Science.gov

Sample records for plasma thrombin generation

  1. Calibrated automated thrombin generation measurement in clotting plasma.

    PubMed

    Hemker, H Coenraad; Giesen, Peter; Al Dieri, Raed; Regnault, Véronique; de Smedt, Eric; Wagenvoord, Rob; Lecompte, Thomas; Béguin, Suzette

    2003-01-01

    Calibrated automated thrombography displays the concentration of thrombin in clotting plasma with or without platelets (platelet-rich plasma/platelet-poor plasma, PRP/PPP) in up to 48 samples by monitoring the splitting of a fluorogenic substrate and comparing it to a constant known thrombin activity in a parallel, non-clotting sample. Thus, the non-linearity of the reaction rate with thrombin concentration is compensated for, and adding an excess of substrate can be avoided. Standard conditions were established at which acceptable experimental variation accompanies sensitivity to pathological changes. The coefficients of variation of the surface under the curve (endogenous thrombin potential) are: within experiment approximately 3%; intra-individual: <5% in PPP, <8% in PRP; interindividual 15% in PPP and 19% in PRP. In PPP, calibrated automated thrombography shows all clotting factor deficiencies (except factor XIII) and the effect of all anticoagulants [AVK, heparin(-likes), direct inhibitors]. In PRP, it is diminished in von Willebrand's disease, but it also shows the effect of platelet inhibitors (e.g. aspirin and abciximab). Addition of activated protein C (APC) or thrombomodulin inhibits thrombin generation and reflects disorders of the APC system (congenital and acquired resistance, deficiencies and lupus antibodies) independent of concomitant inhibition of the procoagulant pathway as for example by anticoagulants.

  2. Inhibition of thrombin generation in plasma by fibrin formation (Antithrombin I).

    PubMed

    de Bosch, N B; Mosesson, M W; Ruiz-Sáez, A; Echenagucia, M; Rodriguez-Lemoin, A

    2002-08-01

    The adsorption of thrombin to fibrin during clotting defines "Antithrombin I" activity. We confirmed that thrombin generation in afibrinogenemic or in Reptilase defibrinated normal plasma was higher than in normal plasma. Repletion of these fibrinogen-deficient plasmas with fibrinogen 1 (gamma A/gamma A), whose fibrin has two "low affinity" non-substrate thrombin binding sites, resulted in moderately reduced thrombin generation by 29-37%. Repletion with fibrinogen 2 (gamma'/gamma A), which in addition to low affinity thrombin-binding sites in fibrin, has a "high affinity" non-substrate thrombin binding site in the carboxy-terminal region of its gamma' chain, was even more effective and reduced thrombin generation by 57-67%. Adding peptides that compete for thrombin binding to fibrin [S-Hir53-64 (hirugen) or gamma'414-427] caused a transient delay in the onset of otherwise robust thrombin generation, indicating that fibrin formation is necessary for full expression of Antithrombin I activity. Considered together, 1) the increased thrombin generation in afibrinogenemic or fibrinogen-depleted normal plasma that is mitigated by fibrinogen replacement; 2) evidence that prothrombin activation is increased in afibrinogenemia and normalized by fibrinogen replacement; 3) the severe thrombophilia that is associated with defective thrombin-binding in dysfibrinogenemias Naples I and New York I, and 4) the association of afibrinogenemia or hypofibrinogenemia with venous or arterial thromboembolism, indicate that Antithrombin I (fibrin) modulates thromboembolic potential by inhibiting thrombin generation in blood.

  3. Fucosylated chondroitin sulfate inhibits plasma thrombin generation via targeting of the factor IXa heparin-binding exosite.

    PubMed

    Buyue, Yang; Sheehan, John P

    2009-10-01

    Depolymerized holothurian glycosaminoglycan (DHG) is a fucosylated chondroitin sulfate with antithrombin-independent antithrombotic properties. Heparin cofactor II (HCII)-dependent and -independent mechanisms for DHG inhibition of plasma thrombin generation were evaluated. When thrombin generation was initiated with 0.2 pM tissue factor (TF), the half maximal effective concentration (EC(50)) for DHG inhibition was identical in mock- or HCII-depleted plasma, suggesting a serpin-independent mechanism. In the presence of excess TF, the EC(50) for DHG was increased 13- to 27-fold, suggesting inhibition was dependent on intrinsic tenase (factor IXa-factor VIIIa) components. In factor VIII-deficient plasma supplemented with 700 pM factor VIII or VIIIa, and factor IX-deficient plasma supplemented with plasma-derived factor IX or 100 pM factor IXa, the EC(50) for DHG was similar. Thus, cofactor and zymogen activation did not contribute to DHG inhibition of thrombin generation. Factor IX-deficient plasma supplemented with mutant factor IX(a) proteins demonstrated resistance to DHG inhibition of thrombin generation [factor IX(a) R233A > R170A > WT] that inversely correlated with protease-heparin affinity. These results replicate the effect of these mutations with purified intrinsic tenase components, and establish the factor IXa heparin-binding exosite as the relevant molecular target for inhibition by DHG. Glycosaminoglycan-mediated intrinsic tenase inhibition is a novel antithrombotic mechanism with physiologic and therapeutic applications.

  4. Plasma Thrombin Generation and Sensitivity to Activated Protein C Among Patients With Myeloma and Monoclonal Gammopathy of Undetermined Significance.

    PubMed

    Crowley, Maeve P; Kevane, Barry; O'Shea, Susan I; Quinn, Shane; Egan, Karl; Gilligan, Oonagh M; Ní Áinle, Fionnuala

    2016-09-01

    The etiology of the prothrombotic state in myeloma has yet to be definitively characterized. Similarly, while recent evidence suggests that patients with monoclonal gammopathy of undetermined significance (MGUS) may also be at increased risk of thrombosis, the magnitude and the etiology of this risk have also yet to be defined. The present study aims to characterize patterns of plasma thrombin generation and sensitivity to the anticoagulant activity of activated protein C (APC) at the time of initial diagnosis of myeloma and in response to therapy in comparison to that observed among patients with MGUS and matched, healthy volunteers. Patients presenting with newly diagnosed/newly relapsed myeloma (n = 8), MGUS (n = 8), and matched healthy volunteers (n = 8) were recruited. Plasma thrombin generation was determined by calibrated automated thrombography. Peak thrombin generation was significantly higher in patients with myeloma (383.4 ± 33.4 nmol/L) and MGUS (353.4 ± 16.5 nmol/L) compared to healthy volunteers (276.7 ± 20.8 nmol/L; P < .05). In the presence of APC, endogenous thrombin potential was significantly lower in control plasma (228.6 ± 44.5 nmol/L × min) than in either myeloma (866.2 ± 241.3 nmol/L × min, P = .01) or MGUS plasma (627 ± 91.5 nmol/L × min, P = .003). Within the myeloma cohort, peak thrombin generation was significantly higher at diagnosis (353.2 ± 15.9 nmol/L) than following completion of the third cycle of therapy (282.1 ± 15.2 nmol/L; P < .005). Moreover, sensitivity to APC increased progressively with each cycle of chemotherapy. Further study of the etiology and evolving patterns of hypercoagulability among patients with these conditions is warranted and may have future implications for thromboprophylaxis strategies. PMID:26759370

  5. Thrombin Generation in Zebrafish Blood.

    PubMed

    Schurgers, Evelien; Moorlag, Martijn; Hemker, Coenraad; Lindhout, Theo; Kelchtermans, Hilde; de Laat, Bas

    2016-01-01

    To better understand hypercoagulability as an underlying cause for thrombosis, the leading cause of death in the Western world, new assays to study ex vivo coagulation are essential. The zebrafish is generally accepted as a good model for human hemostasis and thrombosis, as the hemostatic system proved to be similar to that in man. Their small size however, has been a hurdle for more widespread use in hemostasis related research. In this study we developed a method that enables the measurement of thrombin generation in a single drop of non-anticoagulated zebrafish blood. Pre-treatment of the fish with inhibitors of FXa and thrombin, resulted in a dose dependent diminishing of thrombin generation, demonstrating the validity of the assay. In order to establish the relationship between whole blood thrombin generation and fibrin formation, we visualized the resulting fibrin network by scanning electron microscopy. Taken together, in this study we developed a fast and reliable method to measure thrombin generation in whole blood collected from a single zebrafish. Given the similarities between coagulation pathways of zebrafish and mammals, zebrafish may be an ideal animal model to determine the effect of novel therapeutics on thrombin generation. Additionally, because of the ease with which gene functions can be silenced, zebrafish may serve as a model organism for mechanistical research in thrombosis and hemostasis. PMID:26872266

  6. Thrombin Generation in Zebrafish Blood

    PubMed Central

    Hemker, Coenraad; Lindhout, Theo; Kelchtermans, Hilde; de Laat, Bas

    2016-01-01

    To better understand hypercoagulability as an underlying cause for thrombosis, the leading cause of death in the Western world, new assays to study ex vivo coagulation are essential. The zebrafish is generally accepted as a good model for human hemostasis and thrombosis, as the hemostatic system proved to be similar to that in man. Their small size however, has been a hurdle for more widespread use in hemostasis related research. In this study we developed a method that enables the measurement of thrombin generation in a single drop of non-anticoagulated zebrafish blood. Pre-treatment of the fish with inhibitors of FXa and thrombin, resulted in a dose dependent diminishing of thrombin generation, demonstrating the validity of the assay. In order to establish the relationship between whole blood thrombin generation and fibrin formation, we visualized the resulting fibrin network by scanning electron microscopy. Taken together, in this study we developed a fast and reliable method to measure thrombin generation in whole blood collected from a single zebrafish. Given the similarities between coagulation pathways of zebrafish and mammals, zebrafish may be an ideal animal model to determine the effect of novel therapeutics on thrombin generation. Additionally, because of the ease with which gene functions can be silenced, zebrafish may serve as a model organism for mechanistical research in thrombosis and hemostasis. PMID:26872266

  7. Plasma from chronic liver disease subjects exhibit differential ability to generate thrombin

    PubMed Central

    Yang, Zhineng J.; Sheth, Siddharth H.; Smith, Chad H.; Schmotzer, Amy R.; Lippello, Anita L.; Al-Khafaji, Ali; Chopra, Kapil B.; Smith, Roy E.

    2016-01-01

    Liver fibrosis in chronic liver disease (CLD) results in complex alterations in procoagulant and anticoagulant proteins. Although an elevated International Normalized Ratio (INR) is a prominent feature of progressive fibrosis, the utility of the INR to accurately reflect the net effect of these changes on the coagulation system is uncertain. In subjects with CLD, elevated INRs have been observed in both bleeding and thrombotic complications, suggesting limitations of the INR in characterizing the coagulation status. Unlike the INR, which is preferentially sensitive to the extrinsic pathway, the direct measurement of thrombin generation (TG) better captures the global coagulation cascade. We conducted a pilot study measuring the INR, chromogenic factor X (cFX) and TG in CLD subjects and compared them to control subjects and subjects on warfarin anticoagulation. We observed a large interquartile range (IQR) in TG among compensated CLD subjects across a narrow INR range, suggesting that the INR is a suboptimal surrogate measure of TG in CLD subjects. PMID:26200653

  8. [Thrombin generation assays and their clinical application].

    PubMed

    Kern, Anita; Várnai, Katalin; Vásárhelyi, Barna

    2014-06-01

    Thrombin is a key enzyme of the coagulation system, having both pro- and anticoagulant functions. Thus, the generation of thrombin is one of the most important steps in coagulation. Global haemostasis assay, the so-called thrombin generation test is appropriate for its assessment. Since thrombin generation is sensible for both pro- and anticoagulant processes it can be applied for the general characterisation of the risk of thrombosis and bleeding, too. Clinical studies confirmed augmented thrombin generation in patients with high risk of venous or arterial thrombosis. Anticoagulant therapy (also novel oral anticoagulant treatment) can be monitored by thrombin generation. In case of haemophilia thrombin generation assays reflect bleeding severity. It is applicable for monitoring of both conventional haemophilia treatment and inhibitor-bypassing therapy, which is needed when inhibitors develop in patients. Standardization of thrombin generation methods and determination of cut off values are required before its application in clinical practice.

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

    PubMed

    Doshi, Bhavya S; Gangadharan, Bagirath; Doering, Christopher B; Meeks, Shannon L

    2012-01-01

    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 therapy

  10. Mechanistic Modeling of the Effects of Acidosis on Thrombin Generation

    PubMed Central

    Mitrophanov, Alexander Y.; Rosendaal, Frits R.

    2015-01-01

    BACKGROUND: Acidosis, a frequent complication of trauma and complex surgery, results from tissue hypoperfusion and IV resuscitation with acidic fluids. While acidosis is known to inhibit the function of distinct enzymatic reactions, its cumulative effect on the blood coagulation system is not fully understood. Here, we use computational modeling to test the hypothesis that acidosis delays and reduces the amount of thrombin generation in human blood plasma. Moreover, we investigate the sensitivity of different thrombin generation parameters to acidosis, both at the individual and population level. METHODS: We used a kinetic model to simulate and analyze the generation of thrombin and thrombin–antithrombin complexes (TAT), which were the end points of this study. Large groups of temporal thrombin and TAT trajectories were simulated and used to calculate quantitative parameters, such as clotting time (CT), thrombin peak time, maximum slope of the thrombin curve, thrombin peak height, area under the thrombin trajectory (AUC), and prothrombin time. The resulting samples of parameter values at different pH levels were compared to assess the acidosis-induced effects. To investigate intersubject variability, we parameterized the computational model using the data on clotting factor composition for 472 subjects from the Leiden Thrombophilia Study. To compare acidosis-induced relative parameter changes in individual (“virtual”) subjects, we estimated the probabilities of relative change patterns by counting the pattern occurrences in our virtual subjects. Distribution overlaps for thrombin generation parameters at distinct pH levels were quantified using the Bhattacharyya coefficient. RESULTS: Acidosis in the range of pH 6.9 to 7.3 progressively increased CT, thrombin peak time, AUC, and prothrombin time, while decreasing maximum slope of the thrombin curve and thrombin peak height (P < 10–5). Acidosis delayed the onset and decreased the amount of TAT generation (P

  11. Investigation of the selectivity of thrombin-binding aptamers for thrombin titration in murine plasma.

    PubMed

    Trapaidze, Ana; Hérault, Jean-Pascal; Herbert, Jean-Marc; Bancaud, Aurélien; Gué, Anne-Marie

    2016-04-15

    Detection of thrombin in plasma raises timely challenges to enable therapeutic management of thrombosis in patients under vital threat. Thrombin binding aptamers represent promising candidates as sensing elements for the development of real-time thrombin biosensors; however implementation of such biosensor requires the clear understanding of thrombin-aptamer interaction properties in real-like environment. In this study, we used Surface Plasmon Resonance technique to answer the questions of specificity and sensitivity of thrombin detection by the thrombin-binding aptamers HD1, NU172 and HD22. We systematically characterized their properties in the presence of thrombin, as well as interfering molecular species such as the thrombin precursor prothrombin, thrombin in complex with some of its natural inhibitors, nonspecific serum proteins, and diluted plasma. Kinetic experiments show the multiple binding modes of HD1 and NU172, which both interact with multiple sites of thrombin with low nanomolar affinities and show little specificity of interaction for prothrombin vs. thrombin. HD22, on the other hand, binds specifically to thrombin exosite II and has no affinity to prothrombin at all. While thrombin in complex with some of its inhibitors could not be recognized by any aptamer, the binding of HD1 and NU172 properties is compromised by thrombin inhibitors alone, as well as with serum albumin. Finally, the complex nature of plasma was overwhelming for HD1, but we define conditions for the thrombin detection at 10nM range in 100-fold diluted plasma by HD22. Consequently HD22 showed key advantage over HD1 and NU172, and appears as the only alternative to design an aptasensor.

  12. Results of clot waveform analysis and thrombin generation test for a plasma-derived factor VIIa and X mixture (MC710) in haemophilia patients with inhibitors--phase I trial: 2nd report.

    PubMed

    Shirahata, A; Fukutake, K; Mimaya, J; Takamatsu, J; Shima, M; Hanabusa, H; Takedani, H; Takashima, Y; Matsushita, T; Tawa, A; Higasa, S; Takata, N; Sakai, M; Kawakami, K; Ohashi, Y; Saito, H

    2013-03-01

    We reported the results of a clinical pharmacological study of MC710 (a mixture of plasma-derived FVIIa and FX) in haemophilia patients with inhibitors during a non-haemorrhagic state. This report provides the results of a clot waveform analysis (CWA) and thrombin generation test (TGT) using blood samples obtained in this study. CWA and TGT were conducted using blood samples obtained from a pharmacokinetic and pharmacodynamic study in which MC710 (five dose rates: 20, 40, 80, 100 and 120 μg kg(-1)) was compared with NovoSeven (120 μg kg(-1)) and FEIBA (two dose rates: 50 and 75 U kg(-1)) as control drugs in 11 haemophilia patients with inhibitors without haemorrhagic symptoms. CWA showed that MC710 provided significantly greater improvement than the control drugs in activated partial thromboplastin time (APTT) at 80 μg kg(-1); maximum clot velocity and maximum clot acceleration were more enhanced by MC710 than by control drugs. TGT revealed that MC710 significantly shortened the initiation time of thrombin generation in comparison to FEIBA and induced greater thrombin generation potency than NovoSeven. It was not clear whether or not MC710 caused significant dose-dependent changes in the two measurements; however, differences between MC710 and the control drugs were clarified. MC710 was confirmed to have superior coagulation activity and thrombin productivity and is expected to have superior bypassing activity. PMID:22989180

  13. Low paediatric thrombin generation is caused by an attenuation of prothrombin conversion.

    PubMed

    Kremers, Romy M W; Wagenvoord, Rob J; de Laat, H Bas; Monagle, Paul; Hemker, H Coenraad; Ignjatovic, Vera

    2016-06-01

    Thrombin generation (TG) is decreased in children. TG is determined by two underlying processes: the conversion of prothrombin to thrombin and the inactivation of thrombin. Therefore, lower TG capacity in children can either be caused by a reduction of prothrombin conversion, an increase of thrombin inactivation, or both. In 36 children and 8 adults, TG and the factors that determine thrombin inactivation (antithrombin, α2Macroglobulin (α2M) and fibrinogen) were measured. Prothrombin conversion, thrombin inhibitor complex formation, and the overall thrombin decay capacity were determined. In silico modelling was performed to determine the contribution prothrombin conversion and thrombin inactivation to deviant paediatric TG. Both the amount of prothrombin converted and the maximal prothrombin conversion rate are significantly reduced in children as compared to adults. This is partly due to the prothrombin levels being lower and partly to a lower prothrombin conversion rate. The overall thrombin decay capacity is not significantly different in children, but α2Macroglobulin plays a more important role than it does in adults. In silico experiments demonstrate that reduced prothrombin conversion and to a lesser extent elevated α2M levels provide an explanation for low TG in children. Young age has a dual effect on prothrombin conversion. Lower plasma prothrombin levels result in decreased prothrombin conversion but the rate of prothrombin conversion is also decreased, i. e. the development of prothrombinase is lower than in adults.

  14. Peak Thrombin Generation and Subsequent Venous Thromboembolism: The Longitudinal Investigation of Thromboembolism Etiology (LITE)

    PubMed Central

    Lutsey, Pamela L.; Folsom, Aaron R.; Heckbert, Susan R.; Cushman, Mary

    2009-01-01

    Background Thrombin is an enzyme essential to the acceleration of the coagulation cascade and the conversion of fibrinogen to clottable fibrin. Objectives We evaluated the relation of basal peak thrombin generation to risk of future VTE, and determined whether associations were independent of other coagulation markers. Methods LITE ascertained VTE in two prospective population-based cohorts: the Atherosclerosis Risk in Communities (ARIC) study and the Cardiovascular Health Study (CHS). Peak thrombin generation was measured on stored plasma in a nested case-control sample (434 cases, 1,004 controls). Logistic regression was used to estimate the relation of peak thrombin generation to VTE, adjusted for age, sex, race, center and BMI. Mediation was evaluated by additionally adjusting for factor VIII and D-dimer. Results Relative to the first quartile of peak thrombin generation, the odds ratio (95% CI) of VTE for those above the median was 1.74 (1.28–2.37). The association was modestly attenuated by adjustment for factor VIII and D-dimer 1.47 (1.05–2.05). Associations appeared stronger for idiopathic than for secondary VTE. Elevated peak thrombin generation more than added to the VTE risk associated with Factor V Leiden or low aPTT. Conclusions In this prospective study of two independent cohorts, elevated basal peak thrombin generation was associated with subsequent risk of VTE, independent of established VTE risk factors. PMID:19656279

  15. Measurement of dabigatran in standardly used clinical assays, whole blood viscoelastic coagulation, and thrombin generation assays.

    PubMed

    van Ryn, Joanne; Grottke, Oliver; Spronk, Henri

    2014-09-01

    Dabigatran, a direct thrombin inhibitor, is increasingly used clinically as one of the new oral anticoagulants. This review summarizes the assays available to measure its activity and includes the relative sensitivity of the different assays for this agent. In addition to plasma-based clotting tests, assays commonly used in surgical/emergency settings, such as activated clotting time and thromboelastometry/thromboelastography, are reviewed. In addition, the thrombin generation assay is discussed as an important method to determine the potential risk of thrombosis or bleeding and its relevance to the measurement of direct thrombin inhibitors. PMID:25168938

  16. Platelet activation via PAR4 is involved in the initiation of thrombin generation and in clot elasticity development.

    PubMed

    Vretenbrant, Karin; Ramström, Sofia; Bjerke, Maria; Lindahl, Tomas L

    2007-03-01

    Thrombin is a pivotal enzyme formed in the coagulation cascade and an important and potent platelet activator. The two protease-activated thrombin receptors on human platelets are denoted PAR1 and PAR4. The physiological relevance of PAR4 is still unclear, as both aggregation and secretion can be accomplished by PAR1 activation alone. In the present study we have investigated the role of PARs in platelet activation, blood coagulation, clot elasticity and fibrinolysis. Flow cytometry, free oscillation rheometry and thrombin generation measurements were used to analyze blood or platelet-rich plasma from healthy individuals. Maximum PAR1 activation with the peptide SFLLRN gave fewer fibrinogen-binding platelets with lower mean fluorescent intensity than maximum PAR4 activation with AYPGKF. Inhibition of any of the receptors prolonged clotting times. However, PAR1 is more important for fibrinolysis; inhibition of this receptor prolonged all the steps in the fibrinolytic process. Clot elasticity decreased significantly when the PAR4 receptor was inhibited. In the thrombin generation measurements, PAR4 inhibition delayed the thrombin generation start and peak, but did not affect the total amount of thrombin generated. PAR1 inhibition had no significant impact on thrombin generation. We found that PAR4 is most likely activated by low concentrations of thrombin during the initial phase of thrombin generation and is of importance to the clotting time. Furthermore, we suggest that the PAR4 receptor may have a physiological role in the stabilisation of the coagulum. PMID:17334509

  17. Follow-up of thrombin generation after prostate cancer surgery: global test for increased hypercoagulability.

    PubMed

    Benyo, Matyas; Flasko, Tibor; Molnar, Zsuzsanna; Kerenyi, Adrienne; Batta, Zoltan; Jozsa, Tamas; Harsfalvi, Jolan

    2012-01-01

    Recent studies provided evidence that evaluation of thrombin generation identifies patients at thrombotic risk. Thrombin generation has a central role in hemorrhage control and vascular occlusion and its measurement provides new metrics of these processes providing sufficient evaluation of an individual's hemostatic competence and response to anticoagulant therapy. The objective of the study is to assess a new measure of hypercoagulability that predisposes to venous thromboembolism in the postoperative period after radical prostatectomy. Pre- (day-1) and postoperative (hour 1, day 6, month 1 and 10) blood samples of 24 patients were tested for plasma thrombin generation (peak thrombin), routine hematology and hemostasis. Patients received low molecular weight heparin for thromboprophylaxis. Peak thrombin levels were higher in patients compared to controls at baseline (p<0.001), and elevated further in the early postoperative period (p<0.001). Longer general anesthesia and high body mass index were associated with increased thrombin generation after surgery (p = 0.024 and p = 0.040). D dimer and fibrinogen levels were higher after radical prostatectomy (p = 0.001 and p<0.001). Conventional clotting tests remained within the reference range. Our study contributed to the cognition of the hypercoagulable state in cancer patients undergoing pelvic surgery and revealed the course of thrombin generation after radical prostatectomy. Whilst it is unsurprising that thrombin generation increases after tissue trauma, further evaluation of this condition during the postoperative period would lead urologists to an international and well-supported consensus regarding thromboprophylaxis in order to provide better clinical outcome. Considering the routine evaluation of procoagulant activity and extending prophylactic anticoagulant therapy accordingly may potentially prevent late thrombotic events. PMID:23236465

  18. The modification of the thrombin generation test for the clinical assessment of dabigatran etexilate efficiency

    PubMed Central

    Gribkova, Irina V.; Lipets, Elena N.; Rekhtina, Irina G.; Bernakevich, Alex I.; Ayusheev, Dorzho B.; Ovsepyan, Ruzanna A.; Ataullakhanov, Fazoil I.; Sinauridze, Elena I.

