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  1. Coagulation factor VIIa: prohemostatic drug and biomarker for thrombosis

    NARCIS (Netherlands)

    Schut, Anne Marieke

    2016-01-01

    Stollingsfactor VIIa: prohemostatisch medicijn en biomarker voor trombose Fysiologische activatie van de bloedstolling begint met de activatie van stollings factor VII tot factor VIIa. Een recombinante vorm van factor VIIa (rFVIIa) is ontwikkeld als medicijn om bloedstolling te stimuleren in patiënt

  2. Haemostatic effects of recombinant coagulation factor VIIa

    NARCIS (Netherlands)

    Lisman, Johannes Antonius

    2002-01-01

    Recombinant coagulation factor VIIa (rFVIIa) has recently become available for treatment of patients with inhibitor-complicated haemophilia. It has been postulated that rFVIIa could become a universal haemostatic agent. Case reports and small studies confirm efficacy and safety of rFVIIa in a

  3. Factor VIIa binding and internalization in hepatocytes

    DEFF Research Database (Denmark)

    Hjortoe, G; Sorensen, B B; Petersen, L C

    2005-01-01

    The liver is believed to be the primary clearance organ for coagulation proteases, including factor VIIa (FVIIa). However, at present, clearance mechanisms for FVIIa in liver are unknown. To obtain information on the FVIIa clearance mechanism, we investigated the binding and internalization...

  4. Nonbenzamidine acylsulfonamide tissue factor-factor VIIa inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Glunz, Peter W.; Zhang, Xiaojun; Zou, Yan; Delucca, Indawati; Nirschl, Alexandra H.; Cheng, Xuhong; Weigelt, Carolyn A.; Cheney, Daniel L.; Wei, Anzhi; Anumula, Rushith; Luettgen, Joseph M.; Rendina, Alan R.; Harpel, Mark; Luo, Gang; Knabb, Robert; Wong, Pancras C.; Wexler, Ruth R.; Priestley, E. Scott [BMS

    2017-03-16

    Aminoisoquinoline and isoquinoline groups have successfully replaced the more basic P1 benzamidine group of an acylsulfonamide factor VIIa inhibitor. Inhibitory activity was optimized by the identification of additional hydrophobic and hydrophilic P' binding interactions. The molecular details of these interactions were elucidated by X-ray crystallography and molecular modeling. We also show that decreasing the basicity of the P1 group results in improved oral bioavailability in this chemotype.

  5. Systemic Venous Thrombosis after Recombinant Factor VIIa in the Control of Bleeding after Cardiac Surgery

    OpenAIRE

    Mahmoud, Amr; Al-Ruzzeh, Sharif; McKeague, Helena; Cross, Mike

    2007-01-01

    Recombinant factor VIIa has been licensed in the United Kingdom since 1996 for the control of bleeding in hemophilic patients who are actively bleeding or are about to undergo surgery. Medical practitioners are also applying recombinant factor VIIa toward the control of bleeding in patients without hemophilia. Although the efficacy of recombinant factor VIIa has been shown in many patients, concerns have arisen about the risk of thrombotic adverse events.

  6. A loop of coagulation factor VIIa influencing macromolecular substrate specificity

    DEFF Research Database (Denmark)

    Bjelke, Jais R; Persson, Egon; Rasmussen, Hanne B;

    2006-01-01

    Coagulation factor VIIa (FVIIa) belongs to a family of proteases being part of the stepwise, self-amplifying blood coagulation cascade. To investigate the impact of the mutation Met(298{156})Lys in FVIIa, we replaced the Gly(283{140})-Met(298{156}) loop with the corresponding loop of factor Xa....../Met(298{156})Lys-FVIIa with almost the same activity and specificity profile. We conclude that a lysine residue in position 298{156} of FVIIa requires a hydrophilic environment to be fully accommodated. This position appears critical for substrate specificity among the proteases of the blood coagulation...

  7. Allosteric activation of coagulation factor VIIa visualized by hydrogen exchange

    DEFF Research Database (Denmark)

    Rand, Kasper Dyrberg; Jørgensen, Thomas; Olsen, Ole H;

    2006-01-01

    Coagulation factor VIIa (FVIIa) is a serine protease that, after binding to tissue factor (TF), plays a pivotal role in the initiation of blood coagulation. We used hydrogen exchange monitored by mass spectrometry to visualize the details of FVIIa activation by comparing the exchange kinetics...... tissue factor binding, FVIIa undergoes dramatic structural stabilization as indicated by decreased exchange rates localized throughout the protease domain and in distant parts of the light chain, spanning across 50A and revealing a concerted interplay between functional sites in FVIIa. The results...... of distinct molecular states, namely zymogen FVII, endoproteolytically cleaved FVIIa, TF-bound zymogen FVII, TF-bound FVIIa, and FVIIa in complex with an active site inhibitor. The hydrogen exchange kinetics of zymogen FVII and FVIIa are identical indicating highly similar solution structures. However, upon...

  8. Discovery of Phenylglycine Lactams as Potent Neutral Factor VIIa Inhibitors.

    Science.gov (United States)

    Wurtz, Nicholas R; Parkhurst, Brandon L; Jiang, Wen; DeLucca, Indawati; Zhang, Xiaojun; Ladziata, Vladimir; Cheney, Daniel L; Bozarth, Jeffrey R; Rendina, Alan R; Wei, Anzhi; Luettgen, Joseph M; Wu, Yiming; Wong, Pancras C; Seiffert, Dietmar A; Wexler, Ruth R; Priestley, E Scott

    2016-12-08

    Inhibitors of Factor VIIa (FVIIa), a serine protease in the clotting cascade, have shown strong antithrombotic efficacy in preclinical thrombosis models with minimal bleeding liabilities. Discovery of potent, orally active FVIIa inhibitors has been largely unsuccessful because known chemotypes have required a highly basic group in the S1 binding pocket for high affinity. A recently reported fragment screening effort resulted in the discovery of a neutral heterocycle, 7-chloro-3,4-dihydroisoquinolin-1(2H)-one, that binds in the S1 pocket of FVIIa and can be incorporated into a phenylglycine FVIIa inhibitor. Optimization of this P1 binding group led to the first series of neutral, permeable FVIIa inhibitors with low nanomolar potency.

  9. Molecular Basis of Enhanced Activity in Factor VIIa-Trypsin Variants Conveys Insights into Tissue Factor-mediated Allosteric Regulation of Factor VIIa Activity

    DEFF Research Database (Denmark)

    Sorensen, Anders B.; Madsen, Jesper Jonasson; Svensson, L. Anders;

    2016-01-01

    The complex of coagulation factor VIIa (FVIIa), a trypsin-like serine protease, and membrane-bound tissue factor (TF) initiates blood coagulation upon vascular injury. Binding of TF to FVIIa promotes allosteric conformational changes in the FVIIa protease domain and improves its catalytic propert...

  10. Tissue factor activates allosteric networks in factor VIIa through structural and dynamic changes

    DEFF Research Database (Denmark)

    Madsen, Jesper Jonasson; Persson, E.; Olsen, O. H.

    2015-01-01

    Background: Tissue factor (TF) promotes colocalization of enzyme (factorVIIa) and substrate (FX or FIX), and stabilizes the active conformation of FVIIa. Details on how TF induces structural and dynamic changes in the catalytic domain of FVIIa to enhance its efficiency remain elusive. Objective...

  11. Efficacy of recombinant factor VIIa administered by continuous infusion to haemophilia patients with inhibitors

    NARCIS (Netherlands)

    Mauser-Bunschoten, EP; Koopman, MMW; Goede-Bolder, ADE; Leebeek, FWG; Van der Meer, J; Kooij, GMV; Van der Linden, PWG

    2002-01-01

    We have prospectively monitored treatment of haemophilia patients with inhibitors by recombinant factor VIIa (rFVIIa) administered by continuous infusion to obtain more insight in the underlying factors of the clinical efficacy of this administration method. At present, 43 treatment episodes of 14 d

  12. Use of Recombinant Factor VIIa in US Military Casualties for a Five-Year Period

    Science.gov (United States)

    2010-08-01

    Recombinant factor VIIa as adjunctive therapy for bleeding control in severely injured trauma patients: two parallel randomized, placebo-controlled...particularly Factor VII level, in order that all of us could help learn the ideal plasma to red cell ratio by science rather than by some gestalt ? Dr. Slate

  13. Increased mortality in systemic inflammatory response syndrome patients with high levels of coagulation factor VIIa

    NARCIS (Netherlands)

    Hyseni, A.; Kemperman, H.; De Lange, D. W.; De Groot, P. G.; Linssen, M.; Kesecioglu, J.; Lisman, T.; Roest, M.

    2013-01-01

    BackgroundThe tissue factor (TF)- Factor VIIa (FVIIa) complex has a pivotal role in inflammatory and coagulation responses in patients with systemic inflammatory response syndrome (SIRS) and sepsis. Because zymogen FVII (FVII) and FVIIa compete for binding to TF, their plasma levels determine if a c

  14. Extensive small-angle X-ray scattering studies of blood coagulation factor VIIa reveal interdomain flexibility

    DEFF Research Database (Denmark)

    Mosbæk, Charlotte Rode; Nolan, David; Persson, Egon

    2010-01-01

    Blood coagulation factor VIIa (FVIIa) is used in the treatment of replacement therapy resistant hemophilia patients, and FVIIa is normally activated upon complex formation with tissue factor (TF), potentially in context with structural rearrangements. The solution behavior of uncomplexed FVIIa...

  15. Influence of Cardiopulmonary Bypass on the Interaction of Recombinant Factor VIIa with Activated Platelets

    OpenAIRE

    Kjalke, Marianne; Runge, Marx; Rojkjaer, Rasmus; Steinbruchel, Daniel; Johansson, Pär I

    2009-01-01

    Recombinant factor VIIa (rFVIIa) interacts preferentially with coated platelets characterized by a high exposure of phosphatidyl serine (PS), FV, FVIII, FIX, and FX binding, and fibrinogen. Cardiopulmonary bypass (CPB) is known to impair platelet function. In this study, the influence of CPB on formation of coated platelets and the interaction of rFVIIa with the platelets were studied. Blood was either exposed to a closed CPB circuit or obtained from patients undergoing CPB-assisted cardiac s...

  16. Synthesis and P1' SAR exploration of potent macrocyclic tissue factor-factor VIIa inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Ladziata, Vladimir (Uladzimir); Glunz, Peter W.; Zou†, Yan; Zhang, Xiaojun; Jiang, Wen; Jacutin-Porte, Swanee; Cheney, Daniel L.; Wei, Anzhi; Luettgen, Joseph M.; Harper, Timothy M.; Wong, Pancras C.; Seiffert, Dietmar; Wexler, Ruth R.; Priestley, E. Scott (BMS)

    2016-10-01

    Selective tissue factor-factor VIIa complex (TF-FVIIa) inhibitors are viewed as promising compounds for treating thrombotic disease. In this contribution, we describe multifaceted exploratory SAR studies of S1'-binding moieties within a macrocyclic chemotype aimed at replacing cyclopropyl sulfone P1' group. Over the course of the optimization efforts, the 1-(1H-tetrazol-5-yl)cyclopropane P1' substituent emerged as an improved alternative, offering increased metabolic stability and lower clearance, while maintaining excellent potency and selectivity.

  17. Crystallization and preliminary crystallographic data for a ternary complex between tissue factor, factor VIIa and a BPTI-derived inhibitor

    Science.gov (United States)

    Stura, Enrico A.; Ruf, Wolfram; Wilson, Ian A.

    1996-10-01

    The binding of tissue factor (TF) with the serine protease coagulation factor VIIa (VIIa) is the initial trigger for activation of the coagulation protease cascades. In complex with TF, VIIa has profoundly enhanced function in the limited proteolytic activation of the natural substrate factors X and IX. Here we report the screening and identification of crystallization conditions to produce diffraction quality crystals of the complex between TF · VIIa and a potent inhibitor (5L 15) derived from mutagenesis of the bovine pancreatic trypsin inhibitor (BPTI) sequence. The complex crystals were obtained from the soluble extracellular domain of tissue factor, expressed in Escherichia coli as a fusion protein, VIIa expressed in mammalian cells and recombinant 5L15. Because only 1.5 mg of complex were available for this work, a reverse screening based strategy was used in the search and optimization of the crystallization conditions. Two different crystal forms were obtained from polyethylene glycol 4000 and monomethyl polyethylene glycol 2000 with cacodylate buffer at pH 6.5 in the presence of sodium and calcium ions. The addition of magnesium and zinc have profound effects on the crystallization. Both crystal forms are trigonal with cell parameters a = b = 129.3 Å, c = 110.8 Å and a = b = 67.2 Å, c = 314.8 Å diffracting to 7 and 3.2 Å resolution, respectively, each with one molecule in the asymmetric unit. Complete data sets have been collected from each of these forms to the resolution to which the crystals diffract. A structural understanding of the interaction of VIIa with its cofactor TF to form a binary enzyme, and its inhibition by 5L15 will provide a basis for the development of antithrombotic strategies.

  18. A combined structural dynamics approach identifies a putative switch in factor VIIa employed by tissue factor to initiate blood coagulation

    DEFF Research Database (Denmark)

    Olsen, Ole H; Rand, Kasper D; Østergaard, Henrik;

    2007-01-01

    Coagulation factor VIIa (FVIIa) requires tissue factor (TF) to attain full catalytic competency and to initiate blood coagulation. In this study, the mechanism by which TF allosterically activates FVIIa is investigated by a structural dynamics approach that combines molecular dynamics (MD...

  19. Off-label use of recombinant factor VIIa for treatment of haemorrhage: results from randomized clinical trials

    DEFF Research Database (Denmark)

    Johansson, Per Ingemar

    2008-01-01

    Background Recombinant factor VIIa (rFVIIa) is used for haemophilic patients with inhibitors against coagulation factor VIII or IX, but there is also an off-label use of rFVIIa for patients with massive bleeding. The aim of the present study was to review the randomized clinical trials (RCT...

  20. Recombinant factor VIIa improves clot formation but not fibrolytic potential in patients with cirrhosis and during liver transplantation

    NARCIS (Netherlands)

    Lisman, T; Leebeek, FWG; Meijer, K; Van Der Meer, J; Nieuwenhuis, HK; De Groot, PG

    2002-01-01

    Cirrhosis is associated with a bleeding tendency, which is particularly pronounced during orthotopic liver transplantation (OLT). A novel approach to treating the bleeding diathesis of patients with cirrhosis is administration of recombinant factor VIIa (rFVIIa). This study examined whether the effi

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

    DEFF Research Database (Denmark)

    Bladbjerg, Else-Marie; Jespersen, Jørgen

    2008-01-01

    , but no effects on clotting time indicating that haemodilution does not affect clot formation, but the clot formed at high haemodilution may not be so firm. In conclusion, the activity of recombinant activated factor VII was affected in vitro by pH, temperature, and haemodilution. Additional studies are necessary...... investigated the in-vitro effects of pH, temperature, and haemodilution on the activity of recombinant activated factor VII. Samples from eight healthy volunteers were spiked with recombinant activated factor VII (final concentration 1.7 microg/ml) and adjusted to pH 6.0, 6.5, 7.0, and 7.4 or analysed at 30...... activity in plasma. Significant effects of pH were observed for clotting time, clot formation time, maximum clot firmness, and factor VII coagulant activity in the direction of longer clot formation times and less firm clots with decreasing pH. Temperature had significant effects on clotting time, clot...

  2. Human recombinant factor VIIa may improve heat intolerance in mice by attenuating hypothalamic neuronal apoptosis and damage.

    Science.gov (United States)

    Hsu, Chuan-Chih; Chen, Sheng-Hsien; Lin, Cheng-Hsien; Yung, Ming-Chi

    2014-10-01

    Intolerance to heat exposure is believed to be associated with hypothalamo-pituitary-adrenocortical (HPA) axis impairment [reflected by decreases in blood concentrations of both adrenocorticotrophic-hormone (ACTH) and corticosterone]. The purpose of this study was to determine the effect of human recombinant factor VIIa (rfVIIa) on heat intolerance, HPA axis impairment, and hypothalamic inflammation, ischemic and oxidative damage, and apoptosis in mice under heat stress. Immediately after heat stress (41.2 °C for 1 h), mice were treated with vehicle (1 mL/kg of body weight) or rfVIIa (65-270 µg/kg of body weight) and then returned to room temperature (26 °C). Mice still alive on day 4 of heat exposure were considered survivors. Cellular ischemia markers (e.g., glutamate, lactate-to-pyruvate ratio), oxidative damage markers (e.g., nitric oxide metabolite, hydroxyl radials), and pro-inflammatory cytokines (e.g., interleukin-6, interleukin-1β, tumor necrosis factor-α) in hypothalamus were determined. In addition, blood concentrations of both ACTH and corticosterone were measured. Hypothalamic cell damage was assessed by determing the neuronal damage scores, whereas the hypothalamic cell apoptosis was determined by assessing the numbers of cells stained with terminal deoxynucleotidyl transferase-mediated αUTP nick-end labeling, caspase-3-positive cells, and platelet endothelial cell adhesion molecula-1-positive cells in hypothalamus. Compared with vehicle-treated heated mice, rfVIIa-treated heated mice had significantly higher fractional survival (8/10 vs 1/10), lesser thermoregulatory deficit (34.1 vs 24.8 °C), lesser extents of ischemic, oxidative, and inflammatory markers in hypothalamus, lesser neuronal damage scores and apoptosis in hypothalamus, and lesser HPA axis impairment. Human recombinant factor VIIa appears to exert a protective effect against heatstroke by attenuating hypothalamic cell apoptosis (due to ischemic, inflammatory, and oxidative damage

  3. Use of recombinant factor VIIa for emergency reversal of anticoagulation

    Directory of Open Access Journals (Sweden)

    Ingerslev J

    2007-01-01

    Full Text Available Context: There is limited data regarding the use of activated recombinant factor VII (rFVIIa in anticoagulated patients requiring reversal. Aims: To identify and describe characteristics of subjects who received rFVIIa as part of emergency treatment aimed at improving hemostasis. Settings and Design: Data was obtained from an international peer-reviewed registry haemostasis.com. This registry contains data reported by physicians, who had elected to use rFVIIa to control bleeding in an emergency clinical situation. The contributors′ approval for inclusion in the study was obtained and they were requested to validate and update information. Materials and Methods: Database review of cases receiving rFVIIa to manage bleeding coherent with the use of anticoagulant therapy. Statistical Analysis: The Wilcoxon signed rank test was used to compare requirements for blood products and crystalloids/colloids during the 24h preceding and following rFVIIa administration, as well as changes in the levels of clotting factors during that period. Results: Eighteen patients were treated with rFVIIa (median dose: 87.35 µg/kg; range: 20.0-106.0 µg/kg for bleeding. Anticoagulants requiring reversal included low-molecular-weight heparin (n = 6, unfractionated heparin (n =8, coumarin (n =3 and warfarin (n=1. All patients had failed to respond to traditional antidotes and blood products. Following administration, bleeding stopped in 10, markedly decreased in five and slowed in the remaining three. Amongst 12/16 patients, a response was observed within 2.0 h of first administration. The requirement for blood products and crystalloids/colloids decreased ( P < 0.05 after rFVIIa administration. rFVIIa was well tolerated. Conclusions: rFVIIa may play a role in control of untoward bleeding in subjects receiving anticoagulation therapy.

  4. [Treatment of life-threatening bleeding in obstetrics and gynaecology --NovoSeven (recombinant factor VIIa)].

    Science.gov (United States)

    Nikolov, A; Dimitrov, A; Tanchev, S; Platikanov, V; Nacheva, A; Gateva, Zh; Gerganova, A

    2005-01-01

    The study offers the results from the application of recombinant factor VIIa (NovoSeven) in 19 patients with obstetric or gynaecological problems showing severe haemorrhage of non-surgical origin, which could not be controlled by standard therapy (surgery and resuscitation). Haematological and haemostaseological values as well as final outcome are being monitored. The role of the drug and its special indications in complex urgent treatment of life-threatening bleeding are being discussed. Conclusions. The use of NovoSeven (recombinant factor Vlla) on time and when indicated guarantees rapid and effective haemostasis. Thus laparotomy or relaparotomy can be avoided. If no effect is observed after the application of NovoSeven indicates bleeding from a major blood vessel, demanding laparotomy and surgery. The use of the drug leads to reducing the incidence of blood derivatives transfusions and (being a recombinant product)--no risk of transmissive infections.

  5. Postpartum hemorrhage in a Jehovah's Witness patient controlled with Tisseel, tranexamic acid, and recombinant factor VIIa.

    Science.gov (United States)

    Arab, Tarek Samir; Al-Wazzan, Ahmad Bakr; Maslow, Ken

    2010-10-01

    The management of a patient refusing blood transfusion who subsequently experiences a severe postpartum hemorrhage is a particular clinical challenge. A 30-year-old nulliparous patient (who was a Jehovah's Witness) had labour induced for post-dates at 41+4 weeks' gestational age after an uncomplicated pregnancy. She delivered by Caesarean section for dystocia and suspected chorioamnionitis, and subsequently developed postpartum hemorrhage that required management with oxytocin, ergometrine, carboprost, uterine artery ligation, and Hayman compression sutures. The patient ultimately required two additional visits to the operating room, culminating in hysterectomy. Use of tranexamic acid, recombinant factor VIIa, and Tisseel was instrumental in halting the ongoing hemorrhage. Optimal management of a patient refusing administration of blood products requires a multidisciplinary approach as well as a combination of traditional and novel therapies.

  6. Effect of recombinant Factor VIIa on outcome of acute variceal bleeding

    DEFF Research Database (Denmark)

    Bendtsen, Flemming; D'Amico, Gennaro; Rusch, Ea;

    2014-01-01

    BACKGROUND & AIMS: Two randomized controlled studies have evaluated the effect of recombinant Factor VIIa (rFVIIa) on variceal bleeding in cirrhosis without showing significant benefit. The aim of the present study was to perform a meta-analysis of the two trials on individual patient data...... vasoactive drug infusion and Child-Pugh score >8. RESULTS: 497 patients were eligible for the meta-analysis; 308 (62%) had active variceal bleeding at endoscopy (oozing or spurting) and 283 of these had a Child-Pugh score >8. Analysis on the composite endpoint in all patients with bleeding from oesophageal...... varices did not show any beneficial treatment effect. However, failure rate for the primary composite end-point was significantly lower in treated patients with active bleeding at endoscopy (17%) compared to placebo (26%, p=0.049). This difference was highly significant in patients with Child-Pugh score...

  7. Activation of coagulation by administration of recombinant factor VIIa elicits interleukin 6 (IL-6) and IL-8 release in healthy human subjects

    National Research Council Canada - National Science Library

    Jonge, de, E; Friederich, P.W; Vlasuk, G.P; Rote, W; Vroom, M.B; Levi, M.M; Poll, van der, T

    2003-01-01

    .... Here we report that the activation of coagulation in healthy human subjects by the administration of recombinant factor VIIa also elicits a small but significant increase in the concentrations of interleukin 6 (IL-6) and IL-8 in plasma...

  8. Protein anticoagulants targeting factor VIIa-tissue factor complex: a comprehensive review.

    Science.gov (United States)

    Shah, Karna; Bayoumi, Riad; Banerjee, Yajnavalka

    2013-01-01

    Anticoagulants are pivotal for the treatment of debilitating thromboembolic and associated disorders. Current anticoagulants such as heparin and warfarin are non-specific and have a narrow therapeutic window. These limitations have provided the impetus to develop new anticoagulant therapies/strategies that target specific factors in the blood coagulation cascade, ideally those located upstream in the clotting process. Factor VIIa (FVIIa) presents an attractive target as it, in complex with tissue factor (TF), acts as the prima ballerina for the formation of blood clot. A comprehensive review delineating the structure-activity relationship of protein/peptide anticoagulants targeting FVIIa or TF-FVIIa complex is absent in the literature. In this article, we have addressed this deficit by appraising the peptide/protein anticoagulants that target FVIIa/TF-FVIIa complex. Further, the current status of these anticoagulants, with regard to their performance in different clinical trials has also been presented. Lastly, the unexplored domains of these unique proteins have also been highlighted, which will facilitate further translational research in this paradigm, to improve strategies to counter and treat thromboembolic disorders.

  9. The Clinical and Laboratory Response to Recombinant Factor VIIa in Trauma and Surgical Patients with Acquired Coagulopathy

    Science.gov (United States)

    2006-08-01

    triad” of hypothermia, acidosis, and coagulopathy poses a significant problem in the care of critically ill surgical patients. The sequential and...coagulopathy. In 1990, recombinant factor VIIa (rFVIIa, Novoseven; Novo Nordisk, Bagsvaerd, Denmark) was introduced for the treatment of hemophilia ...No complications were attributable to the administration of rFVIIa. All but 1 patient in this series was determined to be free of continued

  10. Successful Treatment of Intractable Hemothorax with Recombinant Factor VIIa in a Nonhemophilic Patient

    Directory of Open Access Journals (Sweden)

    Yu-Feng Wei

    2006-01-01

    Full Text Available Recombinant factor VIIa (rFVIIa was developed for the treatment of bleeding in hemophilic patients with inhibitors. It has also been used to stop bleeding in nonhemophilic patients who fail to respond to conventional treatment. We report a case of catastrophic hemothorax in which bleeding was stopped by administration of rFVIIa. A 68-year-old woman with chronic hepatitis C-related liver cirrhosis was admitted due to pneumonia and parapneumonic effusion. The patient developed hemothorax and hypovolemic shock after thoracentesis. Conventional therapies including tube thoracostomy and transarterial embolization failed to stop the life-threatening bleeding. The bleeding stopped after administration of rFVIIa 100 μg/kg/BW at 2-hour intervals for a total of two doses on the 3rd day of hospitalization. Despite intensive care, however, the patient died due to nosocomial infection and multiple organ failure on the 12th day of hospitalization. Hemothorax in a nonhemophilic patient can be successfully treated with rFVIIa.

  11. Effects of calcium signaling on coagulation factor VIIa-induced proliferation and migration of the SW620 colon cancer cell line.

    Science.gov (United States)

    Wu, Ying; Wang, Jing; Zhou, Hong; Yu, Xiaoyan; Hu, Lichao; Meng, Fanlu; Jiang, Shuanghong

    2014-12-01

    Tissue factor (TF)/VIIa/protease‑activated receptor 2 (PAR2) has been shown to trigger the ERK1/2 signaling pathway. This was shown to be closely associated with the proliferation and migration of SW620 colon cancer cells; however, the detailed mechanisms remain unclear. The aim of the present study was to elucidate the effects of calcium signaling on the proliferation and migration of SW620 cells induced by coagulation factor VIIa. The results demonstrated that VIIa and PAR2 agonist PAR2‑AP increased [Ca2+]i in SW620 cells. In addition, VIIa‑and PAR2‑AP‑induced ERK1/2 activation was inhibited by thapsigargin (TG)‑induced depletion of intracellular Ca2+ stores and EGTA‑mediated removal of extracellular Ca2+. It was also identified that VIIa and PAR2‑AP‑induced proliferation and migration of SW620 cells was modulated by EGTA and TG. Taken together, the present results indicate that VIIa triggers calcium signaling in SW620 cells, in a TF‑dependent manner, which is critical for VIIa‑induced ERK1/2 activation in SW620 cells. These results suggested that calcium signaling had a vital role in the proliferation and migration of SW620 cells.

  12. The M358R variant of α(1)-proteinase inhibitor inhibits coagulation factor VIIa.

    Science.gov (United States)

    Sheffield, William P; Bhakta, Varsha

    2016-02-12

    The naturally occurring M358R mutation of the plasma serpin α1-proteinase inhibitor (API) changes both its cleavable reactive centre bond to Arg-Ser and the efficacy with which it inhibits different proteases, reducing the rate of inhibition of neutrophil elastase, and enhancing that of thrombin, factor XIa, and kallikrein, by several orders of magnitude. Although another plasma serpin with an Arg-Ser reactive centre, antithrombin (AT), has been shown to inhibit factor VIIa (FVIIa), no published data are available with respect to FVIIa inhibition by API M358R. Recombinant bacterially-expressed API M358R and plasma-derived AT were therefore compared using gel-based and kinetic assays of FVIIa integrity and activity. Under pseudo-first order conditions of excess serpin over protease, both AT and API M358R formed denaturation-resistant inhibitory complexes with FVIIa in reactions accelerated by TF; AT, but not API M358R, also required heparin for maximal activity. The second order rate constant for heparin-independent API M358R-mediated FVIIa inhibition was determined to be 7.8 ± 0.8 × 10(2) M(-1)sec(-1). We conclude that API M358R inhibits FVIIa by forming inhibitory complexes of the serpin type more rapidly than AT in the absence of heparin. The likely 20-fold excess of API M358R over AT in patient plasma during inflammation raises the possibility that it could contribute to the hemorrhagic tendencies manifested by rare individuals expressing this mutant serpin.

  13. Myosin VIIA, important for human auditory function, is necessary for Drosophila auditory organ development.

    Directory of Open Access Journals (Sweden)

    Sokol V Todi

    Full Text Available BACKGROUND: Myosin VIIA (MyoVIIA is an unconventional myosin necessary for vertebrate audition [1]-[5]. Human auditory transduction occurs in sensory hair cells with a staircase-like arrangement of apical protrusions called stereocilia. In these hair cells, MyoVIIA maintains stereocilia organization [6]. Severe mutations in the Drosophila MyoVIIA orthologue, crinkled (ck, are semi-lethal [7] and lead to deafness by disrupting antennal auditory organ (Johnston's Organ, JO organization [8]. ck/MyoVIIA mutations result in apical detachment of auditory transduction units (scolopidia from the cuticle that transmits antennal vibrations as mechanical stimuli to JO. PRINCIPAL FINDINGS: Using flies expressing GFP-tagged NompA, a protein required for auditory organ organization in Drosophila, we examined the role of ck/MyoVIIA in JO development and maintenance through confocal microscopy and extracellular electrophysiology. Here we show that ck/MyoVIIA is necessary early in the developing antenna for initial apical attachment of the scolopidia to the articulating joint. ck/MyoVIIA is also necessary to maintain scolopidial attachment throughout adulthood. Moreover, in the adult JO, ck/MyoVIIA genetically interacts with the non-muscle myosin II (through its regulatory light chain protein and the myosin binding subunit of myosin II phosphatase. Such genetic interactions have not previously been observed in scolopidia. These factors are therefore candidates for modulating MyoVIIA activity in vertebrates. CONCLUSIONS: Our findings indicate that MyoVIIA plays evolutionarily conserved roles in auditory organ development and maintenance in invertebrates and vertebrates, enhancing our understanding of auditory organ development and function, as well as providing significant clues for future research.

  14. Cost effectiveness of recombinant factor VIIa for treatment of intracerebral hemorrhage

    Directory of Open Access Journals (Sweden)

    Eckman Mark H

    2008-05-01

    Full Text Available Abstract Background Phase I/II placebo-controlled clinical trials of recombinant Factor VIIa (rFVIIa suggested that administration of rFVIIa within 4 hours after onset of intracerebral hemorrhage (ICH is safe, limits ICH growth, and improves outcomes. We sought to determine the cost-effectiveness of rFVIIa for acute ICH treatment, using published Phase II data. We hypothesized that rFVIIa would have a low marginal cost-effectiveness ratio (mCER given the poor neurologic outcomes after ICH with conventional management. Methods We performed an incremental cost-effectiveness analysis from the societal perspective, considering conventional management vs. 80 ug/kg rFVIIa treatment for acute ICH cases meeting Phase II inclusion criteria. The time frame for the analysis was 1. 25 years: data from the Phase II trial was used for 90 day outcomes and rFVIIa complications – arterial thromboembolic events (ATE. We assumed no substantial cost differences in care between the two strategies except: 1 cost of rFVIIa (for an 80 mcg/kg dose in an 80 kg patient, assumed cost of $6,408; 2 cost of ATE side effects from rFVIIa (which also decrease quality of life and increase the chance of death; and 3 differential monetary costs of outcomes and their impact on quality of life, including disposition (home vs. nursing home, and outpatient vs. inpatient rehabilitation. Sensitivity analyses were performed to explore uncertainty in parameter estimates, impact of rFVIIa cost, direct cost of neurologic outcomes, probability of ATE, and outcomes after ATE. Results In the "base case", treating ICH with rFVIIa dominates the usual care strategy by being more effective and less costly. rFVIIa maintained a mCER Conclusion Based on data from preliminary trials, treating selected ICH patients with rFVIIa results in lower cost and improved clinical outcomes. This potential cost-effectiveness must be considered in light of the Phase III trial results.

  15. Cargo binding activates myosin VIIA motor function in cells.

    Science.gov (United States)

    Sakai, Tsuyoshi; Umeki, Nobuhisa; Ikebe, Reiko; Ikebe, Mitsuo

    2011-04-26

    Myosin VIIA, thought to be involved in human auditory function, is a gene responsible for human Usher syndrome type 1B, which causes hearing and visual loss. Recent studies have suggested that it can move processively if it forms a dimer. Nevertheless, it exists as a monomer in vitro, unlike the well-known two-headed processive myosin Va. Here we studied the molecular mechanism, which is currently unknown, of activating myosin VIIA as a cargo-transporting motor. Human myosin VIIA was present throughout cytosol, but it moved to the tip of filopodia upon the formation of dimer induced by dimer-inducing reagent. The forced dimer of myosin VIIA translocated its cargo molecule, MyRip, to the tip of filopodia, whereas myosin VIIA without the forced dimer-forming module does not translocate to the filopodial tips. These results suggest that dimer formation of myosin VIIA is important for its cargo-transporting activity. On the other hand, myosin VIIA without the forced dimerization module became translocated to the filopodial tips in the presence of cargo complex, i.e., MyRip/Rab27a, and transported its cargo complex to the tip. Coexpression of MyRip promoted the association of myosin VIIA to vesicles and the dimer formation. These results suggest that association of myosin VIIA monomers with membrane via the MyRip/Rab27a complex facilitates the cargo-transporting activity of myosin VIIA, which is achieved by cluster formation on the membrane, where it possibly forms a dimer. Present findings support that MyRip, a cargo molecule, functions as an activator of myosin VIIA transporter function.

  16. Thromboembolic risks of recombinant factor VIIa Use in warfarin-associated intracranial hemorrhage: a case–control study

    Directory of Open Access Journals (Sweden)

    H-Y Chou Sherry

    2012-12-01

    Full Text Available Abstract Background Recombinant factor VIIa (rFVIIa may be used for rapid hemostasis in life-threatening hemorrhage. In warfarin-associated intracerebral hemorrhage (wICH, FVIIa use is controversial and may carry significant thromboembolic risks. We compared incidence of baseline thromboembolic risk factors and thromboembolism rates in wICH patients treated with additional rFVIIa to those treated with standard therapy of fresh frozen plasma (FFP and vitamin K alone. Methods We identified 45 consecutive wICH patients treated with additional rFVIIa over 5-year period, and 34 consecutive wICH patients treated with standard therapy alone as comparison group. We compared the incidence of post-hemorrhage cardiac and extra-cardiac thromboembolic complications between two treatment groups, and used logistic regression to adjust for significant confounders such as baseline thromboembolic risk factors. We performed secondary analysis comparing the quantity of FFP transfused between two treatment cohorts. Results Both rFVIIa-treated and standard therapy-treated wICH patients had a high prevalence of pre-existing thromboembolic diseases including atrial fibrillation (73% vs 68%, deep venous thrombosis (DVT or pulmonary embolism (PE (22% vs 18%, coronary artery disease (CAD (38% vs 32%, and abnormal electrocardiogram (EKG (78% vs 85%. Troponin elevation following wICH was prevalent in both groups (47% vs 41%. Clinically significant myocardial infarction (MI, defined as troponin > 1.0 ng/dL, occurred in 13% of rFVIIa-treated and 6% of standard therapy-treated patients (p=0.52. Past history of CAD (p=0.0061 and baseline abnormal EKG (p=0.02 were independently associated with clinically significant MI following wICH while rFVIIa use was not. The incidences of DVT/PE (2% vs 9%; p=0.18 and ischemic stroke (2% vs 0%; p=0.38 were similar between two treatment groups. Recombinant FVIIa-treated patients had lower mean INR at 3 (p=0.0001 and 6 hours (p Conclusions Pre

  17. Recombinant Factor VIIa Reduces Bleeding after Blunt Liver Injury in a Pig Model of Dilutional Coagulopathy under Severe Hypothermia.

    Directory of Open Access Journals (Sweden)

    Henri M H Spronk

    Full Text Available Recombinant factor VIIa (rFVIIa is registered for use in haemophilia with inhibitors and other rare bleeding disorders, but has also been used in various other clinical conditions to terminate life-threatening bleeding. Underlying conditions (e.g. coagulopathy and dosing may affect treatment efficacy. The objective of the present study was to evaluate the impact of increasing doses of rFVIIa on blood loss and coagulation assays in haemodiluted and hypothermic pigs undergoing blunt liver injury.A grade III blunt liver injury was induced in 28 pigs after 70% haemodilution and cooling to 32.6-33.4°C. Ten minutes after trauma, animals randomly received placebo or 90, 180 or 360 μg/kg rFVIIa. Global coagulation parameters, thromboelastometry (TEM and plasma thrombin generation (TG were determined at different time points during the observation period of 120 minutes.Total blood loss was significantly lower following 90 μg/kg rFVIIa (1206 [1138-1470] mL relative to placebo (2677 [2337-3068] mL; p<0.05, with no increased effect with higher dose levels of rFVIIa. Following trauma and haemodilution, coagulation was impaired relative to baseline in both TEM and TG analysis. At 60 and 120 minutes after trauma, TEM variables improved in the rFVIIa-treated animals compared with the placebo group. Similarly, rFVIIa improved coagulation kinetics in TG. As was observed with blood loss, no significant effect between different rFVIIa dose levels was found in TEM or TG. Macro- and microscopic post-mortem examination did not reveal any signs of thromboembolic events.Early administration of 90 μg/kg rFVIIa reduced blood loss in pigs undergoing blunt liver injury even after severe haemodilution and hypothermia, with no further effect of higher dose levels. Coagulation assays showed impaired coagulation in coagulopathic animals, with a dose-independent improvement in animals treated with rFVIIa.

  18. Dabigatran and its reversal with recombinant factor VIIa and prothrombin complex concentrate

    DEFF Research Database (Denmark)

    Sølbeck, Sacha; Nilsson, Caroline U; Engström, Martin

    2014-01-01

    different Sonoclot cuvettes: Glassbead, kaolin and tissue factor (diluted) activated. RESULTS: The Sonoclot detected in vitro-induced anticoagulation due to dabigatran with the glassbead- and kaolin-activated cuvettes. There was no reversing effect of PCC, probably due to the presence of heparin in the PCC...

  19. Recombinant factor VIIa (NovoSeven) as a hemostatic agent after surgery for congenital heart disease.

    Science.gov (United States)

    Razon, Yaron; Erez, Eldad; Vidne, Bernardo; Birk, Einat; Katz, Jacob; Tamari, Hanna; Dagan, Ovadia

    2005-03-01

    Postoperative bleeding and blood product requirements can be substantial in children undergoing open-heart surgery, and reexploration is required in 1% of cases. Recombinant activated factor VII (rFVIIa, NovoSeven, NovoNordisk, Denmark) is a hemostatic agent approved for the treatment of hemophilic patients with inhibitors to factor VIII or factor IX. It has also been used with success in other conditions. We present our experience with rFVIIa treatment for uncontrolled bleeding after open-heart surgery in five pediatric patients. The study group consisted of five patients after open-heart surgery with excessive blood loss. The patients were treated with rFVIIa after failure of conventional treatment to control the bleeding. Blood loss, blood product consumption, and coagulation test results were recorded before and after rFVIIa administration. In all cases, blood loss decreased considerably after rFVIIa administration (mean 7.8 ml x kg(-1) x h(-1)), almost eliminating the need for additional blood products, and the prolonged prothrombin time normalized. In two patients with thrombocytopathy, rFVIIa helped to discriminate surgical bleeding from bleeding caused by a defect in hemostasis. No side effects of rFVIIa treatment were noted. These cases support the impression that RFVIIa is efficient and safe in correcting hemostasis in children after cardiopulmonary bypass when other means fail. However, the data are still limited, and more extensive research is needed.

  20. A severe deficiency of coagulation factor VIIa results in attenuation of the asthmatic response in mice.

    Science.gov (United States)

    Shinagawa, Kazuhiko; Ploplis, Victoria A; Castellino, Francis J

    2009-05-01

    Eosinophil counts in the bronchoalveolar lavage fluid of wild-type (WT) mice increased after ovalbumin (OVA) challenge, a response that was diminished in comparably challenged low-expressing coagulation factor VII (FVII(tTA/tTA)) mice. Levels of T helper type 2 (Th2) cytokines, IL-4, IL-5, and IL-13, and eosinophil-attracting chemokines, eotaxin and RANTES, were also lower in the OVA-challenged FVII(tTA/tTA) mice. Eosinophils purified from low-FVII mice underwent apoptosis at a faster rate compared with WT eosinophils, and eosinophil migration in response to eotaxin was reduced in eosinophils obtained from FVII(tTA/tTA) mice. Airway hyperresponsiveness and mucous layer thickness were reduced in OVA-treated FVII(tTA/tTA) mice, and addition of exogenous coagulation factor X (FX) enhanced mucin production in human epithelial NCI-H292 cells. Correspondingly, incubation of FX with NCI-H292 cells resulted in activated (a) FX production, suggesting that the components required for FX activation were present on NCI-H292 cells. These results demonstrate that FVIIa functions in the asthmatic response to an allergen by stimulating lung eosinophilia, airway hyperresponsiveness, and mucin production, this latter effect through its ability to activate FX in conjunction with tissue factor.

  1. Recombinant factor VIIa for variceal bleeding in patients with advanced cirrhosis: A randomized, controlled trial

    DEFF Research Database (Denmark)

    Bosch, Jaime; Thabut, Dominique; Albillos, Agustín;

    2008-01-01

    A beneficial effect of recombinant activated factor VII (rFVIIa) in Child-Pugh class B and C patients with cirrhosis who have variceal bleeding has been suggested. This randomized controlled trial assessed the efficacy and safety of rFVIIa in patients with advanced cirrhosis and active variceal...... events, were comparable between groups. CONCLUSION: Treatment with rFVIIa had no significant effect on the primary composite endpoint compared with placebo. Therefore, decision on the use of this hemostatic agent in acute variceal bleeding should be carefully considered, because results of this study do...

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    of the selective active site in defining specificity. Being a trypsin-like serine protease, FVIIa had P1 specificity exclusively towards arginine and lysine residues. In the S2 pocket, threonine, leucine, phenylalanine and valine residues were the most preferred amino acids. Both S3 and S4 appeared to be rather...... promiscuous, however, with some preference for aromatic amino acids at both positions. Interestingly, a significant degree of interdependence between the S3 and S4 was observed and, as a consequence, the optimal substrate for FVIIa could not be derived directly from a subsite-directed specificity screen...... for FVIIa by marked changes in primary substrate specificity and decreased rates of antithrombin III inhibition. Interestingly, these changes do not necessarily coincide with an altered ability to activate Factor X, demonstrating that inhibitor and macromolecular substrate selectivity may be engineered...

  3. Recombinant factor VIIa in post-partum hemorrhage: A new weapon in obstetrician′s armamentarium

    Directory of Open Access Journals (Sweden)

    Navneet Magon

    2012-01-01

    Full Text Available Post-partum hemorrhage (PPH is a life-threatening obstetric complication and the leading cause of maternal death. The usual manner for its management includes, first, noninvasive and nonsurgical methods, and, then invasive and surgical methods. However, mortality and morbidity related to PPH still remains unacceptably high, contributing to hysterectomy in at least 50% of cases. Early, effective, and preferably noninvasive treatments that can reduce maternal mortality and morbidity due to this entity are therefore essential. One of the most spectacular advancements in the control of PPH has been the use of recombinant activated factor (rFVIIa, both as initial and a life- and uterus-saving therapy. rFVIIa also reduces costs of therapy and use of blood components in massive PPH. In cases of intractable bleeding with no other obvious indications for hysterectomy, administration of rFVIIa should be considered before surgery. A MEDLINE search was done to review relevant articles in English literature on use of rFVIIa in PPH. Data were constructed and issues were reviewed from there. Our experience in a series of three cases of PPH, two of atonic and one of traumatic, successfully managed using rFVIIa is also shared.

  4. Two coagulation factor X activators from Vipera a. ammodytes venom with potential to treat patients with dysfunctional factors IXa or VIIa.

    Science.gov (United States)

    Leonardi, Adrijana; Fox, Jay W; Trampus-Bakija, Alenka; Krizaj, Igor

    2008-10-01

    Two activators of coagulation factor X, 58kDa VAFXA-I and 70kDa VAFXA-II, were purified from the venom of long-nosed viper (Vipera ammodytes ammodytes) by chromatography on gel filtration, affinity, ion-exchange and hydroxyapatite media. Both enzymes are glycoproteins composed of a heavy chain and two C-type lectin-like light chains all joined by disulphide bonds. LC-MS and LC-MS/MS analysis of their tryptic fragments demonstrated that the heavy chain consists of three domains, metalloproteinase, disintegrin-like and cysteine-rich domains. The partial amino acid sequences of VAFXAs are very similar to those of the known factor X activators, RVV-X from Vipera russelli and VLFXA from Vipera lebetina venoms, as well as to other members of the reprolysin family of metalloproteinases. The VAFXAs activate factor X in a Ca(2+)-dependent manner with the same specificity as physiological activators. The activators weakly hydrolyzed insulin B-chain, fibrinogen and some components of the extracellular matrix in vitro, but did not activate prothrombin or plasminogen. VAFXAs inhibit collagen-induced platelet aggregation in vitro. They activate coagulation factor X to Xa without toxic effects. Their application in treating patients with dysfunctional factors IXa or VIIa to restore the normal blood coagulation process is thus promising.

  5. A Budget Impact Model of Hemophilia Bypassing Agent Prophylaxis Relative to Recombinant Factor VIIa On-Demand.

    Science.gov (United States)

    Mehta, Darshan A; Oladapo, Abiola O; Epstein, Joshua D; Novack, Aaron R; Neufeld, Ellis J; Hay, Joel W

    2016-02-01

    Hemophilia patients use factor-clotting concentrates (factor VIII for hemophilia A and factor IX for hemophilia B) for improved blood clotting. These products are used to prevent or stop bleeding episodes. However, some hemophilia patients develop inhibitors (i.e., the patient's immune system develops antibodies against these factor concentrates). Hence, these patients do not respond well to the factor concentrates. A majority of hemophilia patients with inhibitors are managed on-demand with the following bypassing agents: recombinant factor VIIa (rFVIIa) and activated prothrombin complex concentrate (aPCC). The recently published U.S. registries Dosing Observational Study in Hemophilia (DOSE) and Hemostasis and Thrombosis Research Society (HTRS) reported higher rFVIIa on-demand use for bleed management than previously described. To estimate aPCC and rFVIIa prophylaxis costs relative to rFVIIa on-demand treatment cost based on rFVIIa doses reported in U.S. registries. A literature-based cost model was developed assuming a base case on-demand annual bleed rate (ABR) of 28.7 per inhibitor patient, which was taken from a randomized phase 3 clinical trial. The doses for rFVIIa on-demand were taken from the median dose per bleed reported by the DOSE and HTRS registries. Model inputs for aPCC and rFVIIa prophylaxis (i.e., dosing and efficacy) were derived from respective randomized clinical trials. Cost analysis was from the U.S. payer perspective, and only direct drug costs were considered. The drug cost was based on the Medicare Part B 2014 average sale price (ASP). Two-way sensitivity and threshold analyses were performed by simultaneously varying on-demand ABR, prophylaxis efficacy, and unit drug cost. In addition to studying relative costs associated with on-demand and prophylaxis treatments, relative cost per bleeding episode avoided were also calculated for aPCC and rFVIIa prophylaxis treatments. The prophylaxis efficacy reported in the trials were used to

  6. The length of the linker between the epidermal growth factor-like domains in factor VIIa is critical for a productive interaction with tissue factor

    Science.gov (United States)

    Persson, Egon; Madsen, Jesper J; Olsen, Ole H

    2014-01-01

    Formation of the factor VIIa (FVIIa)-tissue factor (TF) complex triggers the blood coagulation cascade. Using a structure-based rationale, we investigated how the length of the linker region between the two epidermal growth factor (EGF)-like domains in FVIIa influences TF binding and the allosteric activity enhancement, as well as the interplay between the γ-carboxyglutamic acid (Gla)-containing and protease domains. Removal of two residues from the native linker was compatible with normal cofactor binding and accompanying stimulation of the enzymatic activity, as was extension by two (Gly-Ser) residues. In sharp contrast, truncation by three or four residues abolished the TF-mediated stabilization of the active conformation of FVIIa and abrogated TF-induced activity enhancement. In addition, FVIIa variants with short linkers associated 80-fold slower with soluble TF (sTF) as compared with wild-type FVIIa, resulting in a corresponding increase in the equilibrium dissociation constant. Molecular modeling suggested that the shortest FVIIa variants would have to be forced into a tense and energetically unfavorable conformation in order to be able to interact productively with TF, explaining our experimental observations. We also found a correlation between linker length and the residual intrinsic enzymatic activity of Ca2+-free FVIIa; stepwise truncation resulting in gradually higher activity with des(83–86)-FVIIa reaching the level of Gla-domainless FVIIa. The linker appears to determine the average distance between the negatively charged Gla domain and a structural element in the protease domain, presumably of opposite charge, and proximity has a negative impact on apo-FVIIa activity. PMID:25234571

  7. A novel supplemental approach to capturing post-marketing safety information on recombinant factor VIIa in acquired hemophilia: the Acquired Hemophilia Surveillance project

    Directory of Open Access Journals (Sweden)

    Lentz SR

    2014-01-01

    Full Text Available Steven R Lentz,1 Anand Tandra,2 Robert Z Gut,3 David L Cooper31Division of Hematology, Oncology and Blood and Marrow Transplantation, Department of Internal Medicine, University of Iowa, Iowa City, IA, USA; 2Hematology, Indiana Hemophilia and Thrombosis Center, Indianapolis, IN, USA; 3Clinical, Medical, and Regulatory Affairs, Novo Nordisk, Inc, Princeton, NJ, USAAcquired hemophilia (AH is a rare (incidence is 1 per 1.5 million but often severe bleeding disorder characterized by autoantibodies to coagulation factor VIII (FVIII. It is associated with life-threatening bleeding and ∼20% mortality.1,2 Recombinant factor VIIa (rFVIIa; NovoSeven® RT, Novo Nordisk A/S, Bagsværd, Denmark received an indication from the US Food and Drug Administration (FDA in October 2006 for the treatment of bleeding episodes and the prevention of bleeding in surgical interventions or invasive procedures in patients with AH.3View original paper by Collins and colleagues.

  8. Sites involved in intra- and interdomain allostery associated with the activation of factor VIIa pinpointed by hydrogen-deuterium exchange and electron transfer dissociation mass spectrometry.

