösungen angegeben werden können. Daher wurden eine Vielzahl von Methoden entwickelt, um eine qualitative oder quantitative Näherung für die Lösungen der Netzwerkgleichung zu erhalten. Oftmals wird beispielsweise eine Kleinsignalanalyse mit Hilfe einer Taylorreihe in einem Arbeitspunkt durchgeführt, die nach den Gliedern erster Ordnung abgebrochen wird. Allerdings ist diese Linearisierung nur in der Nähe des stabilen Arbeitspunktes für hyperbolische Systeme gültig. Besonders für die Analyse des dynamischen Verhaltens von Oszillatoren treten jedoch nicht-hyperbolische Systeme auf, sodass diese Methode nicht angewendet werden kann Mathis (2000). Carleman hat gezeigt, dass nichtlineare Differentialgleichungen mit polynomiellen Nichtlinearitäten in ein unendliches System von linearen Differentialgleichungen transformiert werden können Carleman (1932). Wird das unendlichdimensionale Gleichungssystem für numerische Zwecke abgebrochen, kann bei Oszillatoren der Übergang in eine stationäre Schwingung (Grenzzyklus) nicht wiedergegeben werden. In diesem Beitrag wird eine selbstkonsistente Carleman Linearisierung zur Untersuchung von Oszillatoren vorgestellt, die auch dann anwendbar ist, wenn die Nichtlinearitäten keinen Polynomen entsprechen. Anstelle einer linearen Näherung um einen Arbeitspunkt, erfolgt mit Hilfe der Carleman Linearisierung eine Approximation auf einem vorgegebenen Gebiet. Da es jedoch mit der selbstkonsistenten Technik nicht möglich ist, das stationäre Verhalten von Oszillatoren zu beschreiben, wird die Berechnung einer Poincaré-Abbildung durchgeführt. Mit dieser ist eine anschließende Analyse des Oszillators möglich.

  9. Otto von Habsburg : III maailmasõda on läbi / Otto von Habsburg ; interv. Marianne Mikko

    Index Scriptorium Estoniae

    Habsburg, Otto von, 1912-2011

    2002-01-01

    Otto von Habsburg vastab küsimustele, mis puudutavad Euroopa konvendi presidendi teadet, et Türgi koht ei ole EL-is, Iraagi võimalikku ründamist, Hiina ja Venemaa suhteid, Tšetšeeniat, tshetsheene ja terrorismi, Venemaa, EL-i ja USA suhteid, III maailmasõda, Eesti Vabariigi tulevikku

  10. Zum 215. Gebutstag von Admiral Ferdinand Baron von Wrangell : (29. Dezember 1797 - 25. 25. Mai 1870) / Peter Krienitz

    Index Scriptorium Estoniae

    Krienitz, Peter

    2012-01-01

    Admiral Ferdinand Baron von Wrangellist tema 215. sünniaastapäeva puhul. Silmapaistavast Kirde-Siberi uurijast. Tema poliitilisest tegevusest ja elust Roela mõisas. Ferdinand Baroni poolt seatud viisil tähistati jõulusid Roelas kuni 1944. aasta lõpuni.

  11. Diagnostic imaging of injuries and overuse in soccer players; Bildgebende Diagnostik von Verletzungen und Ueberlastungsschaeden bei Fussballern

    Energy Technology Data Exchange (ETDEWEB)

    Jonge, M.C. de; Maas, M.; Kuijk, C. van [Department of Radiology, Academic Medical Center, University of Amsterdam (Netherlands)

    2002-10-01

    Soccer is one of the most popular sports worldwide. There is a high incidence of injuries in soccer in which several intrinsic and extrinsic factors play a part. Most injuries are minor, self-limiting and do not need extensive medical treatment or imaging. Imaging can be required for several reasons e.g. when the clinical findings are doubtful, to replace arthroscopy (i. e. of the knee) or for prognostic reasons. All imaging modalities available to the radiologist can be used but MRI is the most valuable imaging modality with its superior contrast resolution and multiplanar capabilities. Basically, injuries in the soccer player can occur anywhere in the body like in every sport. The lower extremities, more specific the knee and ankle, are however the most injured parts. (orig.) [German] Fussball ist eine der weltweit populaersten Sportarten, und Verletzungen sind mit hoher Inzidenz zu finden, wobei bestimmte intrinsische und extrinsische Faktoren eine pathogenetisch wesentliche Rolle spielen. Der Schweregrad von Verletzungen ist meist gering und selbstlimitierend, eine ausgiebige Behandlung oder die Durchfuehrung bildgebender diagnostischer Massnahmen sind nicht noetig. Die radiologische Untersuchung ist indiziert bei klinisch unklaren Befunden, zur Planung einer etwaigen Arthroskopie oder zur klinisch-prognostischen Einschaetzung der Veraenderungen. Von den verfuegbaren Modalitaeten ist die MRT von groesster Bedeutung. Verletzungen als Folge des Fussballspielens sind in allen Koerperabschnitten zu beobachten, v. a. an den unteren Extremitaeten und hier besonders an Knie- und Sprunggelenk. (orig.)