    2016-01-01

    A new oral anticoagulant, dabigatran etexilate (DE, a prodrug of direct thrombin inhibitor (DTI) dabigatran), has been used clinically to prevent thrombosis. The assessment of dabigatran efficiency is necessary in some clinical cases, such as renal insufficiency, risk of bleeding, and drug interactions. However, a specific thrombin generation test (TGT) that is one of the most informative and sensitive to anticoagulant therapy (calibrated automated thrombinography (САТ)) shows a paradoxical increase of test parameters, such as endogenous thrombin potential (ETP) and peak thrombin, in patients receiving DE. The paradoxical behaviour of ETP and peak thrombin in these patients in the presence of DTIs is mostly caused by a decrease in the activity of thrombin in the α2-macroglobulin-thrombin complex that is used as a calibrator in CAT. For a correct estimation of the TGT parameters in patient’s plasma containing DTIs we proposed to use our previously described alternative calibration method that is based on the measurement of the fluorescence signal of a well-known concentration of the reaction product (7-amino-4-methylcoumarin). In this study, the validity of such approach was demonstrated in an ex vivo study in patients with knee replacement and two special patients with multiple myeloma, who received DE for thrombosis prophylaxis. PMID:27377013

  19. The modification of the thrombin generation test for the clinical assessment of dabigatran etexilate efficiency.

    PubMed

    Gribkova, Irina V; Lipets, Elena N; Rekhtina, Irina G; Bernakevich, Alex I; Ayusheev, Dorzho B; Ovsepyan, Ruzanna A; Ataullakhanov, Fazoil I; Sinauridze, Elena I

    2016-01-01

    A new oral anticoagulant, dabigatran etexilate (DE, a prodrug of direct thrombin inhibitor (DTI) dabigatran), has been used clinically to prevent thrombosis. The assessment of dabigatran efficiency is necessary in some clinical cases, such as renal insufficiency, risk of bleeding, and drug interactions. However, a specific thrombin generation test (TGT) that is one of the most informative and sensitive to anticoagulant therapy (calibrated automated thrombinography (САТ)) shows a paradoxical increase of test parameters, such as endogenous thrombin potential (ETP) and peak thrombin, in patients receiving DE. The paradoxical behaviour of ETP and peak thrombin in these patients in the presence of DTIs is mostly caused by a decrease in the activity of thrombin in the α2-macroglobulin-thrombin complex that is used as a calibrator in CAT. For a correct estimation of the TGT parameters in patient's plasma containing DTIs we proposed to use our previously described alternative calibration method that is based on the measurement of the fluorescence signal of a well-known concentration of the reaction product (7-amino-4-methylcoumarin). In this study, the validity of such approach was demonstrated in an ex vivo study in patients with knee replacement and two special patients with multiple myeloma, who received DE for thrombosis prophylaxis. PMID:27377013

  20. Cell-derived microparticles circulate in healthy humans and support low grade thrombin generation.

    PubMed

    Berckmans, R J; Nieuwland, R; Böing, A N; Romijn, F P; Hack, C E; Sturk, A

    2001-04-01

    We determined the numbers, cellular origin and thrombin-generating properties of microparticles in healthy individuals (n = 15). Microparticles, isolated from fresh blood samples and identified by flow cytometry, originated from platelets [237 x 10(6)/L (median; range 116-565)], erythrocytes (28 x 10(6)/L; 13-46), granulocytes (46 x 10(6)/L; 16-94) and endothelial cells (64 x 10(6)/L; 16-136). They bound annexin V, indicating surface exposure of phosphatidylserine, and supported coagulation in vitro. Interestingly, coagulation occurred via tissue factor (TF)-independent pathways, because antibodies against TF or factor (F)VII were ineffective. In contrast, in our in vitro experiments coagulation was partially inhibited by antibodies against FXII (12%, p = 0.006), FXI (36%, p <0.001), FIX (28%, p <0.001) or FVIII (32%, p <0.001). Both the number of annexin V-positive microparticles present in plasma and the thrombin-generating capacity inversely correlated to the plasma concentrations of thrombin-antithrombin complex (r = -0.49, p = 0.072 and r = -0.77, p = 0.001, respectively), but did not correlate to prothrombin fragment F1+2 (r = -0.002, p = 0.99). The inverse correlations between the number of microparticles and their thrombin-forming capacity and the levels of thrombin-antithrombin complex in plasma may indicate that microparticles present in the circulation of healthy individuals have an anticoagulant function by promoting the generation of low amounts of thrombin that activate protein C. We conclude that microparticles in blood from healthy individuals support thrombin generation via TF- and FVII-independent pathways, and which may have an anticoagulant function.

  1. Thrombin-activable factor X re-establishes an intrinsic amplification in tenase-deficient plasmas.

    PubMed

    Louvain-Quintard, Virginie B; Bianchini, Elsa P; Calmel-Tareau, Claire; Tagzirt, Madjid; Le Bonniec, Bernard F

    2005-12-16

    Classical hemophilia results from a defect of the intrinsic tenase complex, the main factor X (FX) activator. Binding of factor VIIa to tissue factor triggers coagulation, but little amplification of thrombin production occurs. Handling of hemophilia by injection of the deficient or missing (thus foreign) factor often causes immunological complications. Several strategies have been designed to bypass intrinsic tenase complex, but none induce true auto-amplification of thrombin production. In an attempt to re-establish a cyclic amplification of prothrombin activation in the absence of tenase, we prepared a chimera of FX having fibrinopeptide A for the activation domain (FX(FpA)). We reasoned that cascade initiation would produce traces of thrombin that would activate FX(FpA) (contrary to its normal homologue). Given that the activation domain of FX is released upon activation, thrombin cleavage would produce authentic FXa that would produce more thrombin, which in turn would activate more chimeras. FX(FpA) was indeed activable by thrombin, albeit at a relatively low rate (5 x 10(3) M(-1) s(-1)). Nevertheless, FX(FpA) allowed in vitro amplification of thrombin production, and 100 nM efficiently corrected thrombin generation in tenase-deficient plasmas. A decisive advantage of FX(FpA) could be that the artificial cascade is self-regulating: FX(FpA) had little influence on the clotting time of normal plasma, yet corrected that of tenase deficiency. Another advantage could be the half-life of FX(FpA) in blood; FX has a half-life of about 30 h (less than 3 h for FVIIa). It is also reasonable to expect little or no immunogenicity, because FX and fibrinopeptide A both circulate normally in the blood of hemophiliacs.

  2. Inhibitory effect of apixaban compared with rivaroxaban and dabigatran on thrombin generation assay.

    PubMed

    Wong, Pancras C; White, Andrew; Luettgen, Joseph

    2013-02-01

    The effect of the oral direct activated factor X (factor Xa) inhibitor apixaban on tissue factor-induced thrombin generation in human plasma was investigated in vitro using the calibrated automated thrombogram (CAT) method and compared with the oral direct factor Xa inhibitor rivaroxaban and the direct thrombin inhibitor dabigatran. Pooled citrated, anticoagulated, platelet-poor human plasma was spiked with apixaban, rivaroxaban, or dabigatran at concentrations of 0.01 to 10 μM. The inhibitory potencies of the compounds were quantified by 5 CAT parameters: the control thrombin lag time (LT) and time to thrombin peak (TTP) for the doubling of inhibitor concentration (IC2x); and the control endogenous thrombin potential (ETP), thrombin peak, and maximum rate of thrombin generation (Vmax) for the inhibitor concentration, which inhibited 50% (IC50). The inhibitors modified CAT concentration dependently. Their inhibitory potencies, expressed as IC2x LT, IC2x TTP, IC50 ETP, IC50 peak thrombin, and IC50 Vmax, were as follows: 0.10 ± 0.01, 0.19 ± 0.02, 0.65 ± 0.11, 0.089 ± 0.019, and 0.049 ± 0.007 μM for apixaban; 0.049 ± 0.007, 0.070 ± 0.009, 0.43 ± 0.07, 0.048 ± 0.008, and 0.022 ± 0.005 μM for rivaroxaban; and 0.063 ± 0.019, 0.18 ± 0.06, 0.50 ± 0.08, 0.55 ± 0.06, and 0.57 ± 0.27 μM for dabigatran. In summary, apixaban, rivaroxaban, and dabigatran have similar potencies in the prolongation of LT and TTP. The CAT parameters that are related to the rate of thrombin generation during the propagation phase (ie, peak thrombin and Vmax) are more sensitive to activities of apixaban and rivaroxaban than dabigatran. The ETP is the least sensitive parameter for measuring the activities of these inhibitors. Recombinant activated factor VII at 5 and 50 μg/mL reversed the anticoagulant effects of apixaban more at 0.2 μM than at 2 μM. Our study suggests that the CAT method is a sensitive assay to monitor the pharmacodynamic and pharmacokinetic properties of

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

    PubMed

    Chatterjee, Manash S; Denney, William S; Jing, Huiyan; Diamond, Scott L

    2010-09-30

    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 in the

  4. Inhibition of the generation of thrombin and factor Xa by a fucoidan from the brown seaweed Ecklonia kurome.

    PubMed

    Nishino, T; Fukuda, A; Nagumo, T; Fujihara, M; Kaji, E

    1999-10-01

    The effects of a fucoidan (C-II), which was purified from the brown seaweed Ecklonia kurome, on the generation of thrombin and factor Xa have been investigated by measuring the amidolytic activities by using the respective specific chromogenic substrates in both plasma and purified systems. C-II inhibited significantly the generation of thrombin in both the intrinsic and the extrinsic pathways, although the intrinsic inhibitory effect by C-II was more remarkable than the extrinsic one. On the other hand, C-II was a good inhibitor of the factor Xa generation in the intrinsic pathway, while it was a poor one in the extrinsic pathway. In the purified systems C-II also inhibited the formation of prothrombin-activating complex (i.e., prothrombinase), but not its activity. The concentration of C-II required for 50% inhibition of thrombin generation was about one-tenth to one-seventh of that of the activity of the generated thrombin in plasma. These results indicate that C-II has an inhibitory effect on the generation of thrombin by blocking the formation of prothrombinase and by preventing the generation of intrinsic factor Xa in addition to its antithrombin activity, and also that the generation-inhibitory effect is more remarkable than C-II's enhancement effect on the antithrombin activity by heparin cofactor II in plasma.

  5. Thrombin generation by exposure of blood to endotoxin: a simple model to study disseminated intravascular coagulation.

    PubMed

    Stief, T W

    2006-04-01

    Pathologic disseminated intravascular coagulation (PDIC) is a serious complication in sepsis. In an in-vitro system consisting of incubation of fresh citrated blood with lipopolysaccharides (LPS) or glucans and subsequent plasma recalcification plasmatic thrombin was quantified. Five hundred microliters of freshly drawn citrated blood of healthy donors were incubated with up to 800 ng/mL LPS (Escherichia coli) or up to 80 microg/mL Zymosan A (ZyA; Candida albicans) for 30 minutes at room temperature (RT). The samples were centrifuged, and 30 microL plasma were recalcified with 1 volume or less of CaCl(2) (25 micromoles Ca(2+)/mL plasma). After 0 to 12 minutes (37 degrees C), 20 microL 2.5 M arginine, pH 8.6, were added. Thirty microliters 0.9 mM HD-CHG-Ala-Arg-pNA in 2.3 M arginine were added, and the absorbance increase at 405 nm was determined. Fifty microliters plasma were also incubated with 5 microL 250 mM CaCl2 for 5, 10, or 15 minutes (37 degrees C). Fifty microliters 2.5 M arginine stops coagulation, and 50 microL 0.77 mM HD-CHG-Ala-Arg-pNA in 2.3 M arginine starts the thrombin detection. The standard was 1 IU/mL thrombin in 7% human albumin instead of plasma. Arginine was also added in the endotoxin exposure time (EET) or in the plasma coagulation reaction time (CRT). Tissue factor (TF)-antigen and soluble CD14 were determined. LPS at blood concentrations greater than 10 ng/mL or ZyA at greater than 1 microg/mL severalfold enhance thrombin generation, when the respective plasmas are recalcified. After 30 minutes EET at RT, the thrombin activity at 12 minutes CRT generated by the addition of 200 ng/mL LPS or 20 microg/mL ZyA is approximately 200 mIU/mL compared to approximately 20 mIU/mL without addition of endotoxin, or compared to about 7 mIU/mL thrombin at 0 minutes CRT. Arginine added to blood or to plasma inhibits thrombin generation; the inhibitory concentration 50% (IC 50) is approximately 15 mM plasma concentration. Endotoxin incubation of blood

  6. Monitoring thrombin generation and screening anticoagulants through pulse laser-induced fragmentation of biofunctional nanogold on cellulose membranes.

    PubMed

    Li, Yu-Jia; Chiu, Wei-Jane; Unnikrishnan, Binesh; Huang, Chih-Ching

    2014-09-10

    Thrombin generation (TG) has an important part in the blood coagulation system, and monitoring TG is useful for diagnosing various health issues related to hypo-coagulability and hyper-coagulability. In this study, we constructed probes by using mixed cellulose ester membranes (MCEMs) modified with gold nanoparticles (Au NPs) for monitoring thrombin activity using laser desorption/ionization mass spectrometry (LDI-MS). The LDI process produced Au cationic clusters ([Au(n)](+); n = 1-3) that we detected through MS. When thrombin reacted with fibrinogen on the Au NPs-MCEMs, insoluble fibrin was formed, hindering the formation of Au cationic clusters and, thereby, decreasing the intensity of their signals in the mass spectrum. Accordingly, we incorporated fibrinogen onto the Au NPs-MCEMs to form Fib-Au NPs-MCEM probes to monitor TG with good selectivity (>1000-fold toward thrombin with respect to other proteins or enzymes) and sensitivity (limit of detection for thrombin of ca. 2.5 pM in human plasma samples). Our probe exhibited remarkable performance in monitoring the inhibition of thrombin activity by direct thrombin inhibitors. Analyses of real samples using our new membrane-based probe suggested that it will be highly useful in practical applications for the effective management of hemostatic complications.

  7. Thrombography reveals thrombin generation potential continues to deteriorate following cardiopulmonary bypass surgery despite adequate hemostasis.

    PubMed

    Wong, Raymond K; Sleep, Joseph R; Visner, Allison J; Raasch, David J; Lanza, Louis A; DeValeria, Patrick A; Torloni, Antonio S; Arabia, Francisco A

    2011-03-01

    The intrinsic and extrinsic activation pathways of the hemostatic system converge when prothrombin is converted to thrombin. The ability to generate an adequate thrombin burst is the most central aspect of the coagulation cascade. The thrombin-generating potential in patients following cardiopulmonary bypass (CPB) may be indicative of their hemostatic status. In this report, thrombography, a unique technique for directly measuring the potential of patients' blood samples to generate adequate thrombin bursts, is used to characterize the coagulopathic profile in post-CPB patients. Post-CPB hemostasis is typically achieved with protamine reversal of heparin anticoagulation and occasionally supplemented with blood product component transfusions. In this pilot study, platelet poor plasma samples were derived from 11 primary cardiac surgery patients at five time points: prior to CPB, immediately post-protamine, upon arrival to the intensive care unit (ICU), 3 hours post-ICU admission, and 24 hours after ICU arrival. Thrombography revealed that the Endogenous Thrombin Potential (ETP) was not different between [Baseline] and [PostProtamine] but proceeded to deteriorate in the immediate postoperative period. At the [3HourPostICU] time point, the ETP was significantly lower than the [Baseline] values, 1233 +/- 591 versus 595 +/- 379 nM.min (mean +/- SD; n=9, p < .005), despite continued adequacy of hemostasis. ETPs returned to baseline values the day after surgery. Transfusions received, conventional blood coagulation testing results, and blood loss volumes are also presented. Despite adequate hemostasis, thrombography reveals an underlying coagulopathic process that could put some cardiac surgical patients at risk for postoperative bleeding. Thrombography is a novel technique that could be developed into a useful tool for perfusionists and physicians to identify coagulopathies and optimize blood management following CPB. PMID:21449230

  8. PLASMA GENERATOR

    DOEpatents

    Foster, J.S. Jr.

    1958-03-11

    This patent describes apparatus for producing an electricity neutral ionized gas discharge, termed a plasma, substantially free from contamination with neutral gas particles. The plasma generator of the present invention comprises a plasma chamber wherein gas introduced into the chamber is ionized by a radiofrequency source. A magnetic field is used to focus the plasma in line with an exit. This magnetic field cooperates with a differential pressure created across the exit to draw a uniform and uncontaminated plasma from the plasma chamber.

  9. Factor XIa and Thrombin Generation Are Elevated in Patients with Acute Coronary Syndrome and Predict Recurrent Cardiovascular Events

    PubMed Central

    Loeffen, Rinske; van Oerle, René; Leers, Mathie P. G.; Kragten, Johannes A.; Crijns, Harry; Spronk, Henri M. H.; ten Cate, Hugo

    2016-01-01

    Objective In acute coronary syndrome (ACS) cardiac cell damage is preceded by thrombosis. Therefore, plasma coagulation markers may have additional diagnostic relevance in ACS. By using novel coagulation assays this study aims to gain more insight into the relationship between the coagulation system and ACS. Methods We measured plasma thrombin generation, factor XIa and D-dimer levels in plasma from ACS (n = 104) and non-ACS patients (n = 42). Follow-up measurements (n = 73) were performed at 1 and 6 months. Associations between coagulation markers and recurrent cardiovascular events were calculated by logistic regression analysis. Results Thrombin generation was significantly enhanced in ACS compared to non-ACS patients: peak height 148±53 vs. 122±42 nM. There was a significantly diminished ETP reduction (32 vs. 41%) and increased intrinsic coagulation activation (25 vs. 7%) in ACS compared to non-ACS patients. Furthermore, compared to non-ACS patients factor XIa and D-dimer levels were significantly elevated in ACS patients: 1.9±1.1 vs. 1.4±0.7 pM and 495(310–885) vs. 380(235–540) μg/L. Within the ACS spectrum, ST-elevated myocardial infarction patients had the highest prothrombotic profile. During the acute event, thrombin generation was significantly increased compared to 1 and 6 months afterwards: peak height 145±52 vs. 100±44 vs. 98±33 nM. Both peak height and factor XIa levels on admission predicted recurrent cardiovascular events (OR: 4.9 [95%CI 1.2–20.9] and 4.5 [1.1–18.9]). Conclusion ACS patients had an enhanced prothrombotic profile, demonstrated by an increased thrombin generation potential, factor XIa and D-dimer levels. This study is the first to demonstrate the positive association between factor XIa, thrombin generation and recurrent cardiovascular events. PMID:27419389

  10. Poor prognosis of hypocoagulability assessed by thrombin generation assay in disseminated intravascular coagulation.

    PubMed

    Lee, Kyunghoon; Kim, Ji-Eun; Kwon, Jihyun; Kim, Inho; Yoon, Sung-Soo; Park, Seonyang; Han, Kyou-Sup; Kim, Hyun Kyung

    2014-04-01

    Overall assessment of the hemostatic system including procoagulant and anticoagulant changes may help assess the clinical status and prognosis of disseminated intravascular coagulation (DIC). The thrombin generation assay provides useful information about the global hemostatic status. Therefore, we measured several parameters of global hemostatic potential by the thrombin generation assay in patients suspected of having DIC. A total of 114 patients with suspected DIC were included. The thrombin generation assay was performed on the calibrated automated thrombogram using tissue factor with or without the addition of thrombomodulin, showing three parameters: lag time, endogenous thrombin potential (ETP), and peak thrombin. Both 1 and 5 pmol/l tissue factor-stimulated ETP and peak thrombin were well correlated with DIC severity. Interestingly, antithrombin level greatly affected ETP, whereas protein C influenced lag time. Prognostic analysis revealed that the area under the curve of peak thrombin stimulated by 1 pmol/l tissue factor was superior to that of D-dimer. Moreover, multivariate Cox analysis showed that the lag time and time to peak with both 1 and 5 pmol/l tissue factor were independent prognostic markers. ETP and peak thrombin well reflect DIC severity. Hypocoagulability manifesting as prolonged lag time and time to peak is expected to be an independent prognostic marker in DIC.

  11. Reduced peak, but no diurnal variation, in thrombin generation upon melatonin supplementation in tetraplegia. A randomised, placebo-controlled study.

    PubMed

    Iversen, Per Ole; Dahm, Anders; Skretting, Grethe; Mowinckel, Marie-Christine; Stranda, Annicke; Østerud, Bjarne; Sandset, Per Morten; Kostovski, Emil

    2015-11-01

    Tetraplegic patients have increased risk of venous thrombosis despite anti-thrombotic prophylaxis. Moreover, they have blunted plasma variations in melatonin and altered diurnal variation of several haemostatic markers, compared with able-bodied. However, whether healthy individuals and tetraplegic patients, with or without melatonin, display abnormalities in thrombin generation during a 24-hour (h) cycle, is unknown. We therefore used the Calibrated Automated Thrombogram (CAT) assay to examine diurnal variations and the possible role of melatonin in thrombin generation. Six men with long-standing complete tetraplegia were included in a randomised placebo-controlled cross-over study with melatonin supplementation (2 mg, 4 consecutive nights), whereas six healthy, able-bodied men served as controls. Ten plasma samples were collected frequently during a 24-h awake/sleep cycle. No significant diurnal variation of any of the measured CAT indices was detected in the three study groups. Whereas endogenous thrombin potential (ETP) was independent (p > 0.05) of whether the tetraplegic men received melatonin or placebo, melatonin decreased (p = 0.005) peak values in tetraplegia compared with those given placebo. Able-bodied men had lower (p = 0.019) ETP and Lag-Time (p = 0.018) compared with tetraplegics receiving placebo. Neither the Time-to-Peak nor the Start-Tail was affected (p > 0.05) by melatonin in tetraplegia. In conclusion, indices of thrombin generation are not subjected to diurnal variation in healthy able-bodied or tetraplegia, but peak thrombin generation is reduced in tetraplegic men receiving oral melatonin. PMID:26202881

  12. Retrospective evaluation of bleeding tendency and simultaneous thrombin and plasmin generation in patients with rare bleeding disorders.

    PubMed

    Van Geffen, M; Menegatti, M; Loof, A; Lap, P; Karimi, M; Laros-van Gorkom, B A P; Brons, P; Van Heerde, W L

    2012-07-01

    Rare bleeding disorders (RBDs) are a heterogeneous group of diseases with varying bleeding tendency, only partially explained by their laboratory phenotype. We analysed the separate groups of RBD abnormalities, and we investigated retrospectively whether the novel haemostasis assay (NHA) was able to differentiate between bleeding tendency. We have performed simultaneous thrombin generation (TG) and plasmin generation (PG) measurements in 41 patients affected with deficiencies in prothrombin, factor (F) V, FVII, FX, FXIII and fibrinogen. Parameters of the NHA were classified based on (major or minor) bleeding tendency. Patients with deficiencies in coagulation propagation (FII, FV and FX) and major type of bleedings had diminished TG (expressed as AUC) below 20% of control. FVII deficient patients only had prolonged thrombin lag-time ratio of 1.6 ± 0.2 (P < 0.05) and normal AUC (92-125%). Afibrinogenemic patients demonstrated PG of 2-29% of normal and appeared to correlate with the type of mutation. Thrombin peak-height (57 ± 16%) was reduced (not significant) in these patients and AUC was comparable to the reference (102 ± 27%). FXIII-deficient plasmas resulted in a reduced thrombin peak-height of 59 ± 13% (P < 0.05) and normal AUC (90 ± 14%). Thrombin peak-height (P < 0.01) and plasmin potential (P < 0.05) were lower in the major bleeders compared with the minor bleeders. These results provided distinct TG and PG curves for each individual abnormality and differentiation of bleeding tendency was observed for thrombin and PG parameters. Prospective studies are warranted to confirm these retrospective results.

  13. Thrombin-mediated activation of endogenous factor XI in plasma in the presence of physiological glycosaminoglycans occurs only with high concentrations of thrombin.

    PubMed

    Wuillemin, W A; Mertens, K; ten Cate, H; Hack, C E

    1996-02-01

    The variable bleeding tendency associated with a genetic deficiency of factor XI (FXI) and the lack of bleeding disorders in individuals with a genetic deficiency of factor XII (FXII) suggest an alternative mechanism for FXI activation in vivo. Recently, thrombin has been shown to activate FXI. However, in plasma this activation has been shown to occur only with exogenous FXI and a non-physiological cofactor (sulphatides), and the occurrence of this reaction in a plasma environment has been questioned. Using recently developed sensitive assays for FXIa-inhibitor complexes we found thrombin-mediated and FXII-dependent activation of endogenous FXI in plasma in the presence of heparan sulphate, heparin, dermatan sulphate or dextran sulphate. Using heparan sulphate, which is present in the human vascular system, activation of about 1-2% of plasma FXI was observed, however, only after addition of very high amounts (500 nmol/l) of human alpha-thrombin to FXII-deficient plasma (at a 1 to 4 final dilution). We conclude that endogenous FXI in plasma can be activated by thrombin in the presence of various glycosaminoglycans, including the physiological compounds heparan sulphate and dermatan sulphate, but only at very high concentrations of thrombin, corresponding to 100% prothrombin activation in undiluted plasma.

  14. Active but inoperable thrombin is accumulated in a plasma protein layer surrounding Streptococcus pyogenes.

    PubMed

    Naudin, Clément; Hurley, Sinead M; Malmström, Erik; Plug, Tom; Shannon, Oonagh; Meijers, Joost C M; Mörgelin, Matthias; Björck, Lars; Herwald, Heiko

    2015-10-01

    Activation of thrombin is a critical determinant in many physiological and pathological processes including haemostasis and inflammation. Under physiological conditions many of these functions are involved in wound healing or eradication of an invading pathogen. However, when activated systemically, thrombin can contribute to severe and life-threatening conditions by causing complications such as multiple multi-organ failure and disseminated intravascular coagulation. In the present study we investigated how the activity of thrombin is modulated when it is bound to the surface of Streptococcus pyogenes. Our data show that S. pyogenes bacteria become covered with a proteinaceous layer when incubated with human plasma, and that thrombin is a constituent of this layer. Though the coagulation factor is found attached to the bacteria with a functional active site, thrombin has lost its capacity to interact with its natural substrates and inhibitors. Thus, the interaction of bacteria with human plasma renders thrombin completely inoperable at the streptococcal surface. This could represent a host defense mechanism to avoid systemic activation of coagulation which could be otherwise induced when bacteria enter the circulation and cause systemic infection.

  15. PLASMA GENERATOR

    DOEpatents

    Wilcox, J.M.; Baker, W.R.

    1963-09-17

    This invention is a magnetohydrodynamic device for generating a highly ionized ion-electron plasma at a region remote from electrodes and structural members, thus avoiding contamination of the plasma. The apparatus utilizes a closed, gas-filled, cylindrical housing in which an axially directed magnetic field is provided. At one end of the housing, a short cylindrical electrode is disposed coaxially around a short axial inner electrode. A radial electrical discharge is caused to occur between the inner and outer electrodes, creating a rotating hydromagnetic ionization wave that propagates aiong the magnetic field lines toward the opposite end of the housing. A shorting switch connected between the electrodes prevents the wave from striking the opposite end of the housing. (AEC)

  16. Plasma centrifugation does not influence thrombin-antithrombin and plasmin-antiplasmin levels but determines platelet microparticles count

    PubMed Central

    Gruszczyński, Krzysztof; Kapusta, Przemysław; Kowalik, Artur; Wybrańska, Iwona

    2015-01-01

    Introduction Centrifugation is an essential step for plasma preparation to remove residual elements in plasma, especially platelets and platelet-derived microparticles (PMPs). Our working hypothesis was that centrifugation as a preanalytical step may influence some coagulation parameters. Materials and methods Healthy young men were recruited (N = 17). For centrifugation, two protocols were applied: (A) the first centrifugation at 2500 x g for 15 min and (B) at 2500 x g for 20 min at room temperature with a light brake. In protocol (A), the second centrifugation was carried out at 2500 x g for 15 min, whereas in protocol (B), the second centrifugation involved a 10 min spin at 13,000 x g. Thrombin-antithrombin (TAT) and plasmin-antiplasmin (PAP) complexes concentrations were determined by enzyme-linked immunosorbent assays. PMPs were stained with CD41 antibody and annexin V, and analyzed by flow cytometry method. Procoagulant activity was assayed by the Calibrated Automated Thrombogram method as a slope of thrombin formation (CAT velocity). Results Median TAT and PAP concentrations did not differ between the centrifugation protocols. The high speed centrifugation reduced the median (IQR) PMP count in plasma from 1291 (841-1975) to 573 (391-1010) PMP/µL (P = 0.001), and CAT velocity from 2.01 (1.31-2.88) to 0.97 (0.82-1.73) nM/min (P = 0.049). Spearman’s rank correlation analysis showed correlation between TAT and PMPs in the protocol A plasma which was (rho = 0.52, P < 0.050) and between PMPs and CAT for protocol A (rho = 0.74, P < 0.050) and protocol B (rho = 0.78, P < 0.050). Conclusion Centrifugation protocols do not influence the markers of plasminogen (PAP) and thrombin (TAT) generation but they do affect the PMP count and procoagulant activity. PMID:26110034

  17. Thrombin generation using the calibrated automated thrombinoscope to assess reversibility of dabigatran and rivaroxaban.