    Science.gov (United States)

    Song, Hongjian; Olsen, Ole H; Persson, Egon; Rand, Kasper D

    2014-12-19

    Factor VIIa (FVIIa) is a trypsin-like protease that plays an important role in initiating blood coagulation. Very limited structural information is available for the free, inactive form of FVIIa that circulates in the blood prior to vascular injury and the molecular details of its activity enhancement remain elusive. Here we have applied hydrogen/deuterium exchange mass spectrometry coupled to electron transfer dissociation to pinpoint individual residues in the heavy chain of FVIIa whose conformation and/or local interaction pattern changes when the enzyme transitions to the active form, as induced either by its cofactor tissue factor or a covalent active site inhibitor. Identified regulatory residues are situated at key sites across one continuous surface of the protease domain spanning the TF-binding helix across the activation pocket to the calcium binding site and are embedded in elements of secondary structure and at the base of flexible loops. Thus these residues are optimally positioned to mediate crosstalk between functional sites in FVIIa, particularly the cofactor binding site and the active site. Our results unambiguously show that the conformational allosteric activation signal extends to the EGF1 domain in the light chain of FVIIa, underscoring a remarkable intra- and interdomain allosteric regulation of this trypsin-like protease. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Stellarator Wendelstein VII-AS; Physics and engineering design

    Energy Technology Data Exchange (ETDEWEB)

    Sapper, J.; Renner, H. (Max-Planck-Institut fuer Plasmaphysik, Garching (Germany, F.R.))

    1990-01-01

    The advanced stellarator Wendelstein VII-AS is a medium-sized experimental machine with the following properties and aims: a broadly optimized magnetic configuration with improved plasma equilibrium and smaller neoclassical transport losses compared to classical stellarators; operation with net-current-free plasma; field generation with a modular set of coils instead of the conventional helix/toroidal field coil; system; and good access for plasma heating methods, e.g., neutral beam injection, electron cyclotron heating, and ion cyclotron heating. The physics characteristics and the engineering design of the experiment as well as results from the initial operation period are reported.

  10. RECOMBINANT FACTOR VIIa – NEW TREATMENT OPTION FOR CONTROL OF INTRACTABLE BLEEDING IN SURGICAL AND TRAUMA PATIENTS AND IN OTHER HAEMOSTASIS DISORDERS

    Directory of Open Access Journals (Sweden)

    Samo Zver

    2004-12-01

    Full Text Available Background. Recombinant factor VIIa (rFVIIa, which is currently registered only for the treatment of haemophilia A and B patients with inhibitors, is seen increasingly as a possible universal haemostatic agent in untractable bleedings. One possible mechanism for the efficacy rFVIIa may be a consequence of it’s from the tissue factor (TF and from the level of disfunction in haemostatic system independant activity, which generates »thrombin burst« formation. It seems that rFVIIa remains active only at the site of tissue injury/bleeding.Conclusions. There are two components of bleeding in surgery and trauma patients. One is bleeding from large calibre arteries and veins which requires surgical intervention. The other, which goes along with the first one, is coagulopathic bleeding. The latter is a consequence of consumptional and dilutional coagulopathy, hypothermia, multitransfusion syndrom and metabolic disbalances in patients. rFVIIa effects coagulopathic component of the bleeding. For effective treatment with rFVIIa in such patients, replacement therapy with erythrocytes, platelets and fresh frozen plasma is mandatory and requires a haematologist assistance in the treatment strategy.Most reported cases of effective rFVIIa usage are from the field of traumatology. Until now, there have been no universal recommendations when to start treatment with rFVIIa in a bleeding trauma patient. Most experience with rFVIIa are from Israel and their recommendations are perhaps the most valuable ones. rFVIIa was used several times during intra-operative and post-operative bleeding episodes. There are reports of clinical studies and usage in patients with/ after prostate surgery, cardiovascular operations and liver transplants.There are data about effective rFVIIa usage in neurology and neurosurgery patients (intracranial haemorrhages, obstetrics and gynecology field. Possible future indications are thrombocytopenias, thrombocytopathias (Glanzmann

  11. Recombinant Activated Factor VIIa (rFVIIa) Treatment in Very-Low-Birth-Weight (VLBW) Premature Infants with Acute Pulmonary Hemorrhage: A Single-Center, Retrospective Study.

    Science.gov (United States)

    Cosar, Hese; Isik, Halil; Cakır, Salih Cagrı; Yar, Nese; Goksen, Bulent; Tokbay, Hakan; Kertmen, Hasan; Erdoğan, Nihal; Durak, Ikbal

    2017-02-01

    We aimed to evaluate the efficacy of intravenous administration of recombinant activated factor VIIa (rFVIIa) for acute pulmonary hemorrhage treatment in very-low-birth-weight (VLBW) premature infants. This study was carried out retrospectively in premature infants with pulmonary hemorrhage that were ≤30 weeks gestational age or premature infants with pulmonary hemorrhage who were hospitalized in our neonatal intensive care unit between 01 January 2013 and 31 December 2015 were evaluated. Group 1 (n = 21) received rFVIIa support within the first 30 min of pulmonary hemorrhage plus conventional treatment, while Group 2 (n = 21) received conventional treatment only. The number of patients whose pulmonary hemorrhage was stopped within the first 2 h was significantly higher in Group 1 than Group 2 (n = 14 vs n = 4; p = 0.002). After pulmonary hemorrhage, hemoglobin values of Group 1 were higher than Group 2 (11.12 ± 1.06 vs 10.14 ± 1.59 g/dL; p = 0.024). Erythrocyte suspension (1.43 ± 4.51 vs 5.71 ± 7.46 mL/kg; p = 0.030) and fresh frozen plasma use (5.71 ± 8.10 vs 19.52 ± 12.44 mL/kg; p premature infants.

  12. Design and engineering aspects of the main components for the Wendelstein VII-AS stellarator experiment

    Energy Technology Data Exchange (ETDEWEB)

    Mathis, R.; Sapper, J. (Max-Planck-Institut fuer Plasmaphysik, Garching (Germany, F.R.))

    1990-02-01

    In this paper the design of the essential components of the newly constructed Wendelstein VII-AS stellarator experiment at Garching are described, and the first technical and experimental results are reported. (orig.).

  13. Hindi tagandamine võib viia võimukoalitsiooni lagunemiseni Kohtla-Järvel / Erik Gamzejev

    Index Scriptorium Estoniae

    Gamzejev, Erik, 1967-

    2003-01-01

    Ilmunud ka: Severnoje Poberezhje 26. sept. lk. 1. Keskerakonna soov saada endale Kohtla-Järve linnapea ametikoht võib viia Keskerakonna ja endiste Res Publica liikmete vahel sõlmitud koalitsiooni lagunemiseni

  14. Transcriptional program induced by factor VIIa-tissue factor, PAR1 and PAR2 in MDA-MB-231 cells

    DEFF Research Database (Denmark)

    Albrektsen, T; Sørensen, B B; Hjortø, G M

    2007-01-01

    -regulated genes was also regulated by a PAR1 agonist peptide suggesting extensive redundancy between FVIIa/PAR2 signaling and thrombin/PAR1 signaling. The FVIIa regulated genes encode cytokines, chemokines and growth factors, and the gene repertoire induced by FVIIa in MDA-MB-231 cells is consistent...... with a role for TF-FVIIa signaling in regulation of a wound healing type of response. Interestingly, a number of genes regulated exclusively by FVIIa/PAR2-mediated cell signaling in MDA-MB-231 cells were regulated by thrombin and a PAR1 agonist, but not by FVIIa, in the TF-expressing glioblastoma U373 cell...

  15. Transcriptional program induced by factor VIIa-tissue factor, PAR1 and PAR2 in MDA-MB-231 cells

    DEFF Research Database (Denmark)

    Albrektsen, Tatjana; Sørensen, B B; Hjortø, G M

    2007-01-01

    -activated receptor 1 (PAR1) or PAR2 agonists using MDA-MB-231 breast carcinoma cells that constitutively express TF, PAR1 and PAR2. RESULTS AND CONCLUSIONS: Out of 8500 genes, FVIIa stimulation induced differential regulation of 39 genes most of which were not previously recognized as FVIIa regulated. All genes...... regulated genes encode cytokines, chemokines and growth factors, and the gene repertoire induced by FVIIa in MDA-MB-231 cells is consistent with a role for TF-FVIIa signaling in regulation of a wound healing type of response. Interestingly, a number of genes regulated exclusively by FVIIa/PAR2-mediated cell...... signaling in MDA-MB-231 cells were regulated by thrombin and a PAR1 agonist, but not by FVIIa, in the TF-expressing glioblastoma U373 cell line....

  16. Combination of recombinant factor VIIa and fibrinogen corrects clot formation in primary immune thrombocytopenia at very low platelet counts

    DEFF Research Database (Denmark)

    Larsen, Ole H; Stentoft, Jesper; Radia, Deepti

    2013-01-01

    Haemostatic treatment modalities alternative to platelet transfusion are desirable to control serious acute bleeds in primary immune thrombocytopenia (ITP). This study challenged the hypothesis that recombinant activated factor VII (rFVIIa) combined with fibrinogen concentrate may correct whole b...

  17. Safety and efficacy of a single bolus administration of recombinant factor VIIa in liver transplantation due to chronic liver disease

    NARCIS (Netherlands)

    Planinsic, RM; van der Meer, J; Testa, G; Grande, L; Candela, A; Porte, RJ; Ghobrial, RM; Isoniemi, H; Schelde, PB; Erhardtsen, E; Klintmalm, G; Emre, S

    Orthotopic liver transplantation (OLT) can be associated with excessive blood loss. As a result, there may be increased risk of adverse outcomes. Activated recombinant factor VII (rFVIIa) has demonstrated the ability to improve hemostasis in a variety of disorders; however there has been a limited

  18. Safety and efficacy of a single bolus administration of recombinant factor VIIa in liver transplantation due to chronic liver disease

    NARCIS (Netherlands)

    Planinsic, RM; van der Meer, J; Testa, G; Grande, L; Candela, A; Porte, RJ; Ghobrial, RM; Isoniemi, H; Schelde, PB; Erhardtsen, E; Klintmalm, G; Emre, S

    2005-01-01

    Orthotopic liver transplantation (OLT) can be associated with excessive blood loss. As a result, there may be increased risk of adverse outcomes. Activated recombinant factor VII (rFVIIa) has demonstrated the ability to improve hemostasis in a variety of disorders; however there has been a limited a

  19. Factor VIIa response to a fat-rich meal does not depend on fatty acid composition: A randomized controlled trial

    NARCIS (Netherlands)

    Mennen, L.; Maat, M. de; Meijer, G.; Zock, P.; Grobbee, D.; Kok, F.; Kluft, C.; Schouten, E.

    1998-01-01

    A fat-rich meal increases activated factor VII (FVIIa), but it is not clear whether this increase depends on the fatty acid composition of the meal. Therefore, we studied the FVIIa response to fat-rich meals with different fatty acid composition in a randomized controlled crossover trial and investi

  20. Biochemical characterization of LR769, a new recombinant factor VIIa bypassing agent produced in the milk of transgenic rabbits.

    Science.gov (United States)

    Chevreux, G; Tilly, N; Leblanc, Y; Ramon, C; Faid, V; Martin, M; Dhainaut, F; Bihoreau, N

    2017-07-01

    The bypassing agent factor VII (FVIIa) is a first-line therapy for the treatment of acute bleeding episodes in patients with haemophilia and high-titre inhibitors. FVIIa is a highly post-translationally modified protein that requires eukaryotic expression systems to produce a fully active molecule. A recombinant FVIIa was produced in the milk of transgenic rabbits to increase expression and provide an efficient, safe and affordable product after purification to homogeneity (LR769). To present the biochemical and functional in vitro characteristics of LR769. Mass spectrometric analyses of the intact protein and of heavy and light chains revealed a fully activated, mature and properly post-translationally modified protein notably regarding N/O-glycosylations and γ-carboxylation. Primary structure analysis, performed by peptide mapping, confirmed 100% of the sequence and the low level or absence of product-derived impurities such as oxidized, deamidated and glycated forms. Low levels of aggregates and fragments were observed by different chromatographic methods. Higher order structure investigated by circular dichroism showed appropriate secondary/tertiary structures and conformational change in the presence of Ca(2+) ions. Finally, activated partial thromboplastin time and thrombin generation assays showed the ability of LR769 to decrease coagulation time and to generate thrombin in haemophiliac-A-plasmas, even in the presence of inhibitors. The innovative expression system used to produce LR769 yields a new safe and effective rhFVIIa for the treatment of haemophilia A or B patients with inhibitors. © 2017 LFB Biotechnologies. Haemophilia Published by John Wiley & Sons Ltd.

  1. Ekspertide ettepanek : 25% Eesti Energiast viia börsile / Vallo Toomet

    Index Scriptorium Estoniae

    Toomet, Vallo, 1960-

    2008-01-01

    Eesti Energia vajab lähema kümne aasta jooksul ligi 8 mld. krooni lisakapitali, majandus- ja kommunikatsiooniministeeriumis valminud analüüsi kohaselt oleks üks võimalusi lisakapitali kaasamiseks viia kuni 25% ettevõttest börsile. Minister Juhan Partsi, ministeeriumi asekantsleri Einari Kiseli seisukohtadest. Lisa: Euroopa nõudmise leevenevad

  2. The incidence of thromboembolism formation following the use of recombinant factor VIIa in patients suffering from blunt force trauma compared with penetrating trauma: a systematic review.

    Science.gov (United States)

    Devlin, Raymond; Bonanno, Laura; Badeaux, Jennifer

    2016-03-01

    Rapid replacement of blood loss is critical in patients suffering from traumatic hemorrhage. When the availability of blood products is limited, certain interventions have shown promise in conserving blood supplies. Recombinant factor (rF) VIIa has been administered, as an off-label use, to assist in controlling hemorrhage in trauma patients. Although rFVIIa has a tendency to remain localized to areas of vascular insult, there may be an increase in thromboembolism formation when patients suffer multiple sites of injury as seen in blunt force trauma. This review aimed to synthesize the best available evidence regarding the incidence of thromboembolism formation after receiving rFVIIa as an adjunct to hemorrhage control measures (standard resuscitation efforts consisting of varying amounts of packed red blood cells [PRBCs], fresh frozen plasma [FFP], platelets and crystalloid solutions) in patients suffering from traumatic injuries (blunt force and penetrating trauma). Civilian and combat trauma patients who were 15 years and older suffering from blunt force and penetrating traumatic injuries. Use of rFVIIa as an adjunct to hemorrhage control measures (standard resuscitation efforts consisting of varying amounts of PRBCs, FFP, platelets and crystalloid solutions). This review considered both experimental and epidemiological study designs. Confirmed formation of thromboembolism (confirmation based on specific diagnostic tests such as ultrasound, ventilation-perfusion scan or angiography). The databases searched included CINAHL, Ovid MEDLINE, Web of Science, EMBASE and the Cochrane Control Register of Clinical Trials. Studies published after June 1986 were considered for inclusion in this review. Search for unpublished studies was performed. Studies selected for inclusion were critically appraised by two independent reviewers using standardized critical appraisal instruments from the Joanna Briggs Institute (JBI). Data was extracted from articles using standardized

  3. Analüütikud soovitavad Eesti Energia börsile viia / Piret Reiljan

    Index Scriptorium Estoniae

    Reiljan, Piret, 1983-

    2008-01-01

    Kohalikud analüütikud soovitavad viia Eesti Energia börsile, kuna see elavdaks aktsiaturgu ja tõmbaks ligi välisinvestoreid. Vt. samas: Raivo Vare: raske aeg töötab Eesti Energia börsiletoomise kasuks; Analüüs ootab pääsu valitsuskabinetti; Juhid ei püsi enam Eesti Energias. Diagrammid: Majandusnäitajad; Varade maht

  4. Analüütikud soovitavad Eesti Energia börsile viia / Piret Reiljan

    Index Scriptorium Estoniae

    Reiljan, Piret, 1983-

    2008-01-01

    Kohalikud analüütikud soovitavad viia Eesti Energia börsile, kuna see elavdaks aktsiaturgu ja tõmbaks ligi välisinvestoreid. Vt. samas: Raivo Vare: raske aeg töötab Eesti Energia börsiletoomise kasuks; Analüüs ootab pääsu valitsuskabinetti; Juhid ei püsi enam Eesti Energias. Diagrammid: Majandusnäitajad; Varade maht

  5. Myosin VIIa, harmonin and cadherin 23, three Usher I gene products that cooperate to shape the sensory hair cell bundle.

    Science.gov (United States)

    Boëda, Batiste; El-Amraoui, Aziz; Bahloul, Amel; Goodyear, Richard; Daviet, Laurent; Blanchard, Stéphane; Perfettini, Isabelle; Fath, Karl R; Shorte, Spencer; Reiners, Jan; Houdusse, Anne; Legrain, Pierre; Wolfrum, Uwe; Richardson, Guy; Petit, Christine

    2002-12-16

    Deaf-blindness in three distinct genetic forms of Usher type I syndrome (USH1) is caused by defects in myosin VIIa, harmonin and cadherin 23. Despite being critical for hearing, the functions of these proteins in the inner ear remain elusive. Here we show that harmonin, a PDZ domain-containing protein, and cadherin 23 are both present in the growing stereocilia and that they bind to each other. Moreover, we demonstrate that harmonin b is an F-actin-bundling protein, which is thus likely to anchor cadherin 23 to the stereocilia microfilaments, thereby identifying a novel anchorage mode of the cadherins to the actin cytoskeleton. Moreover, harmonin b interacts directly with myosin VIIa, and is absent from the disorganized hair bundles of myosin VIIa mutant mice, suggesting that myosin VIIa conveys harmonin b along the actin core of the developing stereocilia. We propose that the shaping of the hair bundle relies on a functional unit composed of myosin VIIa, harmonin b and cadherin 23 that is essential to ensure the cohesion of the stereocilia.

  6. Inactivation of factor VIIa by antithrombin in vitro, ex vivo and in vivo: role of tissue factor and endothelial cell protein C receptor.

    Directory of Open Access Journals (Sweden)

    Rit Vatsyayan

    Full Text Available Recent studies have suggested that antithrombin (AT could act as a significant physiologic regulator of FVIIa. However, in vitro studies showed that AT could inhibit FVIIa effectively only when it was bound to tissue factor (TF. Circulating blood is known to contain only traces of TF, at best. FVIIa also binds endothelial cell protein C receptor (EPCR, but the role of EPCR on FVIIa inactivation by AT is unknown. The present study was designed to investigate the role of TF and EPCR in inactivation of FVIIa by AT in vivo. Low human TF mice (low TF, ∼ 1% expression of the mouse TF level and high human TF mice (HTF, ∼ 100% of the mouse TF level were injected with human rFVIIa (120 µg kg(-1 body weight via the tail vein. At varying time intervals following rFVIIa administration, blood was collected to measure FVIIa-AT complex and rFVIIa antigen levels in the plasma. Despite the large difference in TF expression in the mice, HTF mice generated only 40-50% more of FVIIa-AT complex as compared to low TF mice. Increasing the concentration of TF in vivo in HTF mice by LPS injection increased the levels of FVIIa-AT complexes by about 25%. No significant differences were found in FVIIa-AT levels among wild-type, EPCR-deficient, and EPCR-overexpressing mice. The levels of FVIIa-AT complex formed in vitro and ex vivo were much lower than that was found in vivo. In summary, our results suggest that traces of TF that may be present in circulating blood or extravascular TF that is transiently exposed during normal vessel damage contributes to inactivation of FVIIa by AT in circulation. However, TF's role in AT inactivation of FVIIa appears to be minor and other factor(s present in plasma, on blood cells or vascular endothelium may play a predominant role in this process.

  7. The various assays for measuring activity states of factor VIIa in plasma and therapeutic products: Diagnostic value and analytical usefulness in various pathophysiological states.

    Science.gov (United States)

    Amiral, Jean; Dunois, Claire; Amiral, Cédric; Seghatchian, Jerard

    2016-12-29

    The key coagulation factor FVII, and its activated form FVIIa, present a major interest for their role at the initiation phase of blood coagulation, and because they can activate all blood coagulation cascade, through the extrinsic, but also the intrinsic pathway. Blood activation initiated through FVII is first presented, as it is understood nowadays. Measurement of FVII and FVIIa were of main interest for epidemiological studies, but FVIIa contribution to assay results was only deduced. The introduction of specific FVIIa assays, functional or immunoassays, allowed measuring directly FVIIa without any interference of non-activated FVII, or other coagulation factors or their activated forms. The various methods available, and their characteristics are presented, with a special focus on two assays developed by our group for FVIIa (a clotting one and a chromogenic one). The FVIIa clotting assay shows evident superiority for measuring its activity in plasma, in pathophysiological conditions. The normal range is products, or for following recoveries in treated patients, including hemophiliacs with inhibitors, patients with severe bleeding risk (liver diseases, surgery, trauma, …), and lastly for measurement of its activity in therapeutic products.

  8. Local pulmonary administration of factor VIIa (rFVIIa in diffuse alveolar hemorrhage (DAH – a review of a new treatment paradigm

    Directory of Open Access Journals (Sweden)

    Nielsen JD

    2012-03-01

    without thromboembolic complication when FVIIa was administered locally via the air side, because the FVIIa does not penetrate the alveolo-capillary membrane to the blood-side. The incidence of DAH (in the US and Europe is 100,000–150,000, and 50,000 patients annually are at risk of developing DAH following hematopoietic stem cell transplant (HSCT and autoimmune diseases. Finally 50,000–100,000 patients may be falsely categorized as having acute respiratory distress syndrome/acute lung injury (ARDS/ALI because DAH and ARDS cannot be separated clinically. A new treatment paradigm of DAH is proposed as no other intervention has been able to ensure pulmonary hemostasis in DAH. The diagnosis of DAH is simple, a series of broncho-alveolar washes which become increasingly bloody. This test should be performed in all patients with pulmonary opacities in order to separate ARDS/ALI from DAH. FVIIa administrated via pulmonary route is "drug of choice", because it stops bleeding in the life-threatening syndrome DAH. Hemostasis is obtained after only one to two small doses of FVIIa (50 µg/kg body weight per dose and after hemostasis the oxygen transport quickly improves.Conclusion: Intrapulmonary administration of rFVIIa is recommended as the treatment of choice for DAH and blast lung injury (BLI because the treatment has been shown to be successful and uncomplicated in spite of the fact that only a small series of DAH has been documented.Keywords: coagulation factor FVIIa, diffuse alveolar hemorrhage, hemosiderosis, blast lung injury, local pulmonary treatment, biologics, bronchoalveolar lavage, diagnosis, algorithm, new treatment recommendation

  9. Crystal structures of human group-VIIA phospholipase A2 inhibited by organophosphorus nerve agents exhibit non-aged complexes

    Energy Technology Data Exchange (ETDEWEB)

    Samanta, Uttamkumar; Kirby, Stephen D.; Srinivasan, Prabhavathi; Cerasoli, Douglas M.; Bahnson, Brian J.; (Delaware); (USAMRIID)

    2009-09-02

    The enzyme group-VIIA phospholipase A2 (gVIIA-PLA2) is bound to lipoproteins in human blood and hydrolyzes the ester bond at the sn-2 position of phospholipid substrates with a short sn-2 chain. The enzyme belongs to a serine hydrolase superfamily of enzymes, which react with organophosphorus (OP) nerve agents. OPs ultimately exert their toxicity by inhibiting human acetycholinesterase at nerve synapses, but may additionally have detrimental effects through inhibition of other serine hydrolases. We have solved the crystal structures of gVIIA-PLA2 following inhibition with the OPs diisopropylfluorophosphate, sarin, soman and tabun. The sarin and soman complexes displayed a racemic mix of P{sub R} and P{sub S} stereoisomers at the P-chiral center. The tabun complex displayed only the P{sub R} stereoisomer in the crystal. In all cases, the crystal structures contained intact OP adducts that had not aged. Aging refers to a secondary process OP complexes can go through, which dealkylates the nerve agent adduct and results in a form that is highly resistant to either spontaneous or oxime-mediated reactivation. Non-aged OP complexes of the enzyme were corroborated by trypsin digest and matrix-assisted laser desorption ionization mass spectrometry of OP-enzyme complexes. The lack of stereoselectivity of sarin reaction was confirmed by gas chromatography/mass spectrometry using a chiral column to separate and quantitate the unbound stereoisomers of sarin following incubation with enzyme. The structural details and characterization of nascent reactivity of several toxic nerve agents is discussed with a long-term goal of developing gVIIA-PLA2 as a catalytic bioscavenger of OP nerve agents.

  10. Life, limb or off-label recombinant VIIa use in the setting of limited blood assets: a case study.

    Science.gov (United States)

    Carr, Marcus E; Vickaryous, Brian

    2013-06-01

    Due to the lack of adequate controlled trials, the off-label use of recombinant factor VIIa (rFVIIa) to control hemorrhage in trauma patients remains controversial. The decision regarding when to initiate rFVIIa therapy is particularly problematic. Whereas most reports and trials have delayed use until significant bleeding has occurred, there is some evidence that coagulopathy develops early in some trauma patients, raising the possibility that early rFVIIa use may be more clinically efficacious. Herein, we report the case of a hemodynamically unstable patient with massive blood loss from multiple gunshot wounds and who had a potentially salvageable upper extremity. Rapid hemorrhage despite efforts to surgically control the bleeding resulted in virtual exhaustion of the facilities' limited blood component supply. Hemorrhage was controlled when rFVIIa was added to hypotensive resuscitation allowing salvage of the arm and significant conservation of blood products. This case raises the question as to whether earlier off-label use of this agent should be considered when amputation for hemorrhage control is being considered and/or conservation of limited blood assets is needed.

  11. Structure-based design and synthesis of pyrazinones containing novel P1 'side pocket' moieties as inhibitors of TF/VIIa.

    Science.gov (United States)

    Schweitzer, Barbara A; Neumann, William L; Rahman, Hayat K; Kusturin, Carrie L; Sample, Kirby R; Poda, Gennadiy I; Kurumbail, Ravi G; Stevens, Anna M; Stegeman, Roderick A; Stallings, William C; South, Michael S

    2005-06-15

    We describe the structure-based design, synthesis, and enzymatic activity of a series of substituted pyrazinones as inhibitors of the TF/VIIa complex. These inhibitors contain substituents meta to the P(1) amidine designed to explore additional interactions with the VIIa residues in the so-called 'S(1) side pocket'. A crystal structure of the designed inhibitors demonstrates the ability of the P(1) side pocket moiety to engage Lys192 and main chain of Gly216 via hydrogen bond interactions, thus, providing additional possibility for chemical modification to improve selectivity and/or physical properties of inhibitors.

  12. Loomemajandus - Eesti loojad on valmis, Eesti tööstus veel mitte / Erik Terk, Külliki Tafel-Viia, Silja Lassur ; intervjueerinud Mikk Salu

    Index Scriptorium Estoniae

    Terk, Erik, 1952-

    2009-01-01

    Eestis korraldatud uuringu "Eesti loomemajanduse potentsiaal ja arenguks vajalikud riikud toetusmeetmed" tulemustest lähtudes püütakse leida optimaalseid suhteid loovinimeste toetusmeetmete ja iseorganiseerumise vahel. Vestlusringis Eesti Tuleviku-uuringute Instituudi direktor Erik Terk ja teadurid Silja Lassur ja Külliki Tafel-Viia

  13. Klassiõpetaja peab särama / Ly Melesk, Kairis Kontus, Leida Talts, Viia Hang...[jt.] ; küsitles Anu Mõttus

    Index Scriptorium Estoniae

    2007-01-01

    Vestlusringis on Tallinna Kuristiku Gümnaasiumi klassiõpetajad Viia Hang ja Ly Melesk, Tallinna Ülikooli 5. kursuse üliõpilane ja Tallinna Lepistiku Lasteaed-Algkooli õpetaja Kairis Kontus, Tallinna Ülikooli algõpetuse õppetooli juhataja Leida Talts ning algõpetuse õppetooli pedagoogika ja algõpetuse metoodika õppejõud Mare Müürsepp. Kui hästi on Tallinna Ülikool ja tema eelkäijad suutnud algklassiõpetajaid ette valmistada ja mis neil igapäevatöös toime tulla aitab

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    Coagulation in blood is initiated when coagulation factor VII (FVII) binds to exposed TF and is activated to FVIIa, and the TF/ FVIIa complex may therefore provide a marker of vascular injury potentially applicable in diagnostic imaging of acute gastrointestinal (GI) bleeding. Methods: Recombinan...... for stabilizing the 99mTc(CO)3 1-ligand structure in FVIIa were identified. Conclusion: Radiolabelled rFVIIa derivatives may represent a novel tool for the diagnosis of acute gastrointestinal bleeding lesions....

  15. Coagulation factor VIIa-mediated protease-activated receptor 2 activation leads to β-catenin accumulation via the AKT/GSK3β pathway and contributes to breast cancer progression.

    Science.gov (United States)

    Roy, Abhishek; Ansari, Shabbir A; Das, Kaushik; Prasad, Ramesh; Bhattacharya, Anindita; Mallik, Suman; Mukherjee, Ashis; Sen, Prosenjit

    2017-08-18

    Cell migration and invasion are very characteristic features of cancer cells that promote metastasis, which is one of the most common causes of mortality among cancer patients. Emerging evidence has shown that coagulation factors can directly mediate cancer-associated complications either by enhancing thrombus formation or by initiating various signaling events leading to metastatic cancer progression. It is well established that, apart from its distinct role in blood coagulation, coagulation factor FVIIa enhances aggressive behaviors of breast cancer cells, but the underlying signaling mechanisms still remain elusive. To this end, we investigated FVIIa's role in the migration and invasiveness of the breast cancer cell line MDA-MB-231. Consistent with previous observations, we observed that FVIIa increased the migratory and invasive potential of these cells. We also provide molecular evidence that protease-activated receptor 2 activation followed by PI3K-AKT activation and GSK3β inactivation is involved in these processes and that β-catenin, a well known tumor-regulatory protein, contributes to this signaling pathway. The pivotal role of β-catenin was further indicated by the up-regulation of its downstream targets cyclin D1, c-Myc, COX-2, MMP-7, MMP-14, and Claudin-1. β-Catenin knockdown almost completely attenuated the FVIIa-induced enhancement of breast cancer migration and invasion. These findings provide a new perspective to counteract the invasive behavior of breast cancer, indicating that blocking PI3K-AKT pathway-dependent β-catenin accumulation may represent a potential therapeutic approach to control breast cancer. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Molecular and structural advances in tissue factor-dependent coagulation.

    Science.gov (United States)

    Kirchhofer, D; Banner, D W

    1997-11-01

    The tissue factor:factor VIIa (TF-F.VIIa) complex is considered the physiological initiator of blood coagulation. Besides its role in normal hemostasis, this enzyme complex has been found to play an important role in various thrombotic disorders and thus has become an attractive target for the development of new anticoagulants. Recently, significant progress has been made in regard to structural and molecular aspects of TF-VIIa-initiated coagulation. A rather complete picture on how tissue factor binds to factor VIIa has emerged and is discussed in detail in this review. Also, the combined data of the TF-F.VIIa crystal structure, of naturally occurring F.VII variants, and of mutagenesis studies provide a framework to discuss molecular aspects of the tissue factor-mediated enhancement of F.VIIa catalytic efficiency and the recognition of macromolecular substrates. F.VIIa as a member of the serine protease family has an active site homologous to other coagulation factors. The release of the coordinates of the crystal structures of F.X and F.IX, together with the earlier determined thrombin structure, now allows a detailed comparison of these active centers with respect to the development of specific and potent active site inhibitors. This structural and molecular information about the TF-F.VIIa complex and other coagulation enzymes adds to our understanding of blood coagulation and should further the development of new classes of anticoagulants. (Trends Cardiovasc Med 1997;7:316-324). © 1997, Elsevier Science Inc.

  17. Mild Maternal Iron Deficiency Anemia Induces Hearing Impairment Associated with Reduction of Ribbon Synapse Density and Dysregulation of VGLUT3, Myosin VIIa, and Prestin Expression in Young Guinea Pigs.

    Science.gov (United States)

    Yu, Fei; Hao, Shuai; Yang, Bo; Zhao, Yue; Zhang, Wenyue; Yang, Jun

    2016-05-01

    Mild maternal iron deficiency anemia (IDA) adversely affects the development of cochlear hair cells of the young offspring, but the mechanisms underlying the association are incompletely understood. The aim of this study was to evaluate whether mild maternal IDA in guinea pigs could interrupt inner hair cell (IHC) ribbon synapse density and outer hair cell motility of the offspring. Here, we established a dietary restriction model that allows us to study quantitative changes in the number of IHC ribbon synapses and hearing impairment in response to mild maternal IDA in young guinea pig. The offspring were weaned on postnatal day (PND) 9 and then were given the iron-sufficient diet. On PND 24, pups were examined the hearing function by auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) measurements. Then, the cochleae were harvested for assessment of the number of IHC ribbon synapses by immunofluorescence, the morphology of cochlear hair cells, and spiral ganglion cells (SGCs) by scanning electron microscope and hematoxylin-eosin staining, the location, and expression of vesicular glutamate transporter (VGLUT) 3, myosin VIIa, and prestin by immunofluorescence and blotting. Here, we show that mild maternal IDA in guinea pigs induced elevated ABR threshold shifts, declined DPOAE level shifts, and reduced the number of ribbon synapses, impaired the morphology of cochlear hair cells and SGCs in offsprings. In addition, downregulation of VGLUT3 and myosin VIIa, and upregulation of prestin were observed in the cochlea of offsprings from mild maternal IDA in guinea pigs. These data indicate that mild maternal IDA in guinea pigs induced hearing impairment in offsprings, and this deficit may be attributed to the reduction of ribbon synapse density and dysregulation of VGLUT3, myosin VIIa, and prestin.

  18. Effect of Hemodilution on Coagulation and Recombinant Factor VIIa Efficacy in Human Blood In Vitro

    Science.gov (United States)

    2011-11-01

    Support. St. Louis, MO: Mosby JEMS/Elsevier; 2007. 11. Gutierrez G, Reines HD, Wulf- Gutierrez ME. Clinical review: hemor- rhagic shock. Crit Care. 2004;8...Clin North Am. 2007;87:55–72, vi. 18. Gonzalez EA, Moore FA, Holcomb JB, et al. Fresh frozen plasma should be given earlier to patients requiring

  19. Effect of haemodilution, acidosis, and hypothermia on the activity of recombinant factor VIIa (NovoSeven)

    DEFF Research Database (Denmark)

    Viuff, D.; Lauritzen, B.; Pusateri, A.E.

    2008-01-01

    are poorly understood. METHODS: Clot formation was measured by thromboelastography (TEG) using blood from healthy volunteers. In vitro effects of rFVIIa with haemodilution, acidosis, and hypothermia were examined. Conditions were induced by dilution with NaCl (0.9%), lactated Ringer's solution, albumin 5...... bleeding time (BT) in rabbits. RESULTS: Haemodilution progressively altered TEG parameters. rFVIIa improved TEG parameters in the presence of acidosis, hypothermia or 20% haemodilution (P... the BT (Pacidosis or hypothermia Udgivelsesdato: 2008/9...

  20. Tissue factor residues that putatively interact with membrane phospholipids.

    Directory of Open Access Journals (Sweden)

    Ke Ke

    Full Text Available Blood clotting is initiated by the two-subunit enzyme consisting of the plasma protease, factor VIIa (the catalytic subunit, bound to the integral membrane protein, tissue factor (the regulatory subunit. Molecular dynamics simulations have predicted that certain residues in the tissue factor ectodomain interact with phosphatidylserine headgroups to ensure optimal positioning of the tissue factor/factor VIIa complex relative to its membrane-bound protein substrates, factors IX and X. In this study, we individually mutated to alanine all the putative phosphatidylserine-interactive residues in the tissue factor ectodomain and measured their effects on tissue factor cofactor function (activation of factors IX and X by tissue factor/factor VIIa, and clotting of plasma. Some tissue factor mutants exhibited decreased activity in all three assays, with the most profound defects observed from mutations in or near the flexible loop from Lys159 to Gly164. The decreased activity of all of these tissue factor mutants could be partially or completely overcome by increasing the phosphatidylserine content of tissue factor-liposomes. Additionally, yeast surface display was used to screen a random library of tissue factor mutants for enhanced factor VIIa binding. Surprisingly, mutations at a single amino acid (Lys165 predominated, with the Lys165→Glu mutant exhibiting a 3-fold enhancement in factor VIIa binding affinity. Our studies reveal the functional contributions of residues in the C-terminal half of the tissue factor ectodomain that are implicated in interacting with phosphatidylserine headgroups to enhance tissue factor cofactor activity, possibly by allosterically modulating the conformation of the adjacent substrate-binding exosite region of tissue factor.

  1. Potentiation of thrombin generation in hemophilia A plasma by coagulation factor VIII and characterization of antibody-specific inhibition.

    Directory of Open Access Journals (Sweden)

    Bhavya S Doshi

    Full Text Available Development of inhibitory antibodies to coagulation factor VIII (fVIII is the primary obstacle to the treatment of hemophilia A in the developed world. This adverse reaction occurs in 20-30% of persons with severe hemophilia A treated with fVIII-replacement products and is characterized by the development of a humoral and neutralizing immune response to fVIII. Patients with inhibitory anti-fVIII antibodies are treated with bypassing agents including recombinant factor VIIa (rfVIIa. However, some patients display poor hemostatic response to bypass therapy and improved treatment options are needed. Recently, we demonstrated that fVIII inhibitors display widely variable kinetics of inhibition that correlate with their respective target epitopes. Thus, it was hypothesized that for antibodies that display slow rates of inhibition, supplementation of rfVIIa with fVIII would result in improved thrombin generation and be predictive of clinical responses to this novel treatment regimen. In order to test this hypothesis, 10 murine monoclonal antibodies (MAbs with non-overlapping epitopes spanning fVIII, differential inhibition titers, and inhibition kinetics were studied using a thrombin generation assay. Of the 3 MAbs with high inhibitory titers, only the one with fast and complete (classically defined as "type I" kinetics displayed significant inhibition of thrombin generation with no improvement upon supplementation of rfVIIa with fVIII. The other two MAbs that displayed incomplete (classically defined as "type II" inhibition did not suppress the potentiation of thrombin generation by fVIII. All antibodies that did not completely inhibit fVIII activity demonstrated potentiation of thrombin generation by the addition of fVIII as compared to rfVIIa alone. In conclusion, fVIII alone or in combination with rfVIIa corrects the thrombin generation defect produced by the majority of anti-fVIII MAbs better than single agent rfVIIa. Therefore, combined fVIII/rfVIIa

  2. Elective surgery on factor VIII inhibitor patients using continuous infusion of recombinant activated factor VII: plasma factor VII activity of 10 IU/ml is associated with an increased incidence of bleeding.

    Science.gov (United States)

    Smith, M P; Ludlam, C A; Collins, P W; Hay, C R; Wilde, J T; Grigeri, A; Melsen, T; Savidge, G F

    2001-10-01

    We examined recombinant activated factor VII (rVIIa) administered by continuous infusion to eight patients with inhibitors to factor VIII, undergoing elective surgery. rVIIa was infused at a fixed rate of 16.5 microg/kg/h for a median of 13.5 days (range 1-26). There was effective haemostasis at this infusion rate in only one of two minor procedures and two of six major operations. Three patients experienced excessive bleeding despite plasma factor VII activity around 10 IU/ml. Serious bleeding occurred in two other patients caused by procedural errors unrelated to rVIIa and required re-operation. The median rVIIa clearance on day 1 was 57 ml/h/kg (range 18-100) and on day 3 was 100 ml/h/kg (range 61-200). Clearance on the final infusion day was not significantly different from day 3. The infusion did not induce pathological activation of the coagulation mechanism. The only thrombotic adverse events were two episodes of superficial thrombophlebitis of the infused vein in one subject. In conclusion, the 16.5 microg/kg/h infusion rate reliably achieves plasma factor VII activity levels of 10 IU/ml, but this level does not provide reliable haemostasis.

  3. Endothelial-derived tissue factor pathway inhibitor regulates arterial thrombosis but is not required for development or hemostasis.

    NARCIS (Netherlands)

    White, T.A.; Johnson, T.; Zarzhevsky, N.; Tom, C.; Delacroix, S.; Holroyd, E.W.; Maroney, S.A.; Singh, R.; Pan, S.; Fay, W.P.; Deursen, J.M.A. van; Mast, A.E.; Sandhu, G.S.; Simari, R.D.

    2010-01-01

    The antithrombotic surface of endothelium is regulated in a coordinated manner. Tissue factor pathway inhibitor (TFPI) localized at the endothelial cell surface regulates the production of FXa by inhibiting the TF/VIIa complex. Systemic homozygotic deletion of the first Kunitz (K1) domain of TFPI

  4. Juhan Parts soovib Res Publica tagasi tippu viia / Toomas Sildam

    Index Scriptorium Estoniae

    Sildam, Toomas, 1961-

    2004-01-01

    Res Publica esimees peaminister Juhan Parts plaanib minna oma erakonnaga kohalikele valimistele ning uurib võimalusi paremerakondade ühinemiseks. Rakveres toimunud erakonna üldkogust. Lisad: Peaministri neli rasket hetke; Res Publica ministrid said parteilt toetuse. Vt. samas: Reformierakond kiitis Res Publicat hea koostöö eest; Parts: 191 vastuhäält on hea tulemus

  5. Kui arstiteaduskonda taheti Tartust ära viia / Hillar Palamets

    Index Scriptorium Estoniae

    Palamets, Hillar, 1927-

    2010-01-01

    1910. aastal kerkis viletsa materiaalse baasi tõttu küsimuse alla arstiteaduskonna äraviimine Tartust mõnda Venemaa suuremasse linna. Tänu Werner Zoege von Manteuffelile jäi arstiteaduskond Tartusse ja Maarjamõisa ala anti ülikooli käsutusse.

  6. Elion lubab maarahvale kvaliteetse telepildi viia / Henrik Roonemaa

    Index Scriptorium Estoniae

    Roonemaa, Henrik

    2005-01-01

    Elioni juhatuse esimees Valdur Laid lubab digitaalset telepilti lähiaastatel ka nendesse paikadesse, kuhu kaabeltelevisioon praegu ei ulatu. Starmani juht Peeter Kern kahtleb Elioni plaanis haarata 2010. aastaks pool Eesti turust, tema sõnul on Starmani positsioon tugevam. Ka firma Levira tegeleb digitaaltelevisiooni arendamisega

  7. Bianchi $VII_A$ solutions of quadratic gravity

    CERN Document Server

    de Deus, Juliano A

    2011-01-01

    It is believed that soon after the Planck time, Einstein's general relativity theory should be corrected to an effective quadratic theory. Numerical solutions for the anisotropic generalization of the Friedmann "open" model $H^ 3$ for this effective gravity are given. It must be emphasized that although numeric, these solutions are exact in the sense that they depend only on the precision of the machine. The solutions are identified asymptotically in a certain sense. It is found solutions which asymptote de Sitter space, Minkowski space and a singularity.

  8. Ungari uuemad filmid Tartus ja Tallinnas / Viia-Kadi Raudalainen

    Index Scriptorium Estoniae

    Raudalainen, Viia-Kadi

    2003-01-01

    Ungari instituut esitles Tallinnas ja Tartus viit uuemat Ungari filmi - Zoltan Kamondi "Kiusatused", Gabor Dettre "Pilv Gangese kohal", Peter Bacso "Kustuv sigaretikoni", Agnes Incze "I love Budapest"

  9. Ungari uuemad filmid Tartus ja Tallinnas / Viia-Kadi Raudalainen

    Index Scriptorium Estoniae

    Raudalainen, Viia-Kadi

    2003-01-01

    Ungari instituut esitles Tallinnas ja Tartus viit uuemat Ungari filmi - Zoltan Kamondi "Kiusatused", Gabor Dettre "Pilv Gangese kohal", Peter Bacso "Kustuv sigaretikoni", Agnes Incze "I love Budapest"

  10. Juhan Parts soovib Res Publica tagasi tippu viia / Toomas Sildam

    Index Scriptorium Estoniae

    Sildam, Toomas, 1961-

    2004-01-01

    Res Publica esimees peaminister Juhan Parts plaanib minna oma erakonnaga kohalikele valimistele ning uurib võimalusi paremerakondade ühinemiseks. Rakveres toimunud erakonna üldkogust. Lisad: Peaministri neli rasket hetke; Res Publica ministrid said parteilt toetuse. Vt. samas: Reformierakond kiitis Res Publicat hea koostöö eest; Parts: 191 vastuhäält on hea tulemus

  11. Loomemajandus vajab õitsenguks soosivat keskkonda / Külliki Tafel-Viia, Silja Lassur, Andres Viia ; intervjueerinud Tiina Saar

    Index Scriptorium Estoniae

    Tafel-Viia, Külliki

    2009-01-01

    TLÜ Eesti Tuleviku-uuringute Instituudi teadurid vastavad küsimustele, mis puudutavad tavalise ja loovmajanduse erinevusi, Eesti loomemajanduse positsiooni võrreldes teiste riikidega, loomemajandusega seotud valdkondi, loomeettevõtlust ja loomeettevõtteid, loomemajanduses edukas olemiseks vajalikke ressursse ning loomeettevõtete erinevusi võrreldes teiste ettevõtetega

  12. Sites involved in intra- and interdomain allostery associated with the activation of factor VIIa pinpointed by hydrogen-deuterium exchange and electron transfer dissociation mass spectrometry

    DEFF Research Database (Denmark)

    Song, Hongjian; Olsen, Ole H; Persson, Egon;

    2014-01-01

    enhancement remain elusive. Here we have applied hydrogen/deuterium exchange mass spectrometry coupled to electron transfer dissociation to pinpoint individual residues in the heavy chain of FVIIa whose conformation and/or local interaction pattern changes when the enzyme transitions to the active form...

  13. Local pulmonary administration of factor VIIa (rFVIIa) in diffuse alveolar hemorrhage (DAH) - a review of a new treatment paradigm

    DEFF Research Database (Denmark)

    Heslet, Lars; Nielsen, Jørn Dalsgaard; Nepper-Christensen, Steen

    2012-01-01

    Diffuse alveolar hemorrhage (DAH) is a clinical syndrome with typical symptoms dyspnea and hemoptysis. DAH is a complication of specific diseases, in some cases with acute catastrophic hemoptysis, while other patients present low grade alveolar bleeding with a need of chronic transfusion as in pu...

  14. The origins of enhanced activity in factor VIIa analogs and the interplay between key allosteric sites revealed by hydrogen exchange mass spectrometry

    DEFF Research Database (Denmark)

    Rand, Kasper D; Andersen, Mette D; Olsen, Ole H;

    2008-01-01

    to investigate the conformational effects of site-directed mutagenesis at key positions in FVIIa and the origins of enhanced intrinsic activity of FVIIa analogs. The differences in hydrogen exchange of two highly active variants, FVIIa(DVQ) and FVIIa(VEAY), imply that enhanced catalytic efficiency was attained...

  15. Recombinant factor VII (NovoSeven in intraoperative blood saving during neurosurgical treatment of the brain arteriovenous malformation

    Directory of Open Access Journals (Sweden)

    Novak Vesna

    2007-01-01

    Full Text Available Background. Cerebral arteriovenous (AV malformation causes, due to the increased blood flow through a malformation, a massive intraoperative bleeding complicating, so, surgical treatment. The use of intraoperative blood saving apparatus during surgery and a recombinant factor VII-a (NovoSeven significantly reduce complications during surgical treatment. Case report. We reported a case of surgical treatment of the patient with AV malformation of IV stage according to the Spetzler-Martin scale, in the brain. Due to a possible heavy bleeding we used a apparatus for intrasurgical blood recovery, Cell Saver, Sequestra 1 000, Medtronic, U.S.A., and recombinant human factor VIIa (rFVIIa - NovoSeven, NovoNordisk, Denmark to control bleeding and restore an adequate hemostasis. Conclusion. The use of an apparatus for intraoperative blood saving, as well as the NovoSeven preparation in the management of AV malformation of IV stage, showed to be successful.

  16. Tissue factor pathway inhibitor endocytosis.

    Science.gov (United States)

    Schwartz, A L; Broze, G J

    1997-10-01

    Tissue factor pathway inhibitor (TFPI), a 42 kD protein, provides the physiological inhibition of tissue factor initiated coagulation by inhibition of both factor Xa and factor VIIa/tissue factor. In plasma, most TFPI is lipoprotein bound with an additional "releasable" pool bound to the endothelial cell surface. TFPI clearance is via receptor mediated endocytosis into liver. Heparin sulfate proteoglycans and LRP (low density lipoprotein receptor-related protein), an extremely large (∼600 kD) cell surface protein, primarily mediate this clearance, although additional TFPI binding sites and endocytosis pathways exist. (Trends Cardiovasc Med 1997; 7:234-239). © 1997, Elsevier Science Inc.

  17. Tissue Factor Structure and Function

    Directory of Open Access Journals (Sweden)

    Saulius Butenas

    2012-01-01

    Full Text Available Tissue factor (TF is an integral membrane protein that is essential to life. It is a component of the factor VIIa-TF complex enzyme and plays a primary role in both normal hemostasis and thrombosis. With a vascular injury, TF becomes exposed to blood and binds plasma factor VIIa, and the resulting complex initiates a series of enzymatic reactions leading to clot formation and vascular sealing. Many cells, both healthy, and tumor cells, produce detectable amounts of TF, especially when they are stimulated by various agents. Despite the relative simplicity and small size of TF, there are numerous contradictory reports about the synthesis and presentation of TF on blood cells and circulation in normal blood either on microparticles or as a soluble protein. Another subject of controversy is related to the structure/function of TF. It has been almost commonly accepted that cell-surface-associated TF has low (if any activity, that is, is “encrypted” and requires specific conditions/reagents to become active, that is, “decrypted.” However there is a lack of agreement related to the mechanism and processes leading to alterations in TF function. In this paper TF structure, presentation, and function, and controversies concerning these features are discussed.

  18. Tissue factor-factor VIIa-specific up-regulation of IL-8 expression in MDA-MB-231 cells is mediated by PAR-2 and results in increased cell migration

    DEFF Research Database (Denmark)

    Hjortoe, Gertrud M; Petersen, Lars C; Albrektsen, Tatjana

    2004-01-01

    in these processes. To elucidate the potential mechanisms by which TF contributes to tumor invasion and metastasis, we investigated the effect of FVIIa on IL-8 expression and cell migration in a breast carcinoma cell line, MDA-MB-231, a cell line that constitutively expresses abundant TF. Expression of IL-8 m......RNA in MDA-MB-231 cells was markedly up-regulated by plasma concentrations of FVII or an equivalent concentration of FVIIa (10 nM). Neither thrombin nor other proteases involved in hemostasis were effective in stimulating IL-8 in these cells. Increased transcriptional activation of the IL-8 gene...