  12. DIE SPRACHE VON "BAŠĆANSKA PLOČA" (DIE STEINTAFEL VON BAŠKA

    Directory of Open Access Journals (Sweden)

    Stjepan Damjanović

    1990-01-01

    Full Text Available In einer Mehrzahl von Abhandlungen über Bašćanska ploča berücksichtigen die Verfasser auch die Sprache, in der Regel kurz, nur in einem oder zwei Sätzen. Die größten Bemühungen sind auf die Rekonstruirung der unlesbaren Teilen gerichtet, dagegen nicht weinger interessanter lesbarer Teil regte eine Sprachanalyse selten an. Gewöhnlich wird festgestellt, daß die Tafel in der kroatischen Sprache geschrieben ist, während die philologisch gut unterrichtete Forscher vermeiden diesartige Nenunngen, indem sie das Vorhandensein der altslawischen und altkroatischen Sprachelemente entdeckten. Man versuchte noch nicht in einer Analyse sprachliche Grundschichte und darauf geschichtete Sprachelemente zu bestimmen. Nach dem ersten Eindruck wurde bestimmt, ob es sich um "die kroatische Srpache mit den Elementen der alten slawischen liturgischen Sprache" handelt oder um "die altslawische in der manche kroatische Spracheigenschaften hereingekommen sind". Die Analyse mancher Spracheinzelheiten (Halblaute und "Jat" weist auf altslawische Grundschicht hin. Der Verfasser hat sich trotzdem nicht entschieden den Fachausdruck "kroatische Redaktion des altslawischen" zu verwenden, weil er neue Analyse und neue Begriffsbestimmungen als nötig hält, wie z.B. "Redaktion", "Rezension" usw, um mit Sicherkeit sagen zu können, ob es um kroatische Redaktion des altslawischen oder um andere Formen der altslawischen - alt kroatischen Interferenz geht.

  13. Digitale Rekonstruktion von historischem Bibliotheksgut. Projektvorstellung Leibniz-Fragmente und Massendigitalisierung von Flachware

    Directory of Open Access Journals (Sweden)

    Matthias Wehry

    2017-12-01

    Full Text Available Der Universalgelehrte Gottfried Wilhelm Leibniz verwendete eine besondere Form der Wissensordnung: Teile seiner Manuskripte und Arbeitspapiere, z.B. Abschriften und Exzerpte, wurden von ihm zerschnitten und in einem so genannten „Zettel-Schrancken“, einem großen Zettelkasten, geordnet. Im vorgestellten Projekt wurde ein automatisiertes virtuelles Assistenzsystem erarbeitet, um die ursprünglichen Zusammenhänge der Notata im Augenblick ihrer Entstehung wiederherzustellen. Das Ergebnis des Projektes ist ein innovatives Massenverfahren zum Puzzeln und Scannen historischer handschriftlicher Dokumente. The polymath Gottfried Wilhelm Leibniz used a specific technique for knowledge organisation: He cut parts of his manuscripts and working papers, e.g., copies and excerpts, in pieces and filed them systematically in a so called “Zettel-Schrancken”, a hugh slipbox. In the project presented in this paper, an automated virtual reconstruction of the notes’ initial context at the moment of origin was developed. The result of the project is an innovative mass processing method for puzzling and scanning historical handwritten documents

  14. Alternative Regulierungsansätze im Kontext der Better Regulation Agenda : eine Analyse von Konzepten, Potenzialen und Erfolgsfaktoren von Regulierung im Schatten staatlicher Hierarchie

    OpenAIRE

    Denker, Philipp

    2008-01-01

    Der vorliegende Beitrag untersucht das Potential und die Bedingungen alternativer Regulierungsformen vor dem Hintergrund von Better Regulation in Deutschland. Nahezu alle EU- und OECD-Staaten betreiben heute umfassende politische Reformprogramme zur Modernisierung der Regulierungsarchitekturen, die unter dem Label Better Regulation subsumiert werden. Die Zielsetzung dieser Programme besteht zum einen in der wirtschaftsfreundlichen Reduktion von Regulierungskosten und zum anderen in der Effekt...

  15. Rezension von: Gabriele Dietze: Weiße Frauen in Bewegung. Genealogien und Konkurrenzen von Race- und Genderpolitiken. Bielefeld: transcript Verlag 2013.