    PubMed

    Herrmann, Richard; Thom, James; Wood, Alicia; Phillips, Michael; Muhammad, Shoaib; Baker, Ross

    2014-05-01

    The new direct-acting anticoagulants such as dabigatran and rivaroxaban are usually not monitored but may be associated with haemorrhage, particularly where renal impairment occurs. They have no effective "antidotes". We studied 17 patients receiving dabigatran 150 mg twice daily for non-valvular atrial fibrillation and 15 patients receiving rivaroxaban 10 mg daily for the prevention of deep venous thrombosis after hip or knee replacement surgery. We assessed the effect of these drugs on commonly used laboratory tests and Calibrated Automated Thrombogram (CAT) using plasma samples. We also assessed effects in fresh whole blood citrated patient samples using thromboelastography on the TEG and the ROTEM. The efficacy of nonspecific haemostatic agents prothrombin complex concentrate (PCC), Factor VIII Inhibitor By-passing Activity (FEIBA) and recombinant activated factor VII (rVIIa) were tested by reversal of abnormal thrombin generation using the CAT. Concentrations added ex vivo were chosen to reflect doses normally given in vivo. Dabigatran significantly increased the dynamic parameters of the TEG and ROTEM and the lag time of the CAT. It significantly reduced the endogenous thrombin potential (ETP) and reduced the peak height of the CAT. Rivaroxaban did not affect the TEG and ROTEM parameters but did increase the lag time and reduce ETP and peak height of the CAT. For both drugs, these parameters were significantly and meaningfully corrected by PCC and FEIBA and to a lesser but still significant extent by rFVIIa. These results may be useful in devising a reversal strategy in patients but clinical experience will be needed to verify them.

  18. Using the HEMOCLOT direct thrombin inhibitor assay to determine plasma concentrations of dabigatran.

    PubMed

    Stangier, Joachim; Feuring, Martin

    2012-03-01

    The objective of the present study was to assess the suitability of an accurate, sensitive, standardized, chronometric blood coagulation test to determine the anticoagulation activity of dabigatran and to quantify concentrations of dabigatran in plasma. Dabigatran was spiked at increasing concentrations in pooled citrated normal human plasma to measure diluted thrombin time with the HEMOCLOT THROMBIN INHIBITOR assay. Calibration curve linearity, inter-assay and intra-assay precision, and assay accuracy were investigated. Dabigatran stability in plasma and the feasibility of lyophilized dabigatran standards for assay calibration were assessed. Data are presented as back-calculated plasma concentrations of dabigatran using regression analysis. Dabigatran's calibration curve for thrombin clotting time was linear over the concentration range 0-4000  nmol/l (0-1886  ng/ml). The R was 0.99. Total assay imprecision for dabigatran was 4.7-12.0% coefficient of variation, with 1.2-3.1% for intra-run imprecision, 4.0-10.0% for inter-run precision and 0.3-8.3% for between-day imprecision. Assay accuracy was determined at three dabigatran concentrations; deviation from sample target concentrations ranged from -20.7% (100  nmol/l; 47.15  ng/ml) to 5.6% (1500  nmol/l; 707.3  ng/ml). Assay robustness was determined by analysing identical dabigatran samples in two independent laboratories. The mean bias of dabigatran coagulation times between laboratories was 6.6%. The HEMOCLOT Thrombin Inhibitors assay is suitable for determining the anticoagulant activity and calculating plasma concentrations of dabigatran using simple and widely available chronometric coagulation devices. The use of this rapid, established, standardized and calibrated assay should provide accurate and consistent results when assessing the anticoagulant activity of dabigatran. PMID:22227958

  19. Thrombin detection in murine plasma using engineered fluorescence resonance energy transfer aptadimers

    NASA Astrophysics Data System (ADS)

    Trapaidze, Ana; Brut, Marie; Mazères, Serge; Estève, Daniel; Gué, Anne-Marie; Bancaud, Aurélien

    2015-12-01

    Biodetection strategies, in which two sides of one target protein are targeted simultaneously, have been shown to increase specificity, selectivity, and affinity, and it has been suggested that they constitute excellent candidates for protein sensing in complex media. In this study we propose a method to engineer the sequence of a DNA construct dedicated to reversible thrombin detection. This construct, called Fluorescence Resonance Energy Transfer (FRET) aptadimer, is assembled with two aptamers, which target different epitopes of thrombin, interconnected with a DNA linker that contains a FRET couple and a reversible double helix stem. In the absence of target, the stem is stable maintaining a FRET couple in close proximity, and fluorescence is unquenched upon thrombin addition due to the dehybridization of the stem. We define design rules for the conception of FRET aptadimers, and develop a software to optimize their functionality. One engineered FRET aptadimer sequence is subsequently characterized experimentally by temperature scanning fluorimetry, demonstrating the relevance of our technology for thrombin sensing in bulk and diluted murine plasma.

  20. The effect of fibrin(ogen) on thrombin generation and decay.

    PubMed

    Kremers, R M W; Wagenvoord, R J; Hemker, H C

    2014-09-01

    Defibrination causes a ~30% decrease of thrombin generation (TG) which can be restored by adding native fibrinogen in its original concentration (3 mg/ml). The fibrinogen variant γA/γ', which binds thrombin with high affinity, is over four times more efficient in this respect than the more common γA/γA form. By using high tissue factor concentrations we accelerated prothrombin conversion so as to obtain a descending part of the TG curve that was governed by thrombin decay only. From that part we calculated the antithrombin (AT)- and α2-macroglobulin-dependent decay constants at a series of concentrations of native, γA/γA and γA/γ' fibrinogen. We found that the increase of TG in the presence of fibrinogen is primarily due to a dose-dependent decrease of thrombin inactivation by α2-macroglobulin, where the γA/γ' form is much more active than the γA/γA form. AT-dependent decay is somewhat decreased by γA/γ' fibrinogen but hardly by the γA/γA form. We assume that binding of thrombin to fibrin(ogen) interferes with its binding to inhibitors. Attenuation of decay only in part explains the stimulating effect of fibrinogen on TG, as fibrinogen stimulates prothrombin conversion, regardless of the fibrinogen variant.

  1. Ex vivo reversal of effects of rivaroxaban evaluated using thromboelastometry and thrombin generation assay

    PubMed Central

    Schenk, B.; Würtinger, P.; Streif, W.; Sturm, W.; Fries, D.; Bachler, M.

    2016-01-01

    Background In major bleeding events, the new direct oral anticoagulants pose a great challenge for physicians. The aim of the study was to test for ex vivo reversal of the direct oral anticoagulant rivaroxaban with various non-specific reversal agents: prothrombin complex concentrate (PCC), activated prothrombin complex concentrate (aPCC), recombinant activated factor VII (rFVIIa), and fibrinogen concentrate (FI). Methods Blood was obtained from healthy volunteers and from patients treated with rivaroxaban. Blood samples from healthy volunteers were spiked with rivaroxaban to test the correlation between rivaroxaban concentration and coagulation tests. Patient blood samples were spiked with various concentrations of the above-mentioned agents and analysed using thromboelastometry and thrombin generation. Results When added in vitro, rivaroxaban was significantly (P<0.05) correlated with ROTEM® thromboelastometry EXTEM (extrinsic coagulation pathway) clotting time (CT), time to maximal velocity (MaxV−t), and with all measured thrombin generation parameters. In vivo, CT, MaxV−t, lag time, and peak thrombin generation (Cmax) were significantly correlated with rivaroxaban concentrations. Regarding reversal of rivaroxaban, all tested agents significantly (P<0.05) reduced EXTEM CT, but to different extents: rFVIIa by 68%, aPCC by 47%, PCC by 17%, and FI by 9%. Only rFVIIa reversed EXTEM CT to baseline values. Both PCC (+102%) and aPCC (+232%) altered overall thrombin generation (area under the curve) and increased Cmax (+461% for PCC, +87.5% for aPCC). Conclusions Thromboelastometry and thrombin generation assays do not favour the same reversal agents for rivaroxaban anticoagulation. Controlled clinical trials are urgently needed to establish doses and clinical efficacy of potential reversal agents. Clinical trial registration EudracCT trial no. 213-00474-30. PMID:27623677

  2. Comparison of thrombin generation assay with conventional coagulation tests in evaluation of bleeding risk in patients with rare bleeding disorders.

    PubMed

    Zekavat, Omid R; Haghpanah, Sezaneh; Dehghani, Javad; Afrasiabi, Abdolreza; Peyvandi, Flora; Karimi, Mehran

    2014-09-01

    Based on the premise that the capacity of plasma to generate thrombin in vitro is a comprehensive and precise functional test of the clotting system, we designed a cross-sectional, single-center study involving 83 patients with rare bleeding disorders (RBDs) to compare the usefulness of the thrombin generation (TG) assay versus conventional tests including prothrombin time (PT) and activated partial thromboplastin time (aPTT) in predicting bleeding risk in patients with RBD in southern Iran. The TG parameters consisted of endogenous thrombin potential, lag time, peak, time to peak (ttPeak), and start tail. The area under the receiver-operating characteristic (ROC) curve showed statistically significant associations between bleeding risk and lag time, ttPeak, and start tail. We determined cutoff values for these 3 TG parameters and obtained a negative predictive value of 86% to 90% in patients with RBD who had a bleeding score (BS) ≤13. The ROC curves for the association of PT and aPTT with BS did not indicate any significant association. Correlation analysis supported the results of ROC curve analysis, only lag time, ttPeak, and start tail showed significant positive correlations with BS (P < .05). Disease severity based on plasma factor activity was significantly associated with prolonged lag time and ttPeak and with prolonged PT (P <.05). We suggest that TG assay is a potentially more useful tool for predicting the bleeding risk in patients with RBD. However, the small sample size in different RBD subgroups precluded subgroup analysis. Prospective multicenter studies with larger numbers of patients are therefore advisable.

  3. Effects of normoxic and hypoxic exercise regimens on monocyte-mediated thrombin generation in sedentary men.

    PubMed

    Wang, Jong-Shyan; Chang, Ya-Lun; Chen, Yi-Ching; Tsai, Hsing-Hua; Fu, Tieh-Cheng

    2015-08-01

    Exercise and hypoxia paradoxically modulate vascular thrombotic risks. The shedding of procoagulant-rich microparticles from monocytes may accelerate the pathogenesis of atherothrombosis. The present study explores the manner in which normoxic and hypoxic exercise regimens affect procoagulant monocyte-derived microparticle (MDMP) formation and monocyte-promoted thrombin generation (TG). Forty sedentary healthy males were randomized to perform either normoxic (NET; 21% O2, n=20) or hypoxic (HET; 15% O2, n=20) exercise training (60% VO(2max)) for 30 min/day, 5 days/week for 5 weeks. At rest and immediately after HET (100 W under 12% O2 for 30 min), the MDMP characteristics and dynamic TG were measured by flow cytometry and thrombinography respectively. The results demonstrated that acute 12% O2 exercise (i) increased the release of coagulant factor V (FV)/FVIII-rich, phosphatidylserine (PS)-exposed and tissue factor (TF)-expressed microparticles from monocytes, (ii) enhanced the peak height and rate of TG in monocyte-rich plasma (MRP) and (iii) elevated concentrations of norepinephrine/epinephrine, myeloperoxidase (MPO) and interleukin-6 (IL-6) in plasma. Following the 5-week intervention, HET exhibited higher enhancements of peak work-rate and cardiopulmonary fitness than NET did. Moreover, both NET and HET decreased the FV/FVIII-rich, PS-exposed and TF-expressed MDMP counts and the peak height and rate of TG in MRP following the HET. However, HET elicited more suppression for the HE (hypoxic exercise)-enhanced procoagulant MDMP formation and dynamic TG in MPR and catecholamine/peroxide/pro-inflammatory cytokine levels in plasma than NET. Hence, we conclude that HET is superior to NET for enhancing aerobic capacity. Furthermore, HET effectively suppresses procoagulant MDMP formation and monocyte-mediated TG under severe hypoxic stress, compared with NET.

  4. Association between Stable Coronary Artery Disease and In Vivo Thrombin Generation

    PubMed Central

    Baños-González, Manuel Alfonso; Peña-Duque, Marco Antonio; Martínez-Ríos, Marco Antonio; Quintanar-Trejo, Leslie; Aptilon-Duque, Gad; Flores-García, Mirthala; Cruz-Robles, David; Cardoso-Saldaña, Guillermo

    2016-01-01

    Background. Thrombin has been implicated as a key molecule in atherosclerotic progression. Clinical evidence shows that thrombin generation is enhanced in atherosclerosis, but its role as a risk factor for coronary atherosclerotic burden has not been proven in coronary artery disease (CAD) stable patients. Objectives. To evaluate the association between TAT levels and homocysteine levels and the presence of coronary artery disease diagnosed by coronary angiography in patients with stable CAD. Methods and Results. We included 95 stable patients admitted to the Haemodynamics Department, including 63 patients with significant CAD and 32 patients without. We measured the thrombin-antithrombin complex (TAT) and homocysteine concentrations in all the patients. The CAD patients exhibited higher concentrations of TAT (40.76 μg/L versus 20.81 μg/L, p = 0.002) and homocysteine (11.36 μmol/L versus 8.81 μmol/L, p < 0.01) compared to the patients without significant CAD. Specifically, in patients with CAD+ the level of TAT level was associated with the severity of CAD being 36.17 ± 24.48 μg/L in the patients with bivascular obstruction and 42.77 ± 31.81 μg/L in trivascular coronary obstruction, p = 0.002. Conclusions. The level of in vivo thrombin generation, quantified as TAT complexes, is associated with the presence and severity of CAD assessed by coronary angiography in stable CAD patients.

  5. Association between Stable Coronary Artery Disease and In Vivo Thrombin Generation

    PubMed Central

    Baños-González, Manuel Alfonso; Peña-Duque, Marco Antonio; Martínez-Ríos, Marco Antonio; Quintanar-Trejo, Leslie; Aptilon-Duque, Gad; Flores-García, Mirthala; Cruz-Robles, David; Cardoso-Saldaña, Guillermo

    2016-01-01

    Background. Thrombin has been implicated as a key molecule in atherosclerotic progression. Clinical evidence shows that thrombin generation is enhanced in atherosclerosis, but its role as a risk factor for coronary atherosclerotic burden has not been proven in coronary artery disease (CAD) stable patients. Objectives. To evaluate the association between TAT levels and homocysteine levels and the presence of coronary artery disease diagnosed by coronary angiography in patients with stable CAD. Methods and Results. We included 95 stable patients admitted to the Haemodynamics Department, including 63 patients with significant CAD and 32 patients without. We measured the thrombin-antithrombin complex (TAT) and homocysteine concentrations in all the patients. The CAD patients exhibited higher concentrations of TAT (40.76 μg/L versus 20.81 μg/L, p = 0.002) and homocysteine (11.36 μmol/L versus 8.81 μmol/L, p < 0.01) compared to the patients without significant CAD. Specifically, in patients with CAD+ the level of TAT level was associated with the severity of CAD being 36.17 ± 24.48 μg/L in the patients with bivascular obstruction and 42.77 ± 31.81 μg/L in trivascular coronary obstruction, p = 0.002. Conclusions. The level of in vivo thrombin generation, quantified as TAT complexes, is associated with the presence and severity of CAD assessed by coronary angiography in stable CAD patients. PMID:27597926

  6. Association between Stable Coronary Artery Disease and In Vivo Thrombin Generation.

    PubMed

    Valente-Acosta, Benjamin; Baños-González, Manuel Alfonso; Peña-Duque, Marco Antonio; Martínez-Ríos, Marco Antonio; Quintanar-Trejo, Leslie; Aptilon-Duque, Gad; Flores-García, Mirthala; Cruz-Robles, David; Cardoso-Saldaña, Guillermo; de la Peña-Díaz, Aurora

    2016-01-01

    Background. Thrombin has been implicated as a key molecule in atherosclerotic progression. Clinical evidence shows that thrombin generation is enhanced in atherosclerosis, but its role as a risk factor for coronary atherosclerotic burden has not been proven in coronary artery disease (CAD) stable patients. Objectives. To evaluate the association between TAT levels and homocysteine levels and the presence of coronary artery disease diagnosed by coronary angiography in patients with stable CAD. Methods and Results. We included 95 stable patients admitted to the Haemodynamics Department, including 63 patients with significant CAD and 32 patients without. We measured the thrombin-antithrombin complex (TAT) and homocysteine concentrations in all the patients. The CAD patients exhibited higher concentrations of TAT (40.76 μg/L versus 20.81 μg/L, p = 0.002) and homocysteine (11.36 μmol/L versus 8.81 μmol/L, p < 0.01) compared to the patients without significant CAD. Specifically, in patients with CAD+ the level of TAT level was associated with the severity of CAD being 36.17 ± 24.48 μg/L in the patients with bivascular obstruction and 42.77 ± 31.81 μg/L in trivascular coronary obstruction, p = 0.002. Conclusions. The level of in vivo thrombin generation, quantified as TAT complexes, is associated with the presence and severity of CAD assessed by coronary angiography in stable CAD patients. PMID:27597926

  7. Reduced thrombin generation increases host susceptibility to group A streptococcal infection

    PubMed Central

    Sun, Hongmin; Wang, Xixi; Degen, Jay L.

    2009-01-01

    Bacterial plasminogen activators are commonplace among microbial pathogens, implying a central role of host plasmin in supporting bacterial virulence. Group A streptococci (GAS) secrete streptokinase, a specific activator of human plasminogen (PLG). The critical contribution of the streptokinase-PLG interaction to GAS pathogenicity was recently demonstrated using mice expressing human PLG. To examine the importance of thrombin generation in antimicrobial host defense, we challenged mice with deficiency of factor V (FV) in either the plasma or platelet compartment. Reduction of FV in either pool resulted in markedly increased mortality after GAS infection, with comparison to heterozygous F5-deficient mice suggesting a previously unappreciated role for the platelet FV pool in host defense. Mice with complete deficiency of fibrinogen also demonstrated markedly increased mortality to GAS infection relative to controls. Although FV Leiden may be protective in the setting of severe sepsis in humans, no significant survival advantage was observed in GAS-infected mice carrying the FV Leiden mutation. Taken together, our data support the hypothesis that local thrombosis/fibrin deposition limits the survival and dissemination of at least a subset of microbial pathogens and suggest that common variation in hemostatic factors among humans could affect host susceptibility to a variety of infectious diseases. PMID:19056689

  8. Monitoring Low Molecular Weight Heparins at Therapeutic Levels: Dose-Responses of, and Correlations and Differences between aPTT, Anti-Factor Xa and Thrombin Generation Assays

    PubMed Central

    Thomas, Owain; Lybeck, Emanuel; Strandberg, Karin; Tynngård, Nahreen; Schött, Ulf

    2015-01-01

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

  9. Direct thrombin inhibitor-bivalirudin functionalized plasma polymerized allylamine coating for improved biocompatibility of vascular devices.

    PubMed

    Yang, Zhilu; Tu, Qiufen; Maitz, Manfred F; Zhou, Shuo; Wang, Jin; Huang, Nan

    2012-11-01

    The direct thrombin inhibitor of bivalirudin (BVLD), a short peptide derived from hirudin, has drawn an increasing attention in clinical application because it is safer and more effective than heparin for diabetic patients with moderate- or high-risk for acute coronary syndromes (ACS). In this study, BVLD was covalently conjugated on plasma polymerized allylamine (PPAam) coated 316L stainless steel (SS) to develop an anticoagulant surface. QCM-D real time monitoring result shows that 565±20 ng/cm2 of BVLD was bound to the PPAam surface. Infrared spectroscopy (IR) and X-ray photoelectron spectroscopy (XPS) confirmed the immobilization of BVLD. The conjugation of BVLD onto the PPAam coating led to enhanced binding of thrombin, and the activity of the thrombin adsorbed on its surface was effectively inhibited. As a result, the BVLD immobilized PPAam (BVLD-PPAam) substrate prolonged the clotting times, and exhibited inhibition in adhesion and activation of platelets and fibrinogen. We also found that the BVLD-PPAam coating significantly enhanced endothelial cell adhesion, proliferation, migration and release of nitric oxide (NO) and secretion of prostaglandin I2 (PGI2). In vivo results indicate that the BVLD-PPAam surface restrained thrombus formation by rapidly growing a homogeneous and intact endothelium on its surface. These data suggest the potential of this multifunctional BVLD-PPAam coating for the application not only in general vascular devices such as catheters, tubes, oxygenator, hemodialysis membranes but also vascular grafts and stents.

  10. Inhibition of Hageman factor, plasma thromboplastin antecedent, thrombin and other clotting factors by phenylglyoxal hydrate (38500).

    PubMed

    Radnoff, O D; Saito, H

    1975-01-01

    Exposure of purified Hageman factor (HF, Factor XII) to phenylglyoxal hydrate (PHG), an agent reacting with arginine residues in protein, inhibited its coagulant properties upon subsequent exposure of negatively charged agents. Once HF had been exposed to kaolin or ellagic acid, however, subsequent addition of PHG was much less inhibitory. PHG had no effect upon the ability of HF to bind to negatively charged surfaces. PGH also inhibited preparations of activated PTA (Factor XI) and thrombin, and, when incubated with plasma, reduced the titer of coagulable fibrinogen, PTA Christmas factor (Factor IX), antihemophilic factor (Factor VIII), Factor VII, Stuart factor (Factor X), proaccelerin (Factor V) and prothrombin (Factor II), and to a lesser degres, HF.

  11. Thrombin during cardiopulmonary bypass.

    PubMed

    Edmunds, L Henry; Colman, Robert W

    2006-12-01

    Cardiopulmonary bypass (CPB) ignites a massive defense reaction that stimulates all blood cells and five plasma protein systems to produce a myriad of vasoactive and cytotoxic substances, cell-signaling molecules, and upregulated cellular receptors. Thrombin is the key enzyme in the thrombotic portion of the defense reaction and is only partially suppressed by heparin. During CPB, thrombin is produced by both extrinsic and intrinsic coagulation pathways and activated platelets. The routine use of a cell saver and the eventual introduction of direct thrombin inhibitors now offer the possibility of completely suppressing thrombin production and fibrinolysis during cardiac surgery with CPB. PMID:17126170

  12. Thrombin and human plasma kallikrein inhibition during simulated extracorporeal circulation block platelet and neutrophil activation.

    PubMed

    Wachtfogel, Y T; Kettner, C; Hack, C E; Nuijens, J H; Reilly, T M; Knabb, R M; Kucich, U; Niewiarowski, S; Edmunds, L H; Colman, R W

    1998-10-01

    Cardiopulmonary bypass causes hemorrhagic complications, and initiates a chemical and cellular inflammatory response. Contact of blood with synthetic surfaces leads to qualitative and quantitative alterations in platelets, neutrophils, complement, and contact systems. Despite the fact that cardiopulmonary bypass is carried out in the presence of high doses of heparin, there is significant activation of both platelets and neutrophils. Thrombin is protected on cell and fibrin surfaces from antithrombin, even in the presence of high doses of heparin (approximately 5 U/ml). We therefore studied the effect of a small (Mr = 497), highly effective (Ki = 41 pM), reversible tripeptide inhibitor of thrombin, DUP 714 (1 microM), in a well characterized model of simulated extracorporeal circulation. In the absence of DUP 714, platelet counts decreased by 75% 5 min after the start of extracorporeal bypass and increased to 48% at 120 min of recirculation. DUP 714 significantly preserved platelet counts, decreased plasma levels of platelet beta-thromboglobulin levels, but did not prevent a decrease in sensitivity of platelets to adenosine diphosphate. Kallikrein-C1-inhibitor and C1-C1-inhibitor complexes increased progressively from 0.32 U/ml to 0.67 U/ml and from 4.45 U/ml to 7.25 U/ml, respectively, during 120 min of recirculation without DUP 714. Addition of DUP 714 significantly inhibited kallikrein-C1-inhibitor complex formation but did not affect C1-C1-inhibitor complexes. In the absence of DUP 714, human neutrophil elastase levels rose from a baseline of 0.01 +/- 0.00 microg/ml to 1.18 +/- 0.21 microg/ml during 120 min of recirculation. Human neutrophil elastase release at 120 min was significantly inhibited in the presence of DUP 714 to 37% of the value with heparin alone. These results indicated that addition of this novel thrombin (and kallikrein) inhibitor to heparin preserved platelet counts, decreased platelet secretion, and provided the additional benefit of

  13. Aptamer RA36 inhibits of human, rabbit, and rat plasma coagulation activated with thrombin or snake venom coagulases.

    PubMed

    Savchik, E Yu; Kalinina, T B; Drozd, N N; Makarov, V A; Zav'yalova, E G; Lapsheva, E N; Mudrik, N N; Babij, A V; Pavlova, G V; Golovin, A V; Kopylov, A M

    2013-11-01

    RA36 DNA aptamer is a direct anticoagulant prolonging clotting time of human, rabbit, and rat plasma in the thrombin time test. Anticoagulant activity of RA36 is lower than that of recombinant hirudin. During inhibition of human plasma clotting activated with echitox (coagulase from Echis multisquamatus venom), the aptamer presumably binds to meisothrombin exosite I. The sensitivity of human plasma to the aptamer 5-fold surpasses that of rat plasma. Analysis of RA36 binding to coagulase of Agkistrodon halys venom (ancistron) is required for proving the effect of aptamer on polymerization of human fibrinogen. PMID:24319726

  14. Thrombin-Mediated Platelet Activation of Lysed Whole Blood and Platelet-Rich Plasma: A Comparison Between Platelet Activation Markers and Ultrastructural Alterations.