  19. ELi vananev elanikkond võib riigid pankrotti viia / Kaire Uusen

    Index Scriptorium Estoniae

    Uusen, Kaire

    2006-01-01

    Euroopa Komisjoni poolt läbi viidud uuringu tulemused näitavad, et Euroopas kasvab 2050. aastaks 65-aastaste ja vanemate elanike arv 77 protsendini. Selleks, et toime tulla kiiresti vananeva elanikkonna ja suurenevate kuludega, kavandab komisjon üksikasjalikku eelarvekulude projekti aastani 2050. Lisa: Euroopa vananeb 2050. aastaks

  20. Pistisevõtmine võib Voldemar Trummi trellide taha viia / Gerli Romanovitsh

    Index Scriptorium Estoniae

    Romanovitš, Gerli, 1977-

    2007-01-01

    Ilmunud ka: Severnoje Poberezhje, 29. nov. 2007, lk. 1. Kiviõli seiklusturismikeskuse arendajatelt kapo kahtlustuse kohaselt 300 000 krooni altkäemaksu küsinud rahvaliitlasest ekslinnapea, Kohtla-Järve volikogu liige Voldemar Trumm võib süüdimõistmise korral minna kuni viieks aastaks trellide taha

  1. Eesti usaldusväärsus tuleb viia Euroopa tavakodaniku teadvusse / Lennart Meri

    Index Scriptorium Estoniae

    Meri, Lennart, 1929-2006

    1998-01-01

    President Lennart Meri kõne Riigikogus, 14. september 1998. Kõne eel palus Lennart Meri Riigikogu liikmeid austada leinaseisakuga Ernst Jaaksoni peatselt algavat matusetalitust. Ilmunud ka: Hiiu Leht, 18. sept., lk. 2, pealkiri: Head ajad on möödas: [lüh.]; VIII Riigikogu stenogrammid 1998. V köide: VIII istungjärk, 14. september - 22. oktoober. - Tallinn: Riigikogu kantselei dokumendiosakond, 1999, lk. 2-3, pealk.: Vabariigi Presidendi kõne; Meri, Lennart. Riigimured. - Tartu: Ilmamaa, 2001, lk. 521-525, pealk.: Riigikogu avaistungil. - Kõne Riigikogus, 14. september 1998

  2. On see realistlik - 400 ehitust kahe suvega ellu viia? / Raimo Poom

    Index Scriptorium Estoniae

    Poom, Raimo

    2011-01-01

    CO₂ kvoodi müügist rahastatakse üle 400 objekti energiasäästlikumaks renoveerimist. Ehitusettevõtjate liidu tegevdirektori Indrek Petersoni hinnangul töö firmade taha ei jää, pigem nähakse probleemi hankeprotsesside korraldamises ning projekteerimishangete läbiviimises

  3. Ka meeleheide võib poliitikasse viia / Laura Fairrie ; intervjueerinud Tristan Priimägi

    Index Scriptorium Estoniae

    Fairrie, Laura

    2011-01-01

    Intervjuu filmifestivali DocPoint Tallinn 2011 külalise, inglise filmirežissööri Laura Farrie'ga, kes astub festivalil üles Briti valimisvõitlusest rääkiva dokumentaalfilmiga "Lahing Barkingi pärast"

  4. Rahavajadus võib viia Arco Vara börsile / Raigo Neudorf

    Index Scriptorium Estoniae

    Neudorf, Raigo

    2005-01-01

    Kinnisvarafirma Arco Vara loomisest, arengust ning ettevõtte poolt arendatavatest kinnisvaraprojektidest. Vt. samas: Tallinna peaarhitekt Igor Volkov: Arco on korrektselt käitunud; Hindrek Leppsalu: Arco Vara on tugev konkurent; Nimi tuli omanikult. Diagramm: Iga kolmas käibekroon kasumiks. Lisa: Arco Vara numbrites

  5. Eco-label - simple environmental choice / Andres Viia, Külliki Tafel

    Index Scriptorium Estoniae

    Viia, Andres

    2003-01-01

    Autorid selgitavad ökomärgistuse olemust ja vajalikkust tarbijate teavitamisel vähem keskkonda kahjustavatest toodetest ning teenustest. Lisatud näiteid regionaalsetest ja rahvuslikest ökomärkidest EL-is, tuntumatest ökomärkidest väljaspool Euroopat, hoiatavatest ja informatiivsetest keskkonnamärkidest ning libaökomärkidest. Vt. samas: North-East Estonia - a seat of an environment-friendly batteries' recycling

  6. Maitseelamuste väljak Tallinna vanalinna südames / Viia Iital

    Index Scriptorium Estoniae

    Iital, Viia

    2012-01-01

    Tallinna vanalinna südames asuvatest keskaegset toitu ja meeleolu pakkuvatest restoranidest Olde Hansa ja Waggehus, kõrtsist III Draakon ja poest Krambude, samuti 17. sajandi eesti toite pakkuvast restoranist Glad Estlander ning jazzirestoranist Clazz

  7. ELi vananev elanikkond võib riigid pankrotti viia / Kaire Uusen

    Index Scriptorium Estoniae

    Uusen, Kaire

    2006-01-01

    Euroopa Komisjoni poolt läbi viidud uuringu tulemused näitavad, et Euroopas kasvab 2050. aastaks 65-aastaste ja vanemate elanike arv 77 protsendini. Selleks, et toime tulla kiiresti vananeva elanikkonna ja suurenevate kuludega, kavandab komisjon üksikasjalikku eelarvekulude projekti aastani 2050. Lisa: Euroopa vananeb 2050. aastaks

  8. Opositsiooni šanss: viia presidendivalimised II vooru / Vladislav Inozemtsev ; intervjueerinud Jaanus Piirsalu

    Index Scriptorium Estoniae

    Inozemtsev, Vladislav

    2011-01-01

    Vene majandusteadlane on seisukohal, et opositsiooni juhid oleksid pidanud Bolotnõi miitingul ütlema, et duumavalimiste tulemuste muutmine on ebareaalne ning et nüüd on vaja ühineda märtsis toimuvateks presidendivalimisteks. Samas ta ei usu, et Moskva opositsioon suudaks kokku leppida ühises liidris ja presidendikandidaadis

  9. Ka meeleheide võib poliitikasse viia / Laura Fairrie ; intervjueerinud Tristan Priimägi

    Index Scriptorium Estoniae

    Fairrie, Laura

    2011-01-01

    Intervjuu filmifestivali DocPoint Tallinn 2011 külalise, inglise filmirežissööri Laura Farrie'ga, kes astub festivalil üles Briti valimisvõitlusest rääkiva dokumentaalfilmiga "Lahing Barkingi pärast"

  10. On see realistlik - 400 ehitust kahe suvega ellu viia? / Raimo Poom

    Index Scriptorium Estoniae

    Poom, Raimo

    2011-01-01

    CO₂ kvoodi müügist rahastatakse üle 400 objekti energiasäästlikumaks renoveerimist. Ehitusettevõtjate liidu tegevdirektori Indrek Petersoni hinnangul töö firmade taha ei jää, pigem nähakse probleemi hankeprotsesside korraldamises ning projekteerimishangete läbiviimises

  11. Euroopa päevik aitab tunde läbi viia / Epp Adler, Indrek Riigor

    Index Scriptorium Estoniae

    Adler, Epp

    2008-01-01

    Jaanuari lõpuni saavad kõik Eesti koolid tellida tasuta Euroopa päevikut, kus lisaks kalendrile on 96 lehekülge tekste tarbimise, ühiskonna ja Euroopa teemadel. Tallinna Nõmme Gümnaasiumi ajaloo, ühiskonnaõpetuse ja filosoofia õpetaja Indrek Riigor on päevikut kolm aastat tundides kasutanud

  12. Maitseelamuste väljak Tallinna vanalinna südames / Viia Iital

    Index Scriptorium Estoniae

    Iital, Viia

    2012-01-01

    Tallinna vanalinna südames asuvatest keskaegset toitu ja meeleolu pakkuvatest restoranidest Olde Hansa ja Waggehus, kõrtsist III Draakon ja poest Krambude, samuti 17. sajandi eesti toite pakkuvast restoranist Glad Estlander ning jazzirestoranist Clazz

  13. Ester Tuiksoo tahab Eesti toidu Euroopasse viia / Ester Tuiksoo ; interv. Hindrek Riikoja

    Index Scriptorium Estoniae

    Tuiksoo, Ester, 1965-

    2004-01-01

    Vastne põllumajandusminister tahab keskenduda nii põllumeestele kui ka tööstusele ja kaubandusele, tegelda turunduse, viljareservi hoidmise, EL-i seadusandlusega. Vt. samas Jaanus Marrandi soovitusi uuele põllumajandusministrile

  14. Asjatundja soovitab Eesti Energia kiiresti börsile viia / Tiit Nigul ; interv. Andrus Karnau

    Index Scriptorium Estoniae

    Nigul, Tiit

    2008-01-01

    Eesti Energia endine juhatuse liige vastab küsimustele, mis puudutavad riigi energiapoliitikat ja -varustust, elektrienergia hinnatõusu, energiafirma börsileminekut, tasakaalu konkurentsiameti ja Eesti Energia vahel, ettevõtte tulusid, Narva Elektrijaamade tootmisvõimsust, koostööd Leedu tuumajaama projektiga, elektriturgu, ettevõtja Urmas Sõõrumaa süüdistamist siseinfo kasutamises, Eesti Energia strateegilist eesmärki saavutada aastaks 2015 kaks miljonit klienti

  15. Eco-label - simple environmental choice / Andres Viia, Külliki Tafel

    Index Scriptorium Estoniae

    Viia, Andres

    2003-01-01

    Autorid selgitavad ökomärgistuse olemust ja vajalikkust tarbijate teavitamisel vähem keskkonda kahjustavatest toodetest ning teenustest. Lisatud näiteid regionaalsetest ja rahvuslikest ökomärkidest EL-is, tuntumatest ökomärkidest väljaspool Euroopat, hoiatavatest ja informatiivsetest keskkonnamärkidest ning libaökomärkidest. Vt. samas: North-East Estonia - a seat of an environment-friendly batteries' recycling

  16. Asjatundja soovitab Eesti Energia kiiresti börsile viia / Tiit Nigul ; interv. Andrus Karnau

    Index Scriptorium Estoniae

    Nigul, Tiit

    2008-01-01

    Eesti Energia endine juhatuse liige vastab küsimustele, mis puudutavad riigi energiapoliitikat ja -varustust, elektrienergia hinnatõusu, energiafirma börsileminekut, tasakaalu konkurentsiameti ja Eesti Energia vahel, ettevõtte tulusid, Narva Elektrijaamade tootmisvõimsust, koostööd Leedu tuumajaama projektiga, elektriturgu, ettevõtja Urmas Sõõrumaa süüdistamist siseinfo kasutamises, Eesti Energia strateegilist eesmärki saavutada aastaks 2015 kaks miljonit klienti

  17. Rahavajadus võib viia Arco Vara börsile / Raigo Neudorf

    Index Scriptorium Estoniae

    Neudorf, Raigo

    2005-01-01

    Kinnisvarafirma Arco Vara loomisest, arengust ning ettevõtte poolt arendatavatest kinnisvaraprojektidest. Vt. samas: Tallinna peaarhitekt Igor Volkov: Arco on korrektselt käitunud; Hindrek Leppsalu: Arco Vara on tugev konkurent; Nimi tuli omanikult. Diagramm: Iga kolmas käibekroon kasumiks. Lisa: Arco Vara numbrites

  18. Myosin VIIA is a marker for the cone accessory outer segment in zebrafish

    NARCIS (Netherlands)

    Hodel, Corinne; Niklaus, Stephanie; Heidemann, Martina; Klooster, Jan; Kamermans, M.; Biehlmaier, Oliver; Gesemann, Matthias; Neuhauss, Stephan C F

    2014-01-01

    The accessory outer segment, a cytoplasmic structure running alongside the photoreceptor outer segment, has been described in teleost fishes, excluding the model organism zebrafish. So far, the function of the accessory outer segment is unknown. Here, we describe the ultrastructure of the zebrafish

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

    Directory of Open Access Journals (Sweden)

    Said D Abuhasna

    2012-01-01

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

  20. Tumor Angiogenesis Therapy Using Targeted Delivery of Paclitaxel to the Vasculature of Breast Cancer Metastases

    Directory of Open Access Journals (Sweden)

    Shijun Zhu

    2014-01-01

    Full Text Available Breast cancer aberrantly expresses tissue factor (TF in cancer tissues and cancer vascular endothelial cells (VECs. TF plays a central role in cancer angiogenesis, growth, and metastasis and, as such, is a target for therapy and drug delivery. TF is the cognate receptor of factor VIIa (fVIIa. We have coupled PTX (paclitaxel, also named Taxol with a tripeptide, phenylalanine-phenylalanine-arginine chloromethyl ketone (FFRck and conjugated it with fVIIa. The key aim of the work is to evaluate the antiangiogenic effects of PTX-FFRck-fVIIa against a PTX-resistant breast cancer cell line. Matrigel mixed with VEGF and MDA-231 was injected subcutaneously into the flank of athymic nude mice. Animals were treated by tail vein injection of the PTX-FFRck-fVIIa conjugate, unconjugated PTX, or PBS. The PTX-FFRck-fVIIa conjugate significantly reduces microvessel density in matrigel (p<0.01–0.05 compared to PBS and unconjugated PTX. The breast cancer lung metastasis model in athymic nude mice was developed by intravenous injection of MDA-231 cells expressing luciferase. Animals were similarly treated intravenously with the PTX-FFRck-fVIIa conjugate or PBS. The conjugate significantly inhibits lung metastasis as compared to the control, highlighting its potential to antagonize angiogenesis in metastatic carcinoma. In conclusion, PTX conjugated to fVIIa is a promising therapeutic approach for improving selective drug delivery and inhibiting angiogenesis.

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

    Directory of Open Access Journals (Sweden)

    Ampaiwan Chuansumrit

    2010-03-01

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

  2. Rene Tammist: Eesti Energiat ei maksa praegu börsile viia / Rene Tammist ; intervjueerinud Mikk Salu

    Index Scriptorium Estoniae

    Tammist, Rene, 1978-

    2010-01-01

    Autori väitel on pool Eesti Energia investeerimiskavast problemaatiline, poliitiliselt otsustamata, riskid maandamata. Ta soovitab börsile minekuga 2-3 aastat oodata, siis selgub, kas uuest põlevkivitehnoloogiast saab asja ja kas neid investeeringuid on vaja. Eesti Energiale lisakapitali hankimise võimalustest

  3. Rene Tammist: Eesti Energiat ei maksa praegu börsile viia / Rene Tammist ; intervjueerinud Mikk Salu

    Index Scriptorium Estoniae

    Tammist, Rene, 1978-

    2010-01-01

    Autori väitel on pool Eesti Energia investeerimiskavast problemaatiline, poliitiliselt otsustamata, riskid maandamata. Ta soovitab börsile minekuga 2-3 aastat oodata, siis selgub, kas uuest põlevkivitehnoloogiast saab asja ja kas neid investeeringuid on vaja. Eesti Energiale lisakapitali hankimise võimalustest

  4. Anders Härm kuidas viia kunst mutrivõtmega inimeseni / Anders Härm ; intervjueerinud Tanel Veenre

    Index Scriptorium Estoniae

    Härm, Anders, 1977-

    2010-01-01

    Kunstiteadlase ja Tallinna Kunstihoone kuraatori Anders Härmi elust ja tõekspidamistest. Tema kureeritud sotsiaalkriitilise näituse "Blue Collar Blues" Tallinna Kunstihoones põhjal sotsiaalse kunsti rollist ühiskonnas ning annab hinnangu president Toomas Hendrik Ilvesele

  5. FVIIa-sTF and Thrombin Inhibitory Activities of Compounds Isolated from Microcystis aeruginosa K-139.

    Science.gov (United States)

    Anas, Andrea Roxanne J; Mori, Akane; Tone, Mineka; Naruse, Chiaki; Nakajima, Anna; Asukabe, Hirohiko; Takaya, Yoshiaki; Imanishi, Susumu Y; Nishizawa, Tomoyasu; Shirai, Makoto; Harada, Ken-Ichi

    2017-08-30

    The rise of bleeding and bleeding complications caused by oral anticoagulant use are serious problems nowadays. Strategies that block the initiation step in blood coagulation involving activated factor VII-tissue factor (fVIIa-TF) have been considered. This study explores toxic Microcystis aeruginosa K-139, from Lake Kasumigaura, Ibaraki, Japan, as a promising cyanobacterium for isolation of fVIIa-sTF inhibitors. M. aeruginosa K-139 underwent reversed-phase solid-phase extraction (ODS-SPE) from 20% MeOH to MeOH elution with 40%-MeOH increments, which afforded aeruginosin K-139 in the 60% MeOH fraction; micropeptin K-139 and microviridin B in the MeOH fraction. Aeruginosin K-139 displayed an fVIIa-sTF inhibitory activity of ~166 µM, within a 95% confidence interval. Micropeptin K-139 inhibited fVIIa-sTF with EC50 10.62 µM, which was more efficient than thrombin inhibition of EC50 26.94 µM. The thrombin/fVIIa-sTF ratio of 2.54 in micropeptin K-139 is higher than those in 4-amidinophenylmethane sulfonyl fluoride (APMSF) and leupeptin, when used as positive controls. This study proves that M. aeruginosa K-139 is a new source of fVIIa-sTF inhibitors. It also opens a new avenue for micropeptin K-139 and related depsipeptides as fVIIa-sTF inhibitors.

  6. Determination of FVIIa-sTF Inhibitors in Toxic Microcystis Cyanobacteria by LC-MS Technique.

    Science.gov (United States)

    Anas, Andrea Roxanne J; Nakajima, Anna; Naruse, Chiaki; Tone, Mineka; Asukabe, Hirohiko; Harada, Ken-ichi

    2015-12-30

    The blood coagulation cascade involves the human coagulation factors thrombin and an activated factor VII (fVIIa). Thrombin and fVIIa are vitamin-K-dependent clotting factors associated with bleeding, bleeding complications and disorders. Thrombin and fVIIa cause excessive bleeding when treated with vitamin-K antagonists. In this research, we explored different strains of toxic Microcystis aeruginosa and cyanobacteria blooms for the probable fVIIa-soluble Tissue Factor (fVIIa-sTF) inhibitors. The algal cells were subjected to acidification, and reverse phase (ODS) chromatography-solid phase extraction eluted by water to 100% MeOH with 20%-MeOH increments except for M. aeruginosa NIES-89, from the National Institute for Environmental Studies (NIES), which was eluted with 5%-MeOH increments as an isolation procedure to separate aeruginosins 89A and B from co-eluting microcystins. The 40%-80% MeOH fractions of the cyanobacterial extract are active against fVIIa-sTF. The fVIIa-sTF active fractions from cultured cyanobacteria and cyanobacteria blooms were subjected to liquid chromatography-mass spectrometry (LC-MS). The 60% MeOH fraction of M. aeruginosa K139 exhibited an m/z 603 [M + H]⁺ attributed to aeruginosin K139, and the 40% MeOH fraction of M. aeruginosa NIES-89 displayed ions with m/z 617 [M - SO3 + H]⁺ and m/z [M + H]⁺ 717, which attributed to aeruginosin 89. Aeruginosins 102A/B and 298A/B were also observed from other toxic strains of M. aeruginosa with positive fVIIa-sTF inhibitory activity. The active fractions contained cyanobacterial peptides of the aeruginosin class as fVIIa-sTF inhibitors detected by LC-MS.

  7. Wound healing in hemophilia B mice and low tissue factor mice.

    Science.gov (United States)

    Monroe, Dougald M; Mackman, Nigel; Hoffman, Maureane

    2010-04-01

    Wound healing involves a number of physiologic mechanisms including coagulation, inflammation, formation of granulation tissue, and tissue remodeling. Coagulation with robust thrombin generation leading to fibrin formation is necessary for wound healing. It is less clear if there is a requirement for ongoing coagulation to support tissue remodeling. We have studied wound healing in mice with defects in both the initiation (low tissue factor) and propagation (hemophilia B) phases. In hemophilia B mice, dermal wound healing is delayed; this delay is associated with bleeding into the granulation tissue. Mice can be treated with replacement therapy (factor IX) or bypassing agents (factor VIIa) to restore thrombin generation. If treated just prior to wound placement, mice will have normal hemostasis in the first day of wound healing. As the therapeutic agents clear, the mice will revert to hemophilic state. If the primary role of coagulation in wound healing is to provide a stable platelet/fibrin plug that is loaded with thrombin, then treating hemophilic animals just prior to wound placement should restore normal wound healing. The results from this study did not support that hypothesis. Instead the results show that restoring thrombin generation only at the time of wound placement did not improve the delayed wound healing. In preliminary studies on low tissue factor mice, there also appears to be a delay in wound healing with evidence of bleeding into the granulation tissue. The current data suggests that ongoing coagulation function needs to be maintained to support a normal wound healing process.

  8. Bleeding in patients using new anticoagulants or antiplatelet agents: risk factors and management.

    Science.gov (United States)

    Levi, M M; Eerenberg, E; Löwenberg, E; Kamphuisen, P W

    2010-02-01

    The most important adverse effect of antithrombotic treatment is the occurrence of bleeding. In case of serious or even life-threatening bleeding in a patient who uses anticoagulant agents or when patient on anticoagulants needs to undergo an urgent invasive procedure, anticoagulant treatment can be reversed by various specific strategies. Heparin and heparin derivatives can be counteracted by protamine sulphate, whereas the anticoagulant effect of vitamin K antagonists may be neutralised by administration of vitamin K or prothrombin complex concentrates. The antihaemostatic effect of aspirin and other antiplatelet strategies can be corrected by the administration of platelet concentrate and/or desmopressin, if needed. Recently, a new generation of anticoagulants with a greater specificity towards activated coagulation factors has been introduced and most of these agents are currently being evaluated in clinical studies, showing promising results. The new-generation anticoagulants include specific inhibitors of factor IIa or factor Xa (including pentasaccharides) and antiplatelet agents belonging to the class of thienopyridine derivatives. A limitation of the new class of anti-IIa and anti-Xa agents may be the lack of an appropriate strategy to reverse the effect if a bleeding event occurs, although in some cases the administration of recombinant factor VIIa may be an option.

  9. Dilazep and dipyridamole inhibit tissue factor expression on monocytes induced by IgG from patients with antiphospholipid syndrome

    Institute of Scientific and Technical Information of China (English)

    Hong ZHON

    2004-01-01

    AIM: To investigate whether antiplatelet agents, dilazep and dipyridamole, inhibit tissue factor (TF) expression on monocytes induced by IgG from patients with antiphospholipid syndrome (APS). METHODS: Freshly isolated peripheral blood monocytes were allowed to adhere on plastic and then cultured in media containing patient or control antibodies and/or other agonists with or without dilazep or dipyridamole. The TF activity on monocytes was investigated by measuring factor VIIa-dependent generation of factor Xa, using a chromogenic substrate and the TF mRNA expression was examined by real-time PCR (TaqMan PCR). RESULTS: The TF activity on monocytes induced by APS IgG (250 mg/L) was inhibited by dilazep (0.15-150 μmol/L) and dipyridamole (0.2-200 μrmol/L) in a dose-dependent fashion. But, the TF mRNA expression induced by APS IgG was not inhibited. Theophylline (500 μmol/L), an adenosine receptor antagonist, could counteract the inhibitory effect of dilazep and dipyridamole on TF activity. CONCLUSION: Antiplatelet agents, dilazep and dipyridamole, block APS IgG-induced monocytes TF expression at a post-transcriptional level, partly by adenosine receptor pathway. Pharmacological agents that block monocytes TF activity, such as dilazep and dipyridamole, are a novel therapeutic approach in APS.

  10. Meelis Atonen: Siim Kallas võiks Eesti euroni viia / Meelis Atonen ; intervjueerinud Kärt Anvelt ; kommenteerinud Toomas Vilosius, Ignar Fjuk

    Index Scriptorium Estoniae

    Atonen, Meelis, 1966-

    2009-01-01

    Reformierakonna ühe rajaja Meelis Atoneni sõnul oleks Siim Kallasel Eestis väga tänuväärne ülesanne täita: anda Reformierakonnale tagasi tema õige nägu ning lahendada ühiskonna ees seisvaid probleeme - jõuda euroni ja tasakaalus eelarveni

  11. STEADY-STATE TRANSCRIPT LEVELS OF CYTOCHROME-C-OXIDASE GENES DURING HUMAN MYOGENESIS INDICATE SUBUNIT SWITCHING OF SUBUNIT VIA AND COEXPRESSION OF SUBUNIT VIIA ISOFORMS

    NARCIS (Netherlands)

    TAANMAN, JW; HERZBERG, NH; DEVRIES, H; BOLHUIS, PA; VANDENBOGERT, C

    1992-01-01

    Steady-state levels of the mitochondrial rRNAs, of mRNAs for mitochondrially and nuclear-encoded subunits of cytochrome c oxidase and for the beta-subunit of ATP synthase were assessed by Northern blot hybridizations during the in vitro differentiation of human myoblasts. Transcript levels of the so

  12. Sisekoolitused aitavad ettevõtte väärtusi töötajateni viia / Teele Saarma, Laire Suurväli, Kristina Laaneots ; intervjueerinud Annela Laaneots

    Index Scriptorium Estoniae

    Saarma, Teele

    2016-01-01

    Ettevõtte väärtustest ja nende viimisest töötajateni sisekoolituste kaudu. Kogemusi jagavad Swedbanki Akadeemia juht Teele Saarma, DHL Express Eesti kvaliteedi- ja kommunikatsioonijuht Laire Suurväli ja DHL Express Eesti tegevjuht Kristina Laaneots

  13. Huon Terrace VIIa3, Papua New Guinea Fossil and Living Coral Isotope (delta 18O) Data for 130,000 years BP to Present

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Results of analysis of cores collected from 'fossil' massive Porites corals exposed in the raised reefs of the Huon Peninsula, Papua New Guinea (see below for age...

  14. Ühinemine tõotab E.O.Si ja Pakterminali tõusulainele viia / Lauri Linnamäe

    Index Scriptorium Estoniae

    Linnamäe, Lauri

    2008-01-01

    E.O.Si ja Pakterminali ühinemine lubaks ühendfirmal lisaks senisest laiemale teenusteringile osaleda ka naftaturu tõusude ja mõõnadega kaasnevas spekuleerimises. Vt. samas: Sidemeterohke äriabielu; Naftahind kerkis taevasse

  15. Huon Terrace VIIa1, Papua New Guinea Fossil and Living Coral Isotope (delta 18O) Data for 130,000 years BP to Present

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Results of analysis of cores collected from 'fossil' massive Porites corals exposed in the raised reefs of the Huon Peninsula, Papua New Guinea (see below for age...

  16. Huon Terrace VIIa2, Papua New Guinea Fossil and Living Coral Isotope (delta 18O) Data for 130,000 years BP to Present

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Results of analysis of cores collected from 'fossil' massive Porites corals exposed in the raised reefs of the Huon Peninsula, Papua New Guinea (see below for age...

  17. The local phospholipid environment modulates the activation of blood clotting.

    Science.gov (United States)

    Shaw, Andrew W; Pureza, Vincent S; Sligar, Stephen G; Morrissey, James H

    2007-03-02

    Examples abound of membrane-bound enzymes for which the local membrane environment plays an important role, including the ectoenzyme that triggers blood clotting, the plasma serine protease, factor VIIa, bound to the integral membrane protein, tissue factor. The activity of this enzyme complex is markedly influenced by lipid bilayer composition and further by tissue factor partitioning into membrane microdomains on some cell surfaces. Unfortunately, little is known about how membrane microdomain composition controls factor VIIa-tissue factor activity, as reactions catalyzed by membrane-tethered enzymes are typically studied under conditions in which the experimenter cannot control the composition of the membrane in the immediate vicinity of the enzyme. To overcome this problem, we used a nanoscale approach that afforded complete control over the membrane environment surrounding tissue factor by assembling the factor VIIa.tissue factor complex on stable bilayers containing 67 +/- 1 phospholipid molecules/leaflet (Nanodiscs). We investigated how local changes in phospholipid bilayer composition modulate the activity of the factor VIIa.tissue factor complex. We also addressed whether this enzyme requires a pool of membrane-bound protein substrate (factor X) for efficient catalysis, or alternatively if it could efficiently activate factor X, which binds directly to the membrane nanodomain adjacent to tissue factor. We have shown that full proteolytic activity of the factor VIIa.tissue factor complex requires extremely high local concentrations of anionic phospholipids and further that a large pool of membrane-bound factor X is not required to support sustained catalysis.

  18. An accompanying genetic severe deficiency of tissue factor protects mice with a protein C deficiency from lethal endotoxemia.

    Science.gov (United States)

    Castellino, Francis J; Donahue, Deborah L; Navari, Rudolph M; Ploplis, Victoria A; Walsh, Mark

    2011-01-06

    Mice with a severe genetic deficiency of protein C (PC), PC(-/-)PC(tg4), display enhanced susceptibility to lethal effects of gram-negative endotoxemia induced by lipopolysaccharide (LPS), whereas mice severely deficient in tissue factor (TF), TF(-/-)hTF(tg), are protected from LPS-mediated lethality. In this study, we show that a simultaneous severe deficiency of TF protected low-PC mice from LPS-induced death, resulting in a survival profile similar to that experienced by wild-type (WT) mice. Plasma and whole blood coagulation assays, the latter measured by thromboelastography, demonstrated development of coagulopathies in LPS-treated mice, which were more severe in the case of the doubly deficient TF(-/-)hTF(tg)/PC(-/-)PC(tg4) mice, mainly reflecting earlier signs of disseminated intravascular coagulation in this latter cohort. Markers of inflammation were also elevated in response to LPS in both groups of mice at times just preceding death. We conclude that whereas coagulopathies are more exacerbated in LPS-treated TF(-/-)hTF(tg)/PC(-/-)PC(tg4) mice, the lowering of TF levels in mice with an accompanying severe PC deficiency confers protection against death compared with mice with a single severe PC deficiency. This suggests that proteases generated as a result of factor VIIa/TF-mediated thrombin generation play a mechanistic role in the enhanced lethality seen under very low PC conditions in an endotoxemia model in mice.

  19. [Risk assessment of thrombotic events after the use of activated factor VII].

    Science.gov (United States)

    Martínez López, M C; Alcaraz Romero, A J; Martínez López, A B; Fernández-Llamazares, C M; Ramos Navarro, C

    2013-09-01

    The objective of this study was to analyze the incidence of thrombotic complications related to recombinant human factor viia (rFVIIa) therapy for severe postoperative bleeding in cardiac surgery. A retrospective matched case-control study was conducted over two years, including 72 children admitted to intensive care unit and treated with rFVIIa because of a severe bleeding during or after cardiac surgery. A control group of 63 patients was chosen, who were statistically comparable in sex, weight, diagnosis, surgical risk according RASCH-1 score, and surgical characteristics, was chosen. There were no significant differences between cases and controls either in the rate of thrombosis (20% vs 28%, P=.540), or in the mortality rate (16% vs 9.5%, P=.208). In our study, the rFVIIa therapy was shown to be useful in controlling severe operative bleeding in pediatric cardiac surgery, but does not seem to increase the risk of thrombotic complications or mortality rate in the postoperative period. Copyright © 2012 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  20. Characterization of three abnormal factor IX variants (Bm Lake Elsinore, Long Beach, and Los Angeles) of hemophilia-B. Evidence for defects affecting the latent catalytic site.

    Science.gov (United States)

    Usharani, P; Warn-Cramer, B J; Kasper, C K; Bajaj, S P

    1985-01-01

    Abnormal factor IX variant proteins were isolated from the plasmas of three unrelated severe hemophilia-B families that had been previously shown to contain functionally impaired molecules immunologically similar to normal factor IX. The families studied were: (1) a patient with markedly prolonged ox brain prothrombin time, designated factor IX Bm Lake Elsinore (IXBmLE); (b) three patients (brothers) with moderately prolonged ox brain prothrombin time, designated factor IX Long Beach (IXLB); and (c) a patient with normal ox brain prothrombin time designated factor IX Los Angeles (IXLA). Each variant molecule comigrates with normal factor IX (IXN) both in the sodium dodecyl sulfate and in the nondenaturing alkaline gel electrophoresis. All three variant proteins are indistinguishable from IXN in their amino acid compositions, isoelectric points, carbohydrate distributions and number of gamma-carboxyglutamic acid residues. Each variant protein undergoes a similar pattern of cleavage by factor XIa/Ca2+ and by factor VIIa/Ca2+/tissue factor, and is activated at a rate similar to that observed for IXN. All of the three variant proteins also react with an anti-IXN monoclonal antibody that interferes with the binding of activated IXN(IXaN) to thrombin-treated factor VIIIC. However, in contrast to IXaN, the cleaved IXBmLE has negligible activity (approximately 0.2%), and cleaved forms of IXLA and IXLB have significantly reduced activity (approximately 5-6%) in binding to antithrombin-III/heparin, and in activating factor VII (plus Ca2+ and phospholipid) or factor X (plus Ca2+ and phospholipid) +/- factor VIII. These data, taken together, strongly indicate that the defect in these three variant proteins resides near or within the latent catalytic site. This results in virtually a complete loss of catalytic activity of the cleaved IXBmLE molecule and approximately 95% loss of catalytic activity of the cleaved IXLA and IXLB molecules.

  1. rNAPc2 inhibits colorectal cancer in mice through tissue factor.

    Science.gov (United States)

    Zhao, Jingsong; Aguilar, Gerard; Palencia, Servando; Newton, Elizabeth; Abo, Arie

    2009-01-01

    Recombinant nematode anticoagulant protein c2 (rNAPc2) is a specific inhibitor of tissue factor (TF)/factor VIIa complex with novel antithrombotic activity. TF is highly expressed in human colorectal tumors, and levels are positively correlated with disease progression. To explore the therapeutic potential and mechanism of action of rNAPc2 during tumor growth and metastasis, we tested rNAPc2 in several experimental colorectal cancer models in mice. Administration of rNAPc2 inhibited pulmonary metastasis in mice systemically disseminated with CT26 murine colon carcinoma cells in a dose-dependent fashion. Combining rNAPc2 with the cytotoxic agent 5-fluorouracil or bevacizumab (humanized anti-vascular endothelial growth factor monoclonal antibody) resulted in additive growth inhibition and simultaneous reduction of microvessel density in HCT116 human colorectal tumor xenografts in nude mice. Furthermore, rNAPc2 potentiated CPT-11 in inhibiting hepatic metastasis in nude mice with portal vein injection of HCT116 tumor cells. Long-term administration of rNAPc2 significantly suppressed spontaneous formation of intestinal tumors in Apc(Min/+) mice. Using a RNA interference approach, we showed that TF expression is necessary for rNAPc2-mediated inhibition of HCT116 human colorectal tumor xenograft growth in nude mice, indicating that the antitumor effect of rNAPc2 may be transduced through TF that is expressed on tumor cells. rNAPc2 is a potent anticancer agent when used in combination with chemotherapy or antiangiogenic therapy in mouse models of colorectal cancer, and TF positivity appears to be required for its activity.

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

    Science.gov (United States)

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

    2016-06-23

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

  3. 78 FR 65904 - Permanent Discontinuance or Interruption in Manufacturing of Certain Drug or Biological Products

    Science.gov (United States)

    2013-11-04

    ... alpha- galactosidase A, an enzyme needed to metabolize lipids. The Fabrazyme shortage resulted from...(D) Immune Globulin and Hepatitis B Immune Globulin; Coagulation Factor VIIa (Recombinant); and Coagulation Factor IX. Second, the product distribution data is submitted to PPTA (and subsequently to FDA) on...

  4. Effects of sucrose on rFVIIa aggregation and methionine oxidation

    DEFF Research Database (Denmark)

    Soenderkaer, Susanne; Carpenter, John F; van de Weert, Marco

    2004-01-01

    The aim of this study was to characterize the effects of sucrose on the stability of recombinant factor VIIa (rFVIIa), with special emphasis on aggregation and methionine oxidation, as well as to investigate the impact of various environmental conditions on the rFVIIa conformation. The stability ...

  5. Damage Control Resuscitation: A New Paradigm for Fluid Resuscitation of Severely Injured Soldiers

    Science.gov (United States)

    2006-11-01

    R. P., 2004: Uses of recombinant factor VIIa in trauma. Curr Opin Crit Care, 10, 520-528. Stein, D. M., Dutton, R. P., O’Connor, J., Alexander , M...hypertonic saline-dextran-70. Clin Chem, 42, 779-780. Wolfman, E. F., Jr., Neill , S. A., Heaps, D. K., and Zuidema, G. D., 1963: Donor blood and

  6. 1 küsimus noorele juhile : Kuidas on kõige parem tähtsad põhimõtted töötajateni viia? / Kaarel Oja, Reet Roos, Martin Hurt... [jt.

    Index Scriptorium Estoniae

    2010-01-01

    Küsimusele vastavad Teater NO99 tegevjuht Kaarel Oja, meediaagentuuri Inspired, tööõigusbüroo ja trükikoja Digiprint omanik Reet Roos, kaitseministeeriumi asekantsler Martin Hurt, SOL Eesti personalijuht Evely Ellert ning investeerimis- ja varahalduslahendusi pakkuva Sampo Life juhatuse liige Erkki Sadam

  7. 1 küsimus noorele juhile : Kuidas on kõige parem tähtsad põhimõtted töötajateni viia? / Kaarel Oja, Reet Roos, Martin Hurt... [jt.

    Index Scriptorium Estoniae

    2010-01-01

    Küsimusele vastavad Teater NO99 tegevjuht Kaarel Oja, meediaagentuuri Inspired, tööõigusbüroo ja trükikoja Digiprint omanik Reet Roos, kaitseministeeriumi asekantsler Martin Hurt, SOL Eesti personalijuht Evely Ellert ning investeerimis- ja varahalduslahendusi pakkuva Sampo Life juhatuse liige Erkki Sadam

  8. В коалиции продолжаются споры / Туули Кох

    Index Scriptorium Estoniae

    Кох, Туули

    2010-01-01

    Eesti Reformierakond hakkab arutama valimisreformi ettevalmistava delegatsiooni moodustamist konsultatsioonideks teiste erakondadega. Tulevikus on kavas viia Riigikogu ja kohalike volikogude valimised ühele päevale. Skeem

  9. Valitsusparteid trumpavad üksteist üle / Tuuli Koch ; kommenteerinud Tõnis Saarts, Urmo Kübar

    Index Scriptorium Estoniae

    Koch, Tuuli

    2010-01-01

    Eesti Reformierakond hakkab arutama valimisreformi ettevalmistava delegatsiooni moodustamist konsultatsioonideks teiste erakondadega. Tulevikus on kavas viia Riigikogu ja kohalike volikogude valimised ühele päevale. Skeem

  10. Korruptsiooni bioloogilised juured / Jaak Rebane

    Index Scriptorium Estoniae

    Rebane, Jaak

    1999-01-01

    Kuritarvitusele aitavad viia inimese teatud omadused, nagu egoism, piiratus, ahnus, jultumus, tarbimismentaliteet, tõusiklikkus. Korrumptantsaab varumistungi ajel ebaeetilisest käitumisest hoopis positiivse emotsiooni

  11. Veterinarnõje normõ - element politiki / Dmitri Kulikov

    Index Scriptorium Estoniae

    Kulikov, Dmitri

    2004-01-01

    Venemaa kavatseb sisse viia ranged veterinaarnormid kõikidele Euroopa Liidu liikmesriikidele, Euroopa Komisjonist saabuvad inspektorid Eesti toiduainetetööstuse ettevõtete toodangu kontrollimiseks

  12. Korruptsiooni bioloogilised juured / Jaak Rebane

    Index Scriptorium Estoniae

    Rebane, Jaak

    1999-01-01

    Kuritarvitusele aitavad viia inimese teatud omadused, nagu egoism, piiratus, ahnus, jultumus, tarbimismentaliteet, tõusiklikkus. Korrumptantsaab varumistungi ajel ebaeetilisest käitumisest hoopis positiivse emotsiooni

  13. Veterinarnõje normõ - element politiki / Dmitri Kulikov

    Index Scriptorium Estoniae

    Kulikov, Dmitri

    2004-01-01

    Venemaa kavatseb sisse viia ranged veterinaarnormid kõikidele Euroopa Liidu liikmesriikidele, Euroopa Komisjonist saabuvad inspektorid Eesti toiduainetetööstuse ettevõtete toodangu kontrollimiseks

  14. Replacement of isoleucine-397 by threonine in the clotting proteinase factor IXa (Los Angeles and Long Beach variants) affects macromolecular catalysis but not L-tosylarginine methyl ester hydrolysis. Lack of correlation between the ox brain prothrombin time and the mutation site in the variant proteins.

    Science.gov (United States)

    Spitzer, S G; Warn-Cramer, B J; Kasper, C K; Bajaj, S P

    1990-01-01

    Previously, from the plasma of unrelated haemophilia-B patients, we isolated two non-functional Factor IX variants, namely Los Angeles (IXLA) and Long Beach (IXLB). Both variants could be cleaved to yield Factor IXa-like molecules, but were defective in catalysing the cleavage of Factor X (macromolecular substrate) and in binding to antithrombin III (macromolecular inhibitor). In the present study we have identified the mutation of IXLA by amplifying the exons (including flanking regions) as well as the 5' end of the gene by polymerase-chain-reaction (PCR) method and sequencing the amplified DNA by the dideoxy chain-termination method. Comparison of the normal IX and IXLA sequences revealed only one base substitution (T----C) in exon VIII of IXLA, with a predicted replacement of Ile-397 to Thr in the mature protein. This mutation is the same as found recently for IXLB. The observation that IXLB and IXLA have the same mutation is an unexpected finding, since, on the basis of their ox brain prothrombin time (PT, a test that measures the ability of the variant Factor IX molecules to inhibit the activation of Factor X by Factor VIIa-tissue factor complex), these variants have been classified into two different groups and were thought to be genetically different. Our observation thus suggests that the ox brain PT does not reflect the locus of mutation in the coding region of the variant molecules. However, our analysis suggests that the ox brain PT is related to Factor IX antigen concentration in the patient's plasma. Importantly, although the mutation in IXLA or IXLB protein is in the catalytic domain, purified IXaLA and IXaLB hydrolyse L-tosylarginine methyl ester at rates very similar to that of normal IXa. These data, in conjunction with our recent data on Factor IXBm Lake Elsinore (Ala-390----Val mutant), strengthen a conclusion that the peptide region containing residues 390-397 of normal Factor IXa plays an essential role in macromolecular substrate catalysis and

  15. The Senior Visiting Surgeons Program: A Model for Sustained Military-Civilian Collaboration in Times of War and Peace

    Science.gov (United States)

    2012-01-01

    and Air Force) who work collaboratively with the single goal of providing immediate surgical therapy , stabilization, and critical care services while...recombinant factor VIIa (rFVIIa). This drug which was designed and approved for treatment of patients with hemophilia who had developed antibodies to factor...Ohio Wayne Meredith, North Carolina Gene Moore, Colorado Frederick Moore, Florida Peter Musket, Ohio Gage Ochsner, Georgia Andrew Peitzman, Pennsylvania

  16. Molecular and Clinical Based Cardiovascular Care Program and Military Medical Molecular Initiative (M3I) - Integrative Cardiac Health Project. Addendum

    Science.gov (United States)

    2008-11-01

    adinopectin, ghrelin , leptin , interleukin-6 and-8, tumor necrosis factor, triglycerides, glucose, and insulin. This data is currently being analyzed at the...ADMA, hsC-reactive protein, activated factor VII-A, oxidized LDL, PYY, CCK, VCAM-1, adinopectin, ghrelin , leptin , interleukin-6 and-8, tumor necrosis...potentially important in CAD development and/or reversal: insulin, leptin , C-reactive protein, interleukin-6, and interleukin-8. Results are shown

  17. Alternativas farmacológicas a la transfusión sanguínea: ¿Qué hay de nuevo?

    OpenAIRE

    2004-01-01

    Pharmacological approaches to reduce blood transfusion include the protease inhibitor aprotinin, lysine-analogue antifibrinolytics synthetic arginine-vasopressin derivatives (DDAVP) and recombinant factor VII (rfVIIa). These agents are known to prevent the need for blood after major surgery (cardiac, hepatic, and orthopaedic). Among the nonhemostatic agents erythropoietin (EPO) may be effective to reduce blood requirements in medical and surgical patients. Aprotinin is consistently effective ...

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

    Directory of Open Access Journals (Sweden)

    Manash S Chatterjee

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

  19. A New Member of Gamma-Conotoxin Family Isolated from Conus princeps Displays a Novel Molecular Target

    Science.gov (United States)

    Bernáldez, Johanna; Jiménez, Samanta; González, Luis Javier; Ferro, Jesús Noda; Soto, Enrique; Salceda, Emilio; Chávez, Daniela; Aguilar, Manuel B.; Licea-Navarro, Alexei

    2016-01-01

    A novel conotoxin, named as PiVIIA, was isolated from the venom of Conus princeps, a marine predatory cone snail collected in the Pacific Southern Coast of Mexico. Chymotryptic digest of the S-alkylated peptide in combination with liquid chromatography coupled to tandem mass spectrometry, were used to define the sequencing of this peptide. Eleven N-terminal amino acids were verified by automated Edman degradation. PiVIIA is a 25-mer peptide (CDAOTHYCTNYWγCCSGYCγHSHCW) with six cysteine residues forming three disulphide bonds, a hydroxyproline (O) and two gamma carboxyglutamic acid (γ) residues. Based on the arrangement of six Cys residues (C-C-CC-C-C), this conotoxin might belong to the O2-superfamily. Moreover, PiVIIA has a conserved motif (-γCCS-) that characterizes γ-conotoxins from molluscivorous Conus. Peptide PiVIIA has 45% sequence identity with γ-PnVIIA—the prototype of this family. Biological activity of PiVIIA was assessed by voltage-clamp recording in rat dorsal root ganglion neurons. Perfusion of PiVIIA in the µM range produces a significant increase in the Ca2+ currents, without significantly modifying the Na+, K+ or proton-gated acid sensing ionic currents. These results indicate that PiVIIA is a new conotoxin whose activity deserves further studies to define its potential use as a positive modulator of neuronal activity. PMID:26861393

  20. A New Member of Gamma-Conotoxin Family Isolated from Conus princeps Displays a Novel Molecular Target

    Directory of Open Access Journals (Sweden)

    Johanna Bernáldez

    2016-02-01

    Full Text Available A novel conotoxin, named as PiVIIA, was isolated from the venom of Conus princeps, a marine predatory cone snail collected in the Pacific Southern Coast of Mexico. Chymotryptic digest of the S-alkylated peptide in combination with liquid chromatography coupled to tandem mass spectrometry, were used to define the sequencing of this peptide. Eleven N-terminal amino acids were verified by automated Edman degradation. PiVIIA is a 25-mer peptide (CDAOTHYCTNYWγCCSGYCγHSHCW with six cysteine residues forming three disulphide bonds, a hydroxyproline (O and two gamma carboxyglutamic acid (γ residues. Based on the arrangement of six Cys residues (C-C-CC-C-C, this conotoxin might belong to the O2-superfamily. Moreover, PiVIIA has a conserved motif (-γCCS- that characterizes γ-conotoxins from molluscivorous Conus. Peptide PiVIIA has 45% sequence identity with γ-PnVIIA—the prototype of this family. Biological activity of PiVIIA was assessed by voltage-clamp recording in rat dorsal root ganglion neurons. Perfusion of PiVIIA in the µM range produces a significant increase in the Ca2+ currents, without significantly modifying the Na+, K+ or proton-gated acid sensing ionic currents. These results indicate that PiVIIA is a new conotoxin whose activity deserves further studies to define its potential use as a positive modulator of neuronal activity.

  1. Linnukasvatajad kardavad mõõna-aasta saabumist / Kaire Uusen

    Index Scriptorium Estoniae

    Uusen, Kaire

    2006-01-01

    Suure kiirusega Eestile lähenev linnugripp on teinud murelikuks kodulinnukasvatajad, sest haigus võib laostada suure osa linnufarmidest ja viia nende ettevõtmised pankrotti. Lisa: Viiruse H5N1 levik Euroopas

  2. 21 CFR 177.1820 - Styrene-maleic anhydride copolymers.

    Science.gov (United States)

    2010-04-01

    ... articles that contact food of Types I, II, III, IV-A, IV-B, V, VI-B (except carbonated beverages), VII-A...; for use (except carbonated beverage bottles) as articles or as components of articles that contact...

  3. Telekomihiid käis m-maksete luurel / Gert D. Hankewitz

    Index Scriptorium Estoniae

    Hankewitz, Gert D.