    Directory of Open Access Journals (Sweden)

    Philipp Dorestal

    2014-03-01

    Full Text Available Gabriele Dietze zeichnet das Verhältnis der Kategorien Race und Gender innerhalb der US-amerikanischen Geschichte von der Mitte des 19. Jahrhunderts bis zur Präsidentschaftswahl von Barack Obama nach. Dabei demonstriert sie anhand von zentralen Figuren der weißen Frauenbewegung deren ambivalente Positionen, die oftmals für progressive Inhalte wie das Eintreten für Frauenrechte stehen, gleichzeitig aber dann Anliegen von African Americans nicht artikulieren oder gar zum Schweigen bringen. Ebenso zeigt Dietze mithilfe von Texten einiger schwarzer Autor_innen sowie anhand berühmter Gerichtsprozesse, dass schwarze Emanzipation nicht notwendigerweise mit feministischen Positionen einhergehen musste, sondern sich vielmehr eine Konkurrenzsituation zwischen Race und Gender entspann.

  16. The von Auwers reaction - history and synthetic applications.

    Science.gov (United States)

    Dumeunier, Raphaël; Jaeckh, Simon

    2014-01-01

    Dienones obtained from the facile dearomatization of phenols, can be further transformed to semi-benzenes prone to rearomatize in clean, but sometimes unexpected, fashion. Over a hundred years ago, K. von Auwers found that adding Grignards on dienones would lead spontaneously to subsequent dehydration and a novel aromatizing rearrangement. This reaction was ignored for 50 years before Melvin Newman re-investigated these findings, studied the mechanism, and developed variations on the same theme. Since then, despite the tremendous potential of the reactions, those studies were only rarely mentioned, before finally falling into oblivion. This review aims to provide the reader with a detailed history and comprehensive bibliography of the von Auwers rearrangement, some of its synthetic applications, and new unpublished material in the hope to open new perspectives on this forgotten reaction.

  17. Die Ordnung der Weltkulturen. Alexander von Humboldts Ansichten der Kultur

    Directory of Open Access Journals (Sweden)

    Ottmar Ette

    2004-10-01

    Full Text Available Article in German,Abstracts in English, German and Spanish. Focussing Alexander von Humboldt's Vues des Cordillères et Monumens des peuples indigènes de l'Amérique (1810 - 1813 in the context of his monumental work, this essay tries to highlight not only the creation of a new discourse on the Americas but, at the same time, the project(ion of a new order of world cultures. From a transregional perspective, Humboldt's aesthetically most radical book can be fully understood as a musée imaginaire of world cultures whose spatial, temporal, social, literary, frictional, architextual and cultural dimensions allow new insights in one of the most fascinating texts of the early 19th century. Alexander von Humboldt's Vues are creating a transmedial kaleidoscope within a fractal vision of the cultures of the world in the second period of accelerated globalization.

  18. Von eingebetteten Systemen zu Cyber-Physical Systems

    Science.gov (United States)

    Wedde, Rorst F.; Lehnhoff, Sebastian; Rehtanz, Christian; Krause, Olav

    Das Hauptanliegen des Papiers ist, ein Paradigma für Probleme mit neuartigen Integrationsanforderungen für Forschung und Entwicklung in verteilten eingebetteten Echtzeitsystemen zu motivieren und vorzustellen, nämlich den Begriff Cyber-Physical Systems. Bei einer in letzter Zeit stark zunehmenden Anzahl von Realzeitanwendungen können ohne die Berücksichtigung solcher Forderungen keine praktisch brauchbaren Lösungen erwartet werden. Einige Anwendungsfelder werden angesprochen. Im Einzelnen werden dann für Elektroautos, die mit erneuerbaren Energien betrieben werden sollen, einerseits die Management-, verteilte Verhandlungs- und Verteilungsprobleme der benötigten Energie in einem bottom-up Ansatz gelöst. Andererseits wird als Teil unserer Projektarbeit die Bereitstellung von Reserveenergie für den allgemeinen Bedarf durch Autobatterien vorgestellt. Es zeigt sich, dass dies effizienter und wesentlich kurzfristiger in unserem verteilten Vorgehen geschehen kann als in traditionellen Verfahren.

  19. A tribute to Ebba von Fersen Balzan 1957-2008

    OpenAIRE

    Lagana, Louis

    2008-01-01

    Ebba von Fersen Balzan first came to Malta in 1986. She was mostly fascinated by Maltese culture and as an artist she was particularly attracted to the intense light of the Maltese landscape, the colour of the Maltese stone and the megalithic temples. In 1989 she held her first exhibitions in Malta: the first exhibition, in aid of Alternattiva Demokratika, was held at the hotel Phoenicia and another followed at the Museum of Fine Arts in Valletta.

  20. Sonographic findings in the Cruveilhier-von Baumgarten syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Pirschel, J

    1982-07-01

    Portal hypertension is the most common complication of cirrhosis of the liver and leads to a reversal of blood flow and re-opening of pre-formed portal-systemic collaterals. Amongst a variety of possible hepato-fugal collaterals, the Cruveilhier-von Baumgarten syndrome, consisting of the reopening of umbilical veins, is a rare variant. It has been possible to demonstrate this clearly by sonography in 18 patients.