    PubMed

    Augustine, Tanya N; van der Spuy, Wendy J; Kaberry, Lindsay L; Shayi, Millicent

    2016-06-01

    Platelet ultrastructural alterations representing spurious activation have been identified in pathological conditions. A limitation of platelet studies is that sample preparation may lead to artifactual activation processes which may confound results, impacting the use of scanning electron microscopy as a supplemental diagnostic tool. We used scanning electron microscopy and flow cytometry to analyze platelet activation in platelet-rich plasma (PRP) and whole blood (WB) samples. PRP generated using a single high g force centrifugation, and WB samples treated with a red blood cell lysis buffer, were exposed to increasing concentrations of the agonist thrombin. Platelets in lysed WB samples responded to thrombin by elevating the activation marker CD62p definitively, with corresponding ultrastructural changes indicating activation. Conversely, CD62p expression in PRP preparations remained static. Ultrastructural analysis revealed fully activated platelets even under low concentration thrombin stimulation, with considerable fibrin deposition. It is proposed that the method for PRP production induced premature platelet activation, preventable by using an inhibitor of platelet aggregation and fibrin polymerization. Nevertheless, our results show a definitive correspondence between flow cytometry and scanning electron microscopy in platelet activation studies, highlighting the potential of the latter technique as a supplemental diagnostic tool. PMID:27329313

  15. Solid expellant plasma generator

    NASA Technical Reports Server (NTRS)

    Stone, Nobie H. (Inventor); Poe, Garrett D. (Inventor); Rood, Robert (Inventor)

    2010-01-01

    An improved solid expellant plasma generator has been developed. The plasma generator includes a support housing, an electrode rod located in the central portion of the housing, and a mass of solid expellant material that surrounds the electrode rod within the support housing. The electrode rod and the solid expellant material are made of separate materials that are selected so that the electrode and the solid expellant material decompose at the same rate when the plasma generator is ignited. This maintains a point of discharge of the plasma at the interface between the electrode and the solid expellant material.

  16. Preparation and characterization of human thrombin for use in a fibrin glue.

    PubMed

    Rock, G; Neurath, D; Semple, E; Harvey, M; Freedman, M

    2007-06-01

    Cryoprecipitate is frequently combined with thrombin to produce a fibrin sealant to enhance haemostasis during surgical procedures. We evaluated the thrombin produced from plasma using the Thrombin Processing Device (TPD)trade mark (Thermogenesis, Rancho Cordova, CA, USA). Plasma (250 mL) was processed in the CryoSeal FS System using the CP-3 disposable to produce cryoprecipitate by automated freezing and thawing. Simultaneously, thrombin was generated using the attached TPD. The cryoprecipitate and thrombin were harvested after approximately 50 min and then frozen and stored at -80 degrees C until analysis of total protein, fibrinogen, factor VIII (FVIII) activity, von Willebrand factor (vWF) and thrombin activity. Sodium dodecyl sulphate (SDS) gel electrophoresis was used to compare thrombin. After combining the thrombin with cryoprecipitate, the rate of clot initiation and strength was measured using a Thromboelastograph (TEG) (Haemoscope Corp, Skokie, IL, USA). Cryoprecipitate was produced, with a fibrinogen concentration of 22 +/- 7.7 g L(-1) (20 +/- 2% recovery), FVIII activity of 14.2 +/- 4.0 IU mL(-1) and vWF of 19.9 +/- 5.2 IU mL(-1). The separate thrombin product had a concentration of 64.3 +/- 16.7 IU mL(-1) of thrombin and a total protein of 0.39 +/- 0.1 g, with SDS gel electrophoresis showing a major band at 37 kD, as did the commercial human thrombin. The TEG curves of cryoprecipitate and TPD-produced or commercial thrombin were compared. The R values (time to clot initiation) were somewhat slower with the TPD-produced thrombin, but the maximum strength (MA) of the clots was similar. In conclusion, human thrombin can be produced during automated cryoprecipitate production. This thrombin is in sufficient concentration to initiate clotting and cross-linking of fibrin from cryoprecipitate to produce an entirely autologous fibrin glue.

  17. Thrombin-induced reactive oxygen species generation in platelets: A novel role for protease-activated receptor 4 and GPIbα

    PubMed Central

    Carrim, Naadiya; Arthur, Jane F.; Hamilton, Justin R.; Gardiner, Elizabeth E.; Andrews, Robert K.; Moran, Niamh; Berndt, Michael C.; Metharom, Pat

    2015-01-01

    Background Platelets are essential for maintaining haemostasis and play a key role in the pathogenesis of cardiovascular disease. Upon ligation of platelet receptors through subendothelial matrix proteins, intracellular reactive oxygen species (ROS) are generated, further amplifying the platelet activation response. Thrombin, a potent platelet activator, can signal through GPIbα and protease-activated receptor (PAR) 1 and PAR4 on human platelets, and recently has been implicated in the generation of ROS. While ROS are known to have key roles in intra-platelet signalling and subsequent platelet activation, the precise receptors and signalling pathways involved in thrombin-induced ROS generation have yet to be fully elucidated. Objective To investigate the relative contribution of platelet GPIbα and PARs to thrombin-induced reactive oxygen species (ROS) generation. Methods and results Highly specific antagonists targeting PAR1 and PAR4, and the GPIbα-cleaving enzyme, Naja kaouthia (Nk) protease, were used in quantitative flow cytometry assays of thrombin-induced ROS production. Antagonists of PAR4 but not PAR1, inhibited thrombin-derived ROS generation. Removal of the GPIbα ligand binding region attenuated PAR4-induced and completely inhibited thrombin-induced ROS formation. Similarly, PAR4 deficiency in mice abolished thrombin-induced ROS generation. Additionally, GPIbα and PAR4-dependent ROS formation were shown to be mediated through focal adhesion kinase (FAK) and NADPH oxidase 1 (NOX1) proteins. Conclusions Both GPIbα and PAR4 are required for thrombin-induced ROS formation, suggesting a novel functional cooperation between GPIbα and PAR4. Our study identifies a novel role for PAR4 in mediating thrombin-induced ROS production that was not shared by PAR1. This suggests an independent signalling pathway in platelet activation that may be targeted therapeutically. PMID:26569550

  18. Thrombin generation and fibrin clot formation under hypothermic conditions: an in vitro evaluation of tissue factor initiated whole blood coagulation

    PubMed Central

    Whelihan, Matthew F.; Kiankhooy, Armin; Brummel-Ziedins, Kathleen

    2015-01-01

    Background Despite trauma-induced hypothermic coagulopathy being familiar in the clinical setting, empirical experimentation concerning this phenomenon is lacking. In this study we investigated the effects of hypothermia on thrombin generation, clot formation and global hemostatic functions in an in vitro environment using a whole blood model and thromboelastography (TEG) which can recapitulate hypothermia. Methods Blood was collected from healthy individuals through venipuncture and treated with corn trypsin inhibitor, to block the contact pathway. Coagulation was initiated with 5pM tissue factor at temperatures 37°C, 32°C, and 27°C. Reactions were quenched over time with soluble and insoluble components of each time point analyzed for thrombin generation, fibrinogen consumption, factor (f)XIII activation and fibrin deposition. Global coagulation potential was evaluated through TEG. Results Data showed that thrombin generation in samples at 37°C and 32°C had comparable rates while 27°C had a much lower rate (39.2 ± 1.1 and 43 ± 2.4 nM/min vs 28.6 ± 4.4 nM/min, respectively). Fibrinogen consumption and fXIII activation were highest at 37°C followed by 32°C and 27°C (13.8 ± 2.9 percent/min vs 7.8 ± 1.8 percent/min, respectively). Fibrin formation as seen through clot weights also followed this trend. TEG data showed clot formation was fastest in samples at 37°C and lowest at 27°C. Maximum clot strength was similar for each temperature. Also, percent lysis of clots was highest at 37°C followed by 32°C and then 27°C. Conclusions Induced hypothermic conditions directly affect the rate of thrombin generation and clot formation while global clot stability remains intact. PMID:24331944

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

    PubMed

    Arumugam, Jayavel; Bukkapatnam, Satish T S; Narayanan, Krishna R; Srinivasa, Arun R

    2016-01-01

    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. PMID:27171403

  20. In vitro interaction of C1-inhibitor with thrombin.

    PubMed

    Cugno, M; Bos, I; Lubbers, Y; Hack, C E; Agostoni, A

    2001-06-01

    Previous observations of increased generation of thrombin during acute attacks of angioedema in plasma of patients with C1-inhibitor (C1-INH) deficiency prompted us to evaluate the interaction of C1-INH with thrombin in both purified systems and human plasma. For this purpose, we used several methods: (1) sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting analysis; (2) enzyme-linked immunosorbent assays to measure complexes between C1-INH and thrombin and inactivated C1-INH; and (3) kinetic studies using a chromogenic assay. We found that the interaction of purified C1-INH with thrombin is associated with the formation of bimolecular complexes of molecular weight (Mr) 130 000 and 120 000 as well as with the appearance of a cleaved form of C1-INH of Mr 97 000. The kinetic studies of inhibition of thrombin by C1-INH showed an average second-order rate constant of 19/s per mol/l, which was significantly increased in the presence of heparin. The addition of thrombin to human plasma was not associated with detectable C1-INH-thrombin complex formation or with cleavage of C1-INH. In conclusion, our data demonstrate that C1-INH upon interaction with thrombin, in part, forms enzyme-inhibitor complexes and, in part, is cleaved. The low second-order rate constant and the lack of a significant interaction in plasma suggest that the inhibition of thrombin by C1-INH has a minor role in circulating blood; however, its role might be important at the endothelial surface, where high concentrations of glycosaminoglycans occur.

  1. Unfavorably Altered Fibrin Clot Properties in Patients with Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome): Association with Thrombin Generation and Eosinophilia

    PubMed Central

    Mastalerz, Lucyna; Celińska-Lӧwenhoff, Magdalena; Krawiec, Piotr; Batko, Bogdan; Tłustochowicz, Witold; Undas, Anetta

    2015-01-01

    Objectives Given reports on the increased prevalence of thromboembolic incidents in patients with eosinophilic granulomatosis with polyangiitis (EGPA; Churg-Strauss syndrome), we investigated whether fibrin clot properties are unfavorably altered in EGPA. Methods Ex vivo plasma fibrin clot characteristics, including clot permeability, turbidimetry and efficiency of fibrinolysis using two assays, were investigated in 34 consecutive patients with remission in EGPA according to the Birmingham Vasculitis Activity Score version 3 (23 female, 11 male), aged 48 (range, 21–80) years. The control group comprised 34 age- and sex- matched volunteers. Results Compared with controls, patients with EGPA were characterized by denser fiber clots (estimated pore size, Ks, 7.30±0.93 vs 10.14±1.07 10−9 cm2), faster fibrin polymerization (lag phase in a turbidimetric curve, 41.8±3.6 vs 47.4±2.9 s), thicker fibrin fibers (maximum absorbance, ΔAbs, 0.87±0.09 vs 0.72±0.07), higher maximum levels of D-dimer released from clots (DDmax 4.10±0.46 vs 3.54±0.35 mg/L), and prolonged clot lysis time (t50%; 9.50±1.45 vs 7.56±0.87 min); all p<0.0001. Scanning electron microscopy images confirmed denser plasma fibrin networks composed of thinner fibers formed in EGPA. Antineutrophil cytoplasmic antibody status and C-reactive protein did not affect clot variables. Multivariate analysis adjusted for fibrinogen showed that Ks was predicted by eosinophil count, peak thrombin generation, factor VIII, and soluble CD40 ligand, whereas eosinophil count, peak thrombin generation and antiplasmin predicted t50%. Conclusion This study is the first to show that EGPA is associated with prothrombotic plasma fibrin clot phenotype, which may contribute to thromboembolic manifestations reported in this disease. PMID:26540111

  2. Feasibility of using thrombin generation assay (TGA) for monitoring of haemostasis during supplementation therapy in haemophilic patients without inhibitors.

    PubMed

    Ay, Y; Balkan, C; Karapinar, D Y; Akin, M; Bilenoğlu, B; Kavakli, K

    2012-11-01

    Monitoring factor replacement treatment and observing concordance with clinical haemostasis is crucial in vital haemorrhages and major surgeries in haemophilic patients. We aimed to investigate the value of the thrombin generation assay (TGA) and thromboelastography (TEG) for monitoring haemostasis in haemophilic patients during factor replacement treatment. The study group consisted of 29 patients (21 haemophilia A, 8 haemophilia B). All the patients FVIII-inhibitor were negative. A total of 35 bleeding episodes and/or surgical interventions were evaluated. aPTT, FVIII/FIX activity, TEG and TGA tests were conducted before and after factor therapy during the bleeding episode or surgical prophylaxis of haemophilic patients. Correlations among these tests were evaluated and compared with clinical responses. No correlation was found among aPTT, factor activities and clinical outcome. There were also no correlation found between TEG parameters and clinical outcome. The only significant correlation found between TGA parameters and clinical outcome was the correlation between peak thrombin. In conclusion, we found superiority of TGA-peak thrombin over other traditional tests for monitoring haemostasis in haemophilic patients in this study.

  3. Association of thrombin generation potential with platelet PAR-1 regulation and P-selectin expression in patients on dual antiplatelet therapy.

    PubMed

    Badr Eslam, Roza; Posch, Florian; Lang, Irene M; Gremmel, Thomas; Eichelberger, Beate; Ay, Cihan; Panzer, Simon

    2014-02-01

    We studied the association of thrombin generation potential with platelet protease activated receptor (PAR)-1 regulation and platelet activation in 52 stable coronary artery disease patients on continuous therapy with aspirin and clopidogrel (n = 42) or prasugrel (n = 10). Compared to controls, peak thrombin generation potential was elevated in only 11 patients (p > 0.05), while F1.2 was elevated in 26 patients (p < 0.0001). PAR-1 and thrombin inducible P-selectin expression were significantly elevated in patients compared to controls (p < 0.001). There were no significant correlations between levels of thrombin generation potential or F1.2 and PAR-1 regulation. However, there was a significant inverse correlation between levels of peak thrombin generation potential and in vitro thrombin-inducible expression of P-selectin (p = 0.002), suggesting in vivo depletion of platelet alpha granules due to ongoing platelet activation.

  4. Plasma motor generator system

    NASA Technical Reports Server (NTRS)

    Hite, Gerald E.

    1987-01-01

    The significant potential advantages of a plasma motor generator system over conventional systems for the generation of electrical power and propulsion for spacecraft in low Earth orbits warrants its further investigation. The two main components of such a system are a long insulated wire and the plasma generating hollow cathodes needed to maintain electrical contact with the ionosphere. Results of preliminary theoretical and experimental investigations of this system are presented. The theoretical work involved the equilibrium configurations of the wire and the nature of small oscillation about these equilibrium positions. A particularly interesting result was that two different configurations are allowed when the current is above a critical value. Experimental investigations were made of the optimal starting and running conditions for the proposed, low current hollow cathodes. Although optimal ranges of temperature, argon pressure and discharge voltage were identified, start up became progressively more difficult. This supposed depletion or contamination of the emissive surface could be countered by the addition of new emissive material.

  5. Thrombin Time

    MedlinePlus

    ... monitor unfractionated heparin therapy and to detect heparin contamination in a blood sample. While it is still ... thrombin time may sometimes be ordered when heparin contamination of a sample is suspected or when a ...

  6. Influenza virus H1N1 activates platelets through FcγRIIA signaling and thrombin generation.

    PubMed

    Boilard, Eric; Paré, Guillaume; Rousseau, Matthieu; Cloutier, Nathalie; Dubuc, Isabelle; Lévesque, Tania; Borgeat, Pierre; Flamand, Louis

    2014-05-01

    Platelets play crucial functions in hemostasis and the prevention of bleeding. During H1N1 influenza A virus infection, platelets display activation markers. The platelet activation triggers during H1N1 infection remain elusive. We observed that H1N1 induces surface receptor activation, lipid mediator synthesis, and release of microparticles from platelets. These activation processes require the presence of serum/plasma, pointing to the contribution of soluble factor(s). Considering that immune complexes in the H1N1 pandemic were reported to play a pathogenic role, we assessed their contribution in H1N1-induced platelet activation. In influenza-immunized subjects, we observed that the virus scaffolds with immunoglobulin G (IgG) to form immune complexes that promote platelet activation. Mechanistically, this activation occurs through stimulation of low-affinity type 2 receptor for Fc portion of IgG (FcγRIIA), a receptor for immune complexes, independently of thrombin. Using a combination of in vitro and in vivo approaches, we found that the antibodies from H3N2-immunized mice activate transgenic mouse platelets that express FcγRIIA when put in the presence of H1N1, suggesting that cross-reacting influenza antibodies suffice. Alternatively, H1N1 can activate platelets via thrombin formation, independently of complement and FcγRIIA. These observations identify both the adaptive immune response and the innate response against pathogens as 2 intertwined processes that activate platelets during influenza infections.

  7. Effects of Fibrinogen Concentrate on Thrombin Generation, Thromboelastometry Parameters, and Laboratory Coagulation Testing in a 24-Hour Porcine Trauma Model

    PubMed Central

    Zentai, Christian; Solomon, Cristina; van der Meijden, Paola E. J.; Spronk, Henri M. H.; Schnabel, Jonas; Rossaint, Rolf

    2015-01-01

    Introduction: In a 24-hour porcine model of liver injury, we showed that fibrinogen supplementation does not downregulate endogenous fibrinogen synthesis. Here we report data from the same study showing the impact of fibrinogen on coagulation variables. Materials and Methods: Coagulopathy was induced in 20 German land race pigs by hemodilution and blunt liver injury. Animals randomly received fibrinogen concentrate (100 mg/kg) or saline. Coagulation parameters were assessed and thromboelastometry (ROTEM) was performed. Results: Fibrinogen concentrate significantly reduced the prolongations of EXTEM clotting time, EXTEM clot formation time, and prothrombin time induced by hemodilution and liver injury. A decrease in clot strength was also ameliorated. Endogenous thrombin potential was significantly higher in the fibrinogen group than in the control group, 20 minutes (353 ± 24 vs 289 ± 22 nmol/L·min; P < .05) and 100 minutes (315 ± 40 vs 263 ± 38 nmol/L·min; P < .05) after the start of infusion. However, no significant between-group differences were seen in other thrombin generation parameters or in d-dimer or thrombin–antithrombin levels. Fibrinogen–platelet binding was reduced following liver injury, with no significant differences between groups. No significant between-group differences were observed in any parameter at ∼12 and ∼24 hours. Conclusion: This study suggests that, in trauma, fibrinogen supplementation may shorten some measurements of the speed of coagulation initiation and produce a short-lived increase in endogenous thrombin potential, potentially through increased clotting substrate availability. Approximately 12 and 24 hours after starting fibrinogen concentrate/saline infusion, all parameters measured in this study were comparable in the 2 study groups. PMID:25948634

  8. Platelet P2Y12 receptors enhance signalling towards procoagulant activity and thrombin generation. A study with healthy subjects and patients at thrombotic risk.

    PubMed

    van der Meijden, Paola E J; Feijge, Marion A H; Giesen, Peter L A; Huijberts, Maya; van Raak, Lisette P M; Heemskerk, Johan W M

    2005-06-01

    Activated platelets participate in arterial thrombosis by forming aggregates and potentiating the coagulation through exposure of procoagulant phosphatidylserine. The function of the two receptors for ADP, P2Y(1) and P2Y(12), is well-established in aggregation, but is incompletely understood in the platelet procoagulant response. We established that, in PRP from healthy subjects, ADP accelerated and potentiated tissue factor induced thrombin generation exclusively via stimulation of P2Y(12) and not via P2Y(1) receptors. The P2Y(12) receptors also mediated the potentiating effect of PAR-1 stimulation on thrombin generation. Furthermore, ADP enhanced in a P2Y(12)-dependent manner the Ca(2+) response induced by thrombin, which was either added externally or generated in-situ. This ADP effect was in part dependent of phosphoinositide 3-kinase and was paralleled by increased phosphatidylserine exposure. In PRP from (young) patients with either stroke or type-II diabetes, platelet-dependent thrombin generation was similarly enhanced byADP or SFLLRN as in healthy subjects. In PRP from stroke patients of older age, the P2Y(12)-mediated contribution to thrombin generation was variably reduced by two weeks of clopidogrel medication. Remaining P2Y(12) activity after medication correlated with remaining P2Y(12)-dependent P-selectin exposure, i.e. Ca(2+)-dependent secretion, likely due to incomplete antagonism of P2Y(12) receptors. Together, these results indicate that physiological platelet agonists amplify phosphatidylserine exposure and subsequent thrombin generation by release of ADP and P2Y(12)-receptor stimulation. This P2Y(12) response is accomplished by a novel Ca(2+) signalling pathway. It is similarly active in platelets from control subjects and patients at thrombotic risk. Finally, the thrombogram method is useful for measuring incomplete P2Y(12) inhibition with clopidogrel. PMID:15968399

  9. Impact of experimental haemodilution on platelet function, thrombin generation and clot firmness: effects of different coagulation factor concentrates

    PubMed Central

    Caballo, Carolina; Escolar, Gines; Diaz-Ricart, Maribel; Lopez-Vílchez, Irene; Lozano, Miguel; Cid, Joan; Pino, Marcos; Beltrán, Joan; Basora, Misericordia; Pereira, Arturo; Galan, Ana M.

    2013-01-01

    Background Haemodilution during resuscitation after massive haemorrhage may worsen the coagulopathy and perpetuate bleeding. Materials and methods Blood samples from healthy donors were diluted (30 and-60%) using crystalloids (saline, Ringer’s lactate, PlasmalyteTM) or colloids (6% hydroxyethylstarch [HES130/0.4], 5% human albumin, and gelatin). The effects of haemodilution on platelet adhesion (Impact R), thrombin generation (TG), and thromboelastometry (TEM) parameters were analysed as were the effects of fibrinogen, prothrombin complex concentrates (PCC), activated recombinant factor VII (FVIIa), and cryoprecipates on haemodilution. Results Platelet interactions was already significantly reduced at 30% haemodilution. Platelet reactivity was not improved by addition of any of the concentrates tested. A decrease in TG and marked alterations of TEM parameters were noted at 60% haemodilution. HES130/0.4 was the expander with the most deleterious action. TG was significantly enhanced by PCC whereas rFVIIa only caused a mild acceleration of TG initiation. Fibrinogen restored the alterations of TEM parameters caused by haemodilution including those caused by HES 130/0.4. Cryoprecipitates significantly improved the alterations caused by haemodilution on TG and TEM parameters; the effects on TG disappeared after ultracentrifugation of the cryoprecipitates. Discussion The haemostatic alterations caused by haemodilution are multifactorial and affect both blood cells and coagulation. In our in vitro approach, HES 130/0.4 had the most deleterious effect on haemostasis parameters. Coagulation factor concentrates did not improve platelet interactions in the Impact R, but did have favourable effects on coagulation parameters measured by TG and TEM. Fibrinogen notably improved TEM parameters without increasing thrombin generation, suggesting that this concentrate may help to preserve blood clotting abilities during haemodilution without enhancing the prothrombotic risk. PMID

  10. Thrombin interaction with fibrin polymerization sites.

    PubMed

    Hsieh, K

    1997-05-15

    Thrombin is central to hemostasis, and postclotting fibrinolysis and wound healing. During clotting, thrombin transforms plasma fibrinogen into polymerizing fibrin, which selectively adsorbs the enzyme into the clot. This protects thrombin from heparin-antithrombin inactivation, thus preserving the enzyme for postclotting events. To determine how the fibrin N-terminal polymerization sites of A alpha 17-23 (GPRVVER) and B beta 15-25 (GHRPLDKKREE) and their analogs may interact with thrombin, amidolysis vs. plasma- and fibrinogen-clotting assays were used to differentiate blockade of catalytic site vs. other thrombin domains. Amidolysis studies suggest GPRVVER inhibition of thrombin catalytic site through hydrophobic interaction, and GPRVVER inhibited clotting. Neither GPRP nor VVER nor the B beta 15-25 homologs inhibited amidolysis. Contrary to heparin, acyl-DKKREE promoted plasma-clotting, but inhibited fibrinogen-clotting. In addition, acyl-DKKREE reversed the anticoagulant effect of heparin (0.1 U/ml) in plasma. The results suggest fibrin B beta 15-25 interaction with thrombin, possibly by blocking the heparin-binding site. Together with the reported fibrin A alpha 27-50 binding to thrombin, polymerizing fibrin appears to initially bind to thrombin catalytic site and exosite-1 through A alpha 17-50, and to another thrombin site through B beta 15-25. As these fibrin sites are also involved in polymerization, competition of the polymerization process with thrombin-binding could subsequently dislodge thrombin from fibrin alpha-chain. This may re-expose the catalytic site and exosite-1, thus explaining the thrombogenicity of clot-bound thrombin. The implications of these findings in polymerization mechanism and anticoagulant design are discussed.

  11. Method for generating surface plasma

    DOEpatents

    Miller, Paul A.; Aragon, Ben P.

    2003-05-27

    A method for generating a discharge plasma which covers a surface of a body in a gas at pressures from 0.01 Torr to atmospheric pressure, by applying a radio frequency power with frequencies between approximately 1 MHz and 10 GHz across a plurality of paired insulated conductors on the surface. At these frequencies, an arc-less, non-filamentary plasma can be generated to affect the drag characteristics of vehicles moving through the gas. The plasma can also be used as a source in plasma reactors for chemical reaction operations.

  12. Combined administration of FVIII and rFVIIa improves haemostasis in haemophilia A patients with high-responding inhibitors--a thrombin generation-guided pilot study.

    PubMed

    Livnat, T; Martinowitz, U; Azar-Avivi, S; Zivelin, A; Brutman-Barazani, T; Lubetsky, A; Kenet, G

    2013-09-01

    Treatment of haemophilia A patients with inhibitors is challenging, and may require individually tailored regimens. Whereas low titre inhibitor patients may respond to high doses of factor VIII (FVIII), high-responding inhibitor patients render replacement therapy ineffective and often require application of bypassing agents. Thrombin generation (TG) assays may be used to monitor haemostasis and/or predict patients' response to bypass agents. In this study we defined by TG, the potential contribution of FVIII to recombinant activated factor VII (rFVIIa)-induced haemostasis in inhibitor plasma. Based upon results, prospectively designed individual regimens of coadministration of rFVIIa and FVIII were applied. Plasma samples from 14 haemophilia patients with inhibitors (including high titre inhibitors) were tested. The response to increasing concentrations of FVIII, rFVIIa or both was assayed by TG. Eight patients, chosen following consent and at physician's discretion, comprised the combined FVIII-rFVIIa therapy clinical study cohort. Combined spiking with FVIII/rFVIIa improved TG induced by rFVIIa alone in all inhibitor plasmas. Combined rFVIIa and FVIII therapy was applied during bleeding or immune tolerance to eight patients, for a total of 393 episodes. Following a single combined dose, 90% haemostasis was documented and neither thrombosis nor any complications evolved. During study period decline of inhibitor levels and bleeding frequency were noted. Pre-analytical studies enabled us to prospectively tailor individual therapy regimens. We confirmed for the first time that the in vitro advantage of combining FVIII and rFVIIa, indeed accounts for improved haemostasis and may safely be applied to inhibitor patients.