    2007-01-01

    Maailma suurimale telekommunikatsioonifirmale Telefonica pakuvad huvi Eesti e- ja m-teenused, mis võib viia Eestisse investeerimiseni. Lisad: Telefonica kasum teel ülesse; Telefonica; Raketid -maksete tehnoloogia vastu

  4. Saamskije oleni utshat komandu "Vozduhh" / Viktor Kononov

    Index Scriptorium Estoniae

    Kononov, Viktor

    2004-01-01

    NATO plaanib Norras saamide rändealal läbi viia sõjalised õppused, kus kavatsetakse kasutada uusimat lahingutehnikat - lasersihikuga pomme. Saamid on alustanud juriidilist sõda oma huvide kaitseks

  5. 365 dnei tishinõ, no ne poteri pamjati / Raul Kalev

    Index Scriptorium Estoniae

    Kalev, Raul

    2008-01-01

    Autor kirjutab, et probleem, mis oli enne pronkssõduri teisaldamist, on jäänud. Integratsiooni ei saa läbi viia sunniviisiliselt, selleks on vaja tõsta inimeste teadlikkust ja huvi, kirjutab autor

  6. Swedbanki juht jahmatas Eesti ärimehi / Sulev Vedler

    Index Scriptorium Estoniae

    Vedler, Sulev, 1970-

    2010-01-01

    Swedbanki Balti-haru juht Håkan Berg ütles Balti investorite konverentsil, et pank ei kavatse krediidiotsuseid tagasi Balti riikide kontoritesse viia. Balti-haru PR-juhi Kristi Liiva, Håkan Bergi selgitusi

  7. Kurss asteroididele

    Index Scriptorium Estoniae

    2010-01-01

    USA loobus plaanist kasutada Kuud hüppelauana Marsile. NASA soovib end Rahvusvahelises Kosmosejaamas (ISS) kindlamalt sisse seada, arendada uusi rakette ja viia inimesed mõnele Maa-lähedasele asteroidile

  8. Eesti Raudtee astus sammu aktsiate börsile viimise poole / Villy Paimets

    Index Scriptorium Estoniae

    Paimets, Villy, 1972-

    2004-01-01

    Eesti Raudtee nõukogu esimees Edward Burkhardt esitles majandus- ja kommunikatsiooniminister Meelis Atonenile investeerimispanga Suprema soovitust Eesti Raudtee börsile viia. Diagrammid: Eesti Raudtee toodab omanikele üha enam kasumit

  9. Gaza võitmatu armaada / Andres Laasik

    Index Scriptorium Estoniae

    Laasik, Andres, 1960-2016

    2010-01-01

    Katsest viia laevadega humanitaarabi Gaza sektorisse. Autor on arvamusel, et kui Vabaduse laevastik ongi saavutanud soovitu ja murdnud blokaadi, siis uus tasakaal pole julgeoleku mõttes sugugi kindlam

  10. Kurss asteroididele

    Index Scriptorium Estoniae

    2010-01-01

    USA loobus plaanist kasutada Kuud hüppelauana Marsile. NASA soovib end Rahvusvahelises Kosmosejaamas (ISS) kindlamalt sisse seada, arendada uusi rakette ja viia inimesed mõnele Maa-lähedasele asteroidile

  11. Insurance bankruptcy creates political storm

    Index Scriptorium Estoniae

    2005-01-01

    Hoolimata peaminister Algirdas Brazauskase nõudmisest, keeldus Leedu kindlustusinspektsiooni juht Edvinas Vasilis-Vasiliauskas oma kohalt tagasi astumast, kuna soovib viia lõpule kindlustusseltsi Ingo Baltic pankrotiprotsessi

  12. Börs nutab taga Eesti Energia loobumist / Jaana Pikalev ; kommenteerinud Jürgen Ligi, Sandor Liive

    Index Scriptorium Estoniae

    Pikalev, Jaana

    2010-01-01

    SEB privaatpanganduse osakonna strateeg Peeter Koppel, LHV Panga analüütik Sten Pisang, investor Stefan Andresson avaldavad arvamust seoses otsusega Eesti Energia veel mitte börsile viia. Majandus- ja kommunikatsiooniminister Juhan Partsi arvamus

  13. Insurance bankruptcy creates political storm

    Index Scriptorium Estoniae

    2005-01-01

    Hoolimata peaminister Algirdas Brazauskase nõudmisest, keeldus Leedu kindlustusinspektsiooni juht Edvinas Vasilis-Vasiliauskas oma kohalt tagasi astumast, kuna soovib viia lõpule kindlustusseltsi Ingo Baltic pankrotiprotsessi

  14. Miin Tallinna ja kaitseministeeriumi suhetes / Heldur Unt

    Index Scriptorium Estoniae

    Unt, Heldur

    2005-01-01

    OÜ Hat Grupp jurist juhib tähelepanusellele, et Riigikogu on ratifitseerinud Haagi konventsiooni, selle kohaselt tuleks Miinisadam kui militaarobjekt Tallinnast kui UNESCO maailmapärandi nimistusse kuuluvast linnast kohe välja viia

  15. Euroopa väärtuste nimel ja Eesti eest! = За Эстонию и европейские ценности! / Siiri Oviir

    Index Scriptorium Estoniae

    Oviir, Siiri, 1947-

    2009-01-01

    Euroopa Parlamendi liige esitab ettepanekuid, mis puudutavad sotsiaaltoetuste allesjätmist isiku ajutisele tööle mineku korral, ravikindlustusraha, vajadust viia Eestis ellu euroopalik maksureform ning mõningate kaupade ja teenuste käibemaksu alandamist

  16. Aeg panustada nafta hinna langusele / Tarvo Vaarmets

    Index Scriptorium Estoniae

    Vaarmets, Tarvo

    2008-01-01

    Autor analüüsib maailma naftatootmist ning leiab, et vähenev naftanõudlus võib viia nafta hinna langusele. Vt. samas: Kuidas nafta hinna langusest kasu lõigata?; Tabel: Naftaturg; Võrdlusandmed

  17. Debatt: kuidas päästa Eesti majandus? / interv. Aavo Kokk

    Index Scriptorium Estoniae

    2008-01-01

    Juhan Parts, Meelis Atonen ja Edgar Savisaar arutlevad, millest tulenevad praegused majandusprobleemid ja mida peaks Eesti majandusega ette võtma, et olukord paraneks, millised reformid tuleks ellu viia. Üles kirjutanud Jaanus Kõrv

  18. Bõvshii glava narvskoi politsii uhhodit v ohrannuju firmu / Irina Tokareva

    Index Scriptorium Estoniae

    Tokareva, Irina

    2004-01-01

    Narva politseiprefektuuri endine prefekt Artur Pärnoja asub tööle turvafirmasse Securitas, et ellu viia uus projekt ettevõtte töö efektiivsemaks muutmiseks, regioonis toimunud politseistruktuuride muutustega ei ole ta rahul

  19. Iisraeli ühiskond on lõhenemas / Jüri Piirisild

    Index Scriptorium Estoniae

    Piirisild, Jüri

    2004-01-01

    Iisraeli sisepinged seoses juhtkonna plaaniga juudi asunikud Gaza sektorist välja viia ning aastakümneid kestnud konflikt palestiinlastega on mõjutanud nii riigi majandust kui usaldust peaminister Ariel Sharoni vastu

  20. Transpordifirmad peavad oluliseks Tartu maantee ja Venemaa piiriga seotud projekte / Tanel Raig

    Index Scriptorium Estoniae

    Raig, Tanel, 1975-

    2007-01-01

    Küsitlusest, mille käigus anti erinevatele transpordifirmadele võimalus hinnata 2007.-2013. aasta Eesti transpordisektori investeeringutevajaduste nimekirja projekte. Tabel: 2007-2013 transpordisektori investeeringuvajadused. Vt. samas: Millised transpordialased projektid on olulised Eestis ellu viia?

  1. Aeg panustada nafta hinna langusele / Tarvo Vaarmets

    Index Scriptorium Estoniae

    Vaarmets, Tarvo

    2008-01-01

    Autor analüüsib maailma naftatootmist ning leiab, et vähenev naftanõudlus võib viia nafta hinna langusele. Vt. samas: Kuidas nafta hinna langusest kasu lõigata?; Tabel: Naftaturg; Võrdlusandmed

  2. Lennufirmad ägavad nafta hinna surve all / Tõnis Arnover

    Index Scriptorium Estoniae

    Arnover, Tõnis, 1952-

    2004-01-01

    Nafta kõrge hind ähvardab palju kütust tarbivad lennukompaniid kahjumisse viia kuna tiheda konkurentsi tingimustes piletihindu tõsta ei soovita. Diagramm: Nafta hind tänavu kerkinud üle kolmandiku

  3. Võõrsil soetatud tunnistus vajab tunnustamist / Gunnar Vaht ; intervjueerinud Jaanika Meier

    Index Scriptorium Estoniae

    Vaht, Gunnar

    2009-01-01

    Vestlus Sihtasutuse Archimedes struktuuriüksuse Akadeemilise tunnustamise infokeskuse (Eesti ENIK/NARIC keskuse) juhataja Gunnar Vahiga, kes selgitab, et välisriigi haridusdokument tuleb meie haridussüsteemiga vastavusse viia

  4. Gaza võitmatu armaada / Andres Laasik

    Index Scriptorium Estoniae

    Laasik, Andres, 1960-2016

    2010-01-01

    Katsest viia laevadega humanitaarabi Gaza sektorisse. Autor on arvamusel, et kui Vabaduse laevastik ongi saavutanud soovitu ja murdnud blokaadi, siis uus tasakaal pole julgeoleku mõttes sugugi kindlam

  5. Börs nutab taga Eesti Energia loobumist / Jaana Pikalev ; kommenteerinud Jürgen Ligi, Sandor Liive

    Index Scriptorium Estoniae

    Pikalev, Jaana

    2010-01-01

    SEB privaatpanganduse osakonna strateeg Peeter Koppel, LHV Panga analüütik Sten Pisang, investor Stefan Andresson avaldavad arvamust seoses otsusega Eesti Energia veel mitte börsile viia. Majandus- ja kommunikatsiooniminister Juhan Partsi arvamus

  6. WW instituudi direktor Christopher Flavin : Kyoto protokoll viiakse ellu Bushita / Christopher Flavin ; interv. Tarmo Virki

    Index Scriptorium Estoniae

    Flavin, Christopher

    2002-01-01

    World Watch Instituudi direktor leiab, et maailm vajaks globaalset keskkonnaorganisatsiooni, mis tasakaalustaks Maailma Kaubandusorganisatsiooni mõju. Euroopa Liit ja Jaapan suudavad Kyoto protokolli ratifitseerimise ellu viia ka ilma USA-ta. Lisa: Tuumaenergia pole lahendus

  7. Laurentiuse kirik päästab Saueri oreli osi niiskuse käest / Andres Sepp ; kommenteerinud Anti Toplaan

    Index Scriptorium Estoniae

    Sepp, Andres, 1976-

    2009-01-01

    Kuressaare Laurentiuse kiriku kogudus otsib võimalusi viia 1881. a. Wilhelm Saueri firmas valminud vanima Eestis säilinud oreli puidust ja metallist osad kuivemasse kohta. Praegu seisavad need kiriku garaažis

  8. Obutshenije i upravlenije znanijami kak elementõ innovatsionnoi dejatelnosti / T. P Savenkova, T. I Savenkova

    Index Scriptorium Estoniae

    Savenkova, T. P

    2004-01-01

    Autorite hinnangul on personali koolitus organisatsiooni eduka tegutsemise aluseks, võimaldades kergemini saavutada strateegilisi eesmärke, tõsta inimressursi kvaliteeti ja viia hõlpsamini läbi organisatsioonilisi muudatusi. Tabelid

  9. Testing of Intravenous Hemostatic Agents in a Novel Swine Model of Bleeding: Preliminary Results With FXa-PCPs

    Science.gov (United States)

    2005-08-01

    final cumulative dose of 700 pmoles VIIa using a half - life of 147 min for factor Vl~a. Drug administered every 20 min. "a•bHigh dose given first...take into account the extremely short half - life of FXa (᝿ sec). In two of these pigs (#102 and #103), the low dose of drug (2.5 pmoles FXa/4.0 nmoles...using glycopyrrolate and TelazolR. Buprenorphine (0.9 mg, i.m.) was administered for analgesia. They were then and anesthetized (1-4% isoflurane in

  10. Hemorrhagic disease of the newborn despite vitamin K prophylaxis at birth.

    Science.gov (United States)

    Flood, Veronica H; Galderisi, Faith C; Lowas, Stefanie R; Kendrick, Angela; Boshkov, Lynn K

    2008-05-01

    Late hemorrhagic disease of the newborn (HDN) presents 0.5-6 months after birth with mucocutaneous and intracranial bleeding. We describe here two cases of late HDN in infants who received vitamin K. The first case is a previously healthy breastfed male who received one dose of oral vitamin K at birth and developed an intracranial hemorrhage 5 weeks later. He was treated with intravenous vitamin K and recombinant factor VIIa prior to emergent craniectomy. An unrelated infant presented at 5 months of age with diarrhea and easy bruising despite IM vitamin K at birth. These cases illustrate the morbidity associated with late HDN.

  11. Acute hypotension associated with intraoperative cell salvage using a leukocyte depletion filter during management of obstetric hemorrhage due to amniotic fluid embolism.

    Science.gov (United States)

    Rogers, William Kirke; Wernimont, Sarah A; Kumar, Girish C; Bennett, Eliza; Chestnut, David H

    2013-08-01

    Amniotic fluid embolism (AFE) is a rare but catastrophic obstetric complication that can lead to profound coagulopathy and hemorrhage. The role of cell salvage and recombinant human Factor VIIa (rFVIIa) administration in such cases remains unclear. We present a case of AFE and describe our experience with the use of cell salvage and rFVIIa administration during the resuscitation. Cell salvage and transfusion through a leukocyte depletion filter was attempted after the diagnosis of AFE was made, but the attempted transfusion was immediately followed by hypotension and a worsening of hemodynamics. rFVIIa, on the contrary, was used with clinical improvement in coagulopathy and without apparent adverse thrombotic effect.

  12. Changes in thrombin generation in children after cardiac surgery and ex-vivo response to blood products and haemostatic agents

    DEFF Research Database (Denmark)

    Andreasen, Jo B; Ravn, Hanne B; Hvas, Anne-Mette

    2016-01-01

    -poorplasma = 0.013; Pplatelet-richplasma generation potential (Pplatelet-poorandplatelet-richplasma recombinant factor VIIa improved......Impaired haemostasis has been reported in children with congenital heart disease undergoing cardiopulmonary bypass. As thrombin generation encompasses all phases of the coagulation process, this analysis might provide the best assessment of global haemostasis. A prospective study was undertaken...... to test the hypothesis that thrombin generation reveals an impaired haemostasis after paediatric cardiac surgery and that ex-vivo addition of platelet concentrate and haemostatic agents improves thrombin generation. The study comprised 29 children with congenital heart disease, who underwent corrective...

  13. Emergency caesarean delivery in a patient with cerebral malaria-leptospira co infection: Anaesthetic and critical care considerations

    Directory of Open Access Journals (Sweden)

    Sukhen Samanta

    2014-01-01

    Full Text Available Malaria-leptospira co-infection is rarely detected. Emergency surgery in such patients has not been reported. We describe such a case of a 24-year-old primigravida at term pregnancy posted for emergency caesarean delivery who developed pulmonary haemorrhage, acute respiratory distress syndrome, acute kidney injury, and cerebral oedema. Here, we discuss the perioperative management, pain management (with transverse abdominis plane block, intensive care management (special reference to management of pulmonary haemorrhage with intra pulmonary factor VIIa and the role of plasmapheresis in leptospira related jaundice with renal failure.

  14. Intravenous regional analgesia in a patient with Glanzmann thrombastenia.

    Science.gov (United States)

    Goksu, Sitki; Gul, Rauf; Ozen, Onder; Yilmaz, Mehmet; Buyukbebeci, Orhan; Oner, Unsal

    2010-02-01

    Glanzmann thrombastenia (GT) is a rare condition of an inherited autosomal recessive gene characterized with bleeding tendency. The condition is rarely met in the OR. and therefore it is essential that anesthesiologist be cognizant of the risk involved and be prepared with all necessary precautionary measures. We present a GT case in a 27-year-old male with a mass in the anticubital region of right wrist that was successfully excised using the non-invasive intravenous regional analgesia (IVRA). The use of platelet transfusion and the recombinant factor VIIa, are stressed.

  15. Management of the Bleeding Patient Receiving New Oral Anticoagulants: A Role for Prothrombin Complex Concentrates

    Directory of Open Access Journals (Sweden)

    Lisa M. Baumann Kreuziger

    2014-01-01

    Full Text Available Ease of dosing and simplicity of monitoring make new oral anticoagulants an attractive therapy in a growing range of clinical conditions. However, newer oral anticoagulants interact with the coagulation cascade in different ways than traditional warfarin therapy. Replacement of clotting factors will not reverse the effects of dabigatran, rivaroxaban, or apixaban. Currently, antidotes for these drugs are not widely available. Fortunately, withholding the anticoagulant and dialysis are freqnently effective treatments, particularly with rivaroxaban and dabigatran. Emergent bleeding, however, requires utilization of Prothrombin Complex Concentrates (PCCs. PCCs, in addition to recombinant factor VIIa, are used to activate the clotting system to reverse the effects of the new oral anticoagulants. In cases of refractory or emergent bleeding, the recommended factor concentrate in our protocols differs between the new oral anticoagulants. In patients taking dabigatran, we administer an activated PCC (aPCC [FELBA] due to reported benefit in human in vitro studies. Based on human clinical trial evidence, the 4-factor PCC (Kcentra is suggested for patients with refractory rivaroxaban- or apixaban-associated hemorrhage. If bleeding continues, recombinant factor VIIa may be employed. With all of these new procoagulant agents, the risk of thrombosis associated with administration of factor concentrates must be weighed against the relative risk of hemorrhage.

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

    Science.gov (United States)

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

    2015-04-30

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

  17. Synthesis of new 1-(amino)-3-[(1,5-diphenyl-1H-1,2,4-triazol-3-yl) oxy] propan-2-ol and 1-[(1,5-diphenyl- 1H- 1,2,4-triazol-3-yl) oxy]-3-(4-arylpiperazin-1-yl) propan-2-ol derivatives with an expected beta-adrenolytic activity.

    Science.gov (United States)

    Kossakowski, Jerzy; Struga, Marta; Kozioł, Anna E

    2006-01-01

    3-(Oxiran-2-ylmethoxy)-l ,5-diphenyl-lH-1,2,4-triazole [I] was obtained in the reaction of 1,5-di-phenyl-IH-1,2,4-triazol-3-ol with 2-(chloromethyl) oxirane. Then I was converted into the corresponding aminoalkanol derivatives of 1,5-diphenyl-IH-1,2,4-triazol-3-ol, IIa,b -VIIa,b. Molecular structure of I was confirmed by an X- ray structure analysis. The receptor affinities for IVa, VIIa were determined.

  18. The coagulopathy in sepsis: significance and implications for treatment

    Directory of Open Access Journals (Sweden)

    Berardino Pollio

    2011-09-01

    Full Text Available Sepsis related coagulopathy ranges from mild laboratory alterations up to severe disseminated intravascular coagulation (DIC. There is evidence that DIC is involved in the pathogenesis of microvascular dysfunction contributing to organ failure. Additionally, the systemic activation of coagulation, by consuming platelets and coagulation factors, may cause bleeding. Thrombin generation via the tissue factor/factor VIIa route, contemporary depression of antithrombin and protein C anticoagulant system, as well as impaired fibrin degradation, due to high circulating levels of PAI-1, contribute to enhanced intravascular fibrin deposition. This deranged coagulopathy is an independent predictor of clinical outcome in patients with severe sepsis. Innovative supportive strategies aiming at the inhibition of coagulation activation comprise inhibition of tissue factor-mediated activation or restoration of physiological anticoagulant pathways, as the administration of recombinant human activated protein C or concentrate. In spite of some promising initial studies, additional trials are needed to define their clinical effectiveness in adults and children with severe sepsis.

  19. Trombofilia, autoinmunidad y tromboprofilaxis perioperatoria

    OpenAIRE

    Benjamín Rubio-Jurado; Mario Salazar-Páramo; Fabiola Medrano-Muñoz; Alejandro González-Ojeda; Arnulfo Nava

    2007-01-01

    La trombosis es una alteración observada en múltiples trastornos médicos. El flujo sanguíneo se mantiene por el equilibrio de factores procoagulantes y anticoagulantes. Por múltiples causas se puede presentar daño tisular, provocando la formación de un coágulo mediante la activación de la vía de la coagulación por la presencia del complejo factor tisular (F III) + factor tisular VIIa que interactúa con receptores en la célula endotelial y en las plaquetas. Este modelo de la coagulación se des...

  20. Novel Agents in the Management of Pancreatic Adenocarcinoma: Phase I Studies

    Directory of Open Access Journals (Sweden)

    Anastasios T Dimou

    2011-03-01

    Full Text Available Pancreatic adenocarcinoma has repetitively proved refractory to chemotherapy and biologic compounds with only a few drugs offering limited benefit. A number of novel regimens has been tested in phase I trials and reported recently in the 2011 American Society of Clinical Oncology (ASCO Gastrointestinal Cancers Symposium. Specifically, a novel mitogen-activated protein kinase kinase (MEK inhibitor, a connective tissue growth factor inhibitor, a coagulase factor VIIa inhibitor, as well as adenovirus delivery of herpes simplex virus thymidine synthase gene followed by anti-herpetic treatment have all proven to be safe in pancreatic cancer patients. Phase II trials will provide further evidence whether they can become clinically relevant in the future.

  1. Üks küsimus

    Index Scriptorium Estoniae

    2003-01-01

    Euroopa Komisjoni laienemisvoliniku Günther Verheugeni eestkõneleja Jean-Christophe Filori vastab küsimusele, milleni võivad viia valitsuskriisist tulenevad häired Riigikogu töös EL-iga liitumiseks vajalike seaduste vastuvõtmisel

  2. Moldova aitavad jalule majandusreformid / Marianne Mikko

    Index Scriptorium Estoniae

    Mikko, Marianne, 1961-

    2005-01-01

    Moldova on teinud Transnistria konflikti lahendamises panuse koostööle EL-iga ning on alustanud oma seaduste ühtlustamist EL-iga. Kirjeldades Moldova majanduse arengu teel seisvaid raskusi, on autor seisukoha, et eestlastel tasub moldovlasi aktiivsemalt nõustada, aidata arendada demokraatiat ning ellu viia majandusreforme. Lisa: Moldova tee Euroopasse

  3. Armee sundis äärmuslased jõuga alistuma / Karin Volmer

    Index Scriptorium Estoniae

    Volmer, Karin

    2007-01-01

    Ilmunud ka: Postimees : na russkom jazõke, 11. juuli 2007, lk. 7. Postimees : na russkom jazõke autorita. Pakistani armee eriüksuste tormijooks Islamabadis asuvale Punasele mosheele kõigutas riigi poliitilist stabiilsust ja võib viia kodusõja puhkemiseni

  4. Rein Einasto : Eestis valitud ameerikalik valitsemise tee viib meid katastroofini / Rein Einasto ; interv. Kristi Leppik

    Index Scriptorium Estoniae

    Einasto, Rein, 1934-

    2008-01-01

    Kodanikuühiskonna edendamisest Eestis. Aasta missiooniinimese kandidaadiks esitatud professor Rein Einasto arvates päästaks meid avar mõtlemine, et viia inimkond tervikuna teisele teele. Praegune vaba turumajandus on pillamisele, raiskamisele ja kulutamisele üles ehitatud ummiktee. Lisa: Rein Einasto

  5. Orwelli nimekiri / Mihhail Lotman

    Index Scriptorium Estoniae

    Lotman, Mihhail, 1952-

    2014-01-01

    Aleksandr II-le sooritatud atentaadikatsest 1866. aastal. Heinrich Bölli teosest "Katharina Blumi kaotatud au, ehk, Kuidas vägivald võib tekkida ja kuhu välja viia". Senaator Joseph McCarthy'st. George Orwelli poolt Informatsiooniuuringute osakonnale esitatud nimekirjast. Orwelli eluloost

  6. Ajateenistusest, ausalt! / Kim Järvepõld

    Index Scriptorium Estoniae

    Järvepõld, Kim

    2007-01-01

    Ilmunud ka: Postimees : na russkom jazõke, 9. apr. 2007, lk. 7. Autor leiab, et põhiseaduslik nõue, mille järgi on kõik Eesti kodanikud kohustatud osa võtma riigikaitsest, pole vastavuses tegeliku olukorraga, ning arvab, et kohustuslik ajateenistus tuleb kaotada või viia kooskõlla põhiseadusega

  7. 78 FR 65315 - Granting of Request for Early Termination of the Waiting Period Under the Premerger Notification...

    Science.gov (United States)

    2013-10-31

    ... Improvements Act of 1976, requires persons contemplating certain mergers or acquisitions to give the Federal... of Justice. Neither agency intends to take any action with respect to these proposed acquisitions... 20131273 G Providence Equity Partners VII-A L.P.; Shamrock Capital Growth Fund III, L.P.; Providence Equity...

  8. 75 FR 76930 - Amendment to the International Traffic in Arms Regulations: Revision of U.S. Munitions List...

    Science.gov (United States)

    2010-12-10

    ...)(2)(iii): VII(a)(2)(iii) also includes B kits (add-on armor). (iv) (Tier 3) Deep water fording kits... commercial vehicles (e.g., mufflers, resonators, electrical filters/capacitors, acoustic or thermal... square foot. (4) (Tier 2) Transparent ceramic plate greater than or equal to \\1/ 2\\'' thick and...

  9. Üürilepingu erakorraline ülesütlemine üürniku makseviivituse tõttu / Kaidi Urgas, Karin Sein

    Index Scriptorium Estoniae

    Urgas, Kaidi, 1989-

    2013-01-01

    Võlaõigusseaduse § 316 kohaldamise teoreetilistest alustest ja rakendamise praktikast Eesti kohtutes ning seaduse ajakohastamise vajadusest, et poolte õigused ja kohustused paremini tasakaalu viia. Üürileandja ülesütlemisõigus Šveitsi ja Saksa õiguses

  10. Ingliskeelne eesti luule ja glokaalsuse keskenduvad keerud / Lauri Pilter

    Index Scriptorium Estoniae

    Pilter, Lauri, 1971-

    2010-01-01

    Inglise keele rollist eesti luuleteadvuses üldiselt, Bernard Kangro kogust "Earthbound" (1951) kui esimesest ingliskeelsest eesti luuletaja valikkogust ning võimalikest järeldustest, milleni võiks viia metafooride võrdlev uurimine eesti ja inglise luules

  11. Rein Einasto : Eestis valitud ameerikalik valitsemise tee viib meid katastroofini / Rein Einasto ; interv. Kristi Leppik

    Index Scriptorium Estoniae

    Einasto, Rein, 1934-

    2008-01-01

    Kodanikuühiskonna edendamisest Eestis. Aasta missiooniinimese kandidaadiks esitatud professor Rein Einasto arvates päästaks meid avar mõtlemine, et viia inimkond tervikuna teisele teele. Praegune vaba turumajandus on pillamisele, raiskamisele ja kulutamisele üles ehitatud ummiktee. Lisa: Rein Einasto

  12. XXI sajandil võib vabalt puhkeda demokraatia kriis / Jaan Kaplinski

    Index Scriptorium Estoniae

    Kaplinski, Jaan, 1941-

    2007-01-01

    Ilmunud ka: Delovõje Vedomosti 4. apr. lk. 12. Autor usub, et XXI sajand saab otsustavaks ajaks nii inimsoo kui ka demokraatia jätkusuutlikkusele. Pole võimatu, et elatustaseme langus ja suure osa inimeste võimetus sellega leppida ning leida võimalus ka kasinates tingimustes hästi elada võib viia demokraatia kriisile

  13. Birma takistab välisabi jagamist / Hendrik Vosman

    Index Scriptorium Estoniae

    Vosman, Hendrik

    2008-01-01

    Birma sõjaväediktatuur võtab küll tsüklon Nargise põhjustatud looduskatastroofi tõttu välisabi vastu, kuid keelab abiandjatel seda hädalistele kohale viia. Lisa: Ohvrite arv. Vt. samas: Referendum toimus katastroofist hoolimata

  14. Palga kärpimine paneb Kreenholmi töötajad streikima

    Index Scriptorium Estoniae

    2005-01-01

    Kreenholmi juhid kavatsevad vähendada töötajate palka veerandi võrra ja ähvardavad tootmise Eestist mujale viia. Siiani on sõlmimata uus kollektiivleping. Kreenholmi streigikomitee plaanib korraldada piketi Tallinnas Rootsi ja Soome saatkonna ees

  15. Mazheikiu tehast varustav Vene naftajuhe kuival / Martti Kass

    Index Scriptorium Estoniae

    Kass, Martti

    2006-01-01

    Delfi.lv andmetel pole juba kaheksa päeva Mazheikiai naftatehas Venemaalt naftat saanud. Lätis prognoositakse bensiinihinna olulist tõusu. USA suursaadik Leedus Keith Smith on hoiatanud, et Mazheikiai naftatehasel võib uue omaniku käe all tarneprobleeme tekkida, tema väitel on tunda survet, et Mazheikiai naftatehas taas Venemaa omandusse viia

  16. Illusoorne HIV-vaba Eesti / Nastja Portsjonok

    Index Scriptorium Estoniae

    Portsjonok, Nastja

    2011-01-01

    5. juunil 1981 diagnoositi maailmas esimest korda HIV. Eesti on kõige suurema HIV- juhtumite juurdekasvuga riik Euroopa Liidus. Autori hinnangul ei ole me suutnud ennetustööga viia üldist ühiskondlikku ruumi tasemele, mis muudaks vaba seksuaalkäitumise vähem riskantseks

  17. Novosti iz realnoi zhizni : tutshi nad pravitelstvom / Virkko Lepassalu

    Index Scriptorium Estoniae

    Lepassalu, Virkko, 1971-

    2008-01-01

    Alalaekumised riigieelarvesse sunnivad valitsust kulusid vähendama. Endised ministrid Liina Tõnisson, Aivar Sõerd, Mart Opmann, Meelis Atonen ja Kalev Kallo vastavad küsimustele, kas lisaeelarve vastuvõtmine võiks viia valitsuse vahetumiseni, kes on süüdi ebareaalse eelarve vastuvõtmises ja millal võiks majanduslangus asenduda majanduskasvuga

  18. Sostavõ katjatsja mimo kassõ / Andrei Akulistõi

    Index Scriptorium Estoniae

    Akulistõi, Andrei

    2003-01-01

    Eesti võimude lühinägelik ja paindumatu poliitika võib viia Soome Venemaa prioriteetseks transiitkaubaveo partneriks, tõdeb autor. Eriti tormilist arengut on oodata transkontinentaalsete konteinervedude mahu osas Aasia-Vaikse ookeani piirkonnast Lääne-Euroopasse

  19. Peetri maja kant Kadriorus saab peagi uue näo / Ulvar Käärt

    Index Scriptorium Estoniae

    Käärt, Ulvar, 1982-

    2009-01-01

    Kadrioru pargis asuva Peeter I maja ja presidendi kantselei vahelise pargiala uuendustöödest. Vt. samas: Presidendi lossi esine suletakse. Peetri aia rekonstrueerimistööde käigus on plaanis pargi territooriumile üle viia ka praegu presidendi kantselei esist paraadplatsi läbiv kõnnitee, kuna kantseleil on plaanis hoone esine ümbritseda piirdeaiaga

  20. Kolmas vaatus Euroopa võlakriisis - Portugal. Oht Portugali mainel / Sirje Rank

    Index Scriptorium Estoniae

    Rank, Sirje, 1966-

    2011-01-01

    Portugal kavatseb läbi viia riigivõlakirjade emissiooni, samas müüvad teisedki riigid lähiajal võlakirju, mille riskiaste on väiksem. Portugal eitab väidet, nagu oleks Saksamaa ja Prantsusmaa survestanud teda Euroopa kriisifondist abi küsima

  1. Kaitseminister lubab Nursi inimestele rohkem rääkida / Arved Breidaks

    Index Scriptorium Estoniae

    Breidaks, Arved, 1975-

    2004-01-01

    Nursi valla elanikud saatsid kaitseministrile kirja, väljendades oma vastuseisu kaitseväe Nursipalu harjutusväljaku laiendamisele. Kaitseminister Jaak Jõerüüt lubas end küsimuse detailidega kurssi viia ning kinnitas, et kohalike inimeste huvisid tuleb arvestada. Lisa: Nursipalus planeeritavad tegevused

  2. Piirivalve saab 147 miljoni eest uhke helikopteri / Sigrid Laev

    Index Scriptorium Estoniae

    Laev, Sigrid

    2005-01-01

    Eesti piirivalve saab helikopteri Agusta Bell, kopteri soetamine täidab Schnegen Facility programmi eesmärki, mille kohaselt tuleb EL-i välispiiride valve viia vastavusse Schengeni õigusruumi nõuetega. Raha ostmiseks annab abiprogramm Schengen Facility

  3. Orwelli nimekiri / Mihhail Lotman

    Index Scriptorium Estoniae

    Lotman, Mihhail, 1952-

    2014-01-01

    Aleksandr II-le sooritatud atentaadikatsest 1866. aastal. Heinrich Bölli teosest "Katharina Blumi kaotatud au, ehk, Kuidas vägivald võib tekkida ja kuhu välja viia". Senaator Joseph McCarthy'st. George Orwelli poolt Informatsiooniuuringute osakonnale esitatud nimekirjast. Orwelli eluloost

  4. Eesti ja Venemaa uue külma sõja õhutamise avangardis / Herbert Vainu

    Index Scriptorium Estoniae

    Vainu, Herbert, 1929-2011

    2008-01-01

    Eesti ja Venemaa juhtide mängimine rahvustundel tõstab rahvusvahelist pinget, mis võib viia külma sõja taastekkimisele. Autor kritiseerib muuhulgas president Toomas Hendrik Ilvese poliitilist tegevust ja esinemist Hantõ-Manskiiskis toimunud soome-ugri maailmakongressil. Vabariigi President töövisiidil Venemaal 27.-30.06.2008

  5. Illusoorne HIV-vaba Eesti / Nastja Portsjonok

    Index Scriptorium Estoniae

    Portsjonok, Nastja

    2011-01-01

    5. juunil 1981 diagnoositi maailmas esimest korda HIV. Eesti on kõige suurema HIV- juhtumite juurdekasvuga riik Euroopa Liidus. Autori hinnangul ei ole me suutnud ennetustööga viia üldist ühiskondlikku ruumi tasemele, mis muudaks vaba seksuaalkäitumise vähem riskantseks

  6. "Krengolm" obeshtshajet potesnit Pakistan / Irina Tokareva

    Index Scriptorium Estoniae

    Tokareva, Irina

    2008-01-01

    Kreenholmi uue peadirektori Igor Poleshtshuki plaani kohaselt tuleks ettevõtte toodangu müügihinnad viia vastavusse maailmaturu hindadega, alandada tootmise omahinda tellimuste arvu suurendamisega, saada tagasi kaotatud tellijad Euroopast ja leida uusi eelkõige Venemaa turult. Ilmunud ka: Narvskaja Nedelja 13. dets. lk. 3

  7. Ajateenistusest, ausalt! / Kim Järvepõld

    Index Scriptorium Estoniae

    Järvepõld, Kim

    2007-01-01

    Ilmunud ka: Postimees : na russkom jazõke, 9. apr. 2007, lk. 7. Autor leiab, et põhiseaduslik nõue, mille järgi on kõik Eesti kodanikud kohustatud osa võtma riigikaitsest, pole vastavuses tegeliku olukorraga, ning arvab, et kohustuslik ajateenistus tuleb kaotada või viia kooskõlla põhiseadusega

  8. St. Ola sõitis Virumaa lipulaevana Soome / Gerli Romanovitsh

    Index Scriptorium Estoniae

    Romanovitš, Gerli, 1977-

    2005-01-01

    Ilmunud ka: Severnoje Poberezhje 10. juuni lk 1,4. Parvlaev St. Ola alustas sõitu Sillamäelt Kotkasse, et viia Ida-Virumaa esindajad Kouvolas toimuvale messile, millest poole võtab enda alla Virumaa väljapanek. Järgmisel aastal käivitub Sillamäe-Kotka regulaarlaevaliin. Ida-Viru maavanema Ago Silde kommentaar

  9. Mazheikiu tehast varustav Vene naftajuhe kuival / Martti Kass

    Index Scriptorium Estoniae

    Kass, Martti

    2006-01-01

    Delfi.lv andmetel pole juba kaheksa päeva Mazheikiai naftatehas Venemaalt naftat saanud. Lätis prognoositakse bensiinihinna olulist tõusu. USA suursaadik Leedus Keith Smith on hoiatanud, et Mazheikiai naftatehasel võib uue omaniku käe all tarneprobleeme tekkida, tema väitel on tunda survet, et Mazheikiai naftatehas taas Venemaa omandusse viia

  10. Investor wants listing for Estonian Railway, state officials balk at prospect

    Index Scriptorium Estoniae

    2004-01-01

    Eesti Raudtee suuromanik Baltic Rail Service tahab ettevõtte 2005. aasta keskpaigaks börsile viia. Riik, mis on firma vähemusaktsionär, pole plaaniga nõus, kuna BRS-il on täitmata investeerimiskohustused

  11. Kas missioon on moesõna või organisatsiooni "töövahend"? / Alexander Kotchubei

    Index Scriptorium Estoniae

    Kotchubei, Alexander, 1963-

    2004-01-01

    Autor selgitab missiooni olemust, selle sõnastamise vajalikkust organisatsioonis ning arutleb võimalike põhjuste üle, miks missioon ei toimi. Kommenteerivad Marie Edala ja Urmas Kaarlep. Lisa: Sõnumi kujundamiseks vali kahe lähenemise vahel. Vt. samas: Kuidas viia missiooni töötajateni?

  12. Neljanda seisuse võlu ja valu / Karol Kallas

    Index Scriptorium Estoniae

    Kallas, Karol, 1972-

    2007-01-01

    Autor peab Pärnu linnavalitsuse töö tulemuslikkust küsitavaks, leides, et linn vajab mehhanismi, mille abil antaks võimalus osalusdemokraatiale. Samas peab ta vajalikuks läbi viia linnaelanike arvamusküsitluse teemal, kas Mart Viisitamm sobib linnapeaks?

  13. Ettevaatust, kaitsepolitsei! / Roy Strider

    Index Scriptorium Estoniae

    Strider, Roy, 1974-

    2007-01-01

    Ajendatuna anarhistliku liikumise PunaMust meeleavalduse jälgimisest end ajakirjanikuks nimetanud kaitsepolitsei töötaja poolt kirjutab autor kaitsepolitsei mõttetust nuhkimisest oma kodanike järele, mis võib viia jälgimisühiskonnani

  14. Rootsi minister : Eesti majanduses esineb ohumärke / Cecilia Malmström ; interv. Raimo Poom

    Index Scriptorium Estoniae

    Malmström, Cecilia, 1968-

    2008-01-01

    Rootsi eurominister vastab küsimustele, mis puudutavad Läänemere strateegia kavandamist, Rootsi suhtumist võimalusse viia Läänemere strateegiaga ellu täielik teenuste vaba liikumine siinses regioonis, Eesti majandusolukorra halvenemist, Swedbanki otsust loobuda Hansapanga nimest, Nord Streami gaasijuhet, eesseisvat referendumit Iirimaal Lissaboni lepingu üle

  15. AFIS aitab tabada kurjategijaid / Gea Ling

    Index Scriptorium Estoniae

    Ling, Gea

    1999-01-01

    Sõrmejälgede automatiseeritud identifitseerimise süsteem. Kõigis Eesti politseiasutustes on alates 1998. aastast kasutusel daktüloskoopiline andmebaas, mis võimaldab arvutil kahe minutiga sõrmejälje ja isiku kokku viia, lõpliku otsuse langetab loomulikult ekspert

  16. Ida kavalus viib agressiooni tunnustamiseni / Vootele Hansen

    Index Scriptorium Estoniae

    Hansen, Vootele, 1962-

    2005-01-01

    Venemaa president on teinud ettepaneku sõlmida Eesti-Vene piirileping Moskvas 9. mai pidustustel. Eestil oleks mõistlik leppida Lätiga kokku ning viia piirilepingu sidumine võidupühaga Eesti ja Läti vastase agressiooni tunnistamiseni

  17. Käes on aeg masskoondamisteks / Eda-Liis Kann

    Index Scriptorium Estoniae

    Kann, Eda-Liis, 1979-

    2008-01-01

    Töötukassa prognoosib 2008. aasta lõpuks üle nelja tuhande töötu, artikkel selgitab, kuidas koondamist seaduslikult ja valutult läbi viia. Lisa: Suurkoondajad; Eesti Posti ja RMK näide; Töötuks jäämise valu leevendab töötukassa. Kommenteerib personalifirma MPS tegevjuht Pasi Harttunen

  18. Eesti ja Venemaa uue külma sõja õhutamise avangardis / Herbert Vainu

    Index Scriptorium Estoniae

    Vainu, Herbert, 1929-2011

    2008-01-01

    Eesti ja Venemaa juhtide mängimine rahvustundel tõstab rahvusvahelist pinget, mis võib viia külma sõja taastekkimisele. Autor kritiseerib muuhulgas president Toomas Hendrik Ilvese poliitilist tegevust ja esinemist Hantõ-Manskiiskis toimunud soome-ugri maailmakongressil. Vabariigi President töövisiidil Venemaal 27.-30.06.2008

  19. Projektiteater kutsub sauna ja interneti samasooliste jututuppa / Margit Tõnson

    Index Scriptorium Estoniae

    Tõnson, Margit, 1978-

    2004-01-01

    Alanud teatrihooaja eraalgatuslikest teatriprojektidest. Koreograaf T. Jansen kavatseb Vanalinnastuudios lavale tuua saksa noorema generatsiooni näitekirjaniku K. Shagori "Puutumata", M. Karusoo hakkab lavastama Afganistanis sõdinud sõdurite mälestustel põhinevat näidendit ning A. Keil ja I. Põllu tahavad teatri sauna viia.

  20. Peetri maja kant Kadriorus saab peagi uue näo / Ulvar Käärt

    Index Scriptorium Estoniae

    Käärt, Ulvar, 1982-

    2009-01-01

    Kadrioru pargis asuva Peeter I maja ja presidendi kantselei vahelise pargiala uuendustöödest. Vt. samas: Presidendi lossi esine suletakse. Peetri aia rekonstrueerimistööde käigus on plaanis pargi territooriumile üle viia ka praegu presidendi kantselei esist paraadplatsi läbiv kõnnitee, kuna kantseleil on plaanis hoone esine ümbritseda piirdeaiaga

  1. 75 FR 7266 - Roaring Fork Valley Physicians I.P.A.; Analysis of the Agreement Containing Consent Order to Aid...

    Science.gov (United States)

    2010-02-18

    ... designed to remedy the illegal conduct charged in the complaint and prevent its recurrence. It is similar... active and ongoing programs to evaluate and modify their clinical practice patterns in order to control... contracts that were entered into illegally. Paragraph VII.A require RFV to distribute the complaint...

  2. Piirivalve saab 147 miljoni eest uhke helikopteri / Sigrid Laev

    Index Scriptorium Estoniae

    Laev, Sigrid

    2005-01-01

    Eesti piirivalve saab helikopteri Agusta Bell, kopteri soetamine täidab Schnegen Facility programmi eesmärki, mille kohaselt tuleb EL-i välispiiride valve viia vastavusse Schengeni õigusruumi nõuetega. Raha ostmiseks annab abiprogramm Schengen Facility

  3. Linnahalli renoveerimine venib veel vähemalt aasta / Tuuli Aug

    Index Scriptorium Estoniae

    Aug, Tuuli

    2010-01-01

    Tallinna linn ja USA firma Tallinn Entertainment LLC otsustasid Tallinna Linnahalli renoveerimiseks ja seda ümbritsevate kinnistute hoonestamiseks luua ühisettevõtte, mille asutamine ja hoonestusõiguse seadmine loodetakse lõpule viia jaanuaris 2011. Detailplaneeringust ja renoveerimisprojekti koostamisest, ühisfirma ehitusplaanist

  4. Hudozhestvennaja akademija pomogajet naiti svojo litso

    Index Scriptorium Estoniae

    2008-01-01

    Eesti Kunstiakadeemia osalemisest innovatsiooniprogrammis Spinno. Projekti eesmärgiks on viia kokku disainiõppureid ja ettevõtteid, suurendada ettevõtjate teadmisi disainist. Spinno raames käivitati Disainiaasta ja Arhitektuuriaasta projektid. Kommenteerib projektijuht Sven Idarand. Tootedisainiga tegelevast Eesti Kunstiakadeemia esimesest spin-off ettevõttest Taikonaut räägib Kristiina Tuubel

  5. Jiri Shibori konstruktivistlik kujundimaailm / Eilve Manglus

    Index Scriptorium Estoniae

    Manglus, Eilve, 1977-

    2004-01-01

    Metallide tehnoloogiat õppinud Jiri Shibori näitus "Ehtekunsti ja skulptuuri vahel" Deco galeriis kuni 10. IV. Personaalnäitus toimub EKA ehte- ja sepakunsti osakonna kutsel, et viia läbi külmkinnituslike konstruktsioonidega metallitöö workshop

  6. Over my dead body / Martin Kala

    Index Scriptorium Estoniae

    Kala, Martin, 1977-

    2004-01-01

    Arutlus Türgi võimalikust liitumisest Euroopa Liiduga. Autori hinnangul on Türgi tõestanud oma suutlikkust viia läbi järjepidevaid reforme ja Euroopasse sobivad kõik riigid, mis suudavad tõestada oma demokraatlikku elukorraldust

  7. Over my dead body / Martin Kala

    Index Scriptorium Estoniae

    Kala, Martin, 1977-

    2004-01-01

    Arutlus Türgi võimalikust liitumisest Euroopa Liiduga. Autori hinnangul on Türgi tõestanud oma suutlikkust viia läbi järjepidevaid reforme ja Euroopasse sobivad kõik riigid, mis suudavad tõestada oma demokraatlikku elukorraldust

  8. Relvastatud jõu kasutamine / Kalev Stoicescu

    Index Scriptorium Estoniae

    Stoicescu, Kalev

    2006-01-01

    Sõjalistes operatsioonides peavad jõu kasutamise reeglid olema piisavalt selged, nende koostamisel arvestatakse oma riigi seadusi ja rahvusvahelist õigust, kuid ka kohalikku kultuuritausta. Liiga kitsad reeglid võivad piirata sõjalise ülema tegevust, liiga laiad või ähmased reeglid aga võivad viia konflikti eskaleerumisele. Näiteid

  9. Ingliskeelne eesti luule ja glokaalsuse keskenduvad keerud / Lauri Pilter

    Index Scriptorium Estoniae

    Pilter, Lauri, 1971-

    2010-01-01

    Inglise keele rollist eesti luuleteadvuses üldiselt, Bernard Kangro kogust "Earthbound" (1951) kui esimesest ingliskeelsest eesti luuletaja valikkogust ning võimalikest järeldustest, milleni võiks viia metafooride võrdlev uurimine eesti ja inglise luules

  10. Iskusstvo upravlenija zapassami / Andrei Sokolov

    Index Scriptorium Estoniae

    Sokolov, Andrei

    2007-01-01

    Varude juhtimise süsteem. Majanduse kasvu aeglustumise tingimustes peavad ettevõtted kasvatama käivet kulusid vähendades. Tööjõu defitsiidi tingimustes ei saa kokku hoida palgafondi arvelt, kuid selle asemel saab viia miinimumi laovarud. Diagrammid. Kommenteerib Anatoli Polupan

  11. Benzin iz rapsa : utopija ili realnaja perspektiva? / Oleg Samorodni

    Index Scriptorium Estoniae

    Samorodni, Oleg, 1961-

    2006-01-01

    Suurärimees Rein Kilgi eesmärgiks on viia Lõuna Toiduainetööstus Lõuna-Eesti juhtivaks ettevõtteks, seepärast käib ka võitlus rapsitööstuse Werol Tehased ostmise ümber ärimeeste Oliver Kruuda ja Urmas Sõõrumaaga

  12. Poola presidendi kingitus Prantsuse presidentuurile : ei / Kaivo Kopli

    Index Scriptorium Estoniae

    Kopli, Kaivo

    2008-01-01

    Poola president Lech Kaczynski arvates pole mõtet Lissaboni lepingu ratifitseerimist Poolas lõpule viia, kui Iirimaa lepingu tagasi lükkas. Ratifitseerimisprotsessi on peatanud ka Saksamaa president Horst Köhler. Lisa: Käibemaksule piir, rahvale lähemale

  13. PKN Orlen takes share in Mazeikiu Nafta

    Index Scriptorium Estoniae

    2007-01-01

    Poola naftatöötlejatele kuulub peale ostupakkumist väikeaktsionäridele 89% Mazeikiu Nafta aktsiatest, mis võib viia ettevõtte väljaviimiseni börsilt. Jukose väitel pole PKN Orleni raha aktsiate eest endise omanikuni jõudnud

  14. Pension pool keskmist palka? / Eiki Nestor

    Index Scriptorium Estoniae

    Nestor, Eiki, 1953-

    2007-01-01

    Ilmunud ka: Linnaleht : Tartu, 30. okt. 2007, lk. 8. Poliitik, kes lubab viia keskmise pensioni pooleni keskmisest palgast, kuid võõrtööjõudu Eestisse tuua ei taha, pensioniiga ega sotsiaalmaksu tõsta ei soovi, on autori arvates kas rumal või valetab

  15. Fremantle Media ekspordib seriaale kogu maailma / Andrew Edgecliffe-Johnson ; tõlk. Erik Aru

    Index Scriptorium Estoniae

    Edgecliffe-Johnson, Andrew

    2007-01-01

    Teleproduktsioonifirmast Fremantle Media. Saateformaatide eksportimisel saavutatud edu teeb firmast õpikunäite, kuidas viia tooteid üle maailma, muutes neid just piisavalt, et sobida kohaliku maitsega, jäädes samas truuks algideele. Edu ei vaja tõlget

  16. Riigikogu liige ei vaja hooldusassistenti / Ignar Fjuk

    Index Scriptorium Estoniae

    Fjuk, Ignar, 1953-

    2001-01-01

    Ilmunud ka: Järva Teataja, 11. sept. 2001, lk. 2; Nädaline, 11. sept. 2001, lk. 4; Vooremaa, 11. sept. 2001, lk. 2; Võrumaa Teataja, 11. sept. 2001, lk. 2; Valgamaalane, 22. sept. 2001, lk. 2. Noorpoliitikud Keskerakonnast pöördusid Riigikogu poole ettepanekuga viia Eesti parlamendis sisse assitendi süsteem. Autor: Reformierakond. Parlamendisaadik

  17. Omavalitsuste rahastamine vajab muutmist / Olev Raju

    Index Scriptorium Estoniae

    Raju, Olev, 1948-

    2002-01-01

    Autor leiab, et omavalitsuste rahastamise reform tuleks Eestis läbi viia Euroopa riikide praktikast ja Eesti praeguse arenguetapi majanduspoliitilise olukorra analüüsist lähtuvalt. Tabel: tulumaksu eraldamise diferentseerimise variante omavalitsuste vahel. Summary: The need for reform in local government funding. Autor: Keskerakond. Parlamendisaadik

  18. Vertikal bez granits / Svetlana Ragrina

    Index Scriptorium Estoniae

    Ragrina, Svetlana

    2004-01-01

    Moskva elab sõjaaja reaalsuses, terroriaktid ja terrorismioht võimaldavad võimuorganitel sisse viia kodanike kaitseks täiendavaid vabaduste ning õiguste piiranguid. Venemaa president Vladimir Putin tutvustas valitsusele, föderatsiooni subjektidele ja rahvale kavandatavaid muudatusi riigi juhtimises

  19. Jäätmetega kimpus Estonian Cell annab muda põldudele kompostiks / Ulvar Käärt

    Index Scriptorium Estoniae

    Käärt, Ulvar, 1982-

    2007-01-01

    Kundas asuv Estonian Celli tehas jagab ümberkaudsetele talunikele jäätmetest lahtisaamiseks kompostimissegu. Seadused ei sätesta, kuidas Estonian Cellis tekkivaid jäätmeid töödelda. Kommenteerib Peeter Eek: Aasta läbi ei saa muda põllule viia

  20. Gordon Brown lubab valijal riigieelarvet ümber teha / Siim Trumm

    Index Scriptorium Estoniae

    Trumm, Siim

    2007-01-01

    Peaminister Gordon Brown kavandab mitmeid reforme, et viia riigivõim rahvale lähemale. Inglismaa kümne piirkonna inimestele antakse võimalus otsustada rahvahääletuse kaudu kohaliku eelarve jaotamise üle. Lisa: Browni ja leiboristide toetus kasvab

  1. Erik Terk : Eesti vajab arenguhüppeks maailmatasemel ülikoole / Erik Terk ; küsitlenud Vilja Rääsk

    Index Scriptorium Estoniae

    Terk, Erik

    2008-01-01

    Intervjuu Eesti Tuleviku-uuringute Instituudi(ETI) direktori Erik Tergiga, kes leiab, et praegusest kriisist väljumise järel sõltub Eesti areng sellest, kas suudame viia oma ülikoolid maailmatasemele või tuleks kopereeruda Helsingiga