  13. Plasma Generated Spherules

    NASA Astrophysics Data System (ADS)

    Ransom, C. J.

    2005-04-01

    Z-pinch plasma simulations have been performed that indicate the production of spherules under certain experimental parameters. (A. L. Peratt, private communication) While performing experiments dealing with the impact of plasma discharges on various materials, we observed that spherules were created at the surface of some of the materials. For specific materials and conditions, spherules were always produced. Both individual spherules and joined spherules were created. The size and shapes were nearly identical to items found by the Mars rover, Opportunity, and called ``blueberries.'' Sky & Telescope, June 2004, p. 20, among other sources indicated the blueberries were gray spherules composed of hematite. The experiments produced hematite spherules identical in appearance to those found on Mars. These experiments suggest how the newly discovered blueberries were formed on Mars while providing an explanation that does not depend on the presence of water.

  14. Deendothelialization in vivo initiates a thrombogenic reaction at the rabbit aorta surface. Correlation of uptake of fibrinogen and antithrombin III with thrombin generation by the exposed subendothelium.

    PubMed Central

    Hatton, M. W.; Moar, S. L.; Richardson, M.

    1989-01-01

    Purified radiolabeled fibrinogen and antithrombin III (ATIII) were injected intravenously into rabbits before a deendothelializing injury to the aorta, and allowed to circulate for 0.1 to 6 hours before exsanguination, excision of the aorta, and quantification of each protein/unit area of subendothelium (intima-media). Uptake of fibrinogen was rapid (saturation 10 minutes after injury was approximately 13.0 pmol/cm2) compared with that of ATIII (45 to 60 minutes; 3.5 to 4.3 pmol/cm2). Both proteins associated primarily (greater than 90%) with the subendothelium rather than the platelet monolayer. The avidity of the deendothelialized vessel of these proteins was measured after a 20-minute circulation time at various intervals after injury. Whereas turnover of fibrinogen was fairly constant (approximately 100% per hour), that of ATIII was maximal (approximately 200% per hour) at 1 hour, decreasing to approximately 105% per hour at 5 hours after injury. The profile of ATIII turnover mirrored that of thrombin released in vitro from the deendothelialized aorta up to 10 days after injury, whereas the uninjured aorta and the aorta deendothelialized ex vivo adsorbed fibrinogen poorly and released negligible thrombin. Pretreatment of the aorta, deendothelialized ex vivo with thrombin in vitro increased fibrinogen uptake significantly. It is possible that, after deendothelialization in vivo, fibrinogen adsorption is determined largely by thrombin generation at the vessel wall. ATIII binding is limited by the availability of binding sites in the subendothelium, although the rate of thrombin generation influences ATIII turnover. Images Figure 1 PMID:2782381

  15. Evaluation of the bone healing process utilizing platelet-rich plasma activated by thrombin and calcium chloride: a histologic study in rabbit calvaria.

    PubMed

    Betoni-Junior, Walter; Dechichi, Paula; Esteves, Jônatas Caldeira; Zanetta-Barbosa, Darceny; Magalhães, Aparecido Eurípedes Onório

    2013-02-01

    To evaluate the bone healing of defects filled with particulate bone graft in combination with platelet-rich plasma (PRP), added with a mixture of calcium chloride and thrombin or just calcium chloride. Two 5-mm bone defects were created in the calvaria of 24 rabbits. Each defect was filled with particulate bone graft and PRP. In one defect the PRP was activated by a mixture of calcium chloride and thrombin; in the other, PRP was activated by calcium chloride only. The animals were euthanized 1, 2, 4, and 8 weeks after the surgeries, and the calvaria was submitted to histologic processing for histomorphometric analysis. The qualitative analysis has shown that both defects presented the same histologic characteristics so that a better organized, more mature, and well-vascularized bone tissue was noticed in the eighth week. A good bone repair was achieved using either the mixture of calcium chloride and thrombin or the calcium chloride alone as a restarting agent of the coagulation process.

  16. The lack of effect of a prophylactic dose of enoxaparin on thrombin generation in patients subjected to nephrectomy because of kidney cancer.

    PubMed

    Szczepański, M; Szostek, P; Pypno, W; Borówka, A

    2001-12-15

    It is assumed that major surgery, connected with extensive tissue dissection, brings about the release of tissue factor into circulation and subsequent activation of coagulation system. This activation results in the thrombin generation, which is supposed to be suppressed by the low-molecular-mass heparins (LMMH), administered to the surgical patients as the prophylaxis against postoperative venous thromboembolism. We have estimated the concentration of circulating thrombin-antithrombin (TAT) complex in patients subjected to transperitoneal nephrectomy and randomized into controls and who received 40-mg enoxaparin 12 h before and 12 h after the operation and then once daily for 7 days. We have observed a sharp rise of TAT concentration at the end of surgery and it corresponded to the simultaneous drop of antithrombin (AT) activity. TAT concentration gradually decreased and AT activity increased up to the end of observations on the seventh postoperative day, but there were no differences observed between the groups of patients. We have also observed a biphasic increase of plasmin-plasmin inhibitor (PPI) complex concentration in our patients. Again, there were no differences in PPI between the groups of patients. It is our conclusion that under the conditions of this study, the well-known prophylactic effect of enoxaparin against the venous thromboembolic complications was not mediated by the inhibition of intraoperative thrombin generation. The anti-inflammatory or biophysical influence of LMMH may be rather taken into account in surgical patients receiving prophylactic doses of these heparins.

  17. Statins but Not Aspirin Reduce Thrombotic Risk Assessed by Thrombin Generation in Diabetic Patients without Cardiovascular Events: The RATIONAL Trial

    PubMed Central

    Macchia, Alejandro; Laffaye, Nicolás; Comignani, Pablo D.; Cornejo Pucci, Elena; Igarzabal, Cecilia; Scazziota, Alejandra S.; Herrera, Lourdes; Mariani, Javier A.; Bragagnolo, Julio C.; Catalano, Hugo; Tognoni, Gianni; Nicolucci, Antonio

    2012-01-01

    Background The systematic use of aspirin and statins in patients with diabetes and no previous cardiovascular events is controversial. We sought to assess the effects of aspirin and statins on the thrombotic risk assessed by thrombin generation (TG) among patients with type II diabetes mellitus and no previous cardiovascular events. Methodology/Principal Findings Prospective, randomized, open, blinded to events evaluation, controlled, 2×2 factorial clinical trial including 30 patients randomly allocated to aspirin 100 mg/d, atorvastatin 40 mg/d, both or none. Outcome measurements included changes in TG levels after treatment (8 to 10 weeks), assessed by a calibrated automated thrombogram. At baseline all groups had similar clinical and biochemical profiles, including TG levels. There was no interaction between aspirin and atorvastatin. Atorvastatin significantly reduced TG measured as peak TG with saline (85.09±55.34 nmol vs 153.26±75.55 nmol for atorvastatin and control groups, respectively; p = 0.018). On the other hand, aspirin had no effect on TG (121.51±81.83 nmol vs 116.85±67.66 nmol, for aspirin and control groups, respectively; p = 0.716). The effects of treatments on measurements of TG using other agonists were consistent. Conclusions/Significance While waiting for data from ongoing large clinical randomized trials to definitively outline the role of aspirin in primary prevention, our study shows that among diabetic patients without previous vascular events, statins but not aspirin reduce thrombotic risk assessed by TG. Trial Registration ClinicalTrials.gov NCT00793754 PMID:22470429

  18. Thalidomide-prednisone maintenance following autologous stem cell transplant for multiple myeloma: effect on thrombin generation and procoagulant markers in NCIC CTG MY.10.

    PubMed

    Kovacs, Michael J; Davies, Gwynivere A; Chapman, Judy-Anne W; Bahlis, Nizar; Voralia, Michael; Roy, Jean; Kouroukis, C Tom; Chen, Christine; Belch, Andrew; Reece, Donna; Zhu, Liting; Meyer, Ralph M; Shepherd, Lois; Stewart, Keith A

    2015-02-01

    Venous thromboembolism (VTE) has an increased incidence in patients with multiple myeloma (MM), especially during chemotherapy. Mechanisms including upregulation of procoagulant factors, such as factor VIII, have been postulated. The National Cancer Institute of Canada Clinical Trials Group MY.10 phase III clinical trial compared thalidomide-prednisone to observation for 332 patients with MM post-autologous stem cell transplantation (ASCT), with a primary endpoint of overall survival and various secondary endpoints including the incidence of VTE. One hundred and fifty-three patients had biomarker data, including D-dimer, factor VIII and thrombin anti-thrombin (TAT) levels collected post-ASCT at baseline and 2 months after intervention investigating in-vivo thrombin generation. Differences between the time-points included a significant reduction over time in D-dimer, factor VIII and TAT levels in the observation group and sustained elevation of D-dimer, significant increase in factor VIII and reduction in TAT levels in the thalidomide-prednisone group. Eight VTE events were reported in this subset of study patients, all in the thalidomide-prednisone arm, with a trend to increase in D-dimer levels over time in those patients with VTE. This study provides physiological and clinical evidence for an increased risk of VTE associated with thalidomide-prednisone maintenance therapy post-ASCT for MM.

  19. Activation of pro-(matrix metalloproteinase-2) (pro-MMP-2) by thrombin is membrane-type-MMP-dependent in human umbilical vein endothelial cells and generates a distinct 63 kDa active species.

    PubMed Central

    Lafleur, M A; Hollenberg, M D; Atkinson, S J; Knäuper, V; Murphy, G; Edwards, D R

    2001-01-01

    Thrombin, a critical enzyme in the coagulation cascade, has also been associated with angiogenesis and activation of the zymogen form of matrix metalloproteinase-2 (MMP-2 or gelatinase-A). We show that thrombin activated pro-MMP-2 in a dose- and time-dependent manner in cultured human umbilical-vein endothelial cells (HUVECs) to generate a catalytically active 63 kDa protein that accumulated as the predominant form in the conditioned medium. This 63 kDa thrombin-activated MMP-2 is distinct from the 62 kDa species found following concanavalin A or PMA stimulated pro-MMP-2 activation. Hirudin and leupeptin blocked thrombin-induced pro-MMP-2 activation, demonstrating that the proteolytic activity of thrombin is essential. However, activation was also dependent upon membrane-type-MMP (MT-MMP) action, since it was blocked by EDTA, o-phenanthroline, hydroxamate metalloproteinase inhibitors, tissue inhibitor of metalloproteinase-2 (TIMP-2) and TIMP-4, but not TIMP-1. Thrombin inefficiently cleaved recombinant 72 kDa pro-MMP-2, but efficiently cleaved the 64 kDa MT-MMP-processed intermediate form in the presence of cells. Thrombin also rapidly (within 1 h) increased cellular MT-MMP activity, and at longer time points (>6 h) it increased expression of MT1-MMP mRNA and protein. Thus signalling via proteinase-activated receptors (PARs) may play a role in thrombin-induced MMP-2 activation, though this does not appear to involve PAR1, PAR2, or PAR4 in HUVECs. These results indicate that in HUVECs the activation of pro-MMP-2 by thrombin involves increased MT-MMP activity and preferential cleavage of the MT-MMP-processed 64 kDa MMP-2 form in the presence of cells. The integration of these proteinase systems in the vascular endothelium may be important during thrombogenesis and tissue remodelling associated with neovascularization. PMID:11415441

  20. Natural inhibitors of thrombin.

    PubMed

    Huntington, James A

    2014-04-01

    The serine protease thrombin is the effector enzyme of blood coagulation. It has many activities critical for the formation of stable clots, including cleavage of fibrinogen to fibrin, activation of platelets and conversion of procofactors to active cofactors. Thrombin carries-out its multiple functions by utilising three special features: a deep active site cleft and two anion binding exosites (exosite I and II). Similarly, thrombin inhibitors have evolved to exploit the unique features of thrombin to achieve rapid and specific inactivation of thrombin. Exogenous thrombin inhibitors come from several different protein families and are generally found in the saliva of haematophagous animals (blood suckers) as part of an anticoagulant cocktail that allows them to feed. Crystal structures of several of these inhibitors reveal how peptides and proteins can be targeted to thrombin in different and interesting ways. Thrombin activity must also be regulated by endogenous inhibitors so that thrombi do not occlude blood flow and cause thrombosis. A single protein family, the serpins, provides all four of the endogenous thrombin inhibitors found in man. The crystal structures of these serpins bound to thrombin have been solved, revealing a similar exosite-dependence on complex formation. In addition to forming the recognition complex, serpins destroy the structure of thrombin, allowing them to be released from cofactors and substrates for clearance. This review examines how the special features of thrombin have been exploited by evolution to achieve inhibition of the ultimate coagulation protease.

  1. Fibrinogen blocks the autoactivation and thrombin-mediated activation of factor XI on dextran sulfate.

    PubMed Central

    Scott, C F; Colman, R W

    1992-01-01

    The intrinsic pathway of blood coagulation is activated when factor XIa, one of the three contact-system enzymes, is generated and then activates factor IX. Factor XI has been shown to be efficiently activated in vitro by surface-bound factor XIIa after factor XI is transported to the surface by its cofactor, high molecular weight kininogen (HK). However, individuals lacking any of the three contact-system proteins--namely, factor XII, prekallikrein, and HK--do not suffer from bleeding abnormalities. This mystery has led several investigators to search for an "alternate" activation pathway for factor XI. Recently, factor XI has been reported to be autoactivated on the soluble "surface" dextran sulfate, and thrombin was shown to accelerate the autoactivation. However, it was also reported that HK, the cofactor for factor XIIa-mediated activation of factor XI, actually diminishes the thrombin-catalyzed activation rate of factor XI. Nonetheless, it was suggested that thrombin was a more efficient activator than factor XIIa. In this report we investigated the effect of fibrinogen, the major coagulation protein in plasma, on the activation rate of factor XI. Fibrinogen, the preferred substrate for thrombin in plasma, virtually prevented autoactivation of factor XI as well as the thrombin-mediated activation of factor XI, while having no effect on factor XIIa-catalyzed activation. HK dramatically curtailed the autoactivation of factor XI in addition to the thrombin-mediated activation. These data indicate that factor XI would not be autoactivated in a plasma environment, and thrombin would, therefore, be unlikely to potentiate the activation. We believe that the "missing pathway" for factor XI activation remains an enigma that warrants further investigation. PMID:1454798

  2. Inhibition of thrombin activity with DNA-aptamers.

    PubMed

    Dobrovolsky, A B; Titaeva, E V; Khaspekova, S G; Spiridonova, V A; Kopylov, A M; Mazurov, A V

    2009-07-01

    The effects of two DNA aptamers (oligonucleotides) 15TBA and 31TBA (15- and 31-mer thrombin-binding aptamers, respectively) on thrombin activity were studied. Both aptamers added to human plasma dose-dependently increased thrombin time (fibrin formation upon exposure to exogenous thrombin), prothrombin time (clotting activation by the extrinsic pathway), and activated partial thromboplastin time (clotting activation by the intrinsic pathway). At the same time, these aptamers did not modify amidolytic activity of thrombin evaluated by cleavage of synthetic chromogenic substrate. Aptamers also inhibited thrombin-induced human platelet aggregation. The inhibitory effects of 31TBA manifested at lower concentrations than those of 15TBA in all tests. These data indicate that the studied antithrombin DNA aptamers effectively suppress its two key reactions, fibrin formation and stimulation of platelet aggregation, without modifying active center of the thrombin molecule. PMID:19902090

  3. Inhibition of Cellular Adhesion by Immunological Targeting of Osteopontin Neoepitopes Generated through Matrix Metalloproteinase and Thrombin Cleavage

    PubMed Central

    Jürets, Alexander; Le Bras, Marie; Staffler, Günther; Stein, Gesine; Leitner, Lukas; Neuhofer, Angelika; Tardelli, Matteo; Turkof, Edvin; Zeyda, Maximilian; Stulnig, Thomas M.

    2016-01-01

    Osteopontin (OPN), a secreted protein involved in inflammatory processes and cancer, induces cell adhesion, migration, and activation of inflammatory pathways in various cell types. Cells bind OPN via integrins at a canonical RGD region in the full length form as well as to a contiguous cryptic site that some have shown is unmasked upon thrombin or matrix metalloproteinase cleavage. Thus, the adhesive capacity of osteopontin is enhanced by proteolytic cleavage that may occur in inflammatory conditions such as obesity, atherosclerosis, rheumatoid arthritis, tumor growth and metastasis. Our aim was to inhibit cellular adhesion to recombinant truncated proteins that correspond to the N-terminal cleavage products of thrombin- or matrix metalloproteinase-cleaved OPN in vitro. We specifically targeted the cryptic integrin binding site with monoclonal antibodies and antisera induced by peptide immunization of mice. HEK 293 cells adhered markedly stronger to truncated OPN proteins than to full length OPN. Without affecting cell binding to the full length form, the raised monoclonal antibodies specifically impeded cellular adhesion to the OPN fragments. Moreover, we show that the peptides used for immunization were able to induce antisera, which impeded adhesion either to all OPN forms, including the full-length form, or selectively to the corresponding truncated recombinant proteins. In conclusion, we developed immunological tools to selectively target functional properties of protease-cleaved OPN forms, which could find applications in treatment and prevention of various inflammatory diseases and cancers. PMID:26840958

  4. Self-energized plasma compressor. [for compressing plasma discharged from coaxial plasma generator

    NASA Technical Reports Server (NTRS)

    Shriver, E. L.; Igenbergs, E. B. (Inventor)

    1974-01-01

    The self-energized plasma compressor is described which compresses plasma discharged from a coaxial plasma generator. The device includes a helically shaped coil which is coaxially aligned with the center axis of the coaxial plasma generator. The plasma generator creates a current through the helical coil which, in turn, generates a time varying magnetic field that creates a force which acts radially upon the plasma. The coaxial plasma generator and helical coil move the plasma under high pressure and temperature to the narrow end of the coil. Positioned adjacent to the narrow end of the coil are beads which are engaged by the plasma to be accelerated to hypervelocities for simulating meteoroids.

  5. Optical plasma torch electron bunch generation in plasma wakefield accelerators

    NASA Astrophysics Data System (ADS)

    Wittig, G.; Karger, O.; Knetsch, A.; Xi, Y.; Deng, A.; Rosenzweig, J. B.; Bruhwiler, D. L.; Smith, J.; Manahan, G. G.; Sheng, Z.-M.; Jaroszynski, D. A.; Hidding, B.

    2015-08-01

    A novel, flexible method of witness electron bunch generation in plasma wakefield accelerators is described. A quasistationary plasma region is ignited by a focused laser pulse prior to the arrival of the plasma wave. This localized, shapeable optical plasma torch causes a strong distortion of the plasma blowout during passage of the electron driver bunch, leading to collective alteration of plasma electron trajectories and to controlled injection. This optically steered injection is more flexible and faster when compared to hydrodynamically controlled gas density transition injection methods.

  6. In vitro study of the role of thrombin in platelet rich plasma (PRP) preparation: utility for gel formation and impact in growth factors release

    PubMed Central

    Huber, Stephany Cares; Cunha Júnior, José Luiz Rosenberis; Montalvão, Silmara; da Silva, Letícia Queiroz; Paffaro, Aline Urban; da Silva, Francesca Aparecida Ramos; Rodrigues, Bruno Lima; Lana, José Fabio Santos Duarte; Annichino-Bizzacchi, Joyce Maria

    2016-01-01

    Introduction: The use of PRP has been studied for different fields, with promising results in regenerative medicine. Until now, there is no study in the literature evaluating thrombin levels in serum, used as autologous thrombin preparation. Therefore, in the present study we evaluated the role played by different thrombin concentrations in PRP and the impact in the release of growth factors. Also, different activators for PRP gel formation were evaluated. Methods: Thrombin levels were measured in different autologous preparations: serum, L-PRP (PRP rich in leukocytes) and T-PRP (thrombin produced through PRP added calcium gluconate). L-PRP was prepared according to the literature, with platelets and leukocytes being quantified. The effect of autologous thrombin associated or not with calcium in PRP gel was determined by measuring the time of gel formation. The relationship between thrombin concentration and release of growth factors was determined by growth factors (PDGF-AA, VEGF and EGF) multiplex analysis. Results: A similar concentration of thrombin was observed in serum, L-PRP and T-PRP (8.13 nM, 8.63 nM and 7.56 nM, respectively) with a high variation between individuals (CV%: 35.07, 43 and 58.42, respectively). T-PRP and serum with calcium chloride showed similar results in time to promote gel formation. The increase of thrombin concentrations (2.66, 8 and 24 nM) did not promote an increase in growth factor release. Conclusions: The technique of using serum as a thrombin source proved to be the most efficient and reproducible for promoting PRP gel formation, with some advantages when compared to other activation methods, as this technique is easier and quicker with no need of consuming part of PRP. Noteworthy, PRP activation using different thrombin concentrations did not promote a higher release of growth factors, appearing not to be necessary when PRP is used as a suspension. PMID:27397996

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

    PubMed

    Nakamura, S; Iwanaga, S; Suzuki, T

    1975-12-01

    A blood coagulation factor, Factor XIII, was highly purified from bovine fresh plasma by a method similar to those used for human plasma Factor XIII. The isolated Factor XIII consisted of two subunit polypeptides, a and b chains, with molecular weights of 79,000 +/- 2,000 and 75,000 +/- 2,000, respectively. In the conversion of Factor XIII to the active enzyme, Factor XIIIa, by bovine thrombin [EC 3.4.21.5], a peptide was liberated. This peptide, designated tentatively as "activation peptide," was isolated by gel-filtration on a Sephadex G-75 column. It contained a total of 37 amino acid residues with a masked N-terminal residue and C-terminal arginine. The whole amino acid sequence of "Activation peptide" was established by the dansyl-Edman method and standard enzymatic techniques, and the masked N-terminal residue was identified as N-acetylserine by using a rat liver acylamino acid-releasing enzyme. This enzyme specifically cleaved the N-acetylserylglutamyl peptide bond serine and the remaining peptide, which was now reactive to 1-dimethylamino-naphthalene-5-sulfonyl chloride. A comparison of the sequences of human and bovine "Activation peptide" revealed five amino acids replacements, Ser-3 to Thr; Gly-5 to Arg; Ile-14 to Val; Thr-18 to Asn, and Pro-26 to Leu. Another difference was the deletion of Leu-34 in the human peptide. Adsorption chromatography on a hydroxylapatite column in the presence of 0.1% sodium dodecyl sulfate was developed as a preparative procedure for the resolution of the two subunit polypeptides, a or a' chain and b chain, constituting the protein molecule of Factor XIII or Factor XIIIa. End group analyses on the isolated pure chains revealed that the structural change of Factor XIII during activation with thrombin occurs only in the N-terminal portion of the a chain, not in the N-terminal end of the b chain or in the C-terminal ends of the a and b chains. From these results, it was concluded that the activation of bovine plasma Factor XIII

  8. Effect of Chronic Blood Transfusion on Biomarkers of Coagulation Activation and Thrombin Generation in Sickle Cell Patients at Risk for Stroke

    PubMed Central

    Hyacinth, Hyacinth I.; Adams, Robert J.; Greenberg, Charles S.; Voeks, Jenifer H.; Hill, Allyson; Hibbert, Jacqueline M.; Gee, Beatrice E.

    2015-01-01

    Hypercoagulability in sickle cell disease (SCD) is associated with multiple SCD phenotypes, association with stroke risk has not been well described. We hypothesized that serum levels of biomarkers of coagulation activation correlate with high transcranial Doppler ultrasound velocity and decreases with blood transfusion therapy in SCD patients. Stored serum samples from subjects in the Stroke Prevention in Sickle Cell Anemia (STOP) trial were analyzed using ELISA and protein multiplexing techniques. 40 subjects from each treatment arm (Standard Care [SC] and Transfusion [Tx]) at three time points—baseline, study exit and one year post-trial and 10 each of age matched children with SCD but normal TCD (SNTCD) and with normal hemoglobin (HbAA) were analyzed. At baseline, median vWF, TAT and D-dimer levels were significantly higher among STOP subjects than either HbAA or SNTCD. At study exit, median hemoglobin level was significantly higher while median TCD velocity was significantly lower in Tx compared to SC subjects. Median vWF (409.6 vs. 542.9 μg/ml), TAT (24.8 vs. 40.0 ng/ml) and D-dimer (9.2 vs. 19.1 μg/ml) levels were also significantly lower in the Tx compared to the SC group at study exit. Blood levels of biomarkers coagulation activation/thrombin generation correlated positively with TCD velocity and negatively with number of blood transfusions. Biomarkers of coagulation activation/thrombin generation were significantly elevated in children with SCD, at high risk for stroke. Reduction in levels of these biomarkers correlated with reduction in stroke risk (lower TCD velocity), indicating a possible role for hypercoagulation in SCD associated stroke. PMID:26305570

  9. [Measuring thrombin formation].

    PubMed

    Hemker, H C

    2016-01-01

    Measurement of thrombin formation makes it possible to estimate the risk of haemorrhage or thrombosis much more accurately than by using clotting time. This new technique allows better monitoring of the effect of prophylactic and therapeutic anticoagulant therapy. Thrombin formation is, however, not yet routinely measured. PMID:27650017

  10. Plasma plume MHD power generator and method

    DOEpatents

    Hammer, James H.

    1993-01-01

    Highly-conducting plasma plumes are ejected across the interplanetary magnetic field from a situs that is moving relative to the solar wind, such as a spacecraft or an astral body, such as the moon, having no magnetosphere that excludes the solar wind. Discrete plasma plumes are generated by plasma guns at the situs extending in opposite directions to one another and at an angle, preferably orthogonal, to the magnetic field direction of the solar wind plasma. The opposed plumes are separately electrically connected to their source by a low impedance connection. The relative movement between the plasma plumes and the solar wind plasma creates a voltage drop across the plumes which is tapped by placing the desired electrical load between the electrical connections of the plumes to their sources. A portion of the energy produced may be used in generating the plasma plumes for sustained operation.