  2. 3+2 süsteem jätab praegused kraadid ümber hindamata / Jaan Olmaru

    Index Scriptorium Estoniae

    Olmaru, Jaan

    2001-01-01

    Kõrgharidusreform, mida haridusministeerium kavandab lähiaastatel läbi viia, jätab senised bakalaureuste ja magistrite kraadid ümber hindamata. Märtsis̀2001 moodustatud Bologna deklaratsiooni töörühm on sinna kuuluva Tartu Ülikooli rektori Jaak Aaviksoo sõnul ümberhindamiste vastu, kuigi tulevikus õppeastmete kestused muutuvad

  3. Tööandjad : töötajaid tuleb kõvemini kinni hoida / Liis Kängsepp

    Index Scriptorium Estoniae

    Kängsepp, Liis, 1981-

    2007-01-01

    Ilmunud ka: Delovõje Vedomosti 31. jaan. lk. 6. Tööandjate keskliit soovitab pöörata enam tähelepanu inimeste hoidmisele tööturul ning mitte kasvatada avaliku sektori palku kiiremini erasektorist. Vt. samas: Manifest: tulumaks tuleb viia 14%ni

  4. Jäätmetega kimpus Estonian Cell annab muda põldudele kompostiks / Ulvar Käärt

    Index Scriptorium Estoniae

    Käärt, Ulvar, 1982-

    2007-01-01

    Kundas asuv Estonian Celli tehas jagab ümberkaudsetele talunikele jäätmetest lahtisaamiseks kompostimissegu. Seadused ei sätesta, kuidas Estonian Cellis tekkivaid jäätmeid töödelda. Kommenteerib Peeter Eek: Aasta läbi ei saa muda põllule viia

  5. Firmad loodavad abi saada sundpuhkustest / Valdu Toomla

    Index Scriptorium Estoniae

    Toomla, Valdu

    2008-01-01

    Teisel poolaastal on esitanud ning tööinspektsioonilt loa saanud 11 Lääne-Virumaa ettevõtet kokku 222 töötajaga ja menetlemist ootab veel 6 ettevõtet, kes soovisid saata ühtekokku 180 töötajat osaliselt tasustatavale puhkusele või viia osalisele tööajale

  6. Omavalitsuste rahastamine vajab muutmist / Olev Raju

    Index Scriptorium Estoniae

    Raju, Olev, 1948-

    2002-01-01

    Autor leiab, et omavalitsuste rahastamise reform tuleks Eestis läbi viia Euroopa riikide praktikast ja Eesti praeguse arenguetapi majanduspoliitilise olukorra analüüsist lähtuvalt. Tabel: tulumaksu eraldamise diferentseerimise variante omavalitsuste vahel. Summary: The need for reform in local government funding. Autor: Keskerakond. Parlamendisaadik

  7. Miks Ida-Euroopa reformidest väsis / Stefan Wagstyl, Christopher Condon ; tõlk. Erik Aru

    Index Scriptorium Estoniae

    Wagstyl, Stefan

    2006-01-01

    Ungari, Tšehhi, Poola, Slovakkia sisepoliitilisest olukorrast. Autorite sõnul on kõikjal piirkonnas langenud eurotsooniga liitumise kavad poliitika ohvriks; majandusteadlaste väitel jätab Kesk-Euroopa kasutamata võimaluse läbi viia uuendusi, mida peab hiljem niikuinii tegema

  8. Rootsi minister : Eesti majanduses esineb ohumärke / Cecilia Malmström ; interv. Raimo Poom

    Index Scriptorium Estoniae

    Malmström, Cecilia, 1968-

    2008-01-01

    Rootsi eurominister vastab küsimustele, mis puudutavad Läänemere strateegia kavandamist, Rootsi suhtumist võimalusse viia Läänemere strateegiaga ellu täielik teenuste vaba liikumine siinses regioonis, Eesti majandusolukorra halvenemist, Swedbanki otsust loobuda Hansapanga nimest, Nord Streami gaasijuhet, eesseisvat referendumit Iirimaal Lissaboni lepingu üle

  9. Kreeka hakkab üüratut eelarvepuudujääki lõpuks vähendama / Kaivo Kopli

    Index Scriptorium Estoniae

    Kopli, Kaivo

    2010-01-01

    Kreeka eelarvepuudujäägi vähendamiseks tuleb peaminister Georgios Papandreou sõnul külmutada avaliku sektori palgad ja tõsta kütuseaktsiisi. Edaspidi tuleb ellu viia suured reformid sotsiaalsfääris, vähendada õpetajaskonda

  10. Investor wants listing for Estonian Railway, state officials balk at prospect

    Index Scriptorium Estoniae

    2004-01-01

    Eesti Raudtee suuromanik Baltic Rail Service tahab ettevõtte 2005. aasta keskpaigaks börsile viia. Riik, mis on firma vähemusaktsionär, pole plaaniga nõus, kuna BRS-il on täitmata investeerimiskohustused

  11. Kuidas puutuvad ring, kolmnurk ja ruut lillepeenrasse? / Ülle Kikas, Terje Hõim

    Index Scriptorium Estoniae

    Kikas, Ülle, 1949-

    2016-01-01

    2012. aastal alustas haridus- ja teadusministeerium koostöös Tartu Ülikooli ja tarkvara tootva Wolframi konsortsiumiga arvutipõhise statistika arendusprojekti, et viia statistika õpetamine koolides vastavusse tänapäeva võimaluste ja nõudmistega

  12. Üürilepingu erakorraline ülesütlemine üürniku makseviivituse tõttu / Kaidi Urgas, Karin Sein

    Index Scriptorium Estoniae

    Urgas, Kaidi, 1989-

    2013-01-01

    Võlaõigusseaduse § 316 kohaldamise teoreetilistest alustest ja rakendamise praktikast Eesti kohtutes ning seaduse ajakohastamise vajadusest, et poolte õigused ja kohustused paremini tasakaalu viia. Üürileandja ülesütlemisõigus Šveitsi ja Saksa õiguses

  13. Vene tagapõhjaga organisatsiooni väärtuste uurimisplaan (Kreenholmi Valduse AS näitel) / Anne Reino

    Index Scriptorium Estoniae

    Reino, Anne, 1972-

    2004-01-01

    Uurimus Kreenholmi Valdus AS-i väärtustest on plaanis läbi viia 2004. aasta jooksul ning see on üheks osaks suuremast uuringust, mille eesmärgiks on Eesti organisatsioonide väärtuste võrdlev analüüs

  14. PKN Orlen takes share in Mazeikiu Nafta

    Index Scriptorium Estoniae

    2007-01-01

    Poola naftatöötlejatele kuulub peale ostupakkumist väikeaktsionäridele 89% Mazeikiu Nafta aktsiatest, mis võib viia ettevõtte väljaviimiseni börsilt. Jukose väitel pole PKN Orleni raha aktsiate eest endise omanikuni jõudnud

  15. Birma takistab välisabi jagamist / Hendrik Vosman

    Index Scriptorium Estoniae

    Vosman, Hendrik

    2008-01-01

    Birma sõjaväediktatuur võtab küll tsüklon Nargise põhjustatud looduskatastroofi tõttu välisabi vastu, kuid keelab abiandjatel seda hädalistele kohale viia. Lisa: Ohvrite arv. Vt. samas: Referendum toimus katastroofist hoolimata

  16. Fremantle Media ekspordib seriaale kogu maailma / Andrew Edgecliffe-Johnson ; tõlk. Erik Aru

    Index Scriptorium Estoniae

    Edgecliffe-Johnson, Andrew

    2007-01-01

    Teleproduktsioonifirmast Fremantle Media. Saateformaatide eksportimisel saavutatud edu teeb firmast õpikunäite, kuidas viia tooteid üle maailma, muutes neid just piisavalt, et sobida kohaliku maitsega, jäädes samas truuks algideele. Edu ei vaja tõlget

  17. Vanade puumajade korrashoid / Helene Hanes

    Index Scriptorium Estoniae

    Hanes, Helene

    1998-01-01

    "Kodustuudio" vahendab peatüki rootsi arhitektuuriloolase Helene Hanese raportist "Tallinna puitlinnaosad". Peatüki eesmärk on tutvustada, kuidas lihtsate vahenditega viia läbi restaureerimine ja tõsta võimalikult odavalt olemasoleva hoone väärtust. Hoone kandekonstruktsioonidest, majade värvimisest, katustest, soojustamisest ja ventilatsioonist.

  18. XXI sajandil võib vabalt puhkeda demokraatia kriis / Jaan Kaplinski

    Index Scriptorium Estoniae

    Kaplinski, Jaan, 1941-

    2007-01-01

    Ilmunud ka: Delovõje Vedomosti 4. apr. lk. 12. Autor usub, et XXI sajand saab otsustavaks ajaks nii inimsoo kui ka demokraatia jätkusuutlikkusele. Pole võimatu, et elatustaseme langus ja suure osa inimeste võimetus sellega leppida ning leida võimalus ka kasinates tingimustes hästi elada võib viia demokraatia kriisile

  19. Soomlased teevad silma Eesti toidutööstusele / Silva Männik

    Index Scriptorium Estoniae

    Männik, Silva, 1974-

    2004-01-01

    EL-iga liitumise eel plaanivad mitmed Soome ettevõtjad investeerida Eesti toiduainetööstustesse ja viia Eesti tooted Soome turule. Diagrammid: Soomlane sööb üha enam Eesti toitu. Kommenteerivad Joakim Helenius ja Ain Hanschmidt. Lisa: Näiteid soomlaste tehingutest

  20. Vene tagapõhjaga organisatsiooni väärtuste uurimisplaan (Kreenholmi Valduse AS näitel) / Anne Reino

    Index Scriptorium Estoniae

    Reino, Anne, 1972-

    2004-01-01

    Uurimus Kreenholmi Valdus AS-i väärtustest on plaanis läbi viia 2004. aasta jooksul ning see on üheks osaks suuremast uuringust, mille eesmärgiks on Eesti organisatsioonide väärtuste võrdlev analüüs

  1. Riigikogu liige ei vaja hooldusassistenti / Ignar Fjuk

    Index Scriptorium Estoniae

    Fjuk, Ignar, 1953-

    2001-01-01

    Ilmunud ka: Järva Teataja, 11. sept. 2001, lk. 2; Nädaline, 11. sept. 2001, lk. 4; Vooremaa, 11. sept. 2001, lk. 2; Võrumaa Teataja, 11. sept. 2001, lk. 2; Valgamaalane, 22. sept. 2001, lk. 2. Noorpoliitikud Keskerakonnast pöördusid Riigikogu poole ettepanekuga viia Eesti parlamendis sisse assitendi süsteem. Autor: Reformierakond. Parlamendisaadik

  2. Kolmas vaatus Euroopa võlakriisis - Portugal. Oht Portugali mainel / Sirje Rank

    Index Scriptorium Estoniae

    Rank, Sirje, 1966-

    2011-01-01

    Portugal kavatseb läbi viia riigivõlakirjade emissiooni, samas müüvad teisedki riigid lähiajal võlakirju, mille riskiaste on väiksem. Portugal eitab väidet, nagu oleks Saksamaa ja Prantsusmaa survestanud teda Euroopa kriisifondist abi küsima

  3. Pakosta raport võib panna kooliseadusi muutma / Alo Raun

    Index Scriptorium Estoniae

    Raun, Alo, 1981-

    2010-01-01

    Riigikogu liige Liisa Pakosta koostab pikapäevarühmadele keskenduvat raportit, mills selgitab välja koolihoonete tähtsust kogukonnas ning kohalikus elus. Raport võib viia muudatusteni põhikooli- ja gümnaasiumiseaduses

  4. Bulgaaria peaprokurör loob korda / Allan Espenberg

    Index Scriptorium Estoniae

    Espenberg, Allan

    2006-01-01

    Bulgaaria senise peaprokuröri Nikola Filtshevi ajal ei mõistetud süüdi ega saadetud vangi peaaegu mitte ühtki organiseeritud kuritegevuses osalenut. Uus peaprokurör Boris Veltshev kavandab läbi viia mitmeid reforme, muuta prokuratuuri töö läbipaistvamaks ja vähendada politseis korruptsiooni

  5. Gordon Brown lubab valijal riigieelarvet ümber teha / Siim Trumm

    Index Scriptorium Estoniae

    Trumm, Siim

    2007-01-01

    Peaminister Gordon Brown kavandab mitmeid reforme, et viia riigivõim rahvale lähemale. Inglismaa kümne piirkonna inimestele antakse võimalus otsustada rahvahääletuse kaudu kohaliku eelarve jaotamise üle. Lisa: Browni ja leiboristide toetus kasvab

  6. Blood clotting reactions on nanoscale phospholipid bilayers.

    Science.gov (United States)

    Morrissey, James H; Pureza, Vincent; Davis-Harrison, Rebecca L; Sligar, Stephen G; Ohkubo, Y Zenmei; Tajkhorshid, Emad

    2008-01-01

    Blood clotting reactions, such as those catalyzed by the tissue factor:factor VIIa complex (TF:FVIIa), assemble on membrane surfaces containing anionic phospholipids such as phosphatidylserine (PS). In fact, membrane binding is critical for the function of most of the steps in the blood clotting cascade. In spite of this, our understanding of how the membrane contributes to catalysis, or even how these proteins interact with phospholipids, is incomplete. Making matters more complicated, membranes containing mixtures of PS and neutral phospholipids are known to spontaneously form PS-rich membrane microdomains in the presence of plasma concentrations of calcium ions, and it is likely that blood-clotting proteases such as TF:FVIIa partition into these PS-rich microdomains. Unfortunately, little is known about how membrane microdomain composition influences the activity of blood-clotting proteases, which is typically not under experimental control even in "simple" model membranes. Our laboratories have developed and applied new technologies for studying membrane proteins to gain insights into how blood-clotting protease-cofactor pairs assemble and function on membrane surfaces. This includes using a novel, nanoscale bilayer system (Nanodiscs) that permits assembling blood-clotting protease-cofactor pairs on stable bilayers containing from 65 to 250 phospholipid molecules per leaflet. We have used this system to investigate how local (nanometer-scale) changes in phospholipid bilayer composition modulate TF:FVIIa activity. We have also used detailed molecular-dynamics simulations of nanoscale bilayers to provide atomic-scale predictions of how the membrane-binding domain of factor VIIa interacts with PS in membranes.

  7. The effect of GlycoPEGylation on the physical stability of human rFVIIa with increasing calcium chloride concentration

    DEFF Research Database (Denmark)

    Plesner, Bitten; Westh, Peter; Hvidt, Søren

    2011-01-01

    The effects of calcium chloride on the structural, kinetic and thermal stability of recombinant human factor VIIa (rFVIIa) were investigated using rFVIIa and two GlycoPEGylated recombinant human FVIIa derivatives, a linear 10 kDa PEG and a branched 40 kDa PEG, respectively. Three different CaCl(2...... scanning calorimetry (DSC) and circular dichroism (CD), and aggregation behaviour, measured by light scattering (LS), were affected by the increasing calcium concentration. Increasing the CaCl(2) concentration from 10mM to 35 mM resulted in a decrease in the apparent unfolding temperature, T(m), of r......FVIIa compounds was practically independent of the CaCl(2) concentration. From the obtained results, it is concluded that GlycoPEGylation postpones the calcium induced thermal destabilisation of rFVIIa, and a much higher calcium concentration also postpones the thermally induced aggregation of r...

  8. Antidotes for novel oral anticoagulants: current status and future potential.

    Science.gov (United States)

    Crowther, Mark; Crowther, Mark A

    2015-08-01

    The direct thrombin inhibitor dabigatran and the anti-Xa agents rivaroxaban, edoxaban, and apixaban are a new generation of oral anticoagulants. Their advantage over the vitamin K antagonists is the lack of the need for monitoring and dose adjustment. Their main disadvantage is currently the absence of a specific reversal agent. Dabigatran's, unlike the anti-Xa agents, absorption can be reduced by activated charcoal if administered shortly after ingestion and it can be removed from the blood with hemodialysis. Prothrombin complex concentrate, activated prothrombin complex concentrate, and recombinant factor VIIa all show some activity in reversing the anticoagulant effect of these drugs but this is based on ex vivo, animal, and volunteer studies. It is unclear, which, if any, of these drugs is the most suitable for emergency reversal. Three novel molecules (idarucizumab, andexanet, and PER977) may provide the most effective and safest way of reversal. These agents are currently in premarketing studies.

  9. Acquired hemophilia A as a cause of acute upper gastrointestinal hemorrhage.

    Science.gov (United States)

    McCain, Stephen; Gull, Sadaf; Ahmad, Jawad; Carey, Declan

    2014-02-05

    A 71-year-old man presented to the emergency department with his first episode of hematemesis. He was anemic and coagulopathic on admission, and became hemodynamically unstable requiring surgical intervention to control the bleeding. Prior to surgery, he required 100% plasma exchange with human plasma derived prothrombin complex concentrate (Octaplex) as the exchange fluid. At induction of anesthesia, he received tranexamic acid, prothrombin complex concentrate, and platelets. At the time of knife to skin, he was given coagulation factor VIIa intravenously as a bolus. This treatment was on the recommendation of the hematology team who suspected a diagnosis of acquired hemophilia on the basis of his history and coagulation screen. His bleeding was controlled and a diagnosis of acquired hemophilia A was confirmed in the postoperative period. This was managed with immunosuppressive therapy, and at the 2 year follow-up he remains well and is off all treatment.

  10. Probing the coagulation pathway with aptamers identifies combinations that synergistically inhibit blood clot formation.

    Science.gov (United States)

    Bompiani, Kristin M; Lohrmann, Jens L; Pitoc, George A; Frederiksen, James W; Mackensen, George B; Sullenger, Bruce A

    2014-08-14

    Coordinated enzymatic reactions regulate blood clot generation. To explore the contributions of various coagulation enzymes in this process, we utilized a panel of aptamers against factors VIIa, IXa, Xa, and prothrombin. Each aptamer dose-dependently inhibited clot formation, yet none was able to completely impede this process in highly procoagulant settings. However, several combinations of two aptamers synergistically impaired clot formation. One extremely potent aptamer combination was able to maintain human blood fluidity even during extracorporeal circulation, a highly procoagulant setting encountered during cardiopulmonary bypass surgery. Moreover, this aptamer cocktail could be rapidly reversed with antidotes to restore normal hemostasis, indicating that even highly potent aptamer combinations can be rapidly controlled. These studies highlight the potential utility of using sets of aptamers to probe the functions of proteins in molecular pathways for research and therapeutic ends. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Glanzmann thrombasthenia and its perioperative management in head trauma: A rare and challenging situation

    Directory of Open Access Journals (Sweden)

    Neeraj Kumar

    2016-01-01

    Full Text Available Glanzmann thrombasthenia is a rare inherited coagulation disorder, manifesting itself in early childhood as bleeding episodes. The patients with this disease may present with uncontrollable bleeding following trauma. We report a patient of Glanzmann syndrome with head injury, who presented to us following fall from stairs. Platelet transfusion is the mainstay of treatment in emergency situations. As patients generally have a history of platelet transfusion they may be refractory to the same. Leuko reduced or human leukocyte antigen matched platelets should be used. Recombinant factor VIIa can be used to control bleeding in refractory cases and in patients with antibodies against platelets. Anti-fibrinolytics can also be used as adjuvants. There is need of advanced perioperative coagulation screening spot tests in emergency trauma settings as routine coagulation tests may not be able to pick up the abnormality. Thromboelastography/thromboelastometry can be a great tool for perioperative management of such coagulation disorders.

  12. Urgent replacement of a mechanical mitral prosthesis in an anticoagulated patient with Bombay red blood cell phenotype.

    Science.gov (United States)

    Nairn, Travis K; Giulivi, Antonio; Neurath, Doris; Tokessy, Melanie; Sia, Ying T; Ruel, Marc; Wilkes, Peter R H

    2010-06-01

    Bombay red blood cell phenotype is an extremely rare blood type for which patients can receive only autologous or Bombay phenotype red blood cells. We report a case of urgent repeat sternotomy for replacement of a mechanical mitral prosthesis in a patient with Bombay phenotype anticoagulated with warfarin, to emphasize the transfusion challenges in such patients. A male of Indian descent presented to hospital with New York Heart Association IV symptoms. His medical history revealed previous mitral valve replacement with a mechanical prosthesis in 2005 and Bombay phenotype blood. Preoperative transthoracic echocardiography demonstrated thrombus obstruction of the mitral prosthesis despite anticoagulation with warfarin. Right ventricular systolic pressure was >100 mmHg with 3+ tricuspid regurgitation. The patient's condition was temporized with diuretics, bronchodilators, and bi-level positive airway pressure ventilation while transfusion medicine and cardiac surgery were consulted for urgent surgery. The patient received vitamin K and prothrombin complex concentrate prior to repeat sternotomy and successful mitral prosthesis replacement. After cardiopulmonary bypass, heparinization was corrected with protamine and followed by a second dose of prothrombin complex concentrate and recombinant activated factor VIIa. Postoperatively, the patient received four units of packed red blood cells, two autologous units and two units of Bombay specific red blood cells. Right ventricular pressures stabilized at 40 mmHg following surgery. The patient recovered following several days of inotropic support with milrinone, diuretics, and bronchodilators. Patients with Bombay phenotype red blood cells present as type O, but they are unable to receive red blood cells from any phenotype other than Bombay phenotype. They are able to receive all other blood products, including fresh frozen plasma, cryoprecipitate, platelets, prothrombin complex concentrate, and recombinant activated factor

  13. Eesti gaasiküsimustes : õnnis nagu palderjani nuusutanud kass / Virkko Lepassalu

    Index Scriptorium Estoniae

    Lepassalu, Virkko, 1971-

    2008-01-01

    Kehtiva Euroopa Liidu nn gaasidirektiivi 55/2003 järgi soovitatakse gaasi tootmine ja levitamine viia eraldi ettevõtete kätte, praegu ettevalmistatav regulatsioon muudaks selle kohustuslikuks. Seega peaks Gazprom oma 37% -lise osaluse Eesti Gaasis maha müüma. Eesti Gaasi kui sisulise monopolisti hoidmine Gazpromi filiaalina Eestis ohustab otseselt meie julgeolekut. Vt. samas: Välisminister Urmas Paeti kiri Nord Streamile; Nord Streami kaanepoisid

  14. Prognostic Importance of Lesion Location on Functional Outcome in Patients with Cerebellar Ischemic Stroke: a Prospective Pilot Study.

    Science.gov (United States)

    Picelli, Alessandro; Zuccher, Paola; Tomelleri, Giampaolo; Bovi, Paolo; Moretto, Giuseppe; Waldner, Andreas; Saltuari, Leopold; Smania, Nicola

    2017-02-01

    To date, few studies focused on prediction of functional recovery after cerebellar stroke. The main aim of this prospective pilot study was to determine the association between cerebellar lesion location and functional outcome in adults with acute cerebellar infarction. We examined 14 patients with first-ever unilateral cerebellar ischemic stroke within 7 days and at 90 days from the onset of stroke by means of the International Cooperative Ataxia Rating Scale. Cerebellar lesions were traced from magnetic resonance imaging performed within 72 h since stroke and region of interest were generated. The association between the International Cooperative Ataxia Rating Scale score and lesion location was determined with the voxel-based lesion-symptom mapping methods implemented in the MRIcro software. Colored lesion-symptom maps representing the z statistics were generated and overlaid onto the MNI-ICBM 152 linear probabilistic atlas of the human brain and the Johns Hopkins University white matter templates. Our results documented that injuries to the V, VI, VIIA Crus I, VIIA Crus II, VIIB, VIIIA, and VIIIB lobules and the middle cerebellar peduncle are significantly associated with the International Cooperative Ataxia Rating Scale (ICARS) score at 1 week after the onset of stroke. Furthermore, we found that injuries to the VI, VIIA Crus I, VIIA Crus II, VIIB, VIIIA, and VIIIB lobules, the dentate nucleus, and the middle cerebellar peduncle are significantly associated with the ICARS score at 3 months since the cerebellar stroke onset. The findings of this pilot study might improve prognostic accuracy of functional outcome in patients with acute cerebellar infarction.

  15. Eesti gaasiküsimustes : õnnis nagu palderjani nuusutanud kass / Virkko Lepassalu

    Index Scriptorium Estoniae

    Lepassalu, Virkko, 1971-

    2008-01-01

    Kehtiva Euroopa Liidu nn gaasidirektiivi 55/2003 järgi soovitatakse gaasi tootmine ja levitamine viia eraldi ettevõtete kätte, praegu ettevalmistatav regulatsioon muudaks selle kohustuslikuks. Seega peaks Gazprom oma 37% -lise osaluse Eesti Gaasis maha müüma. Eesti Gaasi kui sisulise monopolisti hoidmine Gazpromi filiaalina Eestis ohustab otseselt meie julgeolekut. Vt. samas: Välisminister Urmas Paeti kiri Nord Streamile; Nord Streami kaanepoisid

  16. Latvijas Gaze buyback likely to flop

    Index Scriptorium Estoniae

    2003-01-01

    Veerandi Läti gaasifirma Latvijas Gaze omanik Itera kavatseb lähiajal lõpule viia üheksa protsendi Läti firma aktsiate müügi ettevõttele Gazprom. Gazprom'i kontrolli all on praegu 25 protsenti, Ruhrgas'il 28,66 ning E.ON Energie AG-l 18,06 protsenti Latvijas Gaze aktsiatest

  17. Euroopa hing / Joseph Ratzinger ; tõlk. Külli-Riin Tigasson

    Index Scriptorium Estoniae

    Ratzinger, Joseph

    2005-01-01

    Paavst Benedictus XVI sõnul võib moraalsete väärtuste purunemine viia Euroopa identiteedi enesehävitamiseni. Inimväärikusest ja inimõigustest peab kujunema tingimusteta väärtus, ka on Euroopa identiteedi jaoks keskne tähtsus abielul ja perekonnal. Sõnavabadusel peab olema piir: teise inimese au ega väärikust ei tohi haavata

  18. Tagasi kunagisse Euroopa Liitu / Igor Gräzin

    Index Scriptorium Estoniae

    Gräzin, Igor, 1952-

    2005-01-01

    Riigikogu liikme sõnul on meil lausa moraalne kohustus esitada omapoolne plaan, mis säilitaks EL-i. Aruteluks võiks EL-i tagasi viia 1957. aasta Rooma lepingusse, mis sätestas vabakaubanduse ja tagas ühise turu. EL-i kriis ei tulene selle alustest, vaid kõikvõimalikest "poliitikatest", mis teenivad "poliitikute" ja survegruppide huve

  19. Kultuurivedur 2008 Anne Rande : lapsed ja lugemine, see ei ole mingi tilu-lilu / Rebekka Lotman ; kommenteerinud Evelin Ilves

    Index Scriptorium Estoniae

    Lotman, Rebekka, 1978-

    2009-01-01

    Ajalehe "Postimees" kultuuritoimetus pidas 2008. aasta Kultuuriveduri auhinna vääriliseks Eesti Lastekirjanduse Keskuse direktorit Anne Randet, kes räägib, miks ja kuidas viia lapsi lugemise juurde. President Toomas Hendrik Ilves on Anne Randet kui lastekirjanduse väärtustajat autasustanud Valgetähe V klassi teenetemärgiga. Kommenteerib Eesti Lastekirjanduse Keskuse patroon proua Evelin Ilves. Juuresoleval fotol Anne Rande koos Kadri Keiu Ilvesega

  20. Veel kord riigi poolsest teoprovokatsioonist : kas keelatud või siiski lubatud? / Paavo Randma

    Index Scriptorium Estoniae

    Randma, Paavo, 1977-

    2006-01-01

    Agent provocateur'i mõistest ja lubatavusest Inglismaa, Saksamaa ja Portugali kohtupraktika näitel. Agent provocateur on isik, kes politseiametniku või eraisikuna kriminaalmenetlust toimetavate asutuste ülesandel või heakskiidul kihutab teise isiku kuritegu toime panema eesmärgiga ta kinni võtta ja tema suhtes läbi viia kriminaalmenetlus, mis päädiks karistusega

  1. Kultuurivedur 2008 Anne Rande : lapsed ja lugemine, see ei ole mingi tilu-lilu / Rebekka Lotman ; kommenteerinud Evelin Ilves

    Index Scriptorium Estoniae

    Lotman, Rebekka, 1978-

    2009-01-01

    Ajalehe "Postimees" kultuuritoimetus pidas 2008. aasta Kultuuriveduri auhinna vääriliseks Eesti Lastekirjanduse Keskuse direktorit Anne Randet, kes räägib, miks ja kuidas viia lapsi lugemise juurde. President Toomas Hendrik Ilves on Anne Randet kui lastekirjanduse väärtustajat autasustanud Valgetähe V klassi teenetemärgiga. Kommenteerib Eesti Lastekirjanduse Keskuse patroon proua Evelin Ilves. Juuresoleval fotol Anne Rande koos Kadri Keiu Ilvesega

  2. Genetic analysis of Tunisian families with Usher syndrome type 1: toward improving early molecular diagnosis

    OpenAIRE

    2016-01-01

    Purpose Usher syndrome accounts for about 50% of all hereditary deaf-blindness cases. The most severe form of this syndrome, Usher syndrome type I (USH1), is characterized by profound congenital sensorineural deafness, vestibular dysfunction, and retinitis pigmentosa. Six USH1 genes have been identified, MYO7A, CDH23, PCDH15, USH1C, SANS, and CIB2, encoding myosin VIIA, cadherin-23, protocadherin-15, harmonin, scaffold protein containing ankyrin repeats and a sterile alpha motif (SAM) domain,...

  3. Proceedings of US-Japan heliotron-stellarator workshop: Volume 1

    Energy Technology Data Exchange (ETDEWEB)

    1987-01-01

    This paper is the first of four volumes on the US-Japan Heliotron-Stellarator workshop. It contains talks on the Heliotron E experiment, the compact helical system (CHS) program, the status of the ATF project, the status of the W VII-AS, the status of the TJ-II program, the ATF experimental plans, the ATF diagnostics, the compact Helical system, and the CHS experimental program and diagnostics. (LSP)

  4. Latvijas Gaze buyback likely to flop

    Index Scriptorium Estoniae

    2003-01-01

    Veerandi Läti gaasifirma Latvijas Gaze omanik Itera kavatseb lähiajal lõpule viia üheksa protsendi Läti firma aktsiate müügi ettevõttele Gazprom. Gazprom'i kontrolli all on praegu 25 protsenti, Ruhrgas'il 28,66 ning E.ON Energie AG-l 18,06 protsenti Latvijas Gaze aktsiatest

  5. Mõeldes arhitektuuri välkloengutele = Considering flash lectures on architecture / Margit Mutso

    Index Scriptorium Estoniae

    Mutso, Margit, 1966-

    2010-01-01

    7. veebruaril 2008 Von Krahli Teatris alanud arhitektuuri välkloengutest, mille eesmärk oli haarata avalikkust kaasa mõtlema, rääkima meid ümbritsevast keskkonnast ning viia ühiskonda arusaamist, et arhitektuur on meie kõigi asi. Arhitektuurist kutsuti rääkima tuntud äri- ja kultuuriinimesi. Välkloenguid modereerisid Ülar Mark, Margit Mutso ja Mattias Agabus

  6. IMF soovitab uue töölepinguseaduse kiiresti vastu võtta / Peep Lillemägi

    Index Scriptorium Estoniae

    Lillemägi, Peep, 1967-

    2008-01-01

    Ilmunud ka: Tallinnskii Vestnik juuli 2008, lk. 3. Eestis viibinud IMF-i delegatsiooni hinnangul sõltub Eesti majanduskasvu taastumine suurel määral majanduse konkurentsivõimest, delegatsioon toetab kavatsust leida edasisi võimalusi kokkuhoiuks ning soovitab töölepinguseaduse eelnõu kiiresti vastu võtta ja ellu viia. Rahandusminister Ivari Padari arvamus IMF-i hinnangute kohta

  7. Rohkem kui 300 aastat tagasi surnud pere õnnestus tuvastada / Mati Mandel ; Kalev Jaago

    Index Scriptorium Estoniae

    Mandel, Mati, 1945-

    2016-01-01

    Peanse külas Lihula vallas toimunud kaevamistest. Leiti nelja inimese luustikud. Leiumaterjal võimaldas võrrelda ja kokku viia arheoloogi, numismaatiku, atropoloogi ja arhivaari uurimistulemusi. Suure tõenäosusega võisid leitud maetud olla Leti Andrese Mihkel, tema abikaasa ning lapsed Heinrich ja Ann. Tegu võib olla 1710.- 1711. aasta katku ohvritega. Haruldase juhtumina saab luid seostada konkreetsete ajalooliste isikutega

  8. Euroopa Liit valmistab ette uutmoodi Venemaa-poliitikat / Ahto Lobjakas

    Index Scriptorium Estoniae

    Lobjakas, Ahto, 1970-

    2006-01-01

    EL-i järgmine eesistujariik Saksamaa pakub täielikku paradigma muutust EL-i ja Venemaa suhetes, autori sõnul asenduks senine rõhk "ühistel väärtustel" huvide kaine kalkulatsiooniga. Autor esitab oma seisukoha, kuidas peaks toimima Eesti: probleemid Venemaaga on vaja viia miinimumini ning EL-is tuleb toetada ühiseid valikuid vetoõiguse ja erahuvide vastu

  9. Mõeldes arhitektuuri välkloengutele = Considering flash lectures on architecture / Margit Mutso

    Index Scriptorium Estoniae

    Mutso, Margit, 1966-

    2010-01-01

    7. veebruaril 2008 Von Krahli Teatris alanud arhitektuuri välkloengutest, mille eesmärk oli haarata avalikkust kaasa mõtlema, rääkima meid ümbritsevast keskkonnast ning viia ühiskonda arusaamist, et arhitektuur on meie kõigi asi. Arhitektuurist kutsuti rääkima tuntud äri- ja kultuuriinimesi. Välkloenguid modereerisid Ülar Mark, Margit Mutso ja Mattias Agabus

  10. Euroopa firmad on asunud oma äri ümber korraldama / Ralph Atkins, Peggy Hollinger

    Index Scriptorium Estoniae

    Atkins, Ralph

    2004-01-01

    Euroopa Liidu juhtide sõnul liigutakse aeglaselt 2000. aastal Lissaboni tippkohtumisel seatud sihtidele viia Euroopa majandus konkurentsivõimelt esikohale maailmas. Euroopa ettevõtted on asunud äri ümberstruktureerima eesmärgiga kärpida kulusid ja leida firmade konkurentsieeliseid. Lisad: Muundumine nagu õpikus; Ümberkorraldamise tulemused siiani teadmata; Erik Aru. Eestis on eduka restruktureerimise näiteks Baltika ja Harju Elekter

  11. Kuidas valiti president 1996. aastal? / Rein Toomla

    Index Scriptorium Estoniae

    Toomla, Rein, 1951-

    2002-01-01

    Autor leiab 1996. aasta presidendivalimisi analüüsides, et oluliseks tuleb pidada seda, et valimised suudeti põhiseaduses ettenähtud korras läbi viia ning ei pidanud käivituma erakorraliste valimiste mehhanism. Tabelid: 1995. a. Riigikogu valimised; Riigikogu fraktsioonid 1996. a. suvel; Toetus presidendikandidaatidele; Presidendivalimised Riigikogus; Arvatavasti Lennart Meri poolt; Arvatavasti Arnold Rüütli poolt; Presidendivalimised Valimiskogus

  12. Proceedings of US-Japan heliotron-stellarator workshop: Volume 1

    Energy Technology Data Exchange (ETDEWEB)

    1987-01-01

    This paper is the first of four volumes on the US-Japan Heliotron-Stellarator workshop. It contains talks on the Heliotron E experiment, the compact helical system (CHS) program, the status of the ATF project, the status of the W VII-AS, the status of the TJ-II program, the ATF experimental plans, the ATF diagnostics, the compact Helical system, and the CHS experimental program and diagnostics. (LSP)

  13. Tallinn nimetas Poska stipendiumi saajad

    Index Scriptorium Estoniae

    2006-01-01

    Tallinna linnavalitsus nimetas 10. mai istungil Jaan Poska stipendiumi saajad. Stipendium määrati kümnele Tallinna Tehnikaülikooli üliõpilasele : Eve Eenmaa, Andrus Räämet, Jelena Hartšenko, Andres Viia, Maksim Jenihhin, Raul Naadel, Martins Sarkans, Dmitri Šumigin, Külliki Tafel, Minna Varikmaa. Jaan Poska stipendium määratakse üliõpilasele silmapaistva ühiskondliku tegevuse eest Eesti ja Tallinna arengu heaks

  14. Patterns of regional cerebellar atrophy in genetic frontotemporal dementia

    Directory of Open Access Journals (Sweden)

    Martina Bocchetta

    2016-01-01

    Conclusion: There appears to be a differential pattern of cerebellar atrophy in the major genetic forms of FTD, being relatively spared in GRN, localized to the lobule VIIa-Crus I in the superior-posterior region of the cerebellum in C9orf72, the area connected via the thalamus to the prefrontal cortex and involved in cognitive function, and localized to the vermis in MAPT, the ‘limbic cerebellum’ involved in emotional processing.

  15. Euroopa Liit valmistab ette uutmoodi Venemaa-poliitikat / Ahto Lobjakas

    Index Scriptorium Estoniae

    Lobjakas, Ahto, 1970-

    2006-01-01

    EL-i järgmine eesistujariik Saksamaa pakub täielikku paradigma muutust EL-i ja Venemaa suhetes, autori sõnul asenduks senine rõhk "ühistel väärtustel" huvide kaine kalkulatsiooniga. Autor esitab oma seisukoha, kuidas peaks toimima Eesti: probleemid Venemaaga on vaja viia miinimumini ning EL-is tuleb toetada ühiseid valikuid vetoõiguse ja erahuvide vastu

  16. Euroopa firmad on asunud oma äri ümber korraldama / Ralph Atkins, Peggy Hollinger

    Index Scriptorium Estoniae

    Atkins, Ralph

    2004-01-01

    Euroopa Liidu juhtide sõnul liigutakse aeglaselt 2000. aastal Lissaboni tippkohtumisel seatud sihtidele viia Euroopa majandus konkurentsivõimelt esikohale maailmas. Euroopa ettevõtted on asunud äri ümberstruktureerima eesmärgiga kärpida kulusid ja leida firmade konkurentsieeliseid. Lisad: Muundumine nagu õpikus; Ümberkorraldamise tulemused siiani teadmata; Erik Aru. Eestis on eduka restruktureerimise näiteks Baltika ja Harju Elekter

  17. Veel kord riigi poolsest teoprovokatsioonist : kas keelatud või siiski lubatud? / Paavo Randma

    Index Scriptorium Estoniae

    Randma, Paavo, 1977-

    2006-01-01

    Agent provocateur'i mõistest ja lubatavusest Inglismaa, Saksamaa ja Portugali kohtupraktika näitel. Agent provocateur on isik, kes politseiametniku või eraisikuna kriminaalmenetlust toimetavate asutuste ülesandel või heakskiidul kihutab teise isiku kuritegu toime panema eesmärgiga ta kinni võtta ja tema suhtes läbi viia kriminaalmenetlus, mis päädiks karistusega

  18. Tallinn nimetas Poska stipendiumi saajad

    Index Scriptorium Estoniae

    2006-01-01

    Tallinna linnavalitsus nimetas 10. mai istungil Jaan Poska stipendiumi saajad. Stipendium määrati kümnele Tallinna Tehnikaülikooli üliõpilasele : Eve Eenmaa, Andrus Räämet, Jelena Hartšenko, Andres Viia, Maksim Jenihhin, Raul Naadel, Martins Sarkans, Dmitri Šumigin, Külliki Tafel, Minna Varikmaa. Jaan Poska stipendium määratakse üliõpilasele silmapaistva ühiskondliku tegevuse eest Eesti ja Tallinna arengu heaks

  19. Kevad turul : juba aprillis sihib börsile Arco Vara / Kadi Heinsalu, Virge Lahe

    Index Scriptorium Estoniae

    Heinsalu, Kadi, 1966-

    2007-01-01

    Kinnisvaraettevõte Arco Vara tahab viia ettevõtte börsile. Vt. samas: Arco Varal on vaja arenduseks miljardeid; Suuromanikud Arti Arakas ja Richard Tomingas; Ettevõtte CV. Diagramm: Majandusnäitajad. Kommenteerivad: Tex Vertmann, Malle Aleksius, Peeter Koppel, Rainer Änilane ja Ragnar Plees. Vt. ka Annika Matsoni ja Agnes Ojala art. 21. märtsi Äripäevas lk. 2

  20. Rohkem kui 300 aastat tagasi surnud pere õnnestus tuvastada / Mati Mandel ; Kalev Jaago

    Index Scriptorium Estoniae

    Mandel, Mati, 1945-

    2016-01-01

    Peanse külas Lihula vallas toimunud kaevamistest. Leiti nelja inimese luustikud. Leiumaterjal võimaldas võrrelda ja kokku viia arheoloogi, numismaatiku, atropoloogi ja arhivaari uurimistulemusi. Suure tõenäosusega võisid leitud maetud olla Leti Andrese Mihkel, tema abikaasa ning lapsed Heinrich ja Ann. Tegu võib olla 1710.- 1711. aasta katku ohvritega. Haruldase juhtumina saab luid seostada konkreetsete ajalooliste isikutega

  1. Kevad turul : juba aprillis sihib börsile Arco Vara / Kadi Heinsalu, Virge Lahe

    Index Scriptorium Estoniae

    Heinsalu, Kadi, 1966-

    2007-01-01

    Kinnisvaraettevõte Arco Vara tahab viia ettevõtte börsile. Vt. samas: Arco Varal on vaja arenduseks miljardeid; Suuromanikud Arti Arakas ja Richard Tomingas; Ettevõtte CV. Diagramm: Majandusnäitajad. Kommenteerivad: Tex Vertmann, Malle Aleksius, Peeter Koppel, Rainer Änilane ja Ragnar Plees. Vt. ka Annika Matsoni ja Agnes Ojala art. 21. märtsi Äripäevas lk. 2

  2. Kodanikud, võltsingud ja zombid / Tanel Tammet

    Index Scriptorium Estoniae

    Tammet, Tanel

    2005-01-01

    Autor avaldab arvamust, et e-valimiste vastu olevad erakonnad ja poliitikud pole mures mitte niivõrd nende valimiste turvalisuse pärast, vaid pigem seepärast, et e-valimised võivad suurendada noorema valijaskonna aktiivsust. E-valimiste õnnestumine võib viia mõttele Šveitsi otsedemokraatia mõne põhimõtte rakendamise kohta Eestis. Autor kirjeldab turvariske, mis võivad kaasneda e-valimistel

  3. Euroopa hing / Joseph Ratzinger ; tõlk. Külli-Riin Tigasson

    Index Scriptorium Estoniae

    Ratzinger, Joseph

    2005-01-01

    Paavst Benedictus XVI sõnul võib moraalsete väärtuste purunemine viia Euroopa identiteedi enesehävitamiseni. Inimväärikusest ja inimõigustest peab kujunema tingimusteta väärtus, ka on Euroopa identiteedi jaoks keskne tähtsus abielul ja perekonnal. Sõnavabadusel peab olema piir: teise inimese au ega väärikust ei tohi haavata

  4. Marmorisuvi Pärnus / Mark Soosaar

    Index Scriptorium Estoniae

    Soosaar, Mark, 1946-

    2005-01-01

    Pärnu Uue Kunsti Muuseum korraldab aktinäituse "Mees ja naine" raames marmoripäevad. 20. maiks oodatakse kunstnikelt vähemalt 20 cm kõrgusi mahulisi kavandeid teemal "Vesi, loodus ja armastus". Kavandite alusel valib žürii kuus skulptorit, kes saavad oma idee viia Carrarast toodud marmorisse. Suvel on muuseumis väljas Amandus Adamsoni "Laine ainuke suudlus"

  5. Valitsuse stabiilsus Eestis : soovunelm või tegelikkus? / Olaf Dahlmann

    Index Scriptorium Estoniae

    Dahlmann, Olaf

    2003-01-01

    Autor leiab, et hoolimata sagedastest valitsuste vahetumistest, pingetest sisepoliitikas ja rahva üha süvenevast poliitilisest apaatsusest, on Eesti suutnud edukalt läbi viia poliitilisi reforme. Üldine konsensus põhilistes küsimustes on peamiste poliitiliste eesmärkide ja reformipoliitika püsivuse alus, seega ka ka valitsuse stabiilsuse alus. Tabel: Eesti valitsused alates 1992. aastast. Joonis: Valitsuse stabiilsust mõjutavad tegurid

  6. Devalveerimise pooldajad ja vastased / Edward Hugh ; intervjueerinud Mikk Salu

    Index Scriptorium Estoniae

    Hugh, Edward

    2009-01-01

    RGE Monitori ökonomisti hinnangul oleks Eestil võimalik devalveerimist lihtsamalt, tulemuslikumalt ja valutumalt läbi viia kui Lätil. Praeguses majanduskriisis oleks lahendus Lätile, Eestile ja kogu Ida-Euroopale kohene euroga liitumine. Göran Lind räägib Rootsi kogemusest krooni devalveerimisel, Christopher Rosenberg nimetab põhjused, miks Läti ja IMF-i programm ei sisalda devalveerimist

  7. Kubilius conquers America / Rokas M. Tracevskis

    Index Scriptorium Estoniae

    Tracevskis, Rokas M.

    2010-01-01

    5.- 9. maini kestnud Ameerika Ühendriikide visiidi ajal kohtus Leedu peaminister Andrius Kubilius riigisekretäri Hillary Rodham Clintoniga, kellega räägiti riikidevahelistest suhetest, CIA salavanglast ja Egle Kusaitest, kes väidetavalt plaanis Venemaa sõjalistel objektidel läbi viia terrorirünnakud. Andrius Kubilius kohtus ka IBMi esindajatega. IBM plaanib rajada Leetu uurimiskeskuse

  8. Kuidas valiti president 1996. aastal? / Rein Toomla

    Index Scriptorium Estoniae

    Toomla, Rein, 1951-

    2002-01-01

    Autor leiab 1996. aasta presidendivalimisi analüüsides, et oluliseks tuleb pidada seda, et valimised suudeti põhiseaduses ettenähtud korras läbi viia ning ei pidanud käivituma erakorraliste valimiste mehhanism. Tabelid: 1995. a. Riigikogu valimised; Riigikogu fraktsioonid 1996. a. suvel; Toetus presidendikandidaatidele; Presidendivalimised Riigikogus; Arvatavasti Lennart Meri poolt; Arvatavasti Arnold Rüütli poolt; Presidendivalimised Valimiskogus

  9. Tissue- and Condition-Specific Isoforms of Mammalian Cytochrome c Oxidase Subunits: From Function to Human Disease

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    Christopher A. Sinkler

    2017-01-01

    Full Text Available Cytochrome c oxidase (COX is the terminal enzyme of the electron transport chain and catalyzes the transfer of electrons from cytochrome c to oxygen. COX consists of 14 subunits, three and eleven encoded, respectively, by the mitochondrial and nuclear DNA. Tissue- and condition-specific isoforms have only been reported for COX but not for the other oxidative phosphorylation complexes, suggesting a fundamental requirement to fine-tune and regulate the essentially irreversible reaction catalyzed by COX. This article briefly discusses the assembly of COX in mammals and then reviews the functions of the six nuclear-encoded COX subunits that are expressed as isoforms in specialized tissues including those of the liver, heart and skeletal muscle, lung, and testes: COX IV-1, COX IV-2, NDUFA4, NDUFA4L2, COX VIaL, COX VIaH, COX VIb-1, COX VIb-2, COX VIIaH, COX VIIaL, COX VIIaR, COX VIIIH/L, and COX VIII-3. We propose a model in which the isoforms mediate the interconnected regulation of COX by (1 adjusting basal enzyme activity to mitochondrial capacity of a given tissue; (2 allosteric regulation to adjust energy production to need; (3 altering proton pumping efficiency under certain conditions, contributing to thermogenesis; (4 providing a platform for tissue-specific signaling; (5 stabilizing the COX dimer; and (6 modulating supercomplex formation.

  10. Hemofilia adquirida en el postparto. Presentación de un caso Postpartum Acquired Hemophilia. A Case Report

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    Yenisey Quintero Méndez

    2012-11-01

    Full Text Available Las hemorragias del periparto son la principal causa de morbilidad materna extremadamente grave y de muerte materna en Cuba y en el mundo. La hemofilia A adquirida es un trastorno hemorrágico poco frecuente, caracterizado por la presencia de anticuerpos contra el factor VIII (FVIII circulante. Se presenta el caso de una gestante de 36 años de edad, con embarazo a término, que tiene parto eutócico y presenta manifestaciones hemorrágicas en el postparto inmediato, secundarias a hematoma de la rafia que requiere de hemoterapia. Luego presenta hematoma del miembro superior derecho secundario a accidente vascular que requiere de reparo quirúrgico. La evolución tórpida del puerperio, caracterizada por hemorragia mantenida por la rafia y por el brazo intervenido, hace sospechar la presencia de un trastorno hematológico. Se constata una disminución del factor FVIII, que implica el diagnóstico de hemofilia A adquirida, se impone tratamiento con concentrado de factor VIIa recombinante (FVIIar y ciclofosfamida. La evolución posterior fue favorable, la paciente se egresa sin secuelas.Periparturient hemorrhages are the leading cause of extremely serious maternal morbidity and maternal death in Cuba and the world. Acquired Hemophilia A is a rare bleeding disorder characterized by the presence of antibodies against circulating factor VIII (FVIII. We present the case of a 36 years old pregnant woman with term pregnancy and vaginal delivery that suffers from hemorrhagic manifestations in the immediate postpartum secondary to raffia hematoma, requiring blood transfusion. Then she presents a bruise in the right upper limb secondary to stroke that requires surgical repair. The postpartum torpid evolution characterized by sustained bleeding raffia and the surgically treated arm, makes us suspect of the presence of a blood disorder. We observed a decrease in the FVIII factor, which involves the diagnosis of acquired hemophilia and requires treatment with

  11. Procoagulant properties of human MV3 melanoma cells

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    D.L.A. Geaquinto

    2008-02-01

    Full Text Available A correlation between cancer and prothrombotic states has long been described. More recently, a number of studies have focused on the procoagulant mechanisms exhibited by tumor cells. In the present study, we dissected the molecular mechanisms responsible for the procoagulant activity of MV3, a highly aggressive human melanoma cell line. It was observed that tumor cells strongly accelerate plasma coagulation as a result of: i expression of the blood clotting initiator protein, a tissue factor, as shown by flow cytometry and functional assays (factor Xa formation in the presence of cells and factor VIIa, and ii direct activation of prothrombin to thrombin by cells, as evidenced by hydrolysis of the synthetic substrate, S-2238, and the natural substrate, fibrinogen. This ability was highly potentiated by the addition of exogenous factor Va, which functions as a co-factor for the enzyme factor Xa. In contrast, prothrombin activation was not observed when cells were previously incubated with DEGR-factor Xa, an inactive derivative of the enzyme. Moreover, a monoclonal antibody against bovine factor Xa reduced the prothrombin-converting activity of tumor cells. In conclusion, the data strongly suggest that MV3 cells recruit factor Xa from the culture medium, triggering an uncommon procoagulant mechanism.