  11. Hydrogen ionic plasma generated using Al plasma grid

    NASA Astrophysics Data System (ADS)

    Oohara, W.; Anegawa, N.; Egawa, M.; Kawata, K.; Kamikawa, T.

    2016-08-01

    Negative hydrogen ions are produced in the apertures of a plasma grid made of aluminum under the irradiation of positive ions, generating an ionic plasma consisting of positive and negative ions. The saturation current ratio obtained using a Langmuir probe reflects the existence ratio of electrons and is found to increase in connection with the diffusion of the ionic plasma. The local increment of the current ratio suggests the collapse of negative ions and the replacement of detached electrons.

  12. Hollow-Cathode Source Generates Plasma

    NASA Technical Reports Server (NTRS)

    Deininger, W. D.; Aston, G.; Pless, L. C.

    1989-01-01

    Device generates argon, krypton, or xenon plasma via thermionic emission and electrical discharge within hollow cathode and ejects plasma into surrounding vacuum. Goes from cold start up to full operation in less than 5 s after initial application of power. Exposed to moist air between operations without significant degradation of starting and running characteristics. Plasma generated by electrical discharge in cathode barrel sustained and aided by thermionic emission from emitter tube. Emitter tube does not depend on rare-earth oxides, making it vulnerable to contamination by exposure to atmosphere. Device modified for use as source of plasma in laboratory experiments or industrial processes.

  13. Studies of thrombin-induced proteoglycan release in the degradation of human and bovine cartilage.

    PubMed Central

    Furmaniak-Kazmierczak, E; Cooke, T D; Manuel, R; Scudamore, A; Hoogendorn, H; Giles, A R; Nesheim, M

    1994-01-01

    Because fibrin is commonly observed within arthritic joints, studies were undertaken to determine whether purified coagulation and fibrinolytic proteases degrade cartilage in vitro and to seek evidence for the activation of coagulation in arthritic joints through measurements of the levels of inhibitor-enzyme complexes and several other proteins associated with coagulation and fibrinolysis. The concentrations of 13 plasma proteins and complexes of thrombin and Factor Xa with antithrombin III were measured in synovial fluids recovered at the time of knee replacement surgery. All zymogens necessary to constitute the coagulation cascade were present. Thrombin and the combination of prothrombin plus prothrombinase induced proteoglycan release from both normal and arthritic cartilages. Factor Xa and plasmin induced release from diseased cartilage only, and urokinase, tissue plasminogen activator, and activated protein C were without effect at the levels used. At saturating levels of thrombin (> or = 2.0 microM) 80% of the proteoglycan content of normal cartilage was released within 24 h. Thrombin, which is cationic, reversibly binds cartilage with Kd = 7.0 +/- 1.0 microM and Bmax = 820 +/- 70 ng/mg of human cartilage. Levels of thrombin-antithrombin III complexes in synovial fluids and arthritis were 4-fold higher in osteo (OA) and 43-fold higher in rheumatoid (RA) than in controls (0.98 nM). Factor Xa-antithrombin III complex levels were threefold lower in OA and fivefold higher in RA than in controls (0.24 nM). These elevated levels of enzyme-inhibitor complexes imply a history of activation of coagulation within the joint, especially in RA. Since thrombin degrades cartilage in vitro and had been generated in vivo, as inferred by the existence of thrombin-antithrombin III complexes, intraarticular activation of coagulation may both contribute to the pathology of arthritis and comprise a target for therapy and diagnosis. PMID:8040300

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

    PubMed

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

    2015-12-01

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

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

    PubMed

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

    2015-12-01

    Severe hemophilia A is an X-linked bleeding disorder. Immune tolerance induction (ITI) is the best strategy of treatment when patients develop inhibitors. The objective is to illustrate the benefit of a high-purity human factor VIII/von Willebrand factor (VWF) concentrate (Octanate) in the management of ITI. We also wanted to raise the potential interest of laboratory assays such as thrombin-generation test (TGT) and epitope mapping. Two patients were treated during ITI, first with a recombinant FVIII and then with plasma-derived factor VIII without success, and, finally, with Octanate. Bypassing agents were used based on the results of TGT. Epitope mapping was performed during ITI therapy. These observations suggest the potential contribution of Octanate in the management of ITI in difficult cases. The use of bypassing agents can be necessary in prophylaxis or to treat bleedings, and may be guided by TGT results. Epitope mapping is used to describe the inhibitor. This article shows a decrease of the inhibitor directed against the C2 domain after initiation of Octanate. A high-purity human factor VIII/von Willebrand factor concentrate (Octanate) may be a valuable therapeutical option for ITI therapy. TGT and epitope mapping could be of help in the management of ITI. PMID:26517064

  16. Plasma generating apparatus for large area plasma processing

    DOEpatents

    Tsai, Chin-Chi; Gorbatkin, Steven M.; Berry, Lee A.

    1991-01-01

    A plasma generating apparatus for plasma processing applications is based on a permanent magnet line-cusp plasma confinement chamber coupled to a compact single-coil microwave waveguide launcher. The device creates an electron cyclotron resonance (ECR) plasma in the launcher and a second ECR plasma is created in the line cusps due to a 0.0875 tesla magnetic field in that region. Additional special magnetic field configuring reduces the magnetic field at the substrate to below 0.001 tesla. The resulting plasma source is capable of producing large-area (20-cm diam), highly uniform (.+-.5%) ion beams with current densities above 5 mA/cm.sup.2. The source has been used to etch photoresist on 5-inch diam silicon wafers with good uniformity.

  17. Plasma generating apparatus for large area plasma processing

    DOEpatents

    Tsai, C.C.; Gorbatkin, S.M.; Berry, L.A.

    1991-07-16

    A plasma generating apparatus for plasma processing applications is based on a permanent magnet line-cusp plasma confinement chamber coupled to a compact single-coil microwave waveguide launcher. The device creates an electron cyclotron resonance (ECR) plasma in the launcher and a second ECR plasma is created in the line cusps due to a 0.0875 tesla magnetic field in that region. Additional special magnetic field configuring reduces the magnetic field at the substrate to below 0.001 tesla. The resulting plasma source is capable of producing large-area (20-cm diam), highly uniform (.+-.5%) ion beams with current densities above 5 mA/cm[sup 2]. The source has been used to etch photoresist on 5-inch diam silicon wafers with good uniformity. 3 figures.

  18. Mutant B-Raf(V600E) Promotes Melanoma Paracellular Transmigration by Inducing Thrombin-mediated Endothelial Junction Breakdown.

    PubMed

    Zhang, Pu; Feng, Shan; Liu, Gentao; Wang, Heyong; Zhu, Huifeng; Ren, Qiao; Bai, Huiyuan; Fu, Changliang; Dong, Cheng

    2016-01-29

    Tumor invasiveness depends on the ability of tumor cells to breach endothelial barriers. In this study, we investigated the mechanism by which the adhesion of melanoma cells to endothelium regulates adherens junction integrity and modulates tumor transendothelial migration (TEM) by initiating thrombin generation. We found that the B-Raf(V600E) mutation in metastatic melanoma cells up-regulated tissue factor (TF) expression on cell membranes and promoted thrombin production. Co-culture of endothelial monolayers with metastatic melanoma cells mediated the opening of inter-endothelial spaces near melanoma cell contact sites in the presence of platelet-free plasma (PFP). By using small interfering RNA (siRNA), we demonstrated that B-Raf(V600E) and TF silencing attenuated the focal disassembly of adherens junction induced by tumor contact. Vascular endothelial-cadherin (VE-cadherin) disassembly was dependent on phosphorylation of p120-catenin on Ser-879 and VE-cadherin on Tyr-658, Tyr-685, and Tyr-731, which can be prevented by treatment with the thrombin inhibitor, hirudin, or by silencing the thrombin receptor, protease-activated receptor-1, in endothelial cells. We also provided strong evidence that tumor-derived thrombin enhanced melanoma TEM by inducing ubiquitination-coupled VE-cadherin internalization, focal adhesion formation, and actin assembly in endothelium. Confocal microscopic analysis of tumor TEM revealed that junctions transiently opened and resealed as tumor cells accomplished TEM. In addition, in the presence of PFP, tumor cells preferentially transmigrated via paracellular routes. PFP supported melanoma transmigration under shear conditions via a B-Raf(V600E)-thrombin-dependent mechanism. We concluded that the activation of thrombin generation by cancer cells in plasma is an important process regulating melanoma extravasation by disrupting endothelial junction integrity. PMID:26504080

  19. Thrombin-activatable fibrinolysis inhibitor.

    PubMed

    Marx, Pauline F

    2004-09-01

    The coagulation system is a potent mechanism that prevents blood loss after vascular injury. It consists of a number of linked enzymatic reactions resulting in thrombin generation. Thrombin converts soluble fibrinogen into a fibrin clot. The clot is subsequently removed by the fibrinolytic system upon wound healing. Thrombin-activatable fibrinolysis inhibitor (TAFI), which is identical to the previously identified proteins procarboxypeptidase B, R, and U, forms a link between blood coagulation and fibrinolysis. TAFI circulates as an inactive proenzyme in the bloodstream, and becomes activated during blood clotting. The active form, TAFIa, inhibits fibrinolysis by cleaving off C-terminal lysine residues from partially degraded fibrin that stimulates the tissue-type plasminogen activator-mediated conversion of plasminogen to plasmin. Consequently, removal of these lysines leads to less plasmin formation and subsequently to protection of the fibrin clot from break down. Moreover, TAFI may also play a role in other processes such as, inflammation and tissue repair. In this review, recent developments in TAFI research are discussed. PMID:15379716

  20. Tissue factor and cancer procoagulant expressed by glioma cells participate in their thrombin-mediated proliferation.

    PubMed

    Ogiichi, T; Hirashima, Y; Nakamura, S; Endo, S; Kurimoto, M; Takaku, A

    2000-01-01

    The relationship between coagulation cascade activation and glioma cell proliferation was examined. The human glioma cell lines T98G, TM-1 and normal human astrocyte cell strain (NHA) were examined. Using anti-tissue factor (TF) antibody, immunocytochemical detection of TF antigen was obtained in both cell lines and cell strain. TF antigen in cell lysates was also measured by enzyme linked immunosorbent assay (ELISA). In a one-stage clotting assay, T98G, TM-1 and NHA revealed procoagulant activity (PCA) in normal human plasma and factor VII deficient plasma. PCA in normal human plasma was significantly inhibited by both inhibitory anti-TF antibody and cysteine protease inhibitor HgCl2. This result indicates that T98G, TM-1 and NHA cells express not only TF but also cancer procoagulant (CP) at the same time. In a cell proliferation assay, thrombin induced proliferation in T98G and TM-1 cells in a dose-dependent fashion and in NHA cell in a bell-shaped fashion. This mitogenic stimulant was inhibited by the specific thrombin inhibitor hirudin. The combinations of coagulation factors II, V, and X with or without factor VII induced proliferation in T98G, TM-1, and NHA cells. The maximal mitogenic stimulatory effects were larger in glioma cells than in NHA. These mitogenic stimulatory effects were also inhibited by hirudin. Each coagulation factor on its own or in any other combination of coagulation factors had no proliferative effect. Thus, these mitogenic stimulatory effects were considered to be the effect of thrombin. In conclusion, T98G and TM-1 human glioma cells express two different types of procoagulants TF and CP. In the presence of coagulation factors, these glioma cells can generate thrombin and this thrombin generation is capable of inducing glioma cell proliferation in vitro.

  1. High-harmonic generation in cavitated plasmas

    SciTech Connect

    Schroeder, C. B.; Esarey, E.; Comier-Michel, E.; Leemans, W. P.

    2008-05-15

    A method is proposed for producing coherent x-rays via high-harmonic generation using ultraintense lasers interacting with highly stripped ions in cavitated plasmas. This method relies on plasma cavitation by the wake of an intense drive beam (laser or electron beam) to produce an ion cavity. An ultrashort pulse laser propagating in the plasma-electron-free ion cavity generates laser harmonics. The longitudinal electron motion, which inhibits high-harmonic generation at high laser intensities, can be suppressed by the space-charge field in the ion cavity or by using a counterpropagating laser pulse. Periodic suppression of the longitudinal electron motion may also be used to quasi-phase-match. This method enables harmonic generation to be extended to the sub-A regime.

  2. Surface plasma source with saddle antenna radio frequency plasma generator.

    PubMed

    Dudnikov, V; Johnson, R P; Murray, S; Pennisi, T; Piller, C; Santana, M; Stockli, M; Welton, R

    2012-02-01

    A prototype RF H(-) surface plasma source (SPS) with saddle (SA) RF antenna is developed which will provide better power efficiency for high pulsed and average current, higher brightness with longer lifetime and higher reliability. Several versions of new plasma generators with small AlN discharge chambers and different antennas and magnetic field configurations were tested in the plasma source test stand. A prototype SA SPS was installed in the Spallation Neutron Source (SNS) ion source test stand with a larger, normal-sized SNS AlN chamber that achieved unanalyzed peak currents of up to 67 mA with an apparent efficiency up to 1.6 mA∕kW. Control experiments with H(-) beam produced by SNS SPS with internal and external antennas were conducted. A new version of the RF triggering plasma gun has been designed. A saddle antenna SPS with water cooling is fabricated for high duty factor testing.

  3. Surface plasma source with saddle antenna radio frequency plasma generator

    SciTech Connect

    Dudnikov, V.; Johnson, R. P.; Murray, S.; Pennisi, T.; Piller, C.; Santana, M.; Stockli, M.; Welton, R.

    2012-02-15

    A prototype RF H{sup -} surface plasma source (SPS) with saddle (SA) RF antenna is developed which will provide better power efficiency for high pulsed and average current, higher brightness with longer lifetime and higher reliability. Several versions of new plasma generators with small AlN discharge chambers and different antennas and magnetic field configurations were tested in the plasma source test stand. A prototype SA SPS was installed in the Spallation Neutron Source (SNS) ion source test stand with a larger, normal-sized SNS AlN chamber that achieved unanalyzed peak currents of up to 67 mA with an apparent efficiency up to 1.6 mA/kW. Control experiments with H{sup -} beam produced by SNS SPS with internal and external antennas were conducted. A new version of the RF triggering plasma gun has been designed. A saddle antenna SPS with water cooling is fabricated for high duty factor testing.

  4. Cold plasma brush generated at atmospheric pressure

    SciTech Connect

    Duan Yixiang; Huang, C.; Yu, Q. S.

    2007-01-15

    A cold plasma brush is generated at atmospheric pressure with low power consumption in the level of several watts (as low as 4 W) up to tens of watts (up to 45 W). The plasma can be ignited and sustained in both continuous and pulsed modes with different plasma gases such as argon or helium, but argon was selected as a primary gas for use in this work. The brush-shaped plasma is formed and extended outside of the discharge chamber with typical dimension of 10-15 mm in width and less than 1.0 mm in thickness, which are adjustable by changing the discharge chamber design and operating conditions. The brush-shaped plasma provides some unique features and distinct nonequilibrium plasma characteristics. Temperature measurements using a thermocouple thermometer showed that the gas phase temperatures of the plasma brush are close to room temperature (as low as 42 deg. C) when running with a relatively high gas flow rate of about 3500 ml/min. For an argon plasma brush, the operating voltage from less than 500 V to about 2500 V was tested, with an argon gas flow rate varied from less than 1000 to 3500 ml/min. The cold plasma brush can most efficiently use the discharge power as well as the plasma gas for material and surface treatment. The very low power consumption of such an atmospheric argon plasma brush provides many unique advantages in practical applications including battery-powered operation and use in large-scale applications. Several polymer film samples were tested for surface treatment with the newly developed device, and successful changes of the wettability property from hydrophobic to hydrophilic were achieved within a few seconds.

  5. High Frequency Plasma Generators for Ion Thrusters

    NASA Technical Reports Server (NTRS)

    Divergilio, W. F.; Goede, H.; Fosnight, V. V.

    1981-01-01

    The results of a one year program to experimentally adapt two new types of high frequency plasma generators to Argon ion thrusters and to analytically study a third high frequency source concept are presented. Conventional 30 cm two grid ion extraction was utilized or proposed for all three sources. The two plasma generating methods selected for experimental study were a radio frequency induction (RFI) source, operating at about 1 MHz, and an electron cyclotron heated (ECH) plasma source operating at about 5 GHz. Both sources utilize multi-linecusp permanent magnet configurations for plasma confinement. The plasma characteristics, plasma loading of the rf antenna, and the rf frequency dependence of source efficiency and antenna circuit efficiency are described for the RFI Multi-cusp source. In a series of tests of this source at Lewis Research Center, minimum discharge losses of 220+/-10 eV/ion were obtained with propellant utilization of .45 at a beam current of 3 amperes. Possible improvement modifications are discussed.

  6. The phosphorylation status of extracellular-regulated kinase 1/2 in astrocytes and neurons from rat hippocampus determines the thrombin-induced calcium release and ROS generation.

    PubMed

    Zündorf, Gregor; Reiser, Georg

    2011-12-01

    Challenge of protease-activated receptors induces cytosolic Ca(2+) concentration ([Ca(2+) ](c)) increase, mitogen-activated protein kinase activation and reactive oxygen species (ROS) formation with a bandwidth of responses in individual cells. We detected in this study in situ the thrombin-induced [Ca(2+) ](c) rise and ROS formation in dissociated hippocampal astrocytes and neurons in a mixed culture. In identified cells, single cell responses were correlated with extracellular-regulated kinase (ERK)1/2 phosphorylation level. On average, in astrocytes, thrombin induced a transient [Ca(2+) ](c) rise with concentration-dependent increase in amplitude and extrusion rate and high ERK1/2 phosphorylation level. Correlation analysis of [Ca(2+) ](c) response characteristics of single astrocytes reveals that astrocytes with nuclear phosphoERK1/2 localization have a smaller Ca(2+) amplitude and extrusion rate compared with cells with a cytosolic phosphoERK1/2 localization. In naive neurons, without thrombin challenge, variable ERK1/2 phosphorylation patterns are observed. ROS were detected by hydroethidine. Only in neurons with increased ERK1/2 phosphorylation level, we see sustained intracellular rise in fluorescence of the dye lasting over several minutes. ROS formation was abolished by pre-incubation with the NADPH oxidase inhibitor apocynin. Additionally, thrombin induced an immediate, transient hydroethidine fluorescence increase. This was interpreted as NADPH oxidase-mediated O(2) (•-) -release into the extracellular milieu, because it was decreased by pre-incubation with apocynin, and could be eluted by superfusion. In conclusion, the phosphorylation status of ERK1/2 determines the thrombin-dependent [Ca(2+) ](c) increase and ROS formation and, thus, influences the capacity of thrombin to regulate neuroprotection or neurodegeneration. PMID:21988180

  7. rf-generated ambient-afterglow plasma

    SciTech Connect

    Shakir, Shariff; Mynampati, Sandhya; Pashaie, Bijan; Dhali, Shirshak K.

    2006-04-01

    Atmospheric pressure plasmas have gained importance due to their potential application in polymer surface treatment, surface cleaning of metals, thin film deposition, and destruction of biological hazards. In this paper a radio-frequency driven atmospheric pressure afterglow plasma source in argon and helium is discussed. The light intensity measurement shows that the radio-frequency discharge is continuous in time unlike the intermittent nature of a low frequency dielectric-barrier discharge. The discharge, under ambient conditions, can be generated in argon, helium, and nitrogen. Spectroscopic measurements show that metastables are capable of producing oxygen atoms and other excited species. The argon afterglow, in particular, is capable of dissociating oxygen molecules in the ambient gas. An afterglow model has been developed to study the interaction of the plasma with the ambient gas. Results from applications of the plasma to surface treatment of metals and polymers, and bacterial decontamination are briefly discussed.

  8. Plasma generators, reactor systems and related methods

    DOEpatents

    Kong, Peter C.; Pink, Robert J.; Lee, James E.

    2007-06-19

    A plasma generator, reactor and associated systems and methods are provided in accordance with the present invention. A plasma reactor may include multiple sections or modules which are removably coupled together to form a chamber. Associated with each section is an electrode set including three electrodes with each electrode being coupled to a single phase of a three-phase alternating current (AC) power supply. The electrodes are disposed about a longitudinal centerline of the chamber and are arranged to provide and extended arc and generate an extended body of plasma. The electrodes are displaceable relative to the longitudinal centerline of the chamber. A control system may be utilized so as to automatically displace the electrodes and define an electrode gap responsive to measure voltage or current levels of the associated power supply.

  9. SLOW THROMBIN IS ZYMOGEN-LIKE

    PubMed Central

    Huntington, James A.

    2009-01-01

    Summary Blood coagulation is the result of a cascade of zymogen activation events, however, its initiation is allosteric. Factor VIIa circulates in a zymogen-like state and is allosterically activated by binding to tissue factor. Thrombin, the final protease generated in the blood coagulation cascade, has also been shown to exist in a low activity state in the absence of cofactors, and the structural features of this ‘slow’ form has been studied for many years. In this manuscript I will review the general features that render zymogens inactive and how proteolytic cleavage results in activation, but I will also show how this distinction is blurred by zymogens that have activity (protease-like zymogens) and proteases with low activity (zymogen-like proteases). This will then be applied in the analysis of slow thrombin to reveal how allosteric activation of thrombin simply reflects the conversion from a zymogen-like enzyme to an active serine protease. PMID:19630791

  10. Joint health scores in a haemophilia A cohort from Pakistan with minimal or no access to factor VIII concentrate: correlation with thrombin generation and underlying mutation.

    PubMed

    Khanum, F; Bowen, D J; Kerr, B C; Collins, P W

    2014-05-01

    Haemophilia A is associated with recurrent joint bleeding which leads to synovitis and debilitating arthropathy. Coagulation factor VIII level is an important determinant of bleed number and development of arthropathy . The aim of this study was to compare the haemophilia joint health score (HJHS) and Gilbert score with severity, age, thrombin generation (TG) and underlying mutation in a haemophilia A cohort which had minimal access to haemostatic replacement therapy. Ninety-two haemophilia A individuals were recruited from Pakistan. Age, age at first bleed, target joints, haemophilic arthropathy joints, HJHS and Gilbert score were recorded. A strong correlation was found between HJHS and Gilbert score (r = 0.98), both were significantly higher in severe (n = 59) compared with non-severe (n = 29) individuals before the age of 12 years (P ≤ 0.01) but not thereafter. When individuals were divided according to developmental age (<12 years, 12-16 years and >16 years), both HJHS and Gilbert score were significantly lower in the youngest group (P ≤ 0.001), there was no difference between 12-16 years and >16 years. In severe individuals there was no correlation between in vitro TG and joint score, whereas in non-severe individuals there was a weak negative correlation. In the severe group, no significant difference was observed for either joint score according to the underlying mutation type (inversion, missense, nonsense, frameshift). In this cohort of haemophilia A individuals with minimal access to haemostatic treatment, haemophilic arthropathy correlated with severity and age; among severe individuals, joint health scores did not relate to either the underlying mutation or in vitro TG.

  11. gammaA/gamma' fibrinogen inhibits thrombin-induced platelet aggregation.

    PubMed

    Lovely, Rehana S; Rein, Chantelle M; White, Tara C; Jouihan, Sari A; Boshkov, Lynn K; Bakke, Antony C; McCarty, Owen J; Farrell, David H

    2008-11-01

    The minor gammaA/gamma' fibrinogen isoform contains a high affinity binding site for thrombin exosite II that is lacking in the major gammaA/gammaA fibrinogen isoform. We therefore investigated the biological consequences of the gamma' chain binding to thrombin. Thrombin-induced platelet aggregation was inhibited by gammaA/gamma' fibrinogen. Carboxyl terminal peptide fragment gamma'410-427 from the gamma' chain was also inhibitory, with an IC(50) of approximately 200 microM in whole plasma. Deletion of the peptide from either the amino or carboxyl end significantly decreased inhibition. In contrast to thrombin-induced platelet aggregation, aggregation induced by epinephrine, ADP, arachidonic acid, or SFLLRN peptide showed little inhibition by the gamma' peptide. The inhibition of thrombin-induced platelet aggregation was not due to direct inhibition of the thrombin active site, since cleavage of a small peptidyl substrate was 91% of normal even in the presence of 1 mM gamma'410-427. The gamma'410-427 peptide blocked platelet adhesion to immobilized thrombin under both static and flow conditions, blocked soluble thrombin binding to platelet GPIbalpha, and inhibited PAR1 cleavage by thrombin. These results suggest that the gamma' chain of fibrinogen inhibits thrombin-induced platelet aggregation by binding to thrombin exosite II. Thrombin that is bound to the gamma' chain is thereby prevented from activating platelets, while retaining its amidolytic activity. PMID:18989528

  12. Plasma driven neutron/gamma generator

    SciTech Connect

    Leung, Ka-Ngo; Antolak, Arlyn

    2015-03-03

    An apparatus for the generation of neutron/gamma rays is described including a chamber which defines an ion source, said apparatus including an RF antenna positioned outside of or within the chamber. Positioned within the chamber is a target material. One or more sets of confining magnets are also provided to create a cross B magnetic field directly above the target. To generate neutrons/gamma rays, the appropriate source gas is first introduced into the chamber, the RF antenna energized and a plasma formed. A series of high voltage pulses are then applied to the target. A plasma sheath, which serves as an accelerating gap, is formed upon application of the high voltage pulse to the target. Depending upon the selected combination of source gas and target material, either neutrons or gamma rays are generated, which may be used for cargo inspection, and the like.

  13. Electric-arc steam plasma generator

    NASA Astrophysics Data System (ADS)

    Anshakov, A. S.; Urbakh, E. K.; Radko, S. I.; Urbakh, A. E.; Faleev, V. A.

    2015-01-01

    Investigation results on the arc plasmatorch for water-steam heating are presented. The construction arrangement of steam plasma generator with copper electrodes of the stepped geometry was firstly implemented. The energy characteristics of plasmatorch and erosion of electrodes reflect the features of their behavior at arc glow in the plasma-forming environment of steam. The results of numerical study of the thermal state of the composite copper-steel electrodes had a significant influence on optimization of anode water-cooling aimed at improvement of its operation life.

  14. Terahertz twisted beams generation in plasma

    NASA Astrophysics Data System (ADS)

    Sobhani, Hassan; Vaziri (Khamedi), Mohammad; Rooholamininejad, Hossien; Bahrampour, Alireza

    2016-08-01

    The resonant vortex terahertz beam generation by the cross-focusing of two twisted coaxial laser beams is investigated. For the resonant excitation of terahertz radiation, the rippled density in plasma and the ripple wave number is suitably chosen to satisfy the phase matching condition. The nonlinear current density at terahertz frequency arises due to the spatial variation of two Laguerre-Gaussian coupled field. The terahertz intensity scales as the ponderomotive force of laser beams which imparts an oscillatory velocity to the electrons and, in fact, input Laguerre-Gaussian laser beams properties such as vortex charge number and beam waist. Various laser and plasma parameters are employed to yield vortex terahertz radiation with higher efficiency. Also, it is shown that when the beating frequency approaches plasma frequency, the amplitude of THz radiation increases.

  15. Hemostatic effect and distribution of new rhThrombin formulations in rats

    PubMed Central

    Schmidtová, L'udmila; Sadloňová, Irina; Murányi, Andrej; Zigová, Jana; Múčková, Marta

    2014-01-01

    Recombinant human thrombin (rhThrombin) is a potential hemostatic alternative to bovine and human plasma-derived thrombin. Hemostatic, liver regeneration effect and plasma concentrations of rhThrombin (SCILL) tested in the form of solution and hydrogels (thermo-sensitive poloxamer gel and carbomer gel; hameln rds) were evaluated. In the bleeding model, rhThrombin was applied locally on the bleeding site. The time to hemostasis was measured. The rhThrombin in liquid form as well as the thermo-sensitive gel forming formulation significantly reduced the bleeding time in comparison to saline. In the regeneration model, a cut in the form “V” was made on the liver and rhThrombin in both formulations was applied at defined concentrations to the wound for 5 min. The rats survived 1, 3 and 5 days after the injury and treatment. Histological examination showed better results in the group treated with rh Thrombin gel in comparison to the liquid form – solution; differences were insignificant. Low [125I]-rhThrombin radioactivity was evaluated in plasma after topical application (solution and both hydrogels) at hemostatic effective doses to partial hepatectomy in rats. Locally applied rh Thrombin on the rat damaged liver tissue never reached pharmacologically active systemic levels. The plasmatic levels and the content of this active protein in injured liver tissue were lower after application of its hydrogels versus solution. PMID:26109904

  16. Runaway electron generation in a cooling plasma

    SciTech Connect

    Smith, H.; Helander, P.; Eriksson, L.-G.; Fueloep, T.

    2005-12-15

    The usual calculation of Dreicer [Phys. Rev. 115, 238 (1959); 117, 329 (1960)] generation of runaway electrons assumes that the plasma is in a steady state. In a tokamak disruption this is not necessarily true since the plasma cools down quickly and the collision time for electrons at the runaway threshold energy can be comparable to the cooling time. The electron distribution function then acquires a high-energy tail which can easily be converted to a burst of runaways by the rising electric field. This process is investigated and simple criteria for its importance are derived. If no rapid losses of fast electrons occur, this can be a more important source of runaway electrons than ordinary Dreicer generation in tokamak disruptions.

  17. Pulsed Energy Systems for Generating Plasmas

    NASA Technical Reports Server (NTRS)

    Rose, M. Franklin; Shotts, Z.

    2005-01-01

    This paper will describe the techniques needed to electrically generate highly ionized dense plasmas for a variety of applications. The components needed in pulsed circuits are described in terms of general performance parameters currently available from commercial vendors. Examples of pulsed systems using these components are described and technical data from laboratory experiments presented. Experimental data are given for point designs, capable of multi-megawatt power levels.

  18. Harmonic generation in magnetized quantum plasma

    NASA Astrophysics Data System (ADS)

    Kumar, Punit; Singh, Shiv; Singh, Abhisek Kumar

    2016-05-01

    A study of second harmonic generation by propagation of a linearly polarized electromagnetic wave through homogeneous high density quantum plasma in the presence of transverse magnetic field. The nonlinear current density and dispersion relations for the fundamental and second harmonic frequencies have been obtained using the recently developed quantum hydrodynamic (QHD) model. The effect of quantum Bohm potential, Fermi pressure and the electron spin have been taken into account. The second harmonic is found to be less dispersed than the first.

  19. Loss of high-affinity prostacyclin receptors in platelets and the lack of prostaglandin-induced inhibition of platelet-stimulated thrombin generation in subjects with spinal cord injury.

    PubMed Central

    Kahn, N N; Bauman, W A; Sinha, A K

    1996-01-01

    Coronary artery disease is a leading cause of death in individuals with chronic spinal cord injury (SCI). However, platelets of those with SCI (n = 30) showed neither increased aggregation nor resistance to the antiaggregatory effects of prostacyclin when compared with normal controls (n = 30). Prostanoid-induced cAMP synthesis was similar in both groups. In contrast, prostacyclin, which completely inhibited the platelet-stimulated thrombin generation in normal controls, failed to do so in those with SCI. Scatchard analysis of the binding of [3H]prostaglandin E1, used as a prostacyclin receptor probe, showed the presence of one high-affinity (Kd1 = 8.11 +/- 2.80 nM; n1 = 172 +/- 32 sites per cell) and one low-affinity (Kd2 = 1.01 +/- 0.3 microM; n2 = 1772 +/- 226 sites per cell) prostacyclin receptor in normal platelets. In contrast, the same analysis in subjects with SCI showed significant loss (P < 0.001) of high-affinity receptor sites (Kd1 = 6.34 +/- 1.91 nM; n1 = 43 +/- 10 sites per cell) with no significant change in the low affinity-receptors (Kd2 = 1.22 +/- 0.23; n2 = 1820 +/- 421). Treatment of these platelets with insulin, which has been demonstrated to restore both of the high- and low-affinity prostaglandin receptor numbers to within normal ranges in coronary artery disease, increased high-affinity receptor numbers and restored the prostacyclin effect on thrombin generation. These results demonstrate that the loss of the inhibitory effect of prostacyclin on the stimulation of thrombin generation was due to the loss of platelet high-affinity prostanoid receptors, which may contribute to atherogenesis in individuals with chronic SCI. PMID:8552614

  20. A balance between TFPI and thrombin-mediated platelet activation is required for murine embryonic development

    PubMed Central

    Ellery, Paul E. R.; Maroney, Susan A.; Cooley, Brian C.; Luyendyk, James P.; Zogg, Mark; Weiler, Hartmut

    2015-01-01

    Tissue factor pathway inhibitor (TFPI) is a critical anticoagulant protein present in endothelium and platelets. Mice lacking TFPI (Tfpi−/−) die in utero from disseminated intravascular coagulation. They are rescued by concomitant tissue factor (TF) deficiency, demonstrating that TFPI modulates TF function in vivo. Recent studies have found TFPI inhibits prothrombinase activity during the initiation of coagulation and limits platelet accumulation during thrombus formation, implicating TFPI in modulating platelet procoagulant activity. To examine whether altered platelet function would compensate for the lack of TFPI and rescue TFPI-null embryonic lethality, Tfpi+/− mice lacking the platelet thrombin receptor, protease activated receptor 4 (PAR4; Par4−/−), or its coreceptor, PAR3, were mated. PAR3 deficiency did not rescue Tfpi−/− embryos, but >40% of expected Tfpi−/−:Par4−/− offspring survived to adulthood. Adult Tfpi−/−:Par4−/− mice did not exhibit overt thrombosis. However, they had focal sterile inflammation with fibrin(ogen) deposition in the liver and elevated plasma thrombin-antithrombin complexes, indicating activation of coagulation at baseline. Tfpi−/−:Par4−/− mice have platelet and fibrin accumulation similar to Par4−/− mice following venous electrolytic injury but were more susceptible than Par4−/− mice to TF-induced pulmonary embolism. In addition, ∼30% of the Tfpi−/−:Par4−/− mice were born with short tails. Tfpi−/−:Par4−/− mice are the first adult mice described that lack TFPI with unaltered TF. They demonstrate that TFPI physiologically modulates thrombin-dependent platelet activation in a manner that is required for successful embryonic development and identify a role for TFPI in dampening intravascular procoagulant stimuli that lead to thrombin generation, even in the absence of thrombin-mediated platelet activation. PMID:25954015

  1. Thyristor stack for pulsed inductive plasma generation.

    PubMed

    Teske, C; Jacoby, J; Schweizer, W; Wiechula, J

    2009-03-01

    A thyristor stack for pulsed inductive plasma generation has been developed and tested. The stack design includes a free wheeling diode assembly for current reversal. Triggering of the device is achieved by a high side biased, self supplied gate driver unit using gating energy derived from a local snubber network. The structure guarantees a hard firing gate pulse for the required high dI/dt application. A single fiber optic command is needed to achieve a simultaneous turn on of the thyristors. The stack assembly is used for switching a series resonant circuit with a ringing frequency of 30 kHz. In the prototype pulsed power system described here an inductive discharge has been generated with a pulse duration of 120 micros and a pulse energy of 50 J. A maximum power transfer efficiency of 84% and a peak power of 480 kW inside the discharge were achieved. System tests were performed with a purely inductive load and an inductively generated plasma acting as a load through transformer action at a voltage level of 4.1 kV, a peak current of 5 kA, and a current switching rate of 1 kA/micros. PMID:19334940

  2. Thyristor stack for pulsed inductive plasma generation.

    PubMed

    Teske, C; Jacoby, J; Schweizer, W; Wiechula, J

    2009-03-01

    A thyristor stack for pulsed inductive plasma generation has been developed and tested. The stack design includes a free wheeling diode assembly for current reversal. Triggering of the device is achieved by a high side biased, self supplied gate driver unit using gating energy derived from a local snubber network. The structure guarantees a hard firing gate pulse for the required high dI/dt application. A single fiber optic command is needed to achieve a simultaneous turn on of the thyristors. The stack assembly is used for switching a series resonant circuit with a ringing frequency of 30 kHz. In the prototype pulsed power system described here an inductive discharge has been generated with a pulse duration of 120 micros and a pulse energy of 50 J. A maximum power transfer efficiency of 84% and a peak power of 480 kW inside the discharge were achieved. System tests were performed with a purely inductive load and an inductively generated plasma acting as a load through transformer action at a voltage level of 4.1 kV, a peak current of 5 kA, and a current switching rate of 1 kA/micros.

  3. Volumetric Near-Field Microwave Plasma Generation

    NASA Technical Reports Server (NTRS)

    Exton, R. J.; Balla, R. Jeffrey; Herring, G. C.; Popovic, S.; Vuskovic, L.

    2003-01-01

    A periodic series of microwave-induced plasmoids is generated using the outgoing wave from a microwave horn and the reflected wave from a nearby on-axis concave reflector. The plasmoids are spaced at half-wavelength separations according to a standing-wave pattern. The plasmoids are enhanced by an effective focusing in the near field of the horn (Fresnel region) as a result of a diffractive narrowing. Optical imaging, electron density, and rotational temperature measurements characterize the near field plasma region. Volumetric microwave discharges may have application to combustion ignition in scramjet engines.

  4. The Behavior of Plasma Gases in Explosively-Driven Plasma Generator

    NASA Astrophysics Data System (ADS)

    Seo, Minsu; Choi, Jin Soo; Kim, Inho

    2011-06-01

    The plasma-hydrodynamic computer simulation has been performed in order to investigate the thermodynamic and electrical properties of plasma generated in an explosively-driven cylindrical plasma generator. An one-dimensional hydrodynamic code, One-D, was written for this study and a realistic plasma equation of state model was applied to the code. A couple of plasma generators were manufactured and filled by dry air or pressurized argon gas for plasma medium. The plasma thickness and flow velocity were measured by utilizing the optical and electrical pins. The simulation results of the plasma characteristics were in good agreement with the measured values.

  5. Molecular basis of thrombomodulin activation of slow thrombin

    PubMed Central

    ADAMS, T.E.; LI, W.; HUNTINGTON, J.A.

    2010-01-01

    Summary Background Coagulation is a highly regulated process where the ability to prevent blood loss after injury is balanced against the maintenance of blood fluidity. Thrombin is at the center of this balancing act. It is the critical enzyme for producing and stabilizing a clot, but when complexed with thrombomodulin (TM) it is converted to a powerful anticoagulant. Another cofactor that may play a role in determining thrombin function is the monovalent cation Na+. Its apparent affinity suggests that half of the thrombin generated is in a Na+-free ‘slow’ state and half is in a Na+-coordinated ‘fast’ state. While slow thrombin is a poor procoagulant enzyme, when complexed to TM it is an effective anticoagulant. Methods To better understand this molecular transformation we solved a 2.4 Å structure of thrombin complexed with EGF domains 4–6 of TM in the absence of Na+ and other cofactors or inhibitors. Results We find that TM binds as previously observed, and that the thrombin component resembles structures of the fast form. The Na+ binding loop is observed in a conformation identical to the Na+-bound form, with conserved water molecules compensating for the missing ion. Using the fluorescent probe p-aminobenzamidine we show that activation of slow thrombin by TM principally involves the opening of the primary specificity pocket. Conclusions These data show that TM binding alters the conformation of thrombin in a similar manner as Na+ coordination, resulting in an ordering of the Na+ binding loop and an opening of the adjacent S1 pocket. We conclude that other, more subtle subsite changes are unlikely to influence thrombin specificity toward macromolecular substrates. PMID:19656282

  6. Thrombin and fibrinogen γ' impact clot structure by marked effects on intrafibrillar structure and protofibril packing.

    PubMed

    Domingues, Marco M; Macrae, Fraser L; Duval, Cédric; McPherson, Helen R; Bridge, Katherine I; Ajjan, Ramzi A; Ridger, Victoria C; Connell, Simon D; Philippou, Helen; Ariëns, Robert A S

    2016-01-28

    Previous studies have shown effects of thrombin and fibrinogen γ' on clot structure. However, structural information was obtained using electron microscopy, which requires sample dehydration. Our aim was to investigate the role of thrombin and fibrinogen γ' in modulating fibrin structure under fully hydrated conditions. Fibrin fibers were studied using turbidimetry, atomic force microscopy, electron microscopy, and magnetic tweezers in purified and plasma solutions. Increased thrombin induced a pronounced decrease in average protofibril content per fiber, with a relatively minor decrease in fiber size, leading to the formation of less compact fiber structures. Atomic force microscopy under fully hydrated conditions confirmed that fiber diameter was only marginally decreased. Decreased protofibril content of the fibers produced by high thrombin resulted in weakened clot architecture as analyzed by magnetic tweezers in purified systems and by thromboelastometry in plasma and whole blood. Fibers produced with fibrinogen γ' showed reduced protofibril packing over a range of thrombin concentrations. High-magnification electron microscopy demonstrated reduced protofibril packing in γ' fibers and unraveling of fibers into separate protofibrils. Decreased protofibril packing was confirmed in plasma for high thrombin concentrations and fibrinogen-deficient plasma reconstituted with γ' fibrinogen. These findings demonstrate that, in fully hydrated conditions, thrombin and fibrinogen γ' have dramatic effects on protofibril content and that protein density within fibers correlates with strength of the fibrin network. We conclude that regulation of protofibril content of fibers is an important mechanism by which thrombin and fibrinogen γ' modulate fibrin clot structure and strength. PMID:26608329

  7. Etching with electron beam generated plasmas

    SciTech Connect

    Leonhardt, D.; Walton, S.G.; Muratore, C.; Fernsler, R.F.; Meger, R.A.

    2004-11-01

    A modulated electron beam generated plasma has been used to dry etch standard photoresist materials and silicon. Oxygen-argon mixtures were used to etch organic resist material and sulfur hexafluoride mixed with argon or oxygen was used for the silicon etching. Etch rates and anisotropy were determined with respect to gas compositions, incident ion energy (from an applied rf bias) and plasma duty factor. For 1818 negative resist and i-line resists the removal rate increased nearly linearly with ion energy (up to 220 nm/min at 100 eV), with reasonable anisotropic pattern transfer above 50 eV. Little change in etch rate was seen as gas composition went from pure oxygen to 70% argon, implying the resist removal mechanism in this system required the additional energy supplied by the ions. With silicon substrates at room temperature, mixtures of argon and sulfur hexafluoride etched approximately seven times faster (1375 nm/min) than mixtures of oxygen and sulfur hexafluoride ({approx}200 nm/min) with 200 eV ions, the difference is attributed to the passivation of the silicon by involatile silicon oxyfluoride (SiO{sub x}F{sub y}) compounds. At low incident ion energies, the Ar-SF{sub 6} mixtures showed a strong chemical (lateral) etch component before an ion-assisted regime, which started at {approx}75 eV. Etch rates were independent of the 0.5%-50% duty factors studied in this work.

  8. Plasma Motor Generator (PMG) electrodynamic tether experiment

    NASA Technical Reports Server (NTRS)

    Grossi, Mario D.

    1995-01-01

    The Plasma Motor Generator (PMG) flight of June 26, 1993 has been the most sophisticated and most successful mission that has been carried out thus far with an electrodynamic tether. Three papers from the Smithsonian Astrophysical Observatory, Washington, DC concerned with the PMG, submitted at the Fourth International Space Conference on Tethers in Space, in Washington, DC, in April 1995, are contained in this document. The three papers are (1) Electromagnetic interactions between the PMG tether and the magneto-ionic medium of the Ionosphere; (2) Tether-current-voltage characteristics, as determined by the Hollow Cathode Operation Modes; and (3) Hawaii-Hilo ground observations on the occasion for the PMG flight of June 23, 1993.

  9. Plasmas generated in bubbles immersed in liquids: direct current streamers versus microwave plasma

    NASA Astrophysics Data System (ADS)

    Levko, Dmitry; Sharma, Ashish; Raja, Laxminarayan L.

    2016-07-01

    Two approaches to generate non-equilibrium atmospheric-pressure plasma in bubbles immersed in liquids are compared using high-fidelity 2D fluid simulations. In the first approach, corona/streamer like plasma is generated using high-voltage negative and positive pulses applied between two electrodes (pin-to-plane geometry) immersed in liquid. In the second, the plasma is generated using a remote microwave source (frequency 2.45 GHz). We find that the microwave approach requires less energy, while generating a denser, more chemically reactive and more uniform plasma within the bubble volume, as compared to the plasma generated using high-voltage pulsing.

  10. Generating electron cyclotron resonance plasma using distributed scheme

    SciTech Connect

    Huang, C. C.; Chang, T. H.; Chen, N. C.; Chao, H. W.; Chen, C. C.; Chou, S. F.

    2012-08-06

    This study employs a distributed microwave input system and permanent magnets to generate large-area electron cyclotron resonance (ECR) plasma. ECR plasmas were generated with nitrogen gas, and the plasma density was measured by Langmuir probe. A uniform ECR plasma with the electron density fluctuation of {+-}9.8% over 500 mm Multiplication-Sign 500 mm was reported. The proposed idea of generating uniform ECR plasma can be scaled to a much larger area by using n Multiplication-Sign n microwave input array system together with well-designed permanent magnets.

  11. Scaling Relations for Plasma Streamwise Vortex Generators

    NASA Astrophysics Data System (ADS)

    Thomas, F. O.; Wicks, M.; Corke, T. C.; Patel, M.

    2012-11-01

    A parametric investigation into the performance of plasma streamwise vortex generators (PSVG) for flow control was performed. The study utilized an array of PSVGs, which were flush mounted to a flat, zero pressure gradient turbulent boundary layer development plate. This work focused on characterizing the effect of freestream velocity, peak-to-peak applied voltage, inter-electrode spacing and covered electrode length on the streamwise vorticity produced by these devices. The performance of the PSVGs was also compared to that of passive vortex generators under identical flow conditions. Based upon the results of the parametric study, the flow physics of streamwise vorticity production by the PSVGs was discerned and the mechanisms are described in this paper. In addition, scaling relations are developed and presented for PSVGs, which, can be used in order to design actuator arrays for specific flow control applications. This work was supported by Innovative Technology Applications Company (ITAC), LLC under a Small Business Innovation Research (SBIR) Phase II Contract No. N00014-11-C-0267 issued by the U.S. Department of the Navy.

  12. Evaluation of Potential Thrombin Inhibitors from the White Mangrove (Laguncularia racemosa (L.) C.F. Gaertn.)

    PubMed Central

    Rodrigues, Caroline Fabri Bittencourt; Gaeta, Henrique Hessel; Belchor, Mariana Novo; Ferreira, Marcelo José Pena; Pinho, Marcus Vinícius Terashima; de Oliveira Toyama, Daniela; Toyama, Marcos Hikari

    2015-01-01

    The aim of this work was to verify the effects of methanol (MeOH) and hydroalcoholic (HA) extracts and their respective partition phases obtained from white mangrove (Laguncularia racemosa (L.) C.F. Gaertn.) leaves on human thrombin activity. Among the extracts and phases tested, only the ethyl acetate and butanolic partitions significantly inhibited human thrombin activity and the coagulation of plasma in the presence of this enzyme. Chromatographic analyses of the thrombin samples incubated with these phases revealed that different compounds were able to interact with thrombin. The butanolic phase of the MeOH extract had the most potent inhibitory effects, reducing enzymatic activity and thrombin-induced plasma coagulation. Two glycosylated flavonoids in this partition were identified as the most potent inhibitors of human thrombin activity, namely quercetin-3-O-arabinoside (QAra) and quercetin-3-O-rhamnoside (Qn). Chromatographic analyses of thrombin samples incubated with these flavonoids demonstrated the chemical modification of this enzyme, suggesting that the MeOH extract contained other compounds that both induced structural changes in thrombin and diminished its activity. In this article, we show that despite the near absence of the medical use of mangrove compounds, this plant contains natural compounds with potential therapeutic applications. PMID:26197325

  13. Light-curing polymers for laser plasma generation

    NASA Astrophysics Data System (ADS)

    Loktionov, E. Y.; Protasov, Y. S.; Protasov, Y. Y.; Telekh, V. D.

    2015-07-01

    Solid rather than liquid media are used in pulsed laser plasma generators despite sophisticated transportation and dosing system need for a long-term operation. Liquid media could be more preferable due to transfer and dosing (down to 10-14 L) being well developed, but plasma generation of those results in intense droplet formation and kinetic energy losses. Combination of liquids transportation advantages and solids plasma generation efficiency might resolve this trade-off. Liquid-to-solid transition can be induced by cooling down to sublimation temperature, thermo-, photo- or electron induced polymerization (curing). Light cured polymers seem to be very useful as active media for plasma generators, since they can be solidified very fast (ca. 30 ms) just before impact. We considered experimentally several UV- curing polymer and mixtures ablation regimes and supply schemes for laser plasma generation. The best results were obtained for liquid polymer at high-power pulsed irradiation matching curing optimum wavelength.

  14. Addition of in-vitro generated endothelial microparticles to von-Willebrand plasma improves primary and secondary hemostasis.

    PubMed

    Trummer, Arne; Werwitzke, Sonja; Wermes, Cornelia; Ganser, Arnold; Birschmann, Ingvild; Budde, Ulrich; Tiede, Andreas

    2014-03-01

    Increased endothelial microparticles (EMP) as markers for endothelial activation have been associated with worse outcomes in clinical prothrombotic situations. The procoagulant properties of EMP can be attributed to the expression of phospholipids, tissue factor and von-Willebrand factor on their surface. We therefore investigated whether addition of in-vitro generated EMP modifies hemostasis in plasma from patients with severe von-Willebrand disease (VWD). A large EMP pool was obtained from stimulated endothelial cell lines and EMP concentration was quantified by flow cytometry. The influence of EMP on primary and secondary hemostasis in VWD plasma was assessed using ristocetin-induced platelet aggregation (RIPA) and thrombin generation in a calibrated automated thrombogram (CAT), respectively. After addition of EMP, there was a significant increase in the maximal aggregation level in RIPA as well as a significant shortening of lag time and time-to-peak in CAT in comparison to control buffer. In summary, in vitro-generated EMP have the potential to improve hemostasis in severe VWD plasma and these results warrant further clinical reseach regarding their contribution to the clinical bleeding phenotype as well as their potential to improve replacement therapy.

  15. Tunable microwave pulse generation using discharge plasmas

    NASA Astrophysics Data System (ADS)

    Biggs, David R.; Cappelli, Mark A.

    2016-09-01

    The response of a microwave resonant cavity with a plasma discharge tube inside is (continuously or intermittently) filled with a plasma and studied both numerically and experimentally. The resonance frequency of the cavity-plasma system is sensitive to plasma densities from 1016 to 1020 m-3 corresponding to resonant frequencies of 12.3-18.3 GHz. The system is first characterized for its quasi-steady state response using a low frequency plasma discharge at 70 kHz and 125 V RMS. A plasma discharge is then driven with a high voltage pulse of 4 kV and a CW input microwave signal is converted to a pulsed output signal. The microwave pulse delay and pulse width are varied by selecting the input microwave frequency. The microwave input power is set to +20 dBm. The delay of the microwave pulse is also used as a diagnostic tool for measuring the variation of plasma density in time and, with numerical fitting, the discharge plasma recombination coefficient and diffusion timescales are estimated.

  16. New method for determining thrombin-clottable fibrinogen.

    PubMed

    Frigola, A; Angeloni, S; Cerqueti, A R

    1977-11-01

    We describe a new method for determination of thrombin-clottable fibrinogen, which eliminates the systematic error caused by occlusion of other serum proteins in the fibrin clot and reduces the sensitivity to high concentrations of fibrin degradation products. Essentially, the method consists of densitometric quantitation of the fibrin band after a standard electrophoresis run of plasma, thrombin fixation of the fibrinogen, and removal of the non-clotted proteins by washing in saline. The procedure shows good precision and gives results that are accurate, significantly correlate with results for the classical thrombin clotting method (r = 0.92, P less than .001), and are not affected by fibrin degradation product concentrations up to 900 mg/liter. These characteristics make the method especially valuable in establishing fibrogen concentration in patients who are undergoing thrombolytic therapy.