  12. Random Forests Are Able to Identify Differences in Clotting Dynamics from Kinetic Models of Thrombin Generation.

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    Jayavel Arumugam

    Full Text Available Current methods for distinguishing acute coronary syndromes such as heart attack from stable coronary artery disease, based on the kinetics of thrombin formation, have been limited to evaluating sensitivity of well-established chemical species (e.g., thrombin using simple quantifiers of their concentration profiles (e.g., maximum level of thrombin concentration, area under the thrombin concentration versus time curve. In order to get an improved classifier, we use a 34-protein factor clotting cascade model and convert the simulation data into a high-dimensional representation (about 19000 features using a piecewise cubic polynomial fit. Then, we systematically find plausible assays to effectively gauge changes in acute coronary syndrome/coronary artery disease populations by introducing a statistical learning technique called Random Forests. We find that differences associated with acute coronary syndromes emerge in combinations of a handful of features. For instance, concentrations of 3 chemical species, namely, active alpha-thrombin, tissue factor-factor VIIa-factor Xa ternary complex, and intrinsic tenase complex with factor X, at specific time windows, could be used to classify acute coronary syndromes to an accuracy of about 87.2%. Such a combination could be used to efficiently assay the coagulation system.

  13. Blood coagulation reactions on nanoscale membrane surfaces

    Science.gov (United States)

    Pureza, Vincent S.

    Blood coagulation requires the assembly of several membrane-bound protein complexes composed of regulatory and catalytic subunits. The biomembranes involved in these reactions not only provide a platform for these procoagulant proteins, but can also affect their function. Increased exposure of acidic phospholipids on the outer leaflet of the plasma membrane can dramatically modulate the catalytic efficiencies of such membrane-bound enzymes. Under physiologic conditions, however, these phospholipids spontaneously cluster into a patchwork of membrane microdomains upon which membrane binding proteins may preferentially assemble. As a result, the membrane composition surrounding these proteins is largely unknown. Through the development and use of a nanometer-scale bilayer system that provides rigorous control of the phospholipid membrane environment, I investigated the role of phosphatidylserine, an acidic phospholipid, in the direct vicinity (within nanometers) of two critical membrane-bound procoagulant protein complexes and their respective natural substrates. Here, I present how the assembly and function of the tissue factor˙factor VIIa and factor Va˙factor Xa complexes, the first and final cofactor˙enzyme complexes of the blood clotting cascade, respectively, are mediated by changes in their immediate phospholipid environments.

  14. Mysterious bruises

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    H Chen

    2012-01-01

    Full Text Available A 69-year-old man presented with multiple spontaneous bruises in the past 2 weeks. Several large-sized hematomas were found on examination. The initial investigation revealed a prolonged activated partial thromboplastin time (aPTT with normal platelet count and international normalized ratio. Further investigation revealed a low factor VIII activity secondary to presence of factor VIII inhibitor, making the diagnosis of acquired hemophilia A. Further work-up revealed that pernicious anemia was present and acted as an associated disease. After steroids therapy, his aPTT was normalized and the factor VIII inhibitor titer became undetectable. 2 months later, a relapse occurred and new hematomas appeared at his retropharyngeal space and left arm. His bleeding was controlled by administration of recombinant factor VIIa, and a combined therapy of intravenous steroids and rituximab was given to eradicate the inhibitor. The approach to workup of bleeding disorders as well as treatment of acquired hemophilia A are herein discussed.

  15. The anti-coagulants asis or apc do not protect against renal ischemia/ reperfusion injury

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    Sarah T.B.G. Loubele

    2014-06-01

    Full Text Available Renal ischemia/reperfusion (I/R injury is the main cause of acute renal failure. The severity of injury is determined by endothelial damage as well as inflammatory and apoptotic processes. The anticoagulants active site inhibited factor VIIa (ASIS and activated protein C (APC are besides their anticoagulant function also known for their cytoprotective properties. In this study the effect of ASIS and APC was assessed on renal I/R injury and this in relation to inflammation and apoptosis. Our results showed no effect of ASIS or APC on renal injury as determined by histopathological scoring as well as by blood urea nitrogen (BUN and creatinine levels. Furthermore, no effect on fibrin staining was detected but ASIS did reduce tissue factor activity levels after a 2-hr reperfusion period. Neither ASIS nor APC administration influenced overall inflammation markers, although some inflammatory effects of ASIS on interleukin (IL-1β and tumor necrosis factor (TNF-α were detectable after 2 hr of reperfusion. Finally, neither APC nor ASIS had an influence on cell signaling pathways or on the number of apoptotic cells within the kidneys. From this study we can conclude that the anticoagulants ASIS and APC do not have protective effects in renal I/R injury in the experimental setup as used in this study which is in contrast to the protective effects of these anticoagulants in other models of I/R.

  16. Activation of coagulation in chronic urticaria in relation to disease severity and activity.

    Science.gov (United States)

    Farres, M N; Refaat, M; Melek, N A; Ahmed, E E; Shamseldine, M G; Arafa, N A

    2015-01-01

    The pathogenesis of chronic urticaria is incompletely understood. There is growing interest in the role of the coagulation cascade in chronic urticaria. We aimed to assess the possible activation of the coagulation cascade in chronic spontaneous urticaria (CSU) in relation to disease severity and activity. This study was conducted on 30 patients with active CSU and 30 apparently healthy individuals as controls. Patients with acute urticaria, physical urticaria, or any form of urticaria other than spontaneous urticaria were excluded. Plasma levels of D-dimer and activated factor VII (FVIIa) were measured by ELISA at baseline for all recruited patients and controls. In addition, they were measured for CSU patients after complete disease remission. Plasma levels of D-dimer and FVIIa were significantly higher among patients with active CSU than among healthy controls. D-dimer levels were lowest among patients with grade 1 severity and highest among those with grade 4 severity. Factor VIIa levels did not differ significantly according to disease severity grades. After complete disease remission, there was a significant dramatic drop in levels of D-dimer and FVIIa among patients. We conclude that activation of the coagulation cascade occurs in CSU, and we demonstrate the novel finding that activated factor VII levels are significantly reduced after medical therapy, confirming the implication of the extrinsic pathway activation in CSU. Future controlled studies may investigate the role of anticoagulant therapy in refractory chronic urticaria. Copyright © 2014 SEICAP. Published by Elsevier Espana. All rights reserved.

  17. Desvenlafaxine as a possible cause of acquired hemophilia.

    Science.gov (United States)

    Shaligram, Deepika; Alqassem, Tahani; Koby, Elizabeth

    2010-01-01

    Acquired hemophilia A (AHA) is characterized by the depletion of Factor VIII mediated by specific autoantibodies. While the cause is unknown in 50% of the cases, an association with malignancy, peripartum period, autoimmune disease and the use of drugs has been described. We report a case of AHA possibly induced by desvenlafaxine. Mr. P, a 70-year-old Caucasian male with alcohol and opioid dependence in remission, was started on 50 mg of desvenlafaxine for a moderate depressive episode. After 10 weeks, he developed an ecchymosis of the right upper extremity, in the absence of past or family history of bleeding disorder. He had a prolonged activated partial thromboplastin time (74.5 s) not corrected on performing mixing study, decreased Factor VIII activity (desvenlafaxine was discontinued and the patient was infused with Factor VIIa followed by a 6-week prednisone taper with which he achieved remission. While serotonin inhibitors are known to impair platelet aggregation leading to bleeding, abnormalities in the coagulation cascade have not been described so far. Desvenlafaxine appears to be the probable cause of AHA given the temporal association, remission after withdrawal of the drug and the lack of any other probable cause. New-onset abnormalities of the coagulation cascade such as AHA should be considered in the context of bleeding events with desvenlafaxine and perhaps other serotonin inhibitors, given the significant mortality rates when untreated. Copyright © 2010 Elsevier Inc. All rights reserved.

  18. Hemofilia adquirida en el postparto. Presentación de un caso

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    María Antonia Cabezas Poblet

    2012-09-01

    Full Text Available Las hemorragias del periparto son la principal causa de morbilidad materna extremadamente grave y de muerte materna en Cuba y en el mundo. La hemofilia A adquirida es un trastorno hemorrágico poco frecuente, caracterizado por la presencia de anticuerpos contra el factor VIII (FVIII circulante. Se presenta el caso de una gestante de 36 años de edad, con embarazo a término, que tiene parto eutócico y presenta manifestaciones hemorrágicas en el postparto inmediato, secundarias a hematoma de la rafia que requiere de hemoterapia. Luego presenta hematoma del miembro superior derecho secundario a accidente vascular que requiere de reparo quirúrgico. La evolución tórpida del puerperio, caracterizada por hemorragia mantenida por la rafia y por el brazo intervenido, hace sospechar la presencia de un trastorno hematológico. Se constata una disminución del factor FVIII, que implica el diagnóstico de hemofilia A adquirida, se impone tratamiento con concentrado de factor VIIa recombinante (FVIIar y ciclofosfamida. La evolución posterior fue favorable, la paciente se egresa sin secuelas.

  19. Animal models of FVIIa gene expression: their role in the future development of haemophilia treatment.

    Science.gov (United States)

    Obergfell, A; Nichols, T; Ezban, M

    2010-03-01

    The development of inhibitors to replacement factor therapy is a serious complication in the treatment of patients with haemophilia and requires use of bypassing agents to prevent uncontrolled bleeding. The efficacy of recombinant factor VIIa (rFVIIa) as a bypassing agent in patients with haemophilia has been demonstrated in case studies and clinical trials. However, the perception of a short plasma half-life and consequent need for repeated daily injections means that long-term prophylaxis could potentially be limiting. Canine haemophilia models using a gene transfer approach have been used to evaluate the continuous expression of FVIIa in dogs. These studies show improvement in measurable bleeding parameters that have important clinical ramifications for patients with haemophilia. The combination of gene transfer as the method of delivery and FVII as the transgene overcomes issues associated with the short plasma half-life of rFVIIa, and represents a potentially attractive novel approach to haemostasis in patients with haemophilia and other platelet disorders.

  20. Perioperative coagulation management--fresh frozen plasma.

    Science.gov (United States)

    Kor, Daryl J; Stubbs, James R; Gajic, Ognjen

    2010-03-01

    Clinical studies support the use of perioperative fresh frozen plasma (FFP) in patients who are actively bleeding with multiple coagulation factor deficiencies and for the prevention of dilutional coagulopathy in patients with major trauma and/or massive haemorrhage. In these settings, current FFP dosing recommendations may be inadequate. However, a substantial proportion of FFP is transfused in non-bleeding patients with mild elevations in coagulation screening tests. This practice is not supported by the literature, is unlikely to be of benefit and unnecessarily exposes patients to the risks of FFP. The role of FFP in reversing the effects of warfarin anticoagulation is dependent on the clinical context and availability of alternative agents. Although FFP is commonly transfused in patients with liver disease, this practice needs broad reconsideration. Adverse effects of FFP include febrile and allergic reactions, transfusion-associated circulatory overload and transfusion-related acute lung injury. The latter is the most serious complication, being less common with the preferential use of non-alloimmunised, male-donor predominant plasma. FP24 and thawed plasma are alternatives to FFP with similar indications for administration. Both provide an opportunity for increasing the safe plasma donor pool. Although prothrombin complex concentrates and factor VIIa may be used as alternatives to FFP in a variety of specific clinical contexts, additional study is needed.

  1. Design and synthesis of 4-substituted quinazolines as potent EGFR inhibitors with anti-breast cancer activity.

    Science.gov (United States)

    Ahmed, Marwa; Magdy, Naja

    2016-09-23

    Cancer is a major health problem to human beings around the world. Many quinazoline derivatives were reported to have potent cytotoxic activity. Our aim in this work is the discovery of potent epidermal growth factor receptor (EGFR) inhibitors with anti-breast cancer activity containing 4-substituted quinazoline pharmacophore. Novel series of 4-substituted 6,8-dibromo-2-(4-chlorophenyl)-quinazoline derivatives have been designed and synthesized. New derivatives were tested against MCF-7 (human breast carcinoma cell line) and screened for their inhibition activity against epidermal growth factor receptor tyrosine kinase (EGFR-TK). Most of the tested compounds show potent antiproliferative activity and EGFR-TK inhibitory activity. Compounds VIIIc and VIIIb exerted powerful cytotoxic activity (IC50 3.1 and 6.3 µM) with potent inhibitory percent (91.1 and 88.4%) against EGFR-TK. Compounds IX, VIIa, X, VIIb, VIc, V, IV, VIa and VIb showed promising cytotoxic effects with IC50 range (12-79 µM) with good activity against EGFR-TK with the inhibitory percent (85.4-60.8%). On the other hand, compounds VIIc, VIIIa exerted low cytotoxic effects as revealed from their IC50 value (124 and 144 µM) with low activity against EGFR-TK with inhibitory percent 30.6 and 29.1% respectively.

  2. Recent advances in paediatric cardiac anaesthesia

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    Mahesh Vakamudi

    2012-01-01

    Full Text Available Paediatric cardiac anaesthesia involves anaesthetizing very small children with complex congenital heart disease for major surgical procedures. The unique nature of this patient population requires considerable expertise and in-depth knowledge of the altered physiology. There have been several developments in the last decade in this subspecialty that has contributed to better care and improved outcome in this vulnerable group of patients. The purpose of this review is to present some of the recent advances in the anesthetic management of these children from preoperative evaluation to postoperative care. This article reviews the role of magnetic resonance imaging and contrast-enhanced magnetic resonance angiography in preoperative evaluation, the use of ultrasound to secure vascular access, the use of cuffed endotracheal tubes, the optimal haematocrit and the role of blood products, including the use of recombinant factor VIIa. It also deals with the advances in technology that have led to improved monitoring, the newer developments in cardiopulmonary bypass, the use of centrifugal pumps and extracorporeal membrane oxygenation and the role of DHCA. The role of new drugs, especially the α-2 agonists in paediatric cardiac anesthetic practice, fast tracking and effective postoperative pain management have also been reviewed.

  3. Glanzmann thrombasthenia

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    Nurden Alan T

    2006-04-01

    Full Text Available Abstract Glanzmann thrombasthenia (GT is a rare autosomal recessive bleeding syndrome affecting the megakaryocyte lineage and characterized by lack of platelet aggregation. The molecular basis is linked to quantitative and/or qualitative abnormalities of αIIbβ3 integrin. This receptor mediates the binding of adhesive proteins that attach aggregating platelets and ensure thrombus formation at sites of injury in blood vessels. GT is associated with clinical variability: some patients have only minimal bruising while others have frequent, severe and potentially fatal hemorrhages. The site of bleeding in GT is clearly defined: purpura, epistaxis, gingival hemorrhage, and menorrhagia are nearly constant features; gastrointestinal bleeding and hematuria are less common. In most cases, bleeding symptoms manifest rapidly after birth, even if GT is occasionally only diagnosed in later life. Diagnosis should be suspected in patients with mucocutaneous bleeding with absent platelet aggregation in response to all physiologic stimuli, and a normal platelet count and morphology. Platelet αIIbβ3 deficiency or nonfunction should always be confirmed, for example by flow cytometry. In order to avoid platelet alloimmunisation, therapeutic management must include, if possible, local hemostatic procedures and/or desmopressin (DDAVP administration. Transfusion of HLA-compatible platelet concentrates may be necessary if these measures are ineffective, or to prevent bleeding during surgery. Administration of recombinant factor VIIa is an increasingly used therapeutic alternative. GT can be a severe hemorrhagic disease, however the prognosis is excellent with careful supportive care.

  4. Effects of a recombinant FVIIa analogue, NN1731, on blood loss and survival after liver trauma in the pig

    DEFF Research Database (Denmark)

    Zaar, M; Secher, N H; Johansson, P I

    2009-01-01

    BACKGROUND: We considered whether haemorrhage after a liver trauma would be reduced by early administration of a pro-haemostatic agent and evaluated the effect of i.v. vs i.m. administration of the coagulation factor VIIa analogue NN1731 on haemorrhage after a liver trauma in the pig. METHODS......: The pharmacokinetics of i.v. and i.m. NN1731 was evaluated in eight minipigs, and the effects of dose and administration route of NN1731 (i.v. 180 microg kg(-1), n=6; i.m. 540 microg kg(-1), n=4, or 2000 microg kg(-1), n=6) vs vehicle (n=16) were studied on a liver laceration injury in pigs. To simulate a pre......-hospital setting, the administration of NN1731 was delayed by 1 min for i.m. administration and 7 min for i.v. administration, at which time fluid resuscitation also began. RESULTS: In the minipigs, NN1731 exposure was similar after i.v. 180 microg kg(-1) and i.m. 540 microg kg(-1), with a bioavailability...

  5. Direct Oral Anticoagulant- or Warfarin-Related Major Bleeding: Characteristics, Reversal Strategies, and Outcomes From a Multicenter Observational Study.

    Science.gov (United States)

    Xu, Yan; Schulman, Sam; Dowlatshahi, Dar; Holbrook, Anne M; Simpson, Christopher S; Shepherd, Lois E; Wells, Philip S; Giulivi, Antonio; Gomes, Tara; Mamdani, Muhammad; Khuu, Wayne; Frymire, Eliot; Johnson, Ana P

    2017-07-01

    Direct oral anticoagulants (DOACs) have expanded the armamentarium for antithrombotic therapy. Although DOAC-related major bleeding was associated with favorable outcomes compared with warfarin in clinical trials, warfarin effects were reversed in bleeding events. Red blood cell transfusions occurred more often in DOAC bleeding events than in warfarin events (52.0% vs 39.5%; adjusted relative risk [aRR], 1.32; 95% CI, 1.19-2.47). However, units of blood products transfused were not different between the two groups. Thirty-four DOAC cases (7.4%) received activated prothrombin complex concentrates or recombinant factor VIIa. In-hospital mortality was lower following DOAC bleeding events (9.8% vs 15.2%; aRR, 0.66; 95% CI, 0.49-0.89), although differences in 30-day mortality did not reach statistical significance (12.6% vs 16.3%; aRR, 0.79; 95% CI, 0.61-1.03). In this unselected cohort of patients with oral anticoagulant-related hemorrhage with high rates of warfarin reversal, in-hospital mortality was lower among DOAC-associated bleeding events. These findings support the safety of DOACs in routine care and present useful baseline measures for evaluations of DOAC-specific reversal agents. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Intracerebral hemorrhage due to hemorrhagic disease of the newborn and failure to administer vitamin K at birth.

    Science.gov (United States)

    Hubbard, Dena; Tobias, Joseph D

    2006-11-01

    In infants, intracerebral hemorrhage (ICH) is most likely the result of trauma or disturbances of coagulation function. Routine and standard care of the newborn includes the administration of vitamin K to prevent hemorrhagic disease of the newborn. We present two infants, the products of home deliveries, who did not receive vitamin K at birth. Both infants developed ICH at 5 weeks of age and presented with signs and symptoms of increased IC pressure. In both cases, recombinant factor VIIa was administered to correct coagulation function and allow immediate surgical intervention which included craniotomy and hematoma evacuation in one patient and placement of a ventriculostomy in the other to treat increased IC pressure. Despite this therapy, both infants were left with severe neurologic sequelae. These two cases illustrate that hemorrhagic disease of the newborn can occur when prophylactic vitamin K is not administered and that it can have devastating consequences. Given these issues, the routine administration of vitamin K to all infants is mandatory and should not be considered optional.

  7. Molecular Model of Plasma PAF Acetylhydrolase-Lipoprotein Association: Insights from the Structure

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    Brian J. Bahnson

    2010-03-01

    Full Text Available Plasma platelet-activating factor acetylhydrolase (PAF-AH, also called lipoprotein-associated phospholipase A2 (Lp-PLA2, is a group VIIA PLA2 enzyme that catalyzes the hydrolysis of PAF and certain oxidized phospholipids. Although the role of PAF-AH as a pro- or anti-atherosclerotic enzyme is highly debated, several studies have shown it to be an independent marker of cardiovascular diseases. In humans the majority of plasma PAF-AH is bound to LDL and a smaller portion to HDL; the majority of the enzyme being associated with small dense LDL and VHDL-1 subclasses. Several studies suggest that the anti- or pro-atherosclerotic tendency of PAF-AH might be dependent on the type of lipoprotein it is associated with. Amino acid residues in PAF-AH necessary for binding to LDL and HDL have been identified. However our understanding of the interaction of PAF-AH with LDL and HDL is still incomplete. In this review we present an overview of what is already known about the interaction of PAF-AH with lipoprotein particles, and we pose questions that are yet to be answered. The recently solved crystal structure of PAF-AH, along with functional work done by others is used as a guide to develop a model of interaction of PAF-AH with lipoprotein particles.

  8. Clinical and neuroimaging correlates of antiphospholipid antibodies in multiple sclerosis: a preliminary study

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    Gonzalez-Toledo Eduardo

    2007-10-01

    Full Text Available Abstract Background The presence of antiphospholipid antibodies (APLA in multiple sclerosis (MS patients has been reported frequently but no clear relationship between APLA and the clinical and neuroimaging features of MS have heretofore been shown. We assessed the clinical and neuroimaging features of MS patients with plasma APLA. Methods A consecutive cohort of 24 subjects with relapsing-remitting (RR MS were studied of whom 7 were in remission (Rem and 17 in exacerbation (Exc. All subjects were examined and underwent MRI of brain. Patients' plasma was tested by standard ELISA for the presence of both IgM and IgG antibodies using a panel of 6 targets: cardiolipin (CL, β2 glycoprotein I (β2GPI, Factor VII/VIIa (FVIIa, phosphatidylcholine (PC, phosphatidylserine (PS and phosphatidylethanolamine (PE. Results In exacerbation up to 80% of MS subjects had elevated titers of IgM antibodies directed against the above antigens. However, in remission, less than half of MS patients had elevated titers of IgM antibodies against one or more of the above antigens. This difference was significant, p Conclusion The findings of this preliminary study show that increased APLA IgM is associated with exacerbations of MS. Currently, the significance of this association in pathogenesis of MS remains unknown. However, systematic longitudinal studies to measure APLA in larger cohorts of patients with relapsing-remitting MS, particularly before and after treatment with immunomodulatory agents, are needed to confirm these preliminary findings.

  9. Major obstetric hemorrhage.

    Science.gov (United States)

    Mercier, Frederic J; Van de Velde, Marc

    2008-03-01

    Major obstetric hemorrhage remains the leading cause of maternal mortality and morbidity worldwide, and is associated with a high rate of substandard care. A well-defined and multidisciplinary approach that aims to act quickly and avoid omissions or conflicting strategies is key. The most common etiologies of hemorrhage are abruptio placenta, placenta previa/accreta, uterine rupture in the antepartum period and retained placenta, uterine atony, and genital-tract trauma in the postpartum period. Basic treatment of postpartum hemorrhage relies on manual removal of the placenta or manual exploration of the uterus plus bladder emptying and oxytocin administration. If this does not arrest bleeding, or if there is any suspicion of genital-tract trauma, examination of the vagina and cervix with appropriate valves and analgesia/anesthesia must follow quickly. Postpartum uterine atony resistant to oxytocin must be treated with prostaglandin within 15 to 30 minutes; uterine balloon tamponade can be also useful at this stage. Aggressive transfusion therapy and resuscitation are mandatory in major obstetric hemorrhage. Specific invasive treatment must be considered within no more than 30 to 60 minutes, if previous measures have failed -- and even earlier in some particular etiologies. The two main options are radiologic embolization and surgical artery ligations. Recombinant factor VIIa may also be considered, but should not delay the performance of a life-saving procedure such as embolization or surgery. Hysterectomy must be implemented when all other interventions have failed.

  10. Analysis of Several PLA2 mRNA in Human Meningiomas

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    Yves Denizot

    2009-01-01

    Full Text Available In view of the important oncogenic action of phospholipase A2(PLA2 we investigated PLA2 transcripts in human meningiomas. Real-time PCR was used to investigate PLA2 transcripts in 26 human meningioma tumors. Results indicated that three Ca2+-dependent high molecular weight PLA2 (PLA2-IVA, PLA2-IVB, PLA2-IVC, one Ca2+-independent high molecular weight PLA2 (PLA2-VI and five low molecular weight secreted forms of PLA2 (PLA2-IB, PLA2-IIA, PLA2-III, PLA2-V, and PLA2-XII are expressed with PLA2-IVA, PLA2-IVB, PLA2-VI, and PLA2-XIIA as the major expressed forms. PLA2-IIE, PLA2-IIF, PLA2-IVD, and PLA2-XIIB are not detected. Plasma (PLA2-VIIA and intracellular (PLA2-VIIB platelet-activating factor acetylhydrolase transcripts are expressed in human meningiomas. However no difference was found for PLA2 transcript amounts in relation to the tumor grade, the subtype of meningiomas, the presence of inflammatory infiltrated cells, of an associated edema, mitosis, brain invasion, vascularisation or necrosis. In conclusion numerous genes encoding multiples forms of PLA2 are expressed in meningiomas where they might act on the phospholipid remodeling and on the local eicosanoid and/or cytokine networks.

  11. EIAV-based retinal gene therapy in the shaker1 mouse model for usher syndrome type 1B: development of UshStat.

    Directory of Open Access Journals (Sweden)

    Marisa Zallocchi

    Full Text Available Usher syndrome type 1B is a combined deaf-blindness condition caused by mutations in the MYO7A gene. Loss of functional myosin VIIa in the retinal pigment epithelia (RPE and/or photoreceptors leads to blindness. We evaluated the impact of subretinally delivered UshStat, a recombinant EIAV-based lentiviral vector expressing human MYO7A, on photoreceptor function in the shaker1 mouse model for Usher type 1B that lacks a functional Myo7A gene. Subretinal injections of EIAV-CMV-GFP, EIAV-RK-GFP (photoreceptor specific, EIAV-CMV-MYO7A (UshStat or EIAV-CMV-Null (control vectors were performed in shaker1 mice. GFP and myosin VIIa expression was evaluated histologically. Photoreceptor function in EIAV-CMV-MYO7A treated eyes was determined by evaluating α-transducin translocation in photoreceptors in response to low light intensity levels, and protection from light induced photoreceptor degeneration was measured. The safety and tolerability of subretinally delivered UshStat was evaluated in macaques. Expression of GFP and myosin VIIa was confirmed in the RPE and photoreceptors in shaker1 mice following subretinal delivery of the EIAV-CMV-GFP/MYO7A vectors. The EIAV-CMV-MYO7A vector protected the shaker1 mouse photoreceptors from acute and chronic intensity light damage, indicated by a significant reduction in photoreceptor cell loss, and restoration of the α-transducin translocation threshold in the photoreceptors. Safety studies in the macaques demonstrated that subretinal delivery of UshStat is safe and well-tolerated. Subretinal delivery of EIAV-CMV-MYO7A (UshStat rescues photoreceptor phenotypes in the shaker1 mouse. In addition, subretinally delivered UshStat is safe and well-tolerated in macaque safety studies These data support the clinical development of UshStat to treat Usher type 1B syndrome.

  12. Characterization of the Drosophila ortholog of the human Usher Syndrome type 1G protein sans.

    Directory of Open Access Journals (Sweden)

    Fabio Demontis

    Full Text Available BACKGROUND: The Usher syndrome (USH is the most frequent deaf-blindness hereditary disease in humans. Deafness is attributed to the disorganization of stereocilia in the inner ear. USH1, the most severe subtype, is associated with mutations in genes encoding myosin VIIa, harmonin, cadherin 23, protocadherin 15, and sans. Myosin VIIa, harmonin, cadherin 23, and protocadherin 15 physically interact in vitro and localize to stereocilia tips in vivo, indicating that they form functional complexes. Sans, in contrast, localizes to vesicle-like structures beneath the apical membrane of stereocilia-displaying hair cells. How mutations in sans result in deafness and blindness is not well understood. Orthologs of myosin VIIa and protocadherin 15 have been identified in Drosophila melanogaster and their genetic analysis has identified essential roles in auditory perception and microvilli morphogenesis, respectively. PRINCIPAL FINDINGS: Here, we have identified and characterized the Drosophila ortholog of human sans. Drosophila Sans is expressed in tubular organs of the embryo, in lens-secreting cone cells of the adult eye, and in microvilli-displaying follicle cells during oogenesis. Sans mutants are viable, fertile, and mutant follicle cells appear to form microvilli, indicating that Sans is dispensable for fly development and microvilli morphogenesis in the follicle epithelium. In follicle cells, Sans protein localizes, similar to its vertebrate ortholog, to intracellular punctate structures, which we have identified as early endosomes associated with the syntaxin Avalanche. CONCLUSIONS: Our work is consistent with an evolutionary conserved function of Sans in vesicle trafficking. Furthermore it provides a significant basis for further understanding of the role of this Usher syndrome ortholog in development and disease.

  13. [Luuletused] / William Wordsworth ; tlk. Märt Väljataga

    Index Scriptorium Estoniae

    Wordsworth, William

    2004-01-01

    Sisu: Värsid, mis kirjutatud mõned miilid Tintern Abbeyst ülalpool... ; "Mõnd kirevahku kummalist..." ; "Käis vaikselt ojakalda peal..." ; "Kolm aastat sirguda ta võis..." ; "Mu hinge piiras unesulg..." ; "Kui mere taha viia ma..." ; Jugapuud. Saatesõna lk. 24. Orig.: Lines composed a few miles above Tintern Abbey... ; "Strange fits of passion have I known..." ; "She dwelt among the untrodden ways..." ; "Three years she grew..." ; "A slumber did my spirit seal..." ; "I traveled among unknown men..." ; Yew trees

  14. Hamid Karzai on küll Afganistani riigipea, aga Massoud on kangelane / Leslie Leino

    Index Scriptorium Estoniae

    Leino, Leslie

    2005-01-01

    Afganistani valimistel võitsid opositsionäärid, tugevaim figuur nende hulgas on Ahmad Shah Massoudi kunagine kaasvõitleja Yunus Qanun, kelle siht on võõrväed riigist välja viia ja riik ühendada. Ameeriklased ja nende liitlased on ärevil, sest Qanun pole võõrvägede hulgas populaarne. Lisa: Põhimõtteliselt ameeriklaste vastu. Vt. samas: Afganistanis alustas pärast 30-aastast pausi tööd parlament

  15. Hamid Karzai on küll Afganistani riigipea, aga Massoud on kangelane / Leslie Leino

    Index Scriptorium Estoniae

    Leino, Leslie

    2005-01-01

    Afganistani valimistel võitsid opositsionäärid, tugevaim figuur nende hulgas on Ahmad Shah Massoudi kunagine kaasvõitleja Yunus Qanun, kelle siht on võõrväed riigist välja viia ja riik ühendada. Ameeriklased ja nende liitlased on ärevil, sest Qanun pole võõrvägede hulgas populaarne. Lisa: Põhimõtteliselt ameeriklaste vastu. Vt. samas: Afganistanis alustas pärast 30-aastast pausi tööd parlament

  16. Agenda 21 / Tiina Gaškov

    Index Scriptorium Estoniae

    Gaškov, Tiina

    2000-01-01

    Kuidas säästva eluviisi põhimõtteid ellu viia, sellega on tegelnud PHARE INTERREG õpilaste keskkonnaprojekt "3+3". Projekti elluviijateks olid koos Soome partneritega täiendusõppekeskuse Teave töörühm eesotsas Ene Kalmuse ja Karl Kaasikoviga. "3+3" tähendab, et koostööd, koolitust, kogemustevahetust hakkasid arendama kolm maakonda Eestist (Ida- ja Lääne-Viru- ning Jõgevamaa) ja Soomest Ita-Uusimaa, Kymenlaakso ja Päijät-Häme

  17. Referendum Tšehhi Vabariigis / Helena Rögnerova

    Index Scriptorium Estoniae

    Rögnerova, Helena

    2003-01-01

    Ilmunud ka: Proceedings of the 9th international conference "Estonia and the European Union: Estonia on its way to a changing Europe" : October 30-November 1, 2002, Tallinn, Estonian National Library. - Tallinn, lk. 78-80. Tšehhi senati eurointegratsiooni komisjoni liikme arvates tuleks rahvani viia kaks sõnumit: EL on valmis looma ühesuguseid tingimusi nii praegustele kui uutele liikmetele ja EL-i liikmesriigina on tagatud neile traditsioonilised Euroopa väärtused nagu demokraatia, õigusriik, inimõiguste austamine ja vähemuste kaitsmine

  18. Referendum Tšehhi Vabariigis / Helena Rögnerova

    Index Scriptorium Estoniae

    Rögnerova, Helena

    2003-01-01

    Ilmunud ka: Proceedings of the 9th international conference "Estonia and the European Union: Estonia on its way to a changing Europe" : October 30-November 1, 2002, Tallinn, Estonian National Library. - Tallinn, lk. 78-80. Tšehhi senati eurointegratsiooni komisjoni liikme arvates tuleks rahvani viia kaks sõnumit: EL on valmis looma ühesuguseid tingimusi nii praegustele kui uutele liikmetele ja EL-i liikmesriigina on tagatud neile traditsioonilised Euroopa väärtused nagu demokraatia, õigusriik, inimõiguste austamine ja vähemuste kaitsmine

  19. Agenda 21 / Tiina Gaškov

    Index Scriptorium Estoniae

    Gaškov, Tiina

    2000-01-01

    Kuidas säästva eluviisi põhimõtteid ellu viia, sellega on tegelnud PHARE INTERREG õpilaste keskkonnaprojekt "3+3". Projekti elluviijateks olid koos Soome partneritega täiendusõppekeskuse Teave töörühm eesotsas Ene Kalmuse ja Karl Kaasikoviga. "3+3" tähendab, et koostööd, koolitust, kogemustevahetust hakkasid arendama kolm maakonda Eestist (Ida- ja Lääne-Viru- ning Jõgevamaa) ja Soomest Ita-Uusimaa, Kymenlaakso ja Päijät-Häme

  20. [Luuletused] / William Wordsworth ; tlk. Märt Väljataga

    Index Scriptorium Estoniae

    Wordsworth, William

    2004-01-01

    Sisu: Värsid, mis kirjutatud mõned miilid Tintern Abbeyst ülalpool... ; "Mõnd kirevahku kummalist..." ; "Käis vaikselt ojakalda peal..." ; "Kolm aastat sirguda ta võis..." ; "Mu hinge piiras unesulg..." ; "Kui mere taha viia ma..." ; Jugapuud. Saatesõna lk. 24. Orig.: Lines composed a few miles above Tintern Abbey... ; "Strange fits of passion have I known..." ; "She dwelt among the untrodden ways..." ; "Three years she grew..." ; "A slumber did my spirit seal..." ; "I traveled among unknown men..." ; Yew trees

  1. Specific antidotes in development for reversal of novel anticoagulants: a review.

    Science.gov (United States)

    Gomez-Outes, Antonio; Suarez-Gea, M L; Lecumberri, Ramon; Terleira-Fernandez, Ana I; Vargas-Castrillon, Emilio

    2014-01-01

    In the last decade, several direct oral anticoagulants (DOAC; dabigatran, rivaroxaban, apixaban, edoxaban) have been marketed for prophylaxis and/or treatment of thromboembolism without having specific antidotes available for their reversal. Current management of bleeding associated to DOAC includes the removal of all antithrombotic medications and supportive care. Non-specific procoagulant agents (prothrombin complex concentrates and activated factor VIIa) have been used in case of serious bleeding. Currently, some specific antidotes for the DOAC are under development. Idarucizumab (BI 655075; Boehringer Ingelheim) is a fragment of an antibody (Fab), which is a specific antidote to the oral direct thrombin inhibitor dabigatran. Andexanet alfa (r-Antidote, PRT064445; Portola Pharmaceuticals) is a truncated form of enzymatically inactive factor Xa, which binds and reverses the anticoagulant action of the factor Xa inhibitors (e.g.: rivaroxaban, apixaban and edoxaban). Aripazine (PER-977, ciraparantag; Perosphere Inc.) is a synthetic small molecule (~500 Da) that reverses oral dabigatran, apixaban, rivaroxaban, as well as subcutaneous fondaparinux and LMWH in vivo. These antidotes could provide an alternative for management of life-threatening bleeding events occurring with the above-mentioned anticoagulants. In addition, the specific antidote anivamersen (RB007; Regado Biosciences Inc.) is an RNA aptamer in clinical development to reverse the anticoagulant effect of the parenteral factor IXa inhibitor pegnivacogin, which is also in development. This anticoagulant-antidote pair may provide an alternative in situations in which a fast onset and offset of anticoagulation is needed, like in patients undergoing cardiac surgery with extracorporeal circulation, as an alternative to the heparin/protamine pair. This patent review includes a description of the pharmacological characteristics of the novel specific antidotes, the available results from completed non

  2. Assessment of Novel Anti-thrombotic Fusion Proteins for Inhibition of Stenosis in a Porcine Model of Arteriovenous Graft.

    Directory of Open Access Journals (Sweden)

    Christi M Terry

    Full Text Available Hemodialysis arteriovenous synthetic grafts (AVG provide high volumetric blood flow rates shortly after surgical placement. However, stenosis often develops at the vein-graft anastomosis contributing to thrombosis and early graft failure. Two novel fusion proteins, ANV-6L15 and TAP-ANV, inhibit the tissue factor/factor VIIa coagulation complex and the factor Xa/factor Va complex, respectively. Each inhibitor domain is fused to an annexin V domain that targets the inhibitor activity to sites of vascular injury to locally inhibit thrombosis. This study's objective was to determine if these antithrombotic proteins are safe and effective in inhibiting AVG stenosis.A bolus of either TAP-ANV or ANV-6L15 fusion protein was administered intravenously immediately prior to surgical placement of a synthetic graft between the external jugular vein and common carotid artery in a porcine model. At surgery, the vein and artery were irrigated with the anti-thrombotic fusion protein. Control animals received intravenous heparin. At 4 weeks, MRI was performed to evaluate graft patency, the pigs were then euthanized and grafts and attached vessels were explanted for histomorphometric assessment of neointimal hyperplasia at the vein-graft anastomosis. Blood was collected at surgery, immediately after surgery and at euthanasia for serum metabolic panels and coagulation chemistries.No acute thrombosis occurred in the control group or in either experimental group. No abnormal serum chemistries, activated clotting times or PT, PTT values were observed after treatment in experimental or control animals. However, at the vein-graft anastomosis, there was no difference between the control and experimental groups in cross-sectional lumen areas, as measured on MRI, and no difference in hyperplasia areas as determined by histomorphometry. These results suggest that local irrigation of TAP-ANV or ANV-6L15 intra-operatively was as effective in inhibiting acute graft thrombosis

  3. Ülikooli prioriteedid / Mati Heidmets

    Index Scriptorium Estoniae

    Heidmets, Mati

    2001-01-01

    TPÜ valitsus kiitis oma 10. septembri istungil heaks rektoraadi poolt pakutud 7 projekti, mis määratlevad ülikooli prioriteetsed tegevussuunad 2001/2002 õppeaastal. Õppetöö osas tuleb lõpule viia käimasolev õppekavade reform, eesmärgiga ühitada TPÜ õppekavade süsteem Euroopa Liidus aktsepteeritud ja Bologna deklaratsioonis väljendatud põhimõtetega. Teisena on algatatud õpetajakoolituse kaasajastamisele suunatud projekt, mille sihiks on viia TPÜ-s pakutav õpetajakoolitus paremasse vastavusse maailma tänase kogemuse ning Eesti ühiskonna ootustega. Kolmas projekt on suunatud teadustöö ja doktoriõppe tulemuslikkuse tõstmisele ülikoolis. E-ülikooli projekt on suunatud ülikooli tegevust toetava ühtse elektroonilise tugisüsteemi kujundamisele. Ruumiprogramm seab sihiks kaasajastada TPÜ õppe- ja teadustöö tingimused. Eraldi projekt on suunatud TPÜ administratiivtegevuse kaasajastamisele. Seitsmes projekt lähtub kolme ülikooli - EHI, EKA ja TPÜ rektorite ettepanekust moodustada nimetatud koolide liitmise teel Tallinnas uus ülikool

  4. The E3 ligase Ubr3 regulates Usher syndrome and MYH9 disorder proteins in the auditory organs of Drosophila and mammals

    Science.gov (United States)

    Li, Tongchao; Giagtzoglou, Nikolaos; Eberl, Daniel F; Jaiswal, Sonal Nagarkar; Cai, Tiantian; Godt, Dorothea; Groves, Andrew K; Bellen, Hugo J

    2016-01-01

    Myosins play essential roles in the development and function of auditory organs and multiple myosin genes are associated with hereditary forms of deafness. Using a forward genetic screen in Drosophila, we identified an E3 ligase, Ubr3, as an essential gene for auditory organ development. Ubr3 negatively regulates the mono-ubiquitination of non-muscle Myosin II, a protein associated with hearing loss in humans. The mono-ubiquitination of Myosin II promotes its physical interaction with Myosin VIIa, a protein responsible for Usher syndrome type IB. We show that ubr3 mutants phenocopy pathogenic variants of Myosin II and that Ubr3 interacts genetically and physically with three Usher syndrome proteins. The interactions between Myosin VIIa and Myosin IIa are conserved in the mammalian cochlea and in human retinal pigment epithelium cells. Our work reveals a novel mechanism that regulates protein complexes affected in two forms of syndromic deafness and suggests a molecular function for Myosin IIa in auditory organs. DOI: http://dx.doi.org/10.7554/eLife.15258.001 PMID:27331610

  5. Ebola viral disease: a review literature

    Directory of Open Access Journals (Sweden)

    Saeed Reza Jamali Moghadam

    2015-04-01

    Full Text Available Ebola virus is transmitted to people as a result of direct contact with body fluids containing virus of an infected patient. The incubation period usually lasts 5 to 7 d and approximately 95% of the patients appear signs within 21 d after exposure. Typical features include fever, profound weakness, diarrhea, abdominal pain, cramping, nausea and vomiting for 3-5 days and maybe persisting for up to a week. Laboratory complications including elevated aminotransferase levels, marked lymphocytopenia, and thrombocytopenia may have occurred. Hemorrhagic fever occurs in less than half of patients and it takes place most commonly in the gastrointestinal tract. The symptoms progress over the time and patients suffer from dehydration, stupor, confusion, hypotension, multi-organ failure, leading to fulminant shock and eventually death. The most general assays used for antibody detection are direct IgG and IgM ELISAs and IgM capture ELISA. An IgM or rising IgG titer (four-fold contributes to strong presumptive diagnosis. Currently neither a licensed vaccine nor an approved treatment is available for human use. Passive transfer of serum collected from survivors of Junin virus or Lassa virus, equine IgG product from horses hypervaccinated with Ebola virus, a “cocktail” of humanized-mouse antibodies (ZMapp, recombinant inhibitor of factor VIIa/tissue factor, activated protein C, RNA-polymerase inhibitors and small interfering RNA nano particles are among the therapies in development. Preclinical evaluation is also underway for various vaccine candidates. One is a chimpanzee adenovirus vector vaccine; other vaccines involve replication-defective adenovirus serotype 5 and recombinant vesicular stomatitis virus.

  6. Ebola viral disease: a review literature

    Institute of Scientific and Technical Information of China (English)

    Saeed; Reza; Jamali; Moghadam; Negar; Omidi; Samaneh; Bayrami; Sepideh; Jamali; Moghadam; SeyedAhmad; SeyedAlinaghi

    2015-01-01

    Ebola virus is transmitted to people as a result of direct contact with body fluids containing virus of an infected patient. The incubation period usually lasts 5 to 7 d and approximately95% of the patients appear signs within 21 d after exposure. Typical features include fever,profound weakness, diarrhea, abdominal pain, cramping, nausea and vomiting for 3-5days and maybe persisting for up to a week. Laboratory complications including elevated aminotransferase levels, marked lymphocytopenia, and thrombocytopenia may have occurred.Hemorrhagic fever occurs in less than half of patients and it takes place most commonly in the gastrointestinal tract. The symptoms progress over the time and patients suffer from dehydration, stupor, confusion, hypotension, multi-organ failure, leading to fulminant shock and eventually death. The most general assays used for antibody detection are direct IgG and IgM ELISAs and IgM capture ELISA. An IgM or rising IgG titer(four-fold) contributes to strong presumptive diagnosis. Currently neither a licensed vaccine nor an approved treatment is available for human use. Passive transfer of serum collected from survivors of Junin virus or Lassa virus, equine IgG product from horses hypervaccinated with Ebola virus, a "cocktail"of humanized-mouse antibodies(ZMapp), recombinant inhibitor of factor VIIa/tissue factor,activated protein C, RNA-polymerase inhibitors and small interfering RNA nano particles are among the therapies in development. Preclinical evaluation is also underway for various vaccine candidates. One is a chimpanzee adenovirus vector vaccine; other vaccines involve replication-defective adenovirus serotype 5 and recombinant vesicular stomatitis virus.

  7. Management of Bleeding With Non-Vitamin K Antagonist Oral Anticoagulants in the Era of Specific Reversal Agents.

    Science.gov (United States)

    Ruff, Christian T; Giugliano, Robert P; Antman, Elliott M

    2016-07-19

    Vitamin K antagonists are commonly used by clinicians to provide anticoagulation to patients who have or are at risk of having thrombotic events. In addition to familiarity with the dosing and monitoring of vitamin K antagonists, clinicians are accustomed to using vitamin K if there is a need to reverse the anticoagulant effect of vitamin K antagonists. There are now 4 new non-vitamin K antagonist oral anticoagulants (NOACs) that are attractive alternatives to vitamin K antagonists. Despite similar or lower rates of serious bleeding with NOACs in comparison with warfarin, there is a pressing need for strategies to manage bleeding when it does occur with NOACs and to reverse the pharmacological effect of these agents if needed. Important steps in minimizing bleeding risks with NOACs include dose adjustment of the agents in the setting of renal dysfunction and avoidance of the concomitant use of other antithrombotic agents if feasible. Laboratory measurement of the anticoagulant effect of NOACs is best accomplished with specialized assays, although some of the more widely available coagulation tests can provide information that is potentially useful to clinicians. Nonspecific hemostatic agents such as prothrombin complex concentrates and recombinant factor VIIa can be used to reverse the effect of NOACs. More specific reversing agents include the approved humanized monoclonal antibody fragment idarucizumab for reversing the effects of dabigatran, the investigational factor Xa decoy andexanet alfa, and the synthetic small molecule ciraparantag. Both andexanet and ciraparantag have been reported to reverse the effects of the anti-Xa NOACs (rivaroxaban, apixaban, and edoxaban), and a number of other anticoagulant agents in common clinical use, as well.

  8. Need for Continued Use of Anticoagulants After Intracerebral Hemorrhage.

    Science.gov (United States)

    Estol, Conrado J.; Kase, Carlos S.

    2003-07-01

    One of the unsolved dilemmas in cerebrovascular disease is the ideal timing to restart anticoagulant therapy (ACT) safely in patients who have suffered an intracranial hemorrhage and have an indication to continue ACT. No randomized studies with evidence-based data are available to settle this issue. Only a few reports have been published; their shortcomings include small numbers of patients evaluated retrospectively, a broad spectrum of indications for ACT, different types of hemorrhage, and variable methods of reversing and restarting ACT. Despite this variability, most reports agree that 1) ACT has to be immediately reversed to decrease the risk of hemorrhage progression; 2) a period between 1 and 2 weeks appears sufficient to allow for management and monitoring of the hemorrhage off ACT; and 3) ACT can be safely restarted after the period off of treatment. A physician confronting a patient with intracranial hemorrhage and the need for ACT faces a situation of individually focused clinical decision making. The problem rests in balancing the risks of a worsening or recurring hemorrhage on one side, and the risk of thromboembolism on the other. From available information and personal experience, an unvalidated risk stratification can be proposed to categorize patients in low- and high-risk groups for hemorrhagic complications and embolic phenomena, assigning them to 5 or 15 days off ACT, respectively. Intermediate-risk patients can have ACT restarted in 5 to 15 days from the onset of the intracranial hemorrhage. Anticoagulation should be immediately reversed. Fresh frozen plasma is the standard treatment in most institutions. Prothrombin complex concentrate is an alternative, but issues of availability make its use impractical. The use of recombinant factor VIIa is an attractive new option.

  9. Intracerebral Hemorrhage; towards physiological imaging of hemorrhage risk in acute and chronic bleeding.

    Directory of Open Access Journals (Sweden)

    Raphael eJakubovic

    2012-05-01

    Full Text Available Despite improvements in management and prevention of intracerebral hemorrhage (ICH, there has been little improvement in mortality over the last 30 years. Hematoma expansion, primarily during the first few hours is highly predictive of neurological deterioration, poor functional outcome and mortality. For each 10% increase in ICH size, there is a 5% increase in mortality and an additional 16% chance of poorer functional outcome. As such, both the identification and prevention of hematoma expansion are attractive therapeutic targets in ICH. Previous studies suggest that contrast extravasation seen on CT Angiography (CTA, MRI, and digital subtraction angiography correlates with hematoma growth, indicating ongoing bleeding. Contrast extravasation on the arterial phase of a CTA has been coined the CTA Spot Sign. These easily identifiable foci of contrast enhancement have been identified as independent predictors of hematoma growth, mortality and clinical outcome in primary ICH. The Spot Sign score, developed to stratify risk of hematoma expansion, has shown high inter-observer agreement. Post-contrast leakage or delayed CTA Spot Sign, on post contrast CT following CTA or delayed CTA respectively are seen in an additional ~8% of patients and explain apparently false negative observations on early CTA imaging in patients subsequently undergoing hematoma expansion. CT perfusion provides an opportunity to acquire dynamic imaging and has been shown to quantify rates of contrast extravasation. Intravenous recombinant factor VIIa(rFVIIa within 4 hours of ICH onset has been shown to significantly reduce hematoma growth. However, clinical efficacy has yet to be proven. There is compelling evidence that cerebral amyloid angiopathy (CAA may precede the radiographic evidence of vascular disease and as such contribute to microbleeding. The interplay between microbleeding, CAA,CTA Spot Sign and genetic composition (ApoE genotype may be crucial in developing a

  10. Characteristics of Symptomatic Intracranial Hemorrhage in Patients Receiving Non-Vitamin K Antagonist Oral Anticoagulant Therapy.

    Directory of Open Access Journals (Sweden)

    Hisanao Akiyama

    Full Text Available The first non-vitamin K antagonist oral anticoagulant (NOAC introduced to the market in Japan was dabigatran in March 2011, and three more NOACs, rivaroxaban, apixaban, and edoxaban, have since become available. Randomized controlled trials of NOACs have revealed that intracranial hemorrhage (ICH occurs less frequently with NOACs compared with warfarin. However, the absolute incidence of ICH associated with NOACs has increased with greater use of these anticoagulants, and we wanted to explore the incidence, clinical characteristics, and treatment course of patients with NOACs-associated ICH.We retrospectively analyzed the characteristics of symptomatic ICH patients receiving NOACs between March 2011 and September 2014.ICH occurred in 6 patients (5 men, 1 woman; mean ± SD age, 72.8 ± 3.2 years. Mean time to onset was 146.2 ± 111.5 days after starting NOACs. Five patients received rivaroxaban and 1 patient received apixaban. None received dabigatran or edoxaban. Notably, no hematoma expansion was observed within 24 h of onset in the absence of infusion of fresh frozen plasma, activated prothrombin complex concentrate, recombinant activated factor VIIa or hemodialysis. When NOAC therapy was initiated, mean HAS-BLED and PANWARDS scores were 1.5 ± 0.5 and 39.5 ± 7.7, respectively. Mean systolic blood pressure was 137.8 ± 15.9 mmHg within 1 month before spontaneous ICH onset.Six symptomatic ICHs occurred early in NOAC therapy but hematoma volume was small and did not expand in the absence of infusion of reversal agents or hemodialysis. The occurrence of ICH during NOAC therapy is possible even when there is acceptable mean systolic blood pressure control (137.8 ± 15.9 mmHg and HAS-BLED score ≤ 2. Even stricter blood pressure lowering and control within the acceptable range may be advisable to prevent ICH during NOAC therapy.

  11. Severe perioperative bleeding in renal cell carcinoma after elective pericardiocentesis associated left ventricular puncture: case report

    Directory of Open Access Journals (Sweden)

    Javier Lasala

    2016-07-01

    Full Text Available Resumen En los Estados Unidos se estimó que, durante el 2015, unos 61 560 pacientes serían diagnosticados con cáncer renal y que 14 080 morirían por esta enfermedad. Presentamos el caso de un paciente con carcinoma de células renales y trombo tumoral de vena cava inferior que sufrió una hemorragia perioperatoria grave y coagulopatía después de una esternotomía de emergencia. También abordamos aspectos relevantes del cuidado anestésico perioperatorio incluyendo consideraciones y manejo de coagulopatía, falla renal y hepática en un paciente oncológico. El caso es un hombre de 49 años que fue llevado a embolización tumoral guiada por radiología, nefrectomía radical izquierda y trombectomía de vena cava inferior. En el período postoperatorio desarrolló sepsis, falla orgánica múltiple y efusión pericárdica que requirió pericardiocentesis. Durante la pericardiocentesis sufrió perforación iatrogénica de ventrículo izquierdo que necesitó esternotomía de emergencia y reparación del ventrículo izquierdo. Los pacientes con cáncer son a menudo un reto para el equipo de cirugía y anestesia, y el cuidado de emergencia requiere un abordaje integral y organizado. El uso de factor recombinante VIIa NovoSeven puede ayudar en el manejo de la hemorragia severa perioperatoria después de cirugía cardiotorácica en pacientes oncológicos, pero se deben hacer estudios posteriores para confirmarlo.

  12. Economical comparison of APCC vs. rFVIIa for mild-to-moderate bleeding episodes in haemophilia patients with inhibitors.

    Science.gov (United States)

    Hay, J W; Zhou, Z Y

    2011-09-01

    To construct a cost-minimization model comparing activated prothrombin complex concentrates (APCC) vs. recombinant factor VIIa (rFVIIa) in haemophilia patients with inhibitors from a US third party payer perspective. A literature-based decision model was used to model inhibitor treatment costs and outcomes. As existing clinical trials fail to demonstrate differences in the relative efficacy or safety of APCC vs. rFVIIa, we assumed the same efficacy for both products in the base-case. Regimens of APCC (75 IU kg⁻¹ × 2 doses) and rFVIIa (90 μg kg⁻¹× 3 doses) were assumed according to manufacturer recommendations. If the first-line treatment failed, patients chose to continue the current treatment or switch to another drug. All costs were adjusted to 2009 US dollars. Sensitivity analyses on the infusion frequency, efficacy, unit price, switch rate, re-bleed rate and body weight were performed to assess model robustness. In the base-case, the total medical cost to treat a bleed with APCC or rFVIIa as first-line medication was US$25,969 and US$35,838, respectively. One-way sensitivity analyses showed that results were insensitive to the efficacy of rFVIIa, unit price of APCC or rFVIIa, switch rate, re-bleed rate or body weight. The rFVIIa will reach cost neutrality when the efficacy of APCC is as low as 60%, or rFVIIa is infused only twice for each line, or APCC is infused three times for each line. Two-way sensitivity analyses showed that results were quite sensitive to the assumed infusion frequency for both products. First-line APCC compared with rFVIIa can be a cost-saving alternative for home treatment of mild-to-moderate bleeds in haemophilia patients with inhibitors.

  13. Corruption Factors

    OpenAIRE

    Polterovich, Victor

    1998-01-01

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

  14. β3-integrin is required for differentiation in OC-2 cells derived from mammalian embryonic inner ear

    Directory of Open Access Journals (Sweden)

    Brunetta Ivan

    2012-03-01

    Full Text Available Abstract Background The mammalian inner ear contains the organ of Corti which is responsible for the conversion of sound into neuronal signals. This specialised epithelial tissue is the product of a complex developmental process where a common precursor cell type differentiates into the sound transducing hair cells and the non-innervated supporting cells. We hypothesised that integrin proteins, which are involved in cell attachment to extracellular matrix proteins and cellular signalling, play a role in the differentiation process of the precursor inner ear epithelial cells. To test our hypothesis we have utilised a cell line (OC-2 derived from E13 embryonic immortomouse inner ears. In vitro, by switching the incubation temperature from 33°C to 39°C, the OC-2 cells can be induced to differentiate and express hair cells markers, such as Myosin VIIa. The OC-2 cells are thus a useful model system for testing mechanism of hair cells differentiation. Results We have identified 4 integrin subunits which are expressed in OC-2 cells: α6, αv, β1 and β3. Among these, the relative level of expression of the αv, β1 and β3 subunits increased in a time dependent manner when the cells were exposed to the differentiating temperature of 39°C, most notably so for β3 which was not detectable at 33°C. Treatment of fully differentiated OC-2 cells with siRNA against the four integrin subunits reduced the expression of not only the respective integrin proteins but also of the hair cell marker Myosin VIIa. Conversely over-expression of β3 was sufficient to induce the expression of Myosin VIIa at 33°C. Conclusions Our data demonstrate that modulation of integrin expression is associated with the differentiation process of the OC-2 cells. This suggests that the maturation of the organ of Corti, from where OC-2 cells are derived, may also depend on changes of gene expression associated with integrin expression.

  15. El factoring

    Directory of Open Access Journals (Sweden)

    Alberto Rosenthal

    1988-04-01

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

  16. Robust factorization

    DEFF Research Database (Denmark)

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

    2002-01-01

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

  17. El factoring

    Directory of Open Access Journals (Sweden)

    Alberto Rosenthal

    2015-04-01

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

  18. Equid herpesvirus type 1 activates platelets.

    Directory of Open Access Journals (Sweden)

    Tracy Stokol

    Full Text Available Equid herpesvirus type 1 (EHV-1 causes outbreaks of abortion and neurological disease in horses. One of the main causes of these clinical syndromes is thrombosis in placental and spinal cord vessels, however the mechanism for thrombus formation is unknown. Platelets form part of the thrombus and amplify and propagate thrombin generation. Here, we tested the hypothesis that EHV-1 activates platelets. We found that two EHV-1 strains, RacL11 and Ab4 at 0.5 or higher plaque forming unit/cell, activate platelets within 10 minutes, causing α-granule secretion (surface P-selectin expression and platelet microvesiculation (increased small events double positive for CD41 and Annexin V. Microvesiculation was more pronounced with the RacL11 strain. Virus-induced P-selectin expression required plasma and 1.0 mM exogenous calcium. P-selectin expression was abolished and microvesiculation was significantly reduced in factor VII- or X-deficient human plasma. Both P-selectin expression and microvesiculation were re-established in factor VII-deficient human plasma with added purified human factor VIIa (1 nM. A glycoprotein C-deficient mutant of the Ab4 strain activated platelets as effectively as non-mutated Ab4. P-selectin expression was abolished and microvesiculation was significantly reduced by preincubation of virus with a goat polyclonal anti-rabbit tissue factor antibody. Infectious virus could be retrieved from washed EHV-1-exposed platelets, suggesting a direct platelet-virus interaction. Our results indicate that EHV-1 activates equine platelets and that α-granule secretion is a consequence of virus-associated tissue factor triggering factor X activation and thrombin generation. Microvesiculation was only partly tissue factor and thrombin-dependent, suggesting the virus causes microvesiculation through other mechanisms, potentially through direct binding. These findings suggest that EHV-1-induced platelet activation could contribute to the thrombosis

  19. Effective Gravity and Homogenous Solutions

    CERN Document Server

    Müller, Daniel

    2013-01-01

    Near the singularity, gravity should be modified to an effective theory, in the same sense as with the Euler-Heisenberg electrodynamics. This effective gravity surmounts to higher derivative theory, and as is well known, a much more reacher theory concerning the solution space. On the other hand, as a highly non linear theory, the understanding of this solution space must go beyond the linearized approach. In this talk we will present some results previously published by collaborators and myself, concerning solutions for vacuum spatially homogenous cases of Bianchi types $I$ and $VII_A$. These are the anisotropic generalizations of the cosmological spatially "flat", and "open" models respectively. The solutions present isotropisation in a weak sense depending on the initial condition. Also, depending on the initial condition, singular solutions are obtained.

  20. Effective Gravity and Homogenous Solutions

    Science.gov (United States)

    Müller, Daniel

    2015-01-01

    Near the singularity, gravity should be modified to an effective theory, in the same sense as with the Euler-Heisenberg electrodynamics. This effective gravity surmounts to higher derivative theory, and as is well known, a much more reacher theory concerning the solution space. On the other hand, as a highly non linear theory, the understanding of this solution space must go beyond the linearized approach. In this talk we will present some results previously published by collaborators and myself, concerning solutions for vacuum spatially homogenous cases of Bianchi types I and VIIA. These are the anisotropic generalizations of the cosmological spatially "flat", and "open" models respectively. The solutions present isotropisation in a weak sense depending on the initial condition. Also, depending on the initial condition, singular solutions are obtained.

  1. Drosophila Rho-associated kinase (Drok) links Frizzled-mediated planar cell polarity signaling to the actin cytoskeleton.

    Science.gov (United States)

    Winter, C G; Wang, B; Ballew, A; Royou, A; Karess, R; Axelrod, J D; Luo, L

    2001-04-06

    Frizzled (Fz) and Dishevelled (Dsh) are components of an evolutionarily conserved signaling pathway that regulates planar cell polarity. How this signaling pathway directs asymmetric cytoskeletal reorganization and polarized cell morphology remains unknown. Here, we show that Drosophila Rho-associated kinase (Drok) works downstream of Fz/Dsh to mediate a branch of the planar polarity pathway involved in ommatidial rotation in the eye and in restricting actin bundle formation to a single site in developing wing cells. The primary output of Drok signaling is regulating the phosphorylation of nonmuscle myosin regulatory light chain, and hence the activity of myosin II. Drosophila myosin VIIA, the homolog of the human Usher Syndrome 1B gene, also functions in conjunction with this newly defined portion of the Fz/Dsh signaling pathway to regulate the actin cytoskeleton.

  2. Agenda 21 haridusprogramm / Imbi Henno

    Index Scriptorium Estoniae

    Henno, Imbi

    2000-01-01

    1992. a Rio de Janeiros toimunud ÜRO keskkonna- ja arengukonverentsil võeti vastu "Agenda 21", määrab kindlaks riikide säästva arengu alased põhisuunad käesoleval sajandil. 1997. a. Rio jätkukonverentsil tegi ÜRO Säästva Arengu Komisjon valitsustele ettekirjutuse - viia ellu "Agenda 21" põhimõtted. ÜRO Säästva Arengu Komisjoni eestvõtmisel võeti 1998. a. vastu ka "Agenda 21" 36. peatüki "Haridus, koolitus ja avalikkuse teadlikkus" laiendatud versioon, mille eesmärk on edendada riikidevahelist koostööd ja säästva arengu alast teadlikkust

  3. Agenda 21 haridusprogramm / Imbi Henno

    Index Scriptorium Estoniae

    Henno, Imbi

    2000-01-01

    1992. a Rio de Janeiros toimunud ÜRO keskkonna- ja arengukonverentsil võeti vastu "Agenda 21", määrab kindlaks riikide säästva arengu alased põhisuunad käesoleval sajandil. 1997. a. Rio jätkukonverentsil tegi ÜRO Säästva Arengu Komisjon valitsustele ettekirjutuse - viia ellu "Agenda 21" põhimõtted. ÜRO Säästva Arengu Komisjoni eestvõtmisel võeti 1998. a. vastu ka "Agenda 21" 36. peatüki "Haridus, koolitus ja avalikkuse teadlikkus" laiendatud versioon, mille eesmärk on edendada riikidevahelist koostööd ja säästva arengu alast teadlikkust

  4. Dialoogide pragmaatilise analüüsi tarkvara / Software for pragmatic analysis of dialogues

    Directory of Open Access Journals (Sweden)

    Olga Gerassimenko

    2014-04-01

    Full Text Available Meie uurimisobjektiks on eestikeelsed dialoogid (inimestevaheliste suuliste dialoogide transkriptsioonid ja inim-masindialoogide logifailid. Eesmärgiks on määrata, missuguseid dialoogiakte ja missuguseid suhtlusstrateegiaid kasutavad dialoogis osalejad ning missugustest struktuuriosadest dialoogid koosnevad, s.o läbi viia pragmaatilist analüüsi. Selleks, et lihtsustada dialoogide pragmaatilist analüüsi, arendame tarkvara, mis võimaldab tuvastada ja märgendada dialoogi tekstis dialoogiakte, suhtlusstrateegiaid ja dialoogi struktuuriosi (sh alamdialooge. Dialoogiaktide tuvastamiseks rakendame andmepõhist meetodit, samas suhtlusstrateegiate ja dialoogi struktuuri määramine põhineb reeglitel. Tarkvara kasutavad lingvistid dialoogide uurimisel, mille kaugem eesmärk on dialoogsüsteemi arendamine, mis suhtleks kasutajaga loomulikus keeles, järgides inimestevahelise suhtluse norme.

  5. Design, synthesis and biological evaluation of type-II VEGFR-2 inhibitors based on quinoxaline scaffold.

    Science.gov (United States)

    Shahin, Mai I; Abou El Ella, Dalal A; Ismail, Nasser S M; Abouzid, Khaled A M

    2014-10-01

    In an effort to develop ATP-competitive VEGFR-2 selective inhibitors, a series of new quinoxaline-based derivatives was designed and synthesized. The target compounds were biologically evaluated for their inhibitory activity against VEGFR-2. The design of the target compounds was accomplished after a profound study of the structure activity relationship (SAR) of type-II VEGFR-2 inhibitors. Among the synthesized compounds, 1-(2-((4-methoxyphenyl)amino)-3-oxo-3,4 dihydroquinoxalin-6-yl)-3-phenylurea (VIIa) displayed the highest inhibitory activity against VEGFR-2. Molecular modeling study involving molecular docking and field alignment was implemented to interpret the variable inhibitory activity of the newly synthesized compounds.

  6. Magistritööd : [Merike Angerjärv jt.

    Index Scriptorium Estoniae

    2000-01-01

    TPÜ kasvatusteaduste ja pedagoogika magistritööde kaitsmisnõukogu koosolekul kaitsmisele tulevad magistritööd: 30. nov. 2000 Merike Angerjärv "5-7-aastaste laste vanemate kasvatuskultuur ja koolitusvajadus" ja Marianne Martinson "Õpiraskused ja õpetaja toimetulekuvõimalusi õpiraskustega õpilastel"; 14. dets. Heli Maajärv "Teabekirjanduse kasutamise võimalusi põhikooli keemia tundides" ja Nelli Leosk "Õpitingimuste loomine haigestunud õpilastele"; 15. dets. Kristi Kiilu "Diferentseeritud muusikaline tegevus eelkooliealiste laste muusikatunnis" ja Krista Savitsch "Algkooliõpilase elukeskkond toimetuleku tegurina". 15. dets. 2000 kaitsevad Tiina Kukkes TPÜ kasvatusteaduste (kutseõpetuse ja reaalainete didaktika) magistritööde kaitsmisnõukogu koosolekul magistritööd "Inglise keele ja erialaõpetuse integratsiooni tagamine õdede koolituses" ja Viia Parve magistritööd "Teooria ja praktika seose ning õenduskeskuse realiseerimine õppematerjali sisus (nakkushaiguste õppematerjali näitel)"

  7. Behavioral factors.

    Science.gov (United States)

    Zero, D T; Lussi, A

    2006-01-01

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

  8. Factor analysis

    CERN Document Server

    Gorsuch, Richard L

    2013-01-01

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

  9. Synthesis and fungicidal activity of novel 3-(substituted/unsubstituted phenylselenonyl)-1-ribosyl/deoxyribosyl-1H-1,2,4-triazole.

    Science.gov (United States)

    Singh, Pravin K

    2012-06-13

    Reaction of potassium 1H-1,2,4-triazole-3-selenolate (I) with acetylated ribose/deoxyribose (IIa,b) in the presence of montmorillonite K 10 as a solid adsorbent furnished potassium 1-acetylated ribosyl/deoxyribosyl-1H-1,2,4-triazole-3-selenolate (IIIa,b) with excellent yield under microwave irradiation in solvent-free conditions. This eliminates a series of complex isolation procedures and often minimizes the use of a large amount of expensive, toxic, and hazardous solvents after each step. This procedure reduces reaction time and cost and enhances yield. Reaction of compound (IIIa,b) with substituted/unsubstituted aryl diazonium chloride (IVa-e) at 0-5 °C gave pure 3-(substituted/unsubstituted phenyl selanyl)-1-acetylribosyl/deoxyribosyl-1H-1,2,4-triazole (Va-j). Oxidation of compound (Va-j) with oxone followed by alkaline hydrolysis furnished quantitatively and analytically pure 3-(substituted/unsubstituted phenylselenonyl)-1-ribosyl/deoxyribosyl-1H-1,2,4-triazole (VIIa-j). Compounds VIa-j and VIIa-j were evaluated in vitro for their fungitoxicities against Fusarium oxysporum and Penicillium citrinum. All the compounds were found to be antifungal active. Some of the compounds displayed activities comparable with that of the commercial fungicide Dithane M-45 and griseofulvin. Structure-activity relationships for the screened compounds were discussed. The fact that both of these fungi have developed resistance to several fungicide groups made them optimal candidates as target organisms for ongoing research about the potential application of 1,2,4-triazole and analogue compounds as reduced-risk fungicides.

  10. The subunit composition and function of mammalian cytochrome c oxidase.

    Science.gov (United States)

    Kadenbach, Bernhard; Hüttemann, Maik

    2015-09-01

    Cytochrome c oxidase (COX) from mammals and birds is composed of 13 subunits. The three catalytic subunits I-III are encoded by mitochondrial DNA, the ten nuclear-coded subunits (IV, Va, Vb, VIa, VIb, VIc, VIIa, VIIb, VIIc, VIII) by nuclear DNA. The nuclear-coded subunits are essentially involved in the regulation of oxygen consumption and proton translocation by COX, since their removal or modification changes the activity and their mutation causes mitochondrial diseases. Respiration, the basis for ATP synthesis in mitochondria, is differently regulated in organs and species by expression of tissue-, developmental-, and species-specific isoforms for COX subunits IV, VIa, VIb, VIIa, VIIb, and VIII, but the holoenzyme in mammals is always composed of 13 subunits. Various proteins and enzymes were shown, e.g., by co-immunoprecipitation, to bind to specific COX subunits and modify its activity, but these interactions are reversible, in contrast to the tightly bound 13 subunits. In addition, the formation of supercomplexes with other oxidative phosphorylation complexes has been shown to be largely variable. The regulatory complexity of COX is increased by protein phosphorylation. Up to now 18 phosphorylation sites have been identified under in vivo conditions in mammals. However, only for a few phosphorylation sites and four nuclear-coded subunits could a specific function be identified. Research on the signaling pathways leading to specific COX phosphorylations remains a great challenge for understanding the regulation of respiration and ATP synthesis in mammalian organisms. This article reviews the function of the individual COX subunits and their isoforms, as well as proteins and small molecules interacting and regulating the enzyme.

  11. Brn3c null mutant mice show long-term, incomplete retention of some afferent inner ear innervation

    Directory of Open Access Journals (Sweden)

    Pirvola Ulla

    2003-01-01

    Full Text Available Abstract Background Ears of Brn3c null mutants develop immature hair cells, identifiable only by certain molecular markers, and undergo apoptosis in neonates. This partial development of hair cells could lead to enough neurotrophin expression to sustain sensory neurons through embryonic development. We have therefore investigated in these mutants the patterns of innervation and of expression of known neurotrophins. Results At birth there is a limited expression of BDNF and NT-3 in the mutant sensory epithelia and DiI tracing shows no specific reduction of afferents or efferents that resembles neurotrophin null mutations. At postnatal day 7/8 (P7/8, innervation is severely reduced both qualitatively and quantitatively. 1% of myosin VIIa-positive immature hair cells are present in the mutant cochlea, concentrated in the base. Around 20% of immature hair cells exist in the mutant vestibular sensory epithelia. Despite more severe loss of hair cells (1% compared to 20%, the cochlea retains many more sensory neurons (46% compared to 15% than vestibular epithelia. Even 6 months old mutant mice have some fibers to all vestibular sensory epithelia and many more to the cochlear apex which lacks MyoVIIa positive hair cells. Topologically organized central cochlea projections exist at least until P8, suggesting that functional hair cells are not required to establish such projections. Conclusion The limited expression of neurotrophins in the cochlea of Brn3c null mice suffices to support many sensory neurons, particularly in the cochlea, until birth. The molecular nature of the long term survival of apical spiral neurons remains unclear.

  12. MYC gene delivery to adult mouse utricles stimulates proliferation of postmitotic supporting cells in vitro.

    Directory of Open Access Journals (Sweden)

    Joseph C Burns

    Full Text Available The inner ears of adult humans and other mammals possess a limited capacity for regenerating sensory hair cells, which can lead to permanent auditory and vestibular deficits. During development and regeneration, undifferentiated supporting cells within inner ear sensory epithelia can self-renew and give rise to new hair cells; however, these otic progenitors become depleted postnatally. Therefore, reprogramming differentiated supporting cells into otic progenitors is a potential strategy for restoring regenerative potential to the ear. Transient expression of the induced pluripotency transcription factors, Oct3/4, Klf4, Sox2, and c-Myc reprograms fibroblasts into neural progenitors under neural-promoting culture conditions, so as a first step, we explored whether ectopic expression of these factors can reverse supporting cell quiescence in whole organ cultures of adult mouse utricles. Co-infection of utricles with adenoviral vectors separately encoding Oct3/4, Klf4, Sox2, and the degradation-resistant T58A mutant of c-Myc (c-MycT58A triggered significant levels of supporting cell S-phase entry as assessed by continuous BrdU labeling. Of the four factors, c-MycT58A alone was both necessary and sufficient for the proliferative response. The number of BrdU-labeled cells plateaued between 5-7 days after infection, and then decreased ~60% by 3 weeks, as many cycling cells appeared to enter apoptosis. Switching to differentiation-promoting culture medium at 5 days after ectopic expression of c-MycT58A temporarily attenuated the loss of BrdU-labeled cells and accompanied a very modest but significant expansion of the sensory epithelium. A small number of the proliferating cells in these cultures labeled for the hair cell marker, myosin VIIA, suggesting they had begun differentiating towards a hair cell fate. The results indicate that ectopic expression of c-MycT58A in combination with methods for promoting cell survival and differentiation may restore

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

    OpenAIRE

    Yun-kwong Kwok

    2004-01-01

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

  14. Clinical features and patient management of Lujo hemorrhagic fever.

    Directory of Open Access Journals (Sweden)

    Nivesh H Sewlall

    Full Text Available In 2008 a nosocomial outbreak of five cases of viral hemorrhagic fever due to a novel arenavirus, Lujo virus, occurred in Johannesburg, South Africa. Lujo virus is only the second pathogenic arenavirus, after Lassa virus, to be recognized in Africa and the first in over 40 years. Because of the remote, resource-poor, and often politically unstable regions where Lassa fever and other viral hemorrhagic fevers typically occur, there have been few opportunities to undertake in-depth study of their clinical manifestations, transmission dynamics, pathogenesis, or response to treatment options typically available in industrialized countries.We describe the clinical features of five cases of Lujo hemorrhagic fever and summarize their clinical management, as well as providing additional epidemiologic detail regarding the 2008 outbreak. Illness typically began with the abrupt onset of fever, malaise, headache, and myalgias followed successively by sore throat, chest pain, gastrointestinal symptoms, rash, minor hemorrhage, subconjunctival injection, and neck and facial swelling over the first week of illness. No major hemorrhage was noted. Neurological signs were sometimes seen in the late stages. Shock and multi-organ system failure, often with evidence of disseminated intravascular coagulopathy, ensued in the second week, with death in four of the five cases. Distinctive treatment components of the one surviving patient included rapid commencement of the antiviral drug ribavirin and administration of HMG-CoA reductase inhibitors (statins, N-acetylcysteine, and recombinant factor VIIa.Lujo virus causes a clinical syndrome remarkably similar to Lassa fever. Considering the high case-fatality and significant logistical impediments to controlled treatment efficacy trials for viral hemorrhagic fever, it is both logical and ethical to explore the use of the various compounds used in the treatment of the surviving case reported here in future outbreaks

  15. Clinical Features and Patient Management of Lujo Hemorrhagic Fever

    Science.gov (United States)

    Sewlall, Nivesh H.; Richards, Guy; Duse, Adriano; Swanepoel, Robert; Paweska, Janusz; Blumberg, Lucille; Dinh, Thu Ha; Bausch, Daniel

    2014-01-01

    Background In 2008 a nosocomial outbreak of five cases of viral hemorrhagic fever due to a novel arenavirus, Lujo virus, occurred in Johannesburg, South Africa. Lujo virus is only the second pathogenic arenavirus, after Lassa virus, to be recognized in Africa and the first in over 40 years. Because of the remote, resource-poor, and often politically unstable regions where Lassa fever and other viral hemorrhagic fevers typically occur, there have been few opportunities to undertake in-depth study of their clinical manifestations, transmission dynamics, pathogenesis, or response to treatment options typically available in industrialized countries. Methods and Findings We describe the clinical features of five cases of Lujo hemorrhagic fever and summarize their clinical management, as well as providing additional epidemiologic detail regarding the 2008 outbreak. Illness typically began with the abrupt onset of fever, malaise, headache, and myalgias followed successively by sore throat, chest pain, gastrointestinal symptoms, rash, minor hemorrhage, subconjunctival injection, and neck and facial swelling over the first week of illness. No major hemorrhage was noted. Neurological signs were sometimes seen in the late stages. Shock and multi-organ system failure, often with evidence of disseminated intravascular coagulopathy, ensued in the second week, with death in four of the five cases. Distinctive treatment components of the one surviving patient included rapid commencement of the antiviral drug ribavirin and administration of HMG-CoA reductase inhibitors (statins), N-acetylcysteine, and recombinant factor VIIa. Conclusions Lujo virus causes a clinical syndrome remarkably similar to Lassa fever. Considering the high case-fatality and significant logistical impediments to controlled treatment efficacy trials for viral hemorrhagic fever, it is both logical and ethical to explore the use of the various compounds used in the treatment of the surviving case reported here

  16. Factor II deficiency

    Science.gov (United States)

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

  17. Factor VII deficiency

    Science.gov (United States)

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

  18. Heart disease - risk factors

    Science.gov (United States)

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

  19. Thyroid Cancer Risk Factors

    Science.gov (United States)

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

  20. Risk Factors and Prevention

    Science.gov (United States)

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

  1. Risk Factors for Scleroderma

    Science.gov (United States)

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

  2. Factor V deficiency

    Science.gov (United States)

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

  3. Foundations of factor analysis

    CERN Document Server

    Mulaik, Stanley A

    2009-01-01

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

  4. ISS Payload Human Factors

    Science.gov (United States)

    Ellenberger, Richard; Duvall, Laura; Dory, Jonathan

    2016-01-01

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

  5. Bayesian Exploratory Factor Analysis

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  6. Risk Factors for Thrombosis

    Institute of Scientific and Technical Information of China (English)

    包承鑫

    2002-01-01

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

  7. Factoring Polynomials and Fibonacci.

    Science.gov (United States)

    Schwartzman, Steven

    1986-01-01

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

  8. Coagulation Factors Test

    Science.gov (United States)

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

  9. Annual Adjustment Factors

    Data.gov (United States)

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

  10. Environmental factors in autism

    OpenAIRE

    Andreas Martin Grabrucker

    2013-01-01

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

  11. Environmental Factors in Autism

    OpenAIRE

    Andreas M. Grabrucker

    2013-01-01

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

  12. Mesonic Form Factors

    Energy Technology Data Exchange (ETDEWEB)

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

    2003-07-22

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

  13. Multilevel Mixture Factor Models

    Science.gov (United States)

    Varriale, Roberta; Vermunt, Jeroen K.

    2012-01-01

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

  14. Bayesian Exploratory Factor Analysis

    DEFF Research Database (Denmark)

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

    2014-01-01

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

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

    Science.gov (United States)

    Mackey, Jon; Sehirlioglu, Alp; Dynys, Fred

    2014-01-01

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

  16. Explicit correlation factors

    Science.gov (United States)

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

    2017-09-01

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

  17. Rh Factor Blood Test

    Science.gov (United States)

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

  18. Baryon form factors

    CERN Document Server

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

    1999-01-01

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

  19. Overview of environmental factors

    Science.gov (United States)

    Purvis, C. K.

    1989-01-01

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

  20. The Transcription Factor Encyclopedia

    DEFF Research Database (Denmark)

    Yusuf, Dimas; Butland, Stefanie L; Swanson, Magdalena I

    2012-01-01

    ABSTRACT: Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130...

  1. Factors of schizoid personality.

    Science.gov (United States)

    Raine, A; Allbutt, J

    1989-02-01

    The increasing use of schizoid personality scales with normals has led to a number of validation studies, but to date there are no published analyses of the factorial structure of these scales. This study presents results of factor analyses of schizoid personality scales in an initial attempt to delineate their factorial structure. Questionnaires were administered to 114 male and female undergraduates and factor analysed using Varimax, Quartimax, and Oblique rotations. A two-factor varimax solution yielded a first factor accounting for 49 per cent of total unrotated variance with high (0.70 to 0.91) loadings from Hallucinatory predisposition, Perceptual aberration, Schizophrenism, STA and STB scales, and was interpreted as reflecting a general factor of schizoid personality disorder. Psychoticism and Social anhedonia loaded on a second factor accounting for 20 per cent of the variance which was uncorrelated (r = 0.09) with factor 1. This factor solution was closely replicated using quartimax and oblimin rotation criteria. It is concluded that Social anhedonia and Psychoticism represent a separate dimension from other scales which reflect the more positive features of schizoid personality.

  2. Factorized Graph Matching.

    Science.gov (United States)

    Zhou, Feng; de la Torre, Fernando

    2015-11-19

    Graph matching (GM) is a fundamental problem in computer science, and it plays a central role to solve correspondence problems in computer vision. GM problems that incorporate pairwise constraints can be formulated as a quadratic assignment problem (QAP). Although widely used, solving the correspondence problem through GM has two main limitations: (1) the QAP is NP-hard and difficult to approximate; (2) GM algorithms do not incorporate geometric constraints between nodes that are natural in computer vision problems. To address aforementioned problems, this paper proposes factorized graph matching (FGM). FGM factorizes the large pairwise affinity matrix into smaller matrices that encode the local structure of each graph and the pairwise affinity between edges. Four are the benefits that follow from this factorization: (1) There is no need to compute the costly (in space and time) pairwise affinity matrix; (2) The factorization allows the use of a path-following optimization algorithm, that leads to improved optimization strategies and matching performance; (3) Given the factorization, it becomes straight-forward to incorporate geometric transformations (rigid and non-rigid) to the GM problem. (4) Using a matrix formulation for the GM problem and the factorization, it is easy to reveal commonalities and differences between different GM methods. The factorization also provides a clean connection with other matching algorithms such as iterative closest point; Experimental results on synthetic and real databases illustrate how FGM outperforms state-of-the-art algorithms for GM. The code is available at http://humansensing.cs.cmu.edu/fgm.

  3. Risk Factors for Tuberculosis

    Directory of Open Access Journals (Sweden)

    Padmanesan Narasimhan

    2013-01-01

    Full Text Available The risk of progression from exposure to the tuberculosis bacilli to the development of active disease is a two-stage process governed by both exogenous and endogenous risk factors. Exogenous factors play a key role in accentuating the progression from exposure to infection among which the bacillary load in the sputum and the proximity of an individual to an infectious TB case are key factors. Similarly endogenous factors lead in progression from infection to active TB disease. Along with well-established risk factors (such as human immunodeficiency virus (HIV, malnutrition, and young age, emerging variables such as diabetes, indoor air pollution, alcohol, use of immunosuppressive drugs, and tobacco smoke play a significant role at both the individual and population level. Socioeconomic and behavioral factors are also shown to increase the susceptibility to infection. Specific groups such as health care workers and indigenous population are also at an increased risk of TB infection and disease. This paper summarizes these factors along with health system issues such as the effects of delay in diagnosis of TB in the transmission of the bacilli.

  4. Environmental factors in autism.

    Science.gov (United States)

    Grabrucker, Andreas M

    2012-01-01

    Autism is a neurodevelopmental disorders characterized by impairments in communication and social behavior, and by repetitive behaviors. Although genetic factors might be largely responsible for the occurrence of autism they cannot fully account for all cases and it is likely that in addition to a certain combination of autism-related genes, specific environmental factors might act as risk factors triggering the development of autism. Thus, the role of environmental factors in autism is an important area of research and recent data will be discussed in this review. Interestingly, the results show that many environmental risk factors are interrelated and their identification and comparison might unveil a common scheme of alterations on a contextual as well as molecular level. For example, both, disruption in the immune system and in zinc homeostasis may affect synaptic transmission in autism. Thus, here, a model is proposed that interconnects the most important and scientifically recognized environmental factors. Moreover, similarities in how these risk factors impact synapse function are discussed and a possible influence on an already well described genetic pathway leading to the development of autism via zinc homeostasis is proposed.

  5. Environmental factors in autism

    Directory of Open Access Journals (Sweden)

    Andreas Martin Grabrucker

    2013-01-01

    Full Text Available Autism is a neurodevelopmental disorders characterized by impairments in communication and social behavior, and by repetitive behaviors. Although genetic factors might be largely responsible for the occurrence of autism they cannot fully account for all cases and it is likely that in addition to a certain combination of autism-related genes, specific environmental factors might act as risk factors triggering the development of autism. Thus, the role of environmental factors in autism is an important area of research and recent data will be discussed in this review. Interestingly, the results show that many environmental risk factors are interrelated and their identification and comparison might unveil a common scheme of alterations on a contextual as well as molecular level. For example, both, disruption in the immune system and in zinc homeostasis may affect synaptic transmission in autism. Thus, here, a model is proposed that interconnects the most important and scientifically recognized environmental factors. Moreover, similarities in how these risk factors impact synapse function are discussed and a possible influence on an already well described genetic pathway leading to the development of autism via zinc homeostasis is proposed.

  6. Factor V Leiden thrombophilia.

    Science.gov (United States)

    Kujovich, Jody Lynn

    2011-01-01

    Factor V Leiden is a genetic disorder characterized by a poor anticoagulant response to activated Protein C and an increased risk for venous thromboembolism. Deep venous thrombosis and pulmonary embolism are the most common manifestations, but thrombosis in unusual locations also occurs. The current evidence suggests that the mutation has at most a modest effect on recurrence risk after initial treatment of a first venous thromboembolism. Factor V Leiden is also associated with a 2- to 3-fold increased relative risk for pregnancy loss and possibly other obstetric complications, although the probability of a successful pregnancy outcome is high. The clinical expression of Factor V Leiden is influenced by the number of Factor V Leiden alleles, coexisting genetic and acquired thrombophilic disorders, and circumstantial risk factors. Diagnosis requires the activated Protein C resistance assay (a coagulation screening test) or DNA analysis of the F5 gene, which encodes the Factor V protein. The first acute thrombosis is treated according to standard guidelines. Decisions regarding the optimal duration of anticoagulation are based on an individualized assessment of the risks for venous thromboembolism recurrence and anticoagulant-related bleeding. In the absence of a history of thrombosis, long-term anticoagulation is not routinely recommended for asymptomatic Factor V Leiden heterozygotes, although prophylactic anticoagulation may be considered in high-risk clinical settings. In the absence of evidence that early diagnosis reduces morbidity or mortality, decisions regarding testing at-risk family members should be made on an individual basis.

  7. Two-factor authentication

    CERN Document Server

    Stanislav, Mark

    2015-01-01

    During the book, readers will learn about the various technical methods by which two-factor authentication is implemented, security concerns with each type of implementation, and contextual details to frame why and when these technologies should be used. Readers will also be provided with insight about the reasons that two-factor authentication is a critical security control, events in history that have been important to prove why organization and individual would want to use two factor, and core milestones in the progress of growing the market.

  8. Teratogenic factors affect transcription factor expression.

    Science.gov (United States)

    Kojima, Takuya; Asano, Shinya; Takahashi, Naoki

    2013-01-01

    Chemical compounds are produced every day, many with adverse effects on human health, and hence it is vital to predict the risks to humans simply, rapidly, and accurately. Teratogens have a serious impact on fetal development. This has been studied mainly by phenotypic analysis of experimental animals. However, since phenotypes can vary within different species, we established a new evaluation system based on our recent finding that teratogens influence Hox gene expression in mice. Similarly to the Hox gene expression changes, the expression patterns of several transcription factors involved in development, including the Dlx, Irx, Sall, and T-box families, were altered after 6 h of exposure to retinoic acid (RA) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The expression changes in Dlx4, Dlx6, Irx5, Sall2, Sall3, Sall4, Tbx10, and Tbx22 were linked to teratogen-induced phenotypes, and our results indicate that expression changes in developmental transcription factors can help to predict teratogenic risk.

  9. TMDs, universality and factorization

    CERN Document Server

    D'Alesio, Umberto

    2011-01-01

    We present a short overview on transverse momentum dependent parton distribution and fragmentation functions, giving their partonic interpretation and ways to access them. We then discuss the issue of their universality and its connection to factorization in perturbative QCD.

  10. Factor V Leiden

    Science.gov (United States)

    ... increase your chance of developing abnormal blood clots (thrombophilia), usually in your veins. Most people with factor ... sharp tools. References Bauer KA. Management of inherited thrombophilia. http://www.uptodate.com/home. Accessed June 6, ...

  11. New microbial growth factor

    Science.gov (United States)

    Bok, S. H.; Casida, L. E., Jr.

    1977-01-01

    A screening procedure was used to isolate from soil a Penicillium sp., two bacterial isolates, and a Streptomyces sp. that produced a previously unknown microbial growth factor. This factor was an absolute growth requirement for three soil bacteria. The Penicillium sp. and one of the bacteria requiring the factor, an Arthrobacter sp., were selected for more extensive study concerning the production and characteristics of the growth factor. It did not seem to be related to the siderochromes. It was not present in soil extract, rumen fluid, or any other medium component tested. It appears to be a glycoprotein of high molecular weight and has high specific activity. When added to the diets for a meadow-vole mammalian test system, it caused an increased consumption of diet without a concurrent increase in rate of weight gain.

  12. Factors Affecting Wound Healing

    Science.gov (United States)

    Guo, S.; DiPietro, L.A.

    2010-01-01

    Wound healing, as a normal biological process in the human body, is achieved through four precisely and highly programmed phases: hemostasis, inflammation, proliferation, and remodeling. For a wound to heal successfully, all four phases must occur in the proper sequence and time frame. Many factors can interfere with one or more phases of this process, thus causing improper or impaired wound healing. This article reviews the recent literature on the most significant factors that affect cutaneous wound healing and the potential cellular and/or molecular mechanisms involved. The factors discussed include oxygenation, infection, age and sex hormones, stress, diabetes, obesity, medications, alcoholism, smoking, and nutrition. A better understanding of the influence of these factors on repair may lead to therapeutics that improve wound healing and resolve impaired wounds. PMID:20139336

  13. Factor X assay

    Science.gov (United States)

    ... D, Neff AT. Rare coagulation factor deficiencies. In: Hoffman R, Benz EJ Jr, Silberstein LE, Heslop HE, ... Laboratory evaluation of hemostatic and thrombotic disorders. In: Hoffman R, Benz EJ Jr, Silberstein LE, Heslop HE, ...

  14. Factor XII assay

    Science.gov (United States)

    ... D, Neff AT. Rare coagulation factor deficiencies. In: Hoffman R, Benz EJ Jr, Silberstein LE, Heslop HE, ... Laboratory evaluation of hemostatic and thrombotic disorders. In: Hoffman R, Benz EJ Jr, Silberstein LE, Heslop HE, ...

  15. Rheumatoid Factors: Clinical Applications

    Directory of Open Access Journals (Sweden)

    Francesca Ingegnoli

    2013-01-01

    Full Text Available Rheumatoid factors are antibodies directed against the Fc region of immunoglobulin G. First detected in patients with rheumatoid arthritis 70 years ago, they can also be found in patients with other autoimmune and nonautoimmune conditions, as well as in healthy subjects. Rheumatoid factors form part of the workup for the differential diagnosis of arthropathies. In clinical practice, it is recommended to measure anti-cyclic citrullinated peptide antibodies and rheumatoid factors together because anti-cyclic citrullinated peptide antibodies alone are only moderately sensitive, and the combination of the two markers improves diagnostic accuracy, especially in the case of early rheumatoid arthritis. Furthermore, different rheumatoid factor isotypes alone or in combination can be helpful when managing rheumatoid arthritis patients, from the time of diagnosis until deciding on the choice of therapeutic strategy.

  16. Heart Disease Risk Factors

    Science.gov (United States)

    ... Hearts® WISEWOMAN Program Other Chronic Disease Topics Diabetes Nutrition Obesity Physical Activity Stroke Heart Disease Risk Factors Recommend ... Hearts® WISEWOMAN Program Other Chronic Disease Topics Diabetes Nutrition Obesity Physical Activity Stroke File Formats Help: How do ...

  17. Human Factors Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — Purpose: The purpose of the Human Factors Laboratory is to further the understanding of highway user needs so that those needs can be incorporated in roadway design,...

  18. Factors Affecting Wound Healing

    OpenAIRE

    Guo, S.; DiPietro, L A

    2010-01-01

    Wound healing, as a normal biological process in the human body, is achieved through four precisely and highly programmed phases: hemostasis, inflammation, proliferation, and remodeling. For a wound to heal successfully, all four phases must occur in the proper sequence and time frame. Many factors can interfere with one or more phases of this process, thus causing improper or impaired wound healing. This article reviews the recent literature on the most significant factors that affect cutane...

  19. FGF growth factor analogs

    Science.gov (United States)

    Zamora, Paul O [Gaithersburg, MD; Pena, Louis A [Poquott, NY; Lin, Xinhua [Plainview, NY; Takahashi, Kazuyuki [Germantown, MD

    2012-07-24

    The present invention provides a fibroblast growth factor heparin-binding analog of the formula: ##STR00001## where R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, X, Y and Z are as defined, pharmaceutical compositions, coating compositions and medical devices including the fibroblast growth factor heparin-binding analog of the foregoing formula, and methods and uses thereof.

  20. Brain derived neurotrophic factor

    DEFF Research Database (Denmark)

    Mitchelmore, Cathy; Gede, Lene

    2014-01-01

    Brain Derived Neurotrophic Factor (BDNF) is a neurotrophin with important functions in neuronal development and neuroplasticity. Accumulating evidence suggests that alterations in BDNF expression levels underlie a variety of psychiatric and neurological disorders. Indeed, BDNF therapies are curre......Brain Derived Neurotrophic Factor (BDNF) is a neurotrophin with important functions in neuronal development and neuroplasticity. Accumulating evidence suggests that alterations in BDNF expression levels underlie a variety of psychiatric and neurological disorders. Indeed, BDNF therapies...

  1. General Factors in Graphs.

    Science.gov (United States)

    1986-07-01

    conjectured that the general factor problem can be solved in polynomial time when, in each Bi, all the gaps (if any) have length one. We prove this conjecture...exactly bi edges incident with node i, for each i. This problem is well-solved. A polynomial algorithm is known (Edmonds and Johnson (1970)) as well as a...powerful theorem to characterize the existence of solutions ( Tutte (1952)). The following generalization of the factor problem was studied by Lovtsz

  2. Factors Impacting Knowledge Sharing

    DEFF Research Database (Denmark)

    Schulzmann, David; Slepniov, Dmitrij

    The purpose of this paper is to examine various factors affecting knowledge sharing at the R&D center of a Western MNE in China. The paper employs qualitative methodology and is based on the action research and case study research techniques. The findings of the paper advance our understanding...... about factors that affect knowledge sharing. The main emphasis is given to the discussion on how to improve knowledge sharing in global R&D organizations....

  3. Los factores de riesgo

    Directory of Open Access Journals (Sweden)

    Justo Senado Dumoy

    1999-01-01

    Full Text Available Sobre el fundamento filosófico de los conceptos de la Dialéctica Materialista, se presenta un análisis en relación con el concepto e interpretación de los Factores de Riesgo.A analysis on the concept and interpretation of risk factors is presented based on the philosophical foundation of the concepts of materialist dialectics.

  4. Factors affecting emotional divorce

    Directory of Open Access Journals (Sweden)

    Karim Said Shabanlou

    2016-03-01

    Full Text Available Emotional Divorce is the most important factor in the rupture of the most fundamental structures of society, the family.Due to the sensitivity and position of the familyAnd its functions specifically to investigate the factors underlying emotional divorce has of particular importance.Emotional Divorce phenomenon is not a single factor, but rather a set of related factors together led to Emotional Divorce.In this paper the role of psychological factors such as early maladaptive schemas, negative body image, perfectionism is discussed on an emotional divorce.Also quality of life and family relationships of couples with emotional divorce,Such as quality of health, sexual dissatisfaction, ignoring the needs, expectations and opinions of women by men or vice versa,And also social and economic factors such as subcultures families, couples, the quality of social relationships, social networks couple,Economic situation of the families of the couple, financial crisis, unemployment and economic revenues couples studied and some suggestions are presented based on the findings.

  5. CATTELL AND EYSENCK FACTOR SCORES RELATED TO COMREY PERSONALITY FACTORS.

    Science.gov (United States)

    Comrey, A L; Duffy, K E

    1968-10-01

    The Eysenck Personality Inventory, the Cattell 16 PF Inventory, and the Comrey Personality Inventory were administered to 272 volunteers. Eysenck and Cattell factor scores were correlated with scores over homogeneous item groups (FHIDs) which define the Comrey test factors. This matrix was factor analyzed to relate the Eysenck and Cattell factor scores to the factor structure underlying the Comrey test. The Eysenck Neuroticism, Comrey Neuroticism, and Cattell second-order Anxiety factors appeared to match. The Eysenck Introversion and the Comrey Shyness factors also matched. The 16 Cattell primary factors overlapped but did not match with the Comrey factors.

  6. Breast cancer risk factors

    Directory of Open Access Journals (Sweden)

    Marzena Kamińska

    2015-09-01

    Full Text Available Breast cancer is the most frequently diagnosed neoplastic disease in women around menopause often leading to a significant reduction of these women’s ability to function normally in everyday life. The increased breast cancer incidence observed in epidemiological studies in a group of women actively participating in social and professional life implicates the necessity of conducting multidirectional studies in order to identify risk factors associated with the occurrence of this type of neoplasm. Taking the possibility of influencing the neoplastic transformation process in individuals as a criterion, all the risk factors initiating the process can be divided into two groups. The first group would include inherent factors such as age, sex, race, genetic makeup promoting familial occurrence of the neoplastic disease or the occurrence of benign proliferative lesions of the mammary gland. They all constitute independent parameters and do not undergo simple modification in the course of an individual’s life. The second group would include extrinsic factors conditioned by lifestyle, diet or long-term medical intervention such as using oral hormonal contraceptives or hormonal replacement therapy and their influence on the neoplastic process may be modified to a certain degree. Identification of modifiable factors may contribute to development of prevention strategies decreasing breast cancer incidence.

  7. [Prognostic factors in resuscitation].

    Science.gov (United States)

    Bahloul, F; Le Gall, J R; Loirat, P; Alperovitch, A; Patois, E

    1988-10-08

    The outcome from intensive care is known to be influenced by such factors as age, previous health status, severity of the disease and diagnosis. In order to assess the influence of each individual factor, 3,687 patients from 38 French intensive care units were studied. For each patient were recorded: age, simplified acute physiological score (SAPS), previous health status, diagnosis, type of intensive care unit (medicine, scheduled or elective surgery) and immediate outcome. Each of these factors was found to influence the immediate survival rate. A multivariate analysis ranked the factors in the following order: SAPS, age, type of intensive care unit and previous health status. Diagnosis played a role in the prognosis since with a 10-15 points SAPS mortality was nil for drug overdose, 12 per cent for chronic obstructive pulmonary disease and 38 per cent for cardiogenic shock. However, a single diagnosis was made in only 37 per cent of the patients, as against 3 diagnoses in 17 per cent and 4 diagnoses or more in 7 per cent. When the type of intensive care unit was considered, the mean death rate was 20 per cent in medicine, 27 per cent in scheduled surgery and 5 per cent in elective surgery (P less than 0.001). Since this study showed a definite influence of each of the four factors on immediate survival, intensive care patients can be described and classified according to this system. However, it must be stressed that individual prognoses are extremely vague.

  8. Geothermal Plant Capacity Factors

    Energy Technology Data Exchange (ETDEWEB)

    Greg Mines; Jay Nathwani; Christopher Richard; Hillary Hanson; Rachel Wood

    2015-01-01

    The capacity factors recently provided by the Energy Information Administration (EIA) indicated this plant performance metric had declined for geothermal power plants since 2008. Though capacity factor is a term commonly used by geothermal stakeholders to express the ability of a plant to produce power, it is a term frequently misunderstood and in some instances incorrectly used. In this paper we discuss how this capacity factor is defined and utilized by the EIA, including discussion on the information that the EIA requests from operations in their 923 and 860 forms that are submitted both monthly and annually by geothermal operators. A discussion is also provided regarding the entities utilizing the information in the EIA reports, and how those entities can misinterpret the data being supplied by the operators. The intent of the paper is to inform the facility operators as the importance of the accuracy of the data that they provide, and the implications of not providing the correct information.

  9. Multi-factor authentication

    Energy Technology Data Exchange (ETDEWEB)

    Hamlet, Jason R; Pierson, Lyndon G

    2014-10-21

    Detection and deterrence of spoofing of user authentication may be achieved by including a cryptographic fingerprint unit within a hardware device for authenticating a user of the hardware device. The cryptographic fingerprint unit includes an internal physically unclonable function ("PUF") circuit disposed in or on the hardware device, which generates a PUF value. Combining logic is coupled to receive the PUF value, combines the PUF value with one or more other authentication factors to generate a multi-factor authentication value. A key generator is coupled to generate a private key and a public key based on the multi-factor authentication value while a decryptor is coupled to receive an authentication challenge posed to the hardware device and encrypted with the public key and coupled to output a response to the authentication challenge decrypted with the private key.

  10. The focus factor

    DEFF Research Database (Denmark)

    Nicolaisen, Jeppe; Frandsen, Tove Faber

    2015-01-01

    Introduction. We present a new bibliometric indicator to measure journal specialisation over time, named the focus factor. This new indicator is based on bibliographic coupling and counts the percentage of re-citations given in subsequent years. Method. The applicability of the new indicator....... To validate re-citations as caused by specialisation, other possible causes were measured and correlated (obsolescence, journal self-citations and number of references). Results. The results indicate that the focus factor is capable of distinguishing between general and specialised journals and thus...... effectively measures the intended phenomenon (i.e., journal specialisation). Only weak correlations were found between journal re-citations and obsolescence, journal self-citations, and number of references. Conclusions. The focus factor successfully measures journal specialisation over time. Measures based...

  11. La adolescencia: factores criticos

    Directory of Open Access Journals (Sweden)

    Noé Ardila Espinel

    1980-01-01

    Full Text Available Ten factors, tbat are considered by several psychologists as sensitive and characterístíc of the adolescent period, were tested by means of a Lykert type scale of 50 ítems, Seventy-eight subjects divided in three groups (U·13 years, early adolescence; 14·17 years, middle adolescence; 18-22 years, late adolescence answered the scale, Results índicate age differences. The factors that are in conflict duríng the middle adolescente are: emotional control, self control, social behavior, logical thinking, tendeney toward independency, economic índependency, family índependency, relígíous independency, rules conflict,and affective development, The factors change in direction before, during, and after adolescence

  12. Model Correction Factor Method

    DEFF Research Database (Denmark)

    Christensen, Claus; Randrup-Thomsen, Søren; Morsing Johannesen, Johannes

    1997-01-01

    The model correction factor method is proposed as an alternative to traditional polynomial based response surface techniques in structural reliability considering a computationally time consuming limit state procedure as a 'black box'. The class of polynomial functions is replaced by a limit...... statebased on an idealized mechanical model to be adapted to the original limit state by the model correction factor. Reliable approximations are obtained by iterative use of gradient information on the original limit state function analogously to previous response surface approaches. However, the strength...... of the model correction factor method, is that in simpler form not using gradient information on the original limit state function or only using this information once, a drastic reduction of the number of limit state evaluation is obtained together with good approximations on the reliability. Methods...

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

    Science.gov (United States)

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

    2008-02-01

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

  14. Orthogonal factorizations of digraphs

    Institute of Scientific and Technical Information of China (English)

    Guizhen LIU

    2009-01-01

    Let G be a digraph with vertex set V(G) and arc set E(G) and let g = (g-,g+) and f = (f-, f+) be pairs of positive integer-valued functions defined on V(G) such that g-(x) ≤ f-(x) and g+(x) ≤ f+(x) for each x ∈ V(G). A (g, f)-factor of G is a spanning subdigraph H of G such that g-(x) ≤ idH(x) ≤ f-(x) and g+(x) ≤ odu(x) ≤ f+(x) for each x ∈ V(H); a (g, f)-factorization of G is a partition of E(G) into arc-disjoint (g, f)-factors. Let = {F1,F2,...,Fm} and H be a factorization and a subdigraph of G, respectively, is called k-orthogonal to H if each FI, 1 ≤ I ≤ m, has exactly k arcs in common with H. In this paper it is proved that every (mg+m-1, mf-m+1)-digraph has a (g, f)-factorization k-orthogonal to any given subdigraph with km arcs if k ≤ min{g-(x),g+(x)} for any x ∈ V(G) and that every (mg, mf)-digraph has a (g, f)-factorization orthogonal to any given directed m-star if 0 ≤ g(x) ≤ f(x) for any x ∈ V(G). The results in this paper are in some sense best possible.

  15. Factores de riesgo psicosocial

    OpenAIRE

    Fernández, Borja

    2012-01-01

    Tras un año de estudio de la Prevención de Riesgos Laborales he podido ir adquiriendo, todavía más, una clara concienciación sobre el estudio, supresión y mejora de los factores de riesgo que afectan a los trabajadores en la ejecución de su trabajo. Algo que es fácil de darse cuenta al entrar en profundidad en estas cuestiones, es de la escasa conciencia que tienen las organizaciones y los trabajadores sobre lo perjudiciales que pueden ser para su salud los factores de riesgo ergonómicos. ...

  16. Graph factors modulo k

    DEFF Research Database (Denmark)

    Thomassen, Carsten

    2014-01-01

    We prove a general result on graph factors modulo k . A special case says that, for each natural number k , every (12k−7)-edge-connected graph with an even number of vertices contains a spanning subgraph in which each vertex has degree congruent to k modulo 2k.......We prove a general result on graph factors modulo k . A special case says that, for each natural number k , every (12k−7)-edge-connected graph with an even number of vertices contains a spanning subgraph in which each vertex has degree congruent to k modulo 2k....

  17. Endodontic surgery prognostic factors.

    Science.gov (United States)

    Azarpazhooh, Amir; Shah, Prakesh S

    2011-01-01

    Medline, (PubMed) and the Cochrane databases together with hand searching of the following journals: Journal of Endodontics, International Endodontic Journal, Oral Surgery Oral Medicine Oral Pathology (name changed to Oral Surgery Oral Medicine Oral Pathology Oral Radiology and Endodontics in 1995), Endodontics and Dental Traumatology (name changed to Dental Traumatology in 2001), Journal of Oral and Maxillofacial Surgery, and International Journal of Oral and Maxillofacial Surgery. Clinical studies evaluating apical surgery with placement of a root-end filling were included. Studies on apical surgery with orthograde root canal filling or about apicectomy alone without root-end filling were excluded, as were experimental and animal studies. Only studies with ≥ ten patients with a minimum six month follow-up period and clearly defined radiographic and clinical healing criteria, with healing reported for at least two categories of a specific prognostic factor were accepted. Studies reporting in English, German, French, Spanish, Italian, Portuguese and Scandinavian languages were included. All studies were assessed separately by two of the three authors, with disagreements resolved by discussion. Prognostic factors were divided into patient related, tooth-related or treatment-related factors. The reported percentages of healed teeth were pooled per category. The statistical method of Mantel-Haenszel was applied to estimate the odds ratios and their 95% confidence intervals. Homogeneity was assessed using Woolf's test. With regard to tooth-related factors, the following were identified as predictors of healing: absence of preoperative pain or signs, good density of the root canal filling and a periapical lesion size of ≤ 5 mm. With regard to treatment-related factors, teeth treated with the use of an endoscope tended to have higher healed rates than teeth treated without the use of an endoscope. Although the clinician may be able to control treatment

  18. STEREOTYPICAL FACTORS IN TOURISM

    Directory of Open Access Journals (Sweden)

    Cristina-Elena ALBU

    2013-06-01

    Full Text Available International tourism has grown rapidly nowdays, contributing to the growth of the global economy. The purpose of this essay is to identify and analyze stereotypical factors in the development of strategies concerning the offer for the tourism industry: the image of a tourist destination, brand, country of origin and customer behaviour. Documentary study was the research method used: representative articles were analysed, as recent as possible, to determine the factors mentioned above. Professionals in the industry of tourism need to understand cultural differences between tourists, as well as those of the host country, to be able to create tourist reception offers that live up to the standards expected by clients.

  19. The transcription factor encyclopedia.

    Science.gov (United States)

    Yusuf, Dimas; Butland, Stefanie L; Swanson, Magdalena I; Bolotin, Eugene; Ticoll, Amy; Cheung, Warren A; Zhang, Xiao Yu Cindy; Dickman, Christopher T D; Fulton, Debra L; Lim, Jonathan S; Schnabl, Jake M; Ramos, Oscar H P; Vasseur-Cognet, Mireille; de Leeuw, Charles N; Simpson, Elizabeth M; Ryffel, Gerhart U; Lam, Eric W-F; Kist, Ralf; Wilson, Miranda S C; Marco-Ferreres, Raquel; Brosens, Jan J; Beccari, Leonardo L; Bovolenta, Paola; Benayoun, Bérénice A; Monteiro, Lara J; Schwenen, Helma D C; Grontved, Lars; Wederell, Elizabeth; Mandrup, Susanne; Veitia, Reiner A; Chakravarthy, Harini; Hoodless, Pamela A; Mancarelli, M Michela; Torbett, Bruce E; Banham, Alison H; Reddy, Sekhar P; Cullum, Rebecca L; Liedtke, Michaela; Tschan, Mario P; Vaz, Michelle; Rizzino, Angie; Zannini, Mariastella; Frietze, Seth; Farnham, Peggy J; Eijkelenboom, Astrid; Brown, Philip J; Laperrière, David; Leprince, Dominique; de Cristofaro, Tiziana; Prince, Kelly L; Putker, Marrit; del Peso, Luis; Camenisch, Gieri; Wenger, Roland H; Mikula, Michal; Rozendaal, Marieke; Mader, Sylvie; Ostrowski, Jerzy; Rhodes, Simon J; Van Rechem, Capucine; Boulay, Gaylor; Olechnowicz, Sam W Z; Breslin, Mary B; Lan, Michael S; Nanan, Kyster K; Wegner, Michael; Hou, Juan; Mullen, Rachel D; Colvin, Stephanie C; Noy, Peter John; Webb, Carol F; Witek, Matthew E; Ferrell, Scott; Daniel, Juliet M; Park, Jason; Waldman, Scott A; Peet, Daniel J; Taggart, Michael; Jayaraman, Padma-Sheela; Karrich, Julien J; Blom, Bianca; Vesuna, Farhad; O'Geen, Henriette; Sun, Yunfu; Gronostajski, Richard M; Woodcroft, Mark W; Hough, Margaret R; Chen, Edwin; Europe-Finner, G Nicholas; Karolczak-Bayatti, Magdalena; Bailey, Jarrod; Hankinson, Oliver; Raman, Venu; LeBrun, David P; Biswal, Shyam; Harvey, Christopher J; DeBruyne, Jason P; Hogenesch, John B; Hevner, Robert F; Héligon, Christophe; Luo, Xin M; Blank, Marissa Cathleen; Millen, Kathleen Joyce; Sharlin, David S; Forrest, Douglas; Dahlman-Wright, Karin; Zhao, Chunyan; Mishima, Yuriko; Sinha, Satrajit; Chakrabarti, Rumela; Portales-Casamar, Elodie; Sladek, Frances M; Bradley, Philip H; Wasserman, Wyeth W

    2012-01-01

    Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130 mini review articles on pertinent human, mouse and rat TFs. Notable features of the TFe website include a high-quality PDF generator and web API for programmatic data retrieval. TFe aims to rapidly educate scientists about the TFs they encounter through the delivery of succinct summaries written and vetted by experts in the field. TFe is available at http://www.cisreg.ca/tfe.

  20. The Transcription Factor Encyclopedia

    DEFF Research Database (Denmark)

    Yusuf, Dimas; Butland, Stefanie L; Swanson, Magdalena I

    2012-01-01

    mini review articles on pertinent human, mouse and rat TFs. Notable features of the TFe website include a high-quality PDF generator and web API for programmatic data retrieval. TFe aims to rapidly educate scientists about the TFs they encounter through the delivery of succinct summaries written......ABSTRACT: Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130...

  1. Factors stimulating content marketing

    Directory of Open Access Journals (Sweden)

    Naser Azad

    2016-02-01

    Full Text Available This paper presents an empirical investigation to determine factors influencing on content marketing in banking industry. The study designs a questionnaire consists of 40 questions in Likert scale and distributes it among 550 randomly selected regular customers of Bank Mellat in city of Tehran, Iran and 400 properly filled questionnaires are collected. Cronbach alphas for all components of the survey are well above desirable level. Using principle component analysis with Varimax rotation, the study has determined six factors influencing the most on content marketing including organization, details, having new ideas, quality, sensitivity and power while the last component contains only two subcomponents and is removed from the study.

  2. Human factors in network security

    OpenAIRE

    Jones, Francis B.

    1991-01-01

    Human factors, such as ethics and education, are important factors in network information security. This thesis determines which human factors have significant influence on network security. Those factors are examined in relation to current security devices and procedures. Methods are introduced to evaluate security effectiveness by incorporating the appropriate human factors into network security controls

  3. Introduction to human factors

    Energy Technology Data Exchange (ETDEWEB)

    Winters, J.M.

    1988-03-01

    Some background is given on the field of human factors. The nature of problems with current human/computer interfaces is discussed, some costs are identified, ideal attributes of graceful system interfaces are outlined, and some reasons are indicated why it's not easy to fix the problems. (LEW)

  4. Irrational factor races

    Indian Academy of Sciences (India)

    Sneha Chaubey; Milenda Lanius; Alexandru Zaharescu

    2014-11-01

    We investigate the behavior of the sum of the irrational factor function over arithmetic progressions. We first establish a general asymptotic formula for such a sum, and then obtain some further results in the case of arithmetic progressions 3 ± 1.

  5. Affective Factors: Anxiety

    Science.gov (United States)

    Tasnimi, Mahshad

    2009-01-01

    Affective factors seem to play a crucial role in success or failure in second language acquisition. Negative attitudes can reduce learners' motivation and harm language learning, while positive attitudes can do the reverse. Discovering students' attitudes about language will help both teacher and student in teaching learning process. Anxiety is…

  6. Hyperglycemia: a prothrombotic factor?

    NARCIS (Netherlands)

    B.A. Lemkes; J. Hermanides; J.H. Devries; F. Holleman; J.C.M. Meijers; J.B.L. Hoekstra

    2010-01-01

    Diabetes mellitus is characterized by a high risk of atherothrombotic events. What is more, venous thrombosis has also been found to occur more frequently in this patient group. This prothrombotic condition in diabetes is underpinned by laboratory findings of elevated coagulation factors and impaire

  7. FRUIT NUTRITIVE FACTOR NETWORK

    Institute of Scientific and Technical Information of China (English)

    Yanqing QU; Yumei JIANG; Daren HE

    2009-01-01

    As an research example of the widely existing cooperation-competition systems, the authors present an empirical investigation on a fruit nutritive factor network. It is described by a node-weighted bipartite graph. The fruit nutritive factors are defined as the nodes, and two nodes are connected by an edge if at least one fruit contains these two nutritive factors. The fruits are defined as the collaboration acts. The node-weight Writ, which signifies the "importance degree" of each actor node, is defined as the content of a nutritive factor in a fruit. The empirical investigation results show some unique features.The node-weight distributions take so-called "shifted power law" function forms, but the act-weight distribution takes a normal form. The degree and act-degree distributions show impulsive-spectrum like forms. These observations may be helpful for the study of fruits. The network description method proposed in this article may be universal for a kind of cooperation-competition systems.

  8. Environmental factors and leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Brandt, L.

    1985-01-01

    Investigations on the association between environmental hazards and the development of various types of leukaemia are reviewed. Regarding acute non-lymphocytic leukaemia (ANLL) exposure to ionizing radiation is a well-documented risk factor. According to several recent studies exposure to strong electromagnetic fields may be suspected to be of etiologic importance for ANLL. There is evidence that occupational handling of benzene is a risk factor and other organic solvents may also be leukaemogenic. Occupational exposure to petrol products has been proposed to be a risk factor although the hazardous substances have not yet been defined. Results of cytogenetic studies in ANLL suggest that exposure to certain environmental agents may be associated with relatively specific clonal chromosome aberrations. Exposure in utero to ionizing radiation has been proposed to be a risk factor for acute lymphocytic leukaemia (ALL) in children. Unlike ANLL there seems at present to be little evidence that ALL is related to exposure to some chemicals. Chronic myeloid leukaemia (CML) may follow exposure to high doses of ionizing radiation whereas such exposure seems to be of insignificant importance for the development of chronic lymphocytic leukaemia (CLL). According to some studies an abnormally high incidence of CLL may be found among farmers in the USA. These results have not been confirmed in Scandinavian studies. There seems to be little evidence that CML or CLL are related to occupational handling of some chemicals. 35 references.

  9. Factor Analysis and AIC.

    Science.gov (United States)

    Akaike, Hirotugu

    1987-01-01

    The Akaike Information Criterion (AIC) was introduced to extend the method of maximum likelihood to the multimodel situation. Use of the AIC in factor analysis is interesting when it is viewed as the choice of a Bayesian model; thus, wider applications of AIC are possible. (Author/GDC)

  10. eta ' transition form factors

    NARCIS (Netherlands)

    Amo Sanchez, del P.; Raven, H.G.; Snoek, H.; BaBar, Collaboration

    2011-01-01

    eta((')) transition form factors in the momentum-transfer range from 4 to 40 GeV(2). The analysis is based on 469 fb(-1) of integrated luminosity collected at PEP-II with the BABAR detector at e(+)e(-) center-of-mass energies near 10.6 GeV.

  11. Identificar Factores de Riesgo

    Directory of Open Access Journals (Sweden)

    Luis Carlos Silva Ayçaguer

    2005-01-01

    Full Text Available Se exponen el contexto histórico y las condiciones en que se ha configurado lo que podría caracterizarse como una verdadera "cacería de factores de riesgo" en la epidemiología contemporánea. Entre otros problemas, se ha extendido la práctica de encarar el problema de la determinación o identificación de factores de riesgo a través de un ritual estadístico que roza la caricatura y, lo más importante, que la mayor parte de las veces no conduce a conseguir el objetivo de la investigación, ni a obtener nuevos conocimientos. El trabajo caracteriza dicho ritual y examina críticamente sus pasos. Se realiza una detallada discusión de la endeblez metodológica de tal procedimiento y se ilustra profusamente su empleo.

  12. Smad transcription factors.

    Science.gov (United States)

    Massagué, Joan; Seoane, Joan; Wotton, David

    2005-12-01

    Smad transcription factors lie at the core of one of the most versatile cytokine signaling pathways in metazoan biology-the transforming growth factor-beta (TGFbeta) pathway. Recent progress has shed light into the processes of Smad activation and deactivation, nucleocytoplasmic dynamics, and assembly of transcriptional complexes. A rich repertoire of regulatory devices exerts control over each step of the Smad pathway. This knowledge is enabling work on more complex questions about the organization, integration, and modulation of Smad-dependent transcriptional programs. We are beginning to uncover self-enabled gene response cascades, graded Smad response mechanisms, and Smad-dependent synexpression groups. Our growing understanding of TGFbeta signaling through the Smad pathway provides general principles for how animal cells translate complex inputs into concrete behavior.

  13. Precipitating factors of asthma.

    Science.gov (United States)

    Lee, T H

    1992-01-01

    Asthma is characterised by bronchial hyperresponsiveness. This feature of the asthmatic diathesis predisposes patients to wheezing in response to a number of different factors. These precipitating factors include specific allergen acting via sensitised mediator cells through an IgE-dependent mechanism. There are irritants which may work through a non-specific manner, or stimuli such as exercise and hyperventilation, which probably also act through mediator release via a non-IgE-dependent manner. The mechanism whereby physical stimuli such as exercise induce bronchoconstriction is of interest, because it increases the context in which the mast cell may participate in acute asthmatic bronchoconstriction. Respiratory infections also commonly provoke asthma, especially in infants and may, indeed, precipitate the asthmatic state itself. Finally, drugs can often trigger asthma attacks and the mechanisms of asthma precipitated by non-steroidal anti-inflammatory drugs such as aspirin have been the subject of recent research.

  14. Helicopter human factors

    Science.gov (United States)

    Hart, Sandra G.

    1988-01-01

    The state-of-the-art helicopter and its pilot are examined using the tools of human-factors analysis. The significant role of human error in helicopter accidents is discussed; the history of human-factors research on helicopters is briefly traced; the typical flight tasks are described; and the noise, vibration, and temperature conditions typical of modern military helicopters are characterized. Also considered are helicopter controls, cockpit instruments and displays, and the impact of cockpit design on pilot workload. Particular attention is given to possible advanced-technology improvements, such as control stabilization and augmentation, FBW and fly-by-light systems, multifunction displays, night-vision goggles, pilot night-vision systems, night-vision displays with superimposed symbols, target acquisition and designation systems, and aural displays. Diagrams, drawings, and photographs are provided.

  15. [Streptococcus pyogenes pathogenic factors].

    Science.gov (United States)

    Bidet, Ph; Bonacorsi, S

    2014-11-01

    The pathogenicity of ß-hemolytic group A streptococcus (GAS) is particularly diverse, ranging from mild infections, such as pharyngitis or impetigo, to potentially debilitating poststreptococcal diseases, and up to severe invasive infections such as necrotizing fasciitis or the dreaded streptococcal toxic shock syndrome. This variety of clinical expressions, often radically different in individuals infected with the same strain, results from a complex interaction between the bacterial virulence factors, the mode of infection and the immune system of the host. Advances in comparative genomics have led to a better understanding of how, following this confrontation, GAS adapts to the immune system's pressure, either peacefully by reducing the expression of certain virulence factors to achieve an asymptomatic carriage, or on the contrary, by overexpressing them disproportionately, resulting in the most severe forms of invasive infection.

  16. Power factor compensation

    Energy Technology Data Exchange (ETDEWEB)

    Barra R, Felipe [Schneider Electric Chile (Chile)

    2010-07-01

    Every company is looking for ways to increase productivity as a way to gain a competitive advantage. Energy is a significant element in making any product and so it is important to assess production processes from an energy perspective. This paper discusses the impact of power factor compensation on energy efficiency. The life cycle solution for energy efficiency involves optimization of active energy using automation and regulation. A brief explanation is given of how each component of a company plays a part in this cycle. Examples include simulations and analysis, modeling, performance monitoring facilities, and environmental sustainability. Reactive energy suppliers and the installation of capacitors are also explained. Types of compensation include fixed and automation compensations. Economic advantages include a reduction in the electricity bill and active energy consumption. Technical advantages include reduction in voltage drop and an increase in available power. The power correction factor also improves reliability and contributes to conservation of the environment.

  17. On braid monodromy factorizations

    Energy Technology Data Exchange (ETDEWEB)

    Kharlamov, V M [Institut de Recherche Matematique Avanee Universite Louis Pasteur et CNRS 7 rue Rene Descartes (France); Kulikov, Vik S [Steklov Mathematical Institute, Russian Academy of Sciences (Russian Federation)

    2003-06-30

    We introduce and develop a language of semigroups over the braid groups to study the braid monodromy factorizations (bmf's) of plane algebraic curves and other related objects. As an application, we give a new proof of Orevkov's theorem on the realization of bmf's over a disc by algebraic curves and show that the complexity of such a realization cannot be bounded in terms of the types of factors of the bmf. We also prove that the type of a bmf distinguishes Hurwitz curves with singularities of inseparable type up to H-isotopy and J-holomorphic cuspidal curves in CP{sup 2} up to symplectic isotopy.

  18. The focus factor

    DEFF Research Database (Denmark)

    Nicolaisen, Jeppe; Frandsen, Tove Faber

    2015-01-01

    is demonstrated on a selection of general science journals and on a selection of medical journals. The reference lists of each journal are compared year by year, and the percentage of re-citations is calculated by dividing the number of re-citations with the total number of citations each year. Analysis......Introduction. We present a new bibliometric indicator to measure journal specialisation over time, named the focus factor. This new indicator is based on bibliographic coupling and counts the percentage of re-citations given in subsequent years. Method. The applicability of the new indicator....... To validate re-citations as caused by specialisation, other possible causes were measured and correlated (obsolescence, journal self-citations and number of references). Results. The results indicate that the focus factor is capable of distinguishing between general and specialised journals and thus...

  19. Cross-culturally recurrent personality factors : Analyses of three factors

    NARCIS (Netherlands)

    De Raad, B; Peabody, D

    2005-01-01

    This study proceeds from an earlier one that examined the 'Big Five' factors (Peabody & De Raad, 2002). That study considered the substantive nature of five factors from six European psycholexical studies. The results supported Big Five Factor III (Conscientiousness), but Factors I (Extraversion) an

  20. Information security factors systematization

    OpenAIRE

    Янченко, Вадим Николавевич; Ивченко, Александр Владимирович; Залога, Вильям Александрович; Дынник, Оксана Дмитриевна

    2015-01-01

    In this article the necessity of solving the theoretical and practical task, aimed on development the methodological basis for elaboration and implementation of information security management system, has been considered. Based on research results of scientific works and the requirements in the field of information security management the universal multilevel system of information security factors of organizations (enterprises) in the wood properties form was offered by using quality control ...

  1. The malingering factor.

    Science.gov (United States)

    Williams, J Michael

    2011-04-01

    The influence of malingering and suboptimal performance on neuropsychological tests has become a major interest of clinical neuropsychologists. Methods to detect malingering have focused on specialized tests or embedded patterns associated with malingering present in the conventional neuropsychology tests. There are two stages to the study of their validity. The first stage involves whether the method can discriminate malingering subjects from those who are not malingering. In the second stage, they must be examined for their relationship to the conventional tests used to establish impairment and disability. Constantinou, Bauer, Ashendorf, Fisher, and McCaffrey (2005. Is poor performance on recognition memory effort measures indicative of generalized poor performance on neuropsychological tests? Archives of Clinical Neuropsychology, 20, 191-198.) conducted the only study in which correlations are presented between a commonly used symptom validity test, the Test of Memory Malingering (TOMM) and the subtests of the Wechsler Adult Intelligence Scale-Revised (WAIS-R). A factor analysis was conducted using these correlations. It revealed a clear malingering factor that explained significant variance in the TOMM and the WAIS-R subtests. The relationship of malingering with cognitive tests is complex: some tests are sensitive to malingering and others are not. Factor analysis can summarize the magnitude of variance associated with each test and reveal the patterns of inter-relationships between malingering and clinical tests. The analysis also suggested that malingering assessment methods could be improved by the addition of timing the responses.

  2. Risk Factors for Cholelithiasis.

    Science.gov (United States)

    Pak, Mila; Lindseth, Glenda

    2016-01-01

    Gallstone disease is one of the most common public health problems in the United States. Approximately 10%-20% of the national adult populations currently carry gallstones, and gallstone prevalence is rising. In addition, nearly 750,000 cholecystectomies are performed annually in the United States; direct and indirect costs of gallbladder surgery are estimated to be $6.5 billion. Cholelithiasis is also strongly associated with gallbladder, pancreatic, and colorectal cancer occurrence. Moreover, the National Institutes of Health estimates that almost 3,000 deaths (0.12% of all deaths) per year are attributed to complications of cholelithiasis and gallbladder disease. Although extensive research has tried to identify risk factors for cholelithiasis, several studies indicate that definitive findings still remain elusive. In this review, predisposing factors for cholelithiasis are identified, the pathophysiology of gallstone disease is described, and nonsurgical preventive options are discussed. Understanding the risk factors for cholelithiasis may not only be useful in assisting nurses to provide resources and education for patients who are diagnosed with gallstones, but also in developing novel preventive measures for the disease.

  3. Nucleon Electromagnetic Form Factors

    Energy Technology Data Exchange (ETDEWEB)

    Kees de Jager

    2004-08-01

    Although nucleons account for nearly all the visible mass in the universe, they have a complicated structure that is still incompletely understood. The first indication that nucleons have an internal structure, was the measurement of the proton magnetic moment by Frisch and Stern (1933) which revealed a large deviation from the value expected for a point-like Dirac particle. The investigation of the spatial structure of the nucleon, resulting in the first quantitative measurement of the proton charge radius, was initiated by the HEPL (Stanford) experiments in the 1950s, for which Hofstadter was awarded the 1961 Nobel prize. The first indication of a non-zero neutron charge distribution was obtained by scattering thermal neutrons off atomic electrons. The recent revival of its experimental study through the operational implementation of novel instrumentation has instigated a strong theoretical interest. Nucleon electro-magnetic form factors (EMFFs) are optimally studied through the exchange of a virtual photon, in elastic electron-nucleon scattering. The momentum transferred to the nucleon by the virtual photon can be selected to probe different scales of the nucleon, from integral properties such as the charge radius to scaling properties of its internal constituents. Polarization instrumentation, polarized beams and targets, and the measurement of the polarization of the recoiling nucleon have been essential in the accurate separation of the charge and magnetic form factors and in studies of the elusive neutron charge form factor.

  4. Human Factors Review Plan

    Energy Technology Data Exchange (ETDEWEB)

    Paramore, B.; Peterson, L.R. (eds.)

    1985-12-01

    ''Human Factors'' is concerned with the incorporation of human user considerations into a system in order to maximize human reliability and reduce errors. This Review Plan is intended to assist in the assessment of human factors conditions in existing DOE facilities. In addition to specifying assessment methodologies, the plan describes techniques for improving conditions which are found to not adequately support reliable human performance. The following topics are addressed: (1) selection of areas for review describes techniques for needs assessment to assist in selecting and prioritizing areas for review; (2) human factors engineering review is concerned with optimizing the interfaces between people and equipment and people and their work environment; (3) procedures review evaluates completeness and accuracy of procedures, as well as their usability and management; (4) organizational interface review is concerned with communication and coordination between all levels of an organization; and (5) training review evaluates training program criteria such as those involving: trainee selection, qualification of training staff, content and conduct of training, requalification training, and program management.

  5. Accidents - personal factors

    Energy Technology Data Exchange (ETDEWEB)

    Zaitsev, S.L.; Tsygankov, A.V.

    1982-03-01

    This paper evaluates influence of selected personal factors on accident rate in underground coal mines in the USSR. Investigations show that so-called organizational factors cause from 80 to 85% of all accidents. About 70% of the organizational factors is associated with social, personal and economic features of personnel. Selected results of the investigations carried out in Donbass mines are discussed. Causes of miner dissatisfaction are reviewed: 14% is caused by unsatisfactory working conditions, 21% by repeated machine failures, 16% by forced labor during days off, 14% by unsatisfactory material supply, 16% by hard physical labor, 19% by other reasons. About 25% of miners injured during work accidents are characterized as highly professionally qualified with automatic reactions, and about 41% by medium qualifications. About 60% of accidents is caused by miners with less than a 3 year period of service. About 15% of accidents occurs during the first month after a miner has returned from a leave. More than 30% of accidents occurs on the first work day after a day or days off. Distribution of accidents is also presented: 19% of accidents occurs during the first 2 hours of a shift, 36% from the second to the fourth hour, and 45% occurs after the fourth hour and before the shift ends.

  6. Molecular factors in migraine

    Science.gov (United States)

    Kowalska, Marta; Prendecki, Michał; Kozubski, Wojciech; Lianeri, Margarita; Dorszewska, Jolanta

    2016-01-01

    Migraine is a common neurological disorder that affects 11% of adults worldwide. This disease most likely has a neurovascular origin. Migraine with aura (MA) and more common form - migraine without aura (MO) – are the two main clinical subtypes of disease. The exact pathomechanism of migraine is still unknown, but it is thought that both genetic and environmental factors are involved in this pathological process. The first genetic studies of migraine were focused on the rare subtype of MA: familial hemiplegic migraine (FHM). The genes analysed in familial and sporadic migraine are: MTHFR, KCNK18, HCRTR1, SLC6A4, STX1A, GRIA1 and GRIA3. It is possible that migraine is a multifactorial disease with polygenic influence. Recent studies have shown that the pathomechanisms of migraine involves both factors responsible for immune response and oxidative stress such as: cytokines, tyrosine metabolism, homocysteine; and factors associated with pain transmission and emotions e.g.: serotonin, hypocretin-1, calcitonin gene-related peptide, glutamate. The correlations between genetic variants of the HCRTR1 gene, the polymorphism 5-HTTLPR and hypocretin-1, and serotonin were observed. It is known that serotonin inhibits the activity of hypocretin neurons and may affect the appearance of the aura during migraine attack. The understanding of the molecular mechanisms of migraine, including genotype-phenotype correlations, may contribute to finding markers important for the diagnosis and treatment of this disease. PMID:27191890

  7. Perinatal risk factors for strabismus

    DEFF Research Database (Denmark)

    Torp-Pedersen, Tobias; Boyd, Heather A; Poulsen, Gry;

    2010-01-01

    Little is known about the aetiological factors underlying strabismus. We undertook a large cohort study to investigate perinatal risk factors for strabismus, overall and by subtype.......Little is known about the aetiological factors underlying strabismus. We undertook a large cohort study to investigate perinatal risk factors for strabismus, overall and by subtype....

  8. Purification and characterization of proteinase inhibitors from wild soja (Glycine soja) seeds.

    Science.gov (United States)

    Deshimaru, Masanobu; Hanamoto, Ryuji; Kusano, Chiho; Yoshimi, Shingo; Terada, Shigeyuki

    2002-09-01

    Nine proteinase inhibitors, I-VIIa, VIIb, and VIII, were isolated from wild soja seeds by ammonium sulfate fractionation and successive chromatographies on SP-Toyopearl 650M, Sephacryl S-200SF, and DEAE-Toyopearl 650S columns. Reverse-phase HPLC finally gave pure inhibitors. All of the inhibitors inhibited trypsin with dissociation constants of 3.2-6.2 x 10(-9) M. Some of the inhibitors inhibited chymotrypsin and elastase as well. Two inhibitors (VIIb and VIII) with a molecular weight of 20,000 were classified as a soybean Kunitz inhibitor family. Others (I-VIla) had a molecular weight of about 8,000, and were stable to heat and extreme pH, suggesting that these belonged to the Bowman-Birk inhibitor family. Partial amino acid sequences of four inhibitors were also analyzed. The complete sequence of inhibitor IV was ascertained from the nucleotide sequences of cDNA clones encoding isoinhibitors homologous to soybean C-II.

  9. Phylogenetic analysis of porcine rotavirus in Argentina: increasing diversity of G4 strains and evidence of interspecies transmission.

    Science.gov (United States)

    Parra, Gabriel I; Vidales, Graciela; Gomez, Jorge A; Fernandez, Fernando M; Parreño, Viviana; Bok, Karin

    2008-01-01

    Group A rotaviruses are one of the most frequently detected viral agents associated with neonatal diarrhea in piglets. In order to characterize rotavirus (RV) strains circulating in Argentinean swine, four porcine production farms located in Buenos Aires were studied. RV strains genotyped as P[6]G4, P[6]G8 and P[1]G6 were found in piglets under 30 days of age, without diarrhea. Phylogenetic and sequence analysis of the VP7 gene from G4 strains available in databases, reveals five porcine new lineages (III-VII) and three sublineages (VIIa-VIIc). The G4 porcine Argentinean strains were grouped with a porcine RV strain isolated in Brazil and another RV strain isolated from a child with diarrhea in Mexico, constituting an American lineage (VII). On the other hand, porcine G6 and G8 were closely related to RV's circulating in Argentinean cattle and South-American camelids, respectively. The fact that G4 porcine lineages were epidemiologically related to human strains, and G6 and G8 Argentinean porcine strains were found related to bovine and South-American camelids, respectively, suggests that pigs might play a crucial role as reservoir and generator of newly adapted emerging RV strains for human and other species.

  10. Planar cell polarity in the inner ear: how do hair cells acquire their oriented structure?

    Science.gov (United States)

    Lewis, Julian; Davies, Alex

    2002-11-05

    Sensory hair cells in the ear and lateral line have an asymmetrical hair-bundle structure, essential for their function as directional mechanotransducers. We examine four questions: (1) how does the planar asymmetry of the individual hair cell originate? (2) How are the orientations of neighboring hair cells coordinated? (3) How is the orientation of a group of hair cells controlled in relation to the ear as a whole? (4) How does the initial cell asymmetry lead to creation of the asymmetrical hair bundle? Studies of the development of hairs and bristles in Drosophila, combined with genetic data from vertebrates, suggest that the answer to questions (1) and (2) lies in asymmetries that develop at the cell cortex and at cell-cell junctions, generated by products of a set of primary planar cell polarity genes, including the transmembrane receptor Frizzled. A separate and largely independent mechanism controls asymmmetric allocation of cell fate determinants such as Numb at mitosis, in Drosophila and possibly in the ear also. Little is known about long-range signals that might orient hair cells globally in the ear, but progress has been made in identifying a set of genes responsible for read-out of the primary polarity specification. These genes, in flies and vertebrates, provide a link to assembly of the polarized cytoskeleton; myosin VIIA appears to belong in this group. The mechanism creating the staircase pattern of stereocilium lengths is unknown, but could involve regulation of stereocilium growth by Ca(2+) ions entering via transduction channels.

  11. PENERAPAN MODEL PEMBELAJARAN PROJECT BASED LEARNING BERBASIS LESSON STUDY UNTUK MENINGKATKAN KEAKTIFAN BELAJAR SISWA

    Directory of Open Access Journals (Sweden)

    Aris Yulianto

    2017-03-01

    Full Text Available The purpose of the research is to increase learning activities and learning outcomes students at MTs Sunan Kalijogo. the research is a class action (class action research were conducted in two cycles, each cycle consisting of three meetings. The samples were students of class VII-A second semester of academic year 2014—2015 MTs Sunan Kalijogo the number of students 25 people. The results showed that the students' learning activeness increased learning from the first cycle to the second cycle. Increased student activity occurs because of the learning by applying the model of project based learning is an active student based lesson study to work on worksheets, preparing and completing project tasks with his group. This shows that the project based learning ability increase learning activities and learning outcomes students. Tujuan penelitian ini untuk meningkatkan keaktifan belajar siswa di MTs Sunan Kalijogo. Penelitian ini merupakan penelitian tindakan kelas (PTK yang dilakukan dalam dua siklus dan tiap siklus terdiri atas tiga pertemuan. Sampel penelitian adalah siswa kelas VII A semester genap tahun pelajaran 2014—2015 MTs Sunan Kalijogo dengan jumlah siswa 25 orang. Hasil penelitian ini menunjukkan bahwa keaktifan belajar siswa mengalami peningkatan belajar dari siklus I ke siklus II. Peningkatan keaktifan siswa terjadi karena dalam pembelajaran dengan menerapkan model Project Based Learning berbasis Lesson Study siswa aktif untuk mengerjakan LKS, menyusun dan menyelesaikan tugas proyek bersama kelompoknya. Hal ini menunjukkan bahwa model pembelajaran Project Based Learning dapat meningkatkan keaktifan belajar dan hasil belajar siswa.

  12. An improved strategy for easy process monitoring and advanced purification of recombinant proteins.

    Science.gov (United States)

    Miladi, Baligh; Dridi, Cyrine; El Marjou, Ahmed; Boeuf, Guilhem; Bouallagui, Hassib; Dufour, Florence; Di Martino, Patrick; Elm'selmi, Abdellatif

    2013-11-01

    In this work, a multifunctional expression cassette, termed Multitags, combining different and complementary functionalities, was designed and used to monitor the expression and the purification of two model proteins (Pfu DNA polymerase and Myosin-VIIa- and Rab-Interracting protein : MyRIP). Multitags contains two affinity purification tags, a polyhistidine sequence (10× His) and the streptavidin-binding peptide (SBP) and as a marker tag the heme-binding domain of rat cytochrome b5 followed by the TEV cleavage site. Using the Multitags as fusion partner, more than 90 % of both fusion proteins were produced in soluble form when expressed in Escherichia coli KRX. In addition, high purity (99 %) of recombinant proteins was achieved after two consecutive affinity purification steps. The expression cassette also demonstrated an accurate monitoring capability comparable to that of a dual recognition-based method. The choice of the SBP tag was considered as an integral process that included a method for tag removal. Thus, an immobilized TEV protease fixed on streptavidin-agarose matrix was used for the cleavage of fusion proteins. After digestion, both unprocessed fusion proteins and Multitags were retained on the proteolytic column via their SBP sequence, allowing cleavage and recovery of target proteins on one step. This combined approach may accelerate the development of optimized production processes, while insuring high product quality and a low production cost.

  13. Cell cycle reactivation of cochlear progenitor cells in neonatal FUCCI mice by a GSK3 small molecule inhibitor.

    Science.gov (United States)

    Roccio, M; Hahnewald, S; Perny, M; Senn, P

    2015-12-08

    Due to the lack of regenerative capacity of the mammalian auditory epithelium, sensory hair cell loss results in permanent hearing deficit. Nevertheless, a population of tissue resident stem/progenitor cells has been recently described. Identification of methods to trigger their activity could lead to exploitation of their potential therapeutically. Here we validate the use of transgenic mice reporting cell cycle progression (FUCCI), and stemness (Lgr5-GFP), as a valuable tool to identify regulators of cell cycle re-entry of supporting cells within the auditory epithelium. The small molecule compound CHIR99021 was used to inhibit GSK3 activity. This led to a significant increase in the fraction of proliferating sphere-forming cells, labeled by the FUCCI markers and in the percentage of Lgr5-GFP + cells, as well as a selective increase in the fraction of S-G2-M cells in the Lgr5 + population. Using whole mount cultures of the organ of Corti we detected a statistically significant increment in the fraction of proliferating Sox2 supporting cells after CHIR99021 treatment, but only rarely appearance of novel MyoVIIa +/Edu + hair cells. In conclusion, these tools provide a robust mean to identify novel regulators of auditory organ regeneration and to clarify the contribution of stem cell activity.

  14. Fates of mouse embryonic stem cells transplanted into the inner ears of adult mice and embryonic chickens.

    Science.gov (United States)

    Sakamoto, Tatsunori; Nakagawa, Takayuki; Endo, Tsuyoshi; Kim, Tae-Soo; Iguchi, Fukuichiro; Naito, Yasushi; Sasai, Yoshiki; Ito, Juichi

    2004-03-01

    The potential of embryonic stem (ES) cells to differentiate into inner ear hair cells was examined in this study. Undifferentiated mouse ES cells transplanted into neomycin-damaged mouse inner ears were evaluated by immunohistochemistry 4 weeks after transplantation. Some ES cells were positive for E-cadherin or NCAM, and most transplanted cells were positive for SSEA3 and Ki67. None were positive for Myosin VIIa or MF20. These results indicate that the damaged inner ear may have some activity inducing ES cells to develop into ectoderm cells, but the effect was insufficient to induce inner ear hair cells. Next, SDIA/BMP-treated ES cells were transplanted into embryonic chicken inner ear rudiments. Embryonic chickens were expected to share the same developmental systems as mice. SDIA/BMP treatment drove ES cells to the population including neural crest cells and probably placode cells ES colonies were found next to or in the otic vesicles but were not a part of vesicle walls, indicating that transplanted ES cells could not be expected to be the same kind of cells as chicken otic vesicle cells Some ES colonies were found at the vestibulo-cochlear ganglions. To induce inner ear hair cells in this system, the competency of ES cells and otic induction signals should be defined further.

  15. Ferricytochrome c protects mitochondrial cytochrome c oxidase against hydrogen peroxide-induced oxidative damage.

    Science.gov (United States)

    Sedlák, Erik; Fabian, Marian; Robinson, Neal C; Musatov, Andrej

    2010-11-30

    An excess of ferricytochrome c protects purified mitochondrial cytochrome c oxidase and bound cardiolipin from hydrogen peroxide-induced oxidative modification. All of the peroxide-induced changes within cytochrome c oxidase, such as oxidation of Trp(19,IV) and Trp(48,VIIc), partial dissociation of subunits VIa and VIIa, and generation of cardiolipin hydroperoxide, no longer take place in the presence of ferricytochrome c. Furthermore, ferricytochrome c suppresses the yield of H(2)O(2)-induced free radical detectable by electron paramagnetic resonance spectroscopy within cytochrome c oxidase. These protective effects are based on two mechanisms. The first involves the peroxidase/catalase-like activity of ferricytochrome c, which results in the decomposition of H(2)O(2), with the apparent bimolecular rate constant of 5.1±1.0M(-1)s(-1). Although this value is lower than the rate constant of a specialized peroxidase, the activity is sufficient to eliminate H(2)O(2)-induced damage to cytochrome c oxidase in the presence of an excess of ferricytochrome c. The second mechanism involves ferricytochrome c-induced quenching of free radicals generated within cytochrome c oxidase. These results suggest that ferricytochrome c may have an important role in protection of cytochrome c oxidase and consequently the mitochondrion against oxidative damage.

  16. Ages of subsurface stratigraphic intervals in the Quaternary of Enewetak Atoll, Marshall Islands

    Science.gov (United States)

    Szabo, B. J.; Tracey, J. I.; Goter, E. R.

    1985-01-01

    Drill cores of Enewetak Atoll, Marshall Islands, reveal six stratigraphic intervals, numbered in downward sequence, which represent vertical coral growth during Quaternary interglaciations. Radiocarbon dates indicate that the Holocene sea transgressed the emergent reef platform by about 8000 yr B.P. The reef grew rapidly upward (about 5 to 10 mm/yr) until about 6500 yr B.P. Afterward vertical growth slowed to about 0.5 mm/yr, then lateral development became dominant during the last several thousand years. The second interval is dated at 131,000 ± 3000 yr B.P. by uranium series. This unit correlates with oxygen-isotope substage 5e and with terrace VIIa of Huon Peninsula, New Guinea, and of Main Reef-2 terrace at Atauro Island. The third interval is not dated because corals were recrystallized and it is tentatively correlated with either oxygen-isotope stages 7 or 9. The age of the fourth interval is estimated at 454,000 ± 100,000 yr B.P. from measured {234U }/{238U } activity ratios. This unit is correlated with either oxygen-isotope stage 9, 11, or 13.

  17. Ehlers Danlos Syndrome: An Unusual Presentation You Need to Know about

    Directory of Open Access Journals (Sweden)

    Amel Karaa

    2013-01-01

    Full Text Available The Ehlers Danlos syndromes (EDS comprise a group of connective tissue disorders characterized by tissue fragility of the skin, ligaments, blood vessels and internal organs. Variable degrees of clinical severity and organ involvement are due to the molecular and biochemical heterogeneity of this group of disorders and have led to classification into well-characterized subtypes that are extending with the discovery of new genes and overlapping syndrome. Types include classical EDS (EDS I/II, hypermobility EDS (EDS III, vascular EDS (EDS IV, kyphoscoliosis EDS (EDS VI, arthrochalasia (EDS VIIA, B and Dermatospraxis (EDS VIIC. Even to the well trained professional, the diagnosis of EDS remains a challenge due to overlapping symptoms and cases can remain without a well-defined classification. Life altering complications of this group of disorders include vascular and hollow organ rupture and ligamentous laxity leading to chronic dislocation with ensuing pain and long term disability. Patients initially present to the general practitioner who is expected to recognize the symptoms of EDS and to proceed with appropriate referral for definitive diagnosis and management to prevent devastating complications. In this paper, we describe a male with classical EDS complicated by devastating vascular and orthopedic events.

  18. Underlayer Effect on Perpendicular Magnetic Anisotropy in Co20Fe60B20\\MgO Films.

    Science.gov (United States)

    Chen, P J; Iunin, Y L; Cheng, S F; Shull, R D

    2016-07-01

    Perpendicular Magnetic Tunneling Junctions (pMTJs) with Ta\\CoFeB\\MgO have been extensively studied in recent years. However, the effects of the underlayer on the formation of the CoFeB perpendicular magnetic anisotropy (PMA) are still not well understood. Here we report the results of our systematic use of a wide range of elements (Ti, V, Cr, Zr, Nb, Mo, Ru, Rh, Pd, Ag, Hf, Ta, W, Re, Os, Ir, Pt and Au) encompassed by columns IVA, VA, VIA, VIIA and VIIIA of the periodic table as the underlayer in a underlayer\\Co20Fe60B20\\MgO stack. Our goals were to survey more elements which could conceivably create a PMA in CoFeB and thereby to explore the mechanisms enabling these underlayers to enhance or create the PMA. We found underlayer elements having both an outer shell of 4d electrons (Zr, Nb Mo, and Pd) and 5d electrons (Hf, Ta, W, Re, Ir, and Pt) resulted in the development of a PMA in the MgO-capped Co20Fe60B20. Hybridization between the 3d electrons of the Fe or Co (in the Co20Fe60B20) at the interface with the 4d or 5d electrons of the underlayer is thought to be the cause of the PMA development.

  19. Methods of forming single source precursors, methods of forming polymeric single source precursors, and single source precursors formed by such methods

    Energy Technology Data Exchange (ETDEWEB)

    Fox, Robert V.; Rodriguez, Rene G.; Pak, Joshua J.; Sun, Chivin; Margulieux, Kelsey R.; Holland, Andrew W.

    2016-04-19

    Methods of forming single source precursors (SSPs) include forming intermediate products having the empirical formula 1/2{L.sub.2N(.mu.-X).sub.2M'X.sub.2}.sub.2, and reacting MER with the intermediate products to form SSPs of the formula L.sub.2N(.mu.-ER).sub.2M'(ER).sub.2, wherein L is a Lewis base, M is a Group IA atom, N is a Group IB atom, M' is a Group IIIB atom, each E is a Group VIB atom, each X is a Group VIIA atom or a nitrate group, and each R group is an alkyl, aryl, vinyl, (per)fluoro alkyl, (per)fluoro aryl, silane, or carbamato group. Methods of forming polymeric or copolymeric SSPs include reacting at least one of HE.sup.1R.sup.1E.sup.1H and MER with one or more substances having the empirical formula L.sub.2N(.mu.-ER).sub.2M'(ER).sub.2 or L.sub.2N(.mu.-X).sub.2M'(X).sub.2 to form a polymeric or copolymeric SSP. New SSPs and intermediate products are formed by such methods.

  20. A biochemically distinct form of cytochrome oxidase (COX) deficiency in the Saguenay-Lac-Saint-Jean region of Quebec.

    Science.gov (United States)

    Merante, F; Petrova-Benedict, R; MacKay, N; Mitchell, G; Lambert, M; Morin, C; De Braekeleer, M; Laframboise, R; Gagné, R; Robinson, B H

    1993-08-01

    We report the results of biochemical and molecular investigations on a group of patients from the Saguenay-Lac-Saint-Jean region of Quebec who have an unusual form of cytochrome oxidase deficiency and Leigh disease. This group can be distinguished from the classical presentation of cytochrome oxidase deficiency with Leigh disease, by the severity of the biochemical defect in different tissues. The activity in skin fibroblasts, amniocytes, and skeletal muscle of cytochrome oxidase is 50% of normal, while in kidney and heart it is close to normal values. Brain and liver, on the other hand, have very low activities. The defect in activity appears to result from a failure of assembly of the cytochrome oxidase complex in liver, but levels of mRNA for both mitochondrially encoded and nuclear-encoded subunits in liver and skin fibroblasts were found to be the same as those in controls. The cDNA sequence of the liver-specific cytochrome oxidase subunits VIa and VIIa were determined in samples from patient liver and skin fibroblasts and showed normal coding sequence.