  17. Thrombin-Responsive Gated Silica Mesoporous Nanoparticles As Coagulation Regulators.

    PubMed

    Bhat, Ravishankar; Ribes, Àngela; Mas, Núria; Aznar, Elena; Sancenón, Félix; Marcos, M Dolores; Murguía, Jose R; Venkataraman, Abbaraju; Martínez-Máñez, Ramón

    2016-02-01

    The possibility of achieving sophisticated actions in complex biological environments using gated nanoparticles is an exciting prospect with much potential. We herein describe new gated mesoporous silica nanoparticles (MSN) loaded with an anticoagulant drug and capped with a peptide containing a thrombin-specific cleavage site. When the coagulation cascade was triggered, active thrombin degraded the capping peptidic sequence and induced the release of anticoagulant drugs to delay the clotting process. The thrombin-dependent response was assessed and a significant increase in coagulation time in plasma from 2.6 min to 5 min was found. This work broadens the application of gated silica nanoparticles and demonstrates their ability to act as controllers in a complex scenario such as hemostasis. PMID:26794474

  18. Inactivation of thrombin by a fucosylated chondroitin sulfate from echinoderm.

    PubMed

    Mourão, P A; Boisson-Vidal, C; Tapon-Bretaudière, J; Drouet, B; Bros, A; Fischer, A

    2001-04-15

    A polysaccharide extracted from the sea cucumber body wall has the same backbone structure as the mammalian chondroitin sulfate, but some of the glucuronic acid residues display sulfated fucose branches. These branches confer high anticoagulant activity to the polysaccharide. Since the sea cucumber chondroitin sulfate has analogy in structure with mammalian glycosaminoglycans and sulfated fucans from brown algae, we compared its anticoagulant action with that of heparin and of a homopolymeric sulfated fucan with approximately the same level of sulfation as the sulfated fucose branches found in the sea cucumber polysaccharide. These various compounds differ not only in their anticoagulant potencies but also in the mechanisms of thrombin inhibition. Fucosylated chondroitin sulfate, like heparin, requires antithrombin or heparin cofactor II for thrombin inhibition. Sulfated fucans from brown algae have an antithrombin effect mediated by antithrombin and heparin cofactor II, plus a direct antithrombin effect more pronounced for some fractions. But even in the case of these two polysaccharides, we observed some differences. In contrast with heparin, total inhibition of thrombin in the presence of antithrombin is not achieved with fucosylated chondroitin sulfate, possibly reflecting a less specific interaction. Fucosylated chondroitin sulfate is able to inhibit thrombin generation after stimulation by both contact-activated and thromboplastin-activated systems. It delayed only the contact-induced thrombin generation, as expected for an anticoagulant without direct thrombin inhibition. Overall, the specific spatial array of the sulfated fucose branches in the fucosylated chondroitin sulfate not only confer high anticoagulant activity to the polysaccharide but also determine differences in the way it inhibits thrombin.

  19. Coupling of the thrombin receptor to G12 may account for selective effects of thrombin on gene expression and DNA synthesis in 1321N1 astrocytoma cells.

    PubMed Central

    Post, G R; Collins, L R; Kennedy, E D; Moskowitz, S A; Aragay, A M; Goldstein, D; Brown, J H

    1996-01-01

    In 1321N1 astrocytoma cells, thrombin, but not carbachol, induces AP-1-mediated gene expression and DNA synthesis. To understand the divergent effects of these G protein-coupled receptor agonists on cellular responses, we examined Gq-dependent signaling events induced by thrombin receptor and muscarinic acetylcholine receptor stimulation. Thrombin and carbachol induce comparable changes in phosphoinositide and phosphatidylcholine hydrolysis, mobilization of intracellular Ca2+, diglyceride generation, and redistribution of protein kinase C; thus, activation of these Gq-signaling pathways appears to be insufficient for gene expression and mitogenesis. Thrombin increases Ras and mitogen-activated protein kinase activation to a greater extent than carbachol in 1321N1 cells. The effects of thrombin are not mediated through Gi, since ribosylation of Gi/Go proteins by pertussis toxin does not prevent thrombin-induced gene expression or thrombin-stimulated DNA synthesis. We recently reported that the pertussis toxin-insensitive G12 protein is required for thrombin-induced DNA synthesis. We demonstrate here, using transfection of receptors and G proteins in COS-7 cells, that G alpha 12 selectively couples the thrombin receptor to AP-1-mediated gene expression. This does not appear to result from increased mitogen-activated protein kinase activity but may reflect activation of a tyrosine kinase pathway. We suggest that preferential coupling of the thrombin receptor to G12 accounts for the selective ability of thrombin to stimulate Ras, mitogen-activated protein kinase, gene expression, and mitogenesis in 1321N1 cells. Images PMID:8930892

  20. Conceptual Design of Electron-Beam Generated Plasma Tools

    NASA Astrophysics Data System (ADS)

    Agarwal, Ankur; Rauf, Shahid; Dorf, Leonid; Collins, Ken; Boris, David; Walton, Scott

    2015-09-01

    Realization of the next generation of high-density nanostructured devices is predicated on etching features with atomic layer resolution, no damage and high selectivity. High energy electron beams generate plasmas with unique features that make them attractive for applications requiring monolayer precision. In these plasmas, high energy beam electrons ionize the background gas and the resultant daughter electrons cool to low temperatures via collisions with gas molecules and lack of any accelerating fields. For example, an electron temperature of <0.6 eV with densities comparable to conventional plasma sources can be obtained in molecular gases. The chemistry in such plasmas can significantly differ from RF plasmas as the ions/radicals are produced primarily by beam electrons rather than those in the tail of a low energy distribution. In this work, we will discuss the conceptual design of an electron beam based plasma processing system. Plasma properties will be discussed for Ar, Ar/N2, and O2 plasmas using a computational plasma model, and comparisons made to experiments. The fluid plasma model is coupled to a Monte Carlo kinetic model for beam electrons which considers gas phase collisions and the effect of electric and magnetic fields on electron motion. The impact of critical operating parameters such as magnetic field, beam energy, and gas pressure on plasma characteristics in electron-beam plasma processing systems will be discussed. Partially supported by the NRL base program.

  1. Atorvastatin neutralises the thrombin-induced tissue factor expresion in endothelial cells via geranylgeranyl pyrophosphate.

    PubMed

    Martínez-Sales, Vicenta; Vila, Virtudes; Ferrando, Marcos; Reganon, Edelmiro

    2011-01-01

    Statins may have beneficial effects in atherogenesis given their antithrombotic properties involving non-lipid mechanisms that modify endothelial function of tissue factor induction by thrombin. In this study, we investigate the effect of atorvastatin on tissue factor (TF) activity in thrombin-stimulated endothelial cells and its regulation through mevalonate or its derivatives. First subculture of human umbilical endothelial cells was used for this study. Cells were treated with thrombin and atorvastatin for different time intervals and dosage. Tissue factor activity was measured as Factor Xa generation induced by Tissue Factor-Factor VIIa complex on confluent cells. Our results show that atorvastatin prevents the thrombin-induced up-regulation of tissue factor activity in a concentration-dependent manner. Mevalonate and geranylgeranyl pyrophosphate reversed this inhibitory effect of atorvastatin on tissue factor activity, while the presence of farnesyl pyrophosphate did not prevent the atorvastatin effect on thrombin-induced tissue factor activity. Rho-kinase inhibitor did not affect the thrombin stimulation of tissue factor activity. High amount of hydrophobic isoprenoid groups decreases the thrombin-induced TF activity and may promote endothelial cell anti-thrombotic action. Rho kinase pathways do not have a major role in the thrombin-mediated TF activity. The inhibitory effect of atorvastatin on thrombin-induced TF activity was partially reversed by MVA and GGPP but not FPP.

  2. Terahertz generation in multiple laser-induced air plasmas

    SciTech Connect

    Chen, M.-K.; Kim, Jae Hun; Yang, C.-E.; Yin, Stuart Shizhuo; Hui Rongqing; Ruffin, Paul

    2008-12-08

    An investigation of the terahertz wave generation in multiple laser-induced air plasmas is presented. First, it is demonstrated that the intensity of the terahertz wave increases as the number of air plasmas increases. Second, the physical mechanism of this enhancement effect of the terahertz generation is studied by quantitatively measuring the intensity of the generated terahertz wave as a function of phase difference between adjacent air plasmas. It is found out that the superposition is the main mechanism to cause this enhancement. Thus, the results obtained in this paper not only provide a technique to generate stronger terahertz wave but also enable a better understanding of the mechanism of the terahertz generation in air plasma.

  3. Slot-Antenna/Permanent-Magnet Device for Generating Plasma

    NASA Technical Reports Server (NTRS)

    Foster, John E.

    2007-01-01

    A device that includes a rectangular-waveguide/slot-antenna structure and permanent magnets has been devised as a means of generating a substantially uniform plasma over a relatively large area, using relatively low input power and a low gas flow rate. The device utilizes electron cyclotron resonance (ECR) excited by microwave power to efficiently generate plasma in a manner that is completely electrodeless in the sense that, in principle, there is no electrical contact between the plasma and the antenna. Plasmas generated by devices like this one are suitable for use as sources of ions and/or electrons for diverse material-processing applications (e.g., etching or deposition) and for ion thrusters. The absence of plasma/electrode contact essentially prevents plasma-induced erosion of the antenna, thereby also helping to minimize contamination of the plasma and of objects exposed to the plasma. Consequently, the operational lifetime of the rectangular-waveguide/ slot-antenna structure is long and the lifetime of the plasma source is limited by the lifetime of the associated charged-particle-extraction grid (if used) or the lifetime of the microwave power source. The device includes a series of matched radiating slot pairs that are distributed along the length of a plasma-source discharge chamber (see figure). This arrangement enables the production of plasma in a distributed fashion, thereby giving rise to a uniform plasma profile. A uniform plasma profile is necessary for uniformity in any electron- or ion-extraction electrostatic optics. The slotted configuration of the waveguide/ antenna structure makes the device scalable to larger areas and higher powers. All that is needed for scaling up is the attachment of additional matched radiating slots along the length of the discharge chamber. If it is desired to make the power per slot remain constant in scaling up, then the input microwave power must be increased accordingly. Unlike in prior ECR microwave plasma-generating

  4. Investigation of thermal plasma generator of technological function

    NASA Astrophysics Data System (ADS)

    Anshakov, A. S.; Urbakh, E. K.; Cherednichenko, V. S.; Kuzmin, M. G.; Urbakh, A. E.

    2015-11-01

    Experimental results on energy characteristics of electric-arc plasma generator for heating technical nitrogen with the power of up to 500 kW are presented. The features of arc discharge glow, thermal efficiency, and service life of the electrodes were determined under the regime of melting the metallurgical raw material in the test plasma electric furnace.

  5. Plasma treatment for next-generation nanobiointerfaces.

    PubMed

    Levchenko, Igor; Keidar, Michael; Mai-Prochnow, Anne; Modic, Martina; Cvelbar, Uros; Fang, Jinghua; Ostrikov, Kostya Ken

    2015-01-01

    Energy deficiency, global poverty, chronic hunger, chronic diseases, and environment conservation are among the major problems threatening the whole mankind. Nanostructure-based technologies could be a possible solution. Such techniques are now used for the production of many vitally important products including cultured and fermented food, antibiotics, various medicines, and biofuels. On the other hand, the nanostructure-based technologies still demonstrate low efficiency and controllability, and thus still are not capable to decisively address the global problems. Furthermore, future technologies should ensure lowest possible environmental impact by implementing green production principles. One of the most promising approaches to address these challenges are the sophisticatedly engineered biointerfaces. Here, the authors briefly evaluate the potential of the plasma-based techniques for the fabrication of complex biointerfaces. The authors consider mainly the atmospheric and inductively coupled plasma environments and show several examples of the artificial plasma-created biointerfaces, which can be used for the biotechnological and medical processes, as well as for the drug delivery devices, fluidised bed bioreactors, catalytic reactors, and others. A special attention is paid to the plasma-based treatment and processing of the biointerfaces formed by arrays of carbon nanotubes and graphene flakes. PMID:26104191

  6. Inductively generated streaming plasma ion source

    DOEpatents

    Glidden, Steven C.; Sanders, Howard D.; Greenly, John B.

    2006-07-25

    A novel pulsed, neutralized ion beam source is provided. The source uses pulsed inductive breakdown of neutral gas, and magnetic acceleration and control of the resulting plasma, to form a beam. The beam supplies ions for applications requiring excellent control of ion species, low remittance, high current density, and spatial uniformity.

  7. Ultra-High Intensity Magnetic Field Generation in Dense Plasma

    SciTech Connect

    Fisch, Nathaniel J

    2014-01-08

    I. Grant Objective The main objective of this grant proposal was to explore the efficient generation of intense currents. Whereasthefficient generation of electric current in low-­energy-­density plasma has occupied the attention of the magnetic fusion community for several decades, scant attention has been paid to carrying over to high-­energy-­density plasma the ideas for steady-­state current drive developed for low-­energy-­density plasma, or, for that matter, to inventing new methodologies for generating electric current in high-­energy-­density plasma. What we proposed to do was to identify new mechanisms to accomplish current generation, and to assess the operation, physics, and engineering basis of new forms of current drive in regimes appropriate for new fusion concepts.

  8. A research program in magnetogasdynamics utilizing hypervelocity coaxial plasma generators

    NASA Technical Reports Server (NTRS)

    Spight, C.

    1976-01-01

    A broadly-gauged research program in magnetogasdynamics utilizing hypervelocity coaxial plasma generators is presented. A complete hypervelocity coaxial plasma generator facility was assembled and tested. Significant progress was made in the direction of understanding the important processes in the interaction of hypervelocity MGD flow with transverse applied fields. It is now proposed to utilize the accumulated experimental capability and theoretical analysis in application to the analysis and design parameterization of pulsed magnetogasdynamic direct energy convertor configurations.

  9. Electron beam manipulation, injection and acceleration in plasma wakefield accelerators by optically generated plasma density spikes

    NASA Astrophysics Data System (ADS)

    Wittig, Georg; Karger, Oliver S.; Knetsch, Alexander; Xi, Yunfeng; Deng, Aihua; Rosenzweig, James B.; Bruhwiler, David L.; Smith, Jonathan; Sheng, Zheng-Ming; Jaroszynski, Dino A.; Manahan, Grace G.; Hidding, Bernhard

    2016-09-01

    We discuss considerations regarding a novel and robust scheme for optically triggered electron bunch generation in plasma wakefield accelerators [1]. In this technique, a transversely propagating focused laser pulse ignites a quasi-stationary plasma column before the arrival of the plasma wake. This localized plasma density enhancement or optical "plasma torch" distorts the blowout during the arrival of the electron drive bunch and modifies the electron trajectories, resulting in controlled injection. By changing the gas density, and the laser pulse parameters such as beam waist and intensity, and by moving the focal point of the laser pulse, the shape of the plasma torch, and therefore the generated trailing beam, can be tuned easily. The proposed method is much more flexible and faster in generating gas density transitions when compared to hydrodynamics-based methods, and it accommodates experimentalists needs as it is a purely optical process and straightforward to implement.

  10. The Importance of Thrombin in Cerebral Injury and Disease

    PubMed Central

    Krenzlin, Harald; Lorenz, Viola; Danckwardt, Sven; Kempski, Oliver; Alessandri, Beat

    2016-01-01

    There is increasing evidence that prothrombin and its active derivative thrombin are expressed locally in the central nervous system. So far, little is known about the physiological and pathophysiological functions exerted by thrombin in the human brain. Extra-hepatic prothrombin expression has been identified in neuronal cells and astrocytes via mRNA measurement. The actual amount of brain derived prothrombin is expected to be 1% or less compared to that in the liver. The role in brain injury depends upon its concentration, as higher amounts cause neuroinflammation and apoptosis, while lower concentrations might even be cytoprotective. Its involvement in numerous diseases like Alzheimer’s, multiple sclerosis, cerebral ischemia and haemorrhage is becoming increasingly clear. This review focuses on elucidation of the cerebral thrombin expression, local generation and its role in injury and disease of the central nervous system. PMID:26761005

  11. Millimeter-wave generation via plasma three-wave mixing

    NASA Astrophysics Data System (ADS)

    Schumacher, Robert W.; Santoru, Joseph

    1988-06-01

    Plasma three-wave mixing is a collective phenomena whereby electron-beam-driven electron plasma waves (EPWs) are nonlinearly coupled to an electromagnetic (EM) radiation field. The basic physics of three-wave mixing is investigated in the mm-wave regime and the scaling of mm-wave characteristics established with beam and plasma parameters. Our approach is to employ two counterinjected electron beams in a plasma-loaded circular waveguide to drive counterstreaming EPWs. The nonlinear coupling of these waves generates an EM waveguide mode which oscillates at twice the plasma frequency and is coupled out into rectangular waveguides. Independent control of the waveguide plasma, beam voltage, and beam current is exercised to allow a careful parametric investigation of beam transport, EPW dynamics and three-wave-mixing physics. The beam-plasma experiment, which employs a wire-anode discharge to generate high-density plasma in a 3.8 cm-diameter waveguide, has been used to generate radiation at frequencies from 7 to 60 GHz. Two cold-cathode, secondary-emission electron guns are used to excite the EPWs. Output radiation is observed only when both beams are injected, and the total beam current exceeds a threshold value of 3 A. The threshold is related to the self-magnetic pinch of each beam which increases the beam density and growth rate of the EPWs.

  12. Plasma erosion switches with imploding plasma loads on the pithon generator

    NASA Astrophysics Data System (ADS)

    Stringfield, R.; Schneider, R.; Genuario, R. D.; Roth, I.; Childers, K.; Stallings, C.; Dakin, D.

    1981-03-01

    Plasma erosion switches have been fielded on the PITHON generator during imploding plasma experiments. Theta pinch plasma guns were used to inject carbon plasmas of densities in the range 10 12-10 14/cm 3 between the electrodes of the vacuum power feed region, upstream from an imploding plasma load. Current monitors indicated that the erosion switches carried substantial current early in time, diverting it from the load. Late in the pulse the erosion switches opened, transferring the current to an imploding plasma with the effect of sharpening the current risetime at the load. Associated with the sharper risetime was an improvement in the quality of the plasma implosions. The results of varying the density and total number of particles in the plasma of the switches are presented with regard to the effect on the current along the vacuum feed and on the behavior of vacuum flowing electrons.

  13. Plasma erosion switches with imploding plasma loads on a multiterawatt pulsed power generator

    NASA Astrophysics Data System (ADS)

    Stringfield, R.; Schneider, R.; Genuario, R. D.; Roth, I.; Childers, K.; Stallings, C.; Dakin, D.

    1981-03-01

    Plasma erosion switches have been fielded on the PITHON generator during imploding plasma experiments. Theta pinch plasma guns were used to inject carbon plasmas of densities in the range of 10 to the 12th to 10 to the 14th/cu cm between the electrodes of the vacuum power feed region, upstream from an imploding plasma load. Current monitors indicated that the erosion switches carried substantial current early in time, diverting it from the load. Late in the pulse the erosion switches opened, transferring the current to an imploding plasma with the effect of sharpening the current rise time at the load. Associated with the sharper rise time was an improvement in the quality of the plasma implosions. The results of varying the density and total number of particles in the plasma of the switches are presented with regard to the effect on the current along the vacuum feed and on the behavior of vacuum flowing electrons.

  14. A large volume uniform plasma generator for the experiments of electromagnetic wave propagation in plasma

    SciTech Connect

    Yang Min; Li Xiaoping; Xie Kai; Liu Donglin; Liu Yanming

    2013-01-15

    A large volume uniform plasma generator is proposed for the experiments of electromagnetic (EM) wave propagation in plasma, to reproduce a 'black out' phenomenon with long duration in an environment of the ordinary laboratory. The plasma generator achieves a controllable approximate uniform plasma in volume of 260 mm Multiplication-Sign 260 mm Multiplication-Sign 180 mm without the magnetic confinement. The plasma is produced by the glow discharge, and the special discharge structure is built to bring a steady approximate uniform plasma environment in the electromagnetic wave propagation path without any other barriers. In addition, the electron density and luminosity distributions of plasma under different discharge conditions were diagnosed and experimentally investigated. Both the electron density and the plasma uniformity are directly proportional to the input power and in roughly reverse proportion to the gas pressure in the chamber. Furthermore, the experiments of electromagnetic wave propagation in plasma are conducted in this plasma generator. Blackout phenomena at GPS signal are observed under this system and the measured attenuation curve is of reasonable agreement with the theoretical one, which suggests the effectiveness of the proposed method.

  15. A portable microchip for ultrasensitive and high-throughput assay of thrombin by rolling circle amplification and hemin/G-quadruplex system.

    PubMed

    Lin, Xuexia; Chen, Qiushui; Liu, Wu; Li, Haifang; Lin, Jin-Ming

    2014-06-15

    In this work, a convenient and high-throughput colorimetric assay was developed on an aptamer-modified microchip for ultrasensitive detection of thrombin using rolling circle amplification and G-quadruplex DNAzyme. This system consisted of an aptamer-modified microchip and a secondary aptamer. The secondary aptamer contained a thrombin aptamer and a primer with a G-quadruplex circular template. RCA technology was used to improve the sensitivity by producing the multiple G-quadruplex units. To generate colorimetric signal, G-quadruplex DNAzyme was used to catalyze the H2O2-mediated oxidation of 2,2'-azinobis (3-ethylbenzothiozoline)-6-sulfonic acid. At the optimal conditions, the linear range for thrombin was 0.100-50.000 pg/mL, and the limit of detection was down to 0.083 pg/mL. Moreover, the developed method was successfully applied to detect thrombin from human plasma and serum, indicating that this approach has great potential in clinical diagnosis and medical investigation.

  16. Thrombostatin FM compounds: direct thrombin inhibitors – mechanism of action in vitro and in vivo

    PubMed Central

    Nieman, M. T.; Burke, F.; Warnock, M.; Zhou, Y.; Sweigart, J.; Chen, A.; Ricketts, D.; Lucchesi, B. R.; Chen, Z.; Di Cera, E.; Hilfinger, J.; Kim, J. S.; Mosberg, H. I.; Schmaier, A. H.

    2009-01-01

    Summary Background Novel pentapeptides called Thrombostatin FM compounds consisting mostly of D-isomers and unusual amino acids were prepared based upon the stable angiotensin converting enzyme breakdown product of bradykinin – RPPGF. Methods and Results These peptides are direct thrombin inhibitors prolonging the thrombin clotting time, activated partial thromboplastin time, and prothrombin time at ≥0.78, 1.6, and 1.6 µm, respectively. They competitively inhibit α-thrombin-induced cleavage of a chromogenic substrate at 4.4–8.2 µm. They do not significantly inhibit plasma kallikrein, factor (F) XIIa, FXIa, FIXa, FVIIa-TF, FXa, plasmin or cathepsin G. One form, FM19 [rOicPaF(p-Me)], blocks α-thrombin-induced calcium flux in fibroblasts with an IC50 of 6.9 ± 1.2 µm. FM19 achieved 100% inhibition of threshold α- or γ-thrombin-induced platelet aggregation at 8.4 ± 4.7 µm and 16 ± 4 µm, respectively. The crystal structure of thrombin in complex with FM19 shows that the N-terminal D-Arg retrobinds into the S1 pocket, its second residue Oic interacts with His-57, Tyr-60a and Trp-60d, and its C-terminal p-methyl Phe engages thrombin_s aryl binding site composed of Ile-174, Trp-215, and Leu-99. When administered intraperitoneal, intraduodenal, or orally to mice, FM19 prolongs thrombin clotting times and delays carotid artery thrombosis. Conclusion FM19, a low affinity reversible direct thrombin inhibitor, might be useful as an add-on agent to address an unmet need in platelet inhibition in acute coronary syndromes in diabetics and others who with all current antiplatelet therapy still have reactive platelets. PMID:18315550

  17. Optical monitoring of laser-generated plasma during laser welding

    NASA Astrophysics Data System (ADS)

    Connolly, John O.; Beirne, Gareth J.; O'Connor, Gerard M.; Glynn, Thomas J.; Conneely, Alan J.

    2000-03-01

    Process monitoring is a vital part of industrial laser applications that enables intelligent control of processes by observing acoustic, optical, thermal and other emissions. By monitoring these emission during laser processing, it is possible to ascertain characteristics that help diagnose features of the laser processed material and hence to optimize the technique. An experimental set up of observing plasmas during laser spot welding is described here. A pulsed Nd:YAG laser was used to spot-weld a variety of materials of different thickness, the plasmas generated during welding were monitored by a number of techniques, and the data obtained was used to characterize the welds. In the study photodiodes were set at different angles and observed the intensity and generation of the plasmas during the laser spot-welding process thereby giving a weld 'signature.' A portable spectrometer was used off-axis to obtain spectra of the emissions from the plasmas. Post process analysis was performed on the materials by mechanical polishing and chemical etching and observations of weld penetration depth and weld quality were correlated with the data collected on the plasmas. Different cover gases were also used during laser welding and the results of the effects of the various gases on the plasma are shown. The results indicate the relationship between laser weld generated plasma characteristics and weld features such as penetration depth. A direct correlation between the intensities of the photodiode and portable spectrometer signals was observed with weld penetration depth.

  18. How Na+ Activates Thrombin – A Review of the Functional and Structural Data

    PubMed Central

    Huntington, James A.

    2009-01-01

    Thrombin is often referred to as the ultimate blood coagulation protease. This is true in both senses: it is the final protease generated in the series of proteolytic events known as the blood coagulation cascade, and it is the effector of clot formation, cleaving over twelve different substrates and interacting with at least six cofactors. Regulation of thrombin activity is thus of great relevance to determining the correct haemostatic balance, with dysregulation leading to bleeding or thrombosis. One of the most enigmatic and controversial regulators of thrombin activity is the monovalent cation Na+. When bound to Na+, thrombin adopts a ‘fast’ conformation which cleaves all procoagulant substrates more rapidly, and when free of Na+, thrombin reverts to a ‘slow’ state which preferentially activates the protein C anticoagulant pathway. Thus, Na+ binding allosterically modulates the activity of thrombin and helps determine the haemostatic balance. Over the last 30 years there has been a great deal of research into the structural basis of thrombin allostery. Biochemical and mutagenesis studies established which regions and residues are involved in the slow→fast conformational change, and recently several crystal structures of the putative slow form have been solved. In this article I review the biochemical and crystallographic data to see if we are any closer to understanding the conformational basis of the Na+ activation of thrombin. PMID:18979627

  19. Thrombin-linked aptamer assay for detection of platelet derived growth factor BB on magnetic beads in a sandwich format.

    PubMed

    Guo, Limin; Zhao, Qiang

    2016-09-01

    Here we describe a thrombin-linked aptamer assay (TLAA) for protein by using thrombin as an enzyme label, harnessing enzyme activity of thrombin and aptamer affinity binding. TLAA converts detection of specific target proteins to the detection of thrombin by using a DNA sequence that consists of two aptamers with the first aptamer binding to the specific target protein and the second aptamer binding to thrombin. Through the affinity binding, the thrombin enzyme is labeled on the protein target, and thrombin catalyzes the hydrolysis of small peptide substrate into product, generating signals for quantification. As a proof of principle, we show a sandwich TLAA for platelet derived growth factor BB (PDGF-BB) by using anti-PDGF-BB antibody coated on magnetic beads and an oligonucleotide containing the aptamer for PDGF-BB and the aptamer for thrombin. The binding of PDGF-BB to both the antibody and the aptamer results in labeling the complex with thrombin. We achieved detection of PDGF-BB at 16 pM. This TLAA contributes a new application of thrombin and its aptamer in bioanalysis, and shows potentials in assay developments. PMID:27343590

  20. Generation of Diffuse Large Volume Plasma by an Ionization Wave from a Plasma Jet

    NASA Astrophysics Data System (ADS)

    Laroussi, Mounir; Razavi, Hamid

    2015-09-01

    Low temperature plasma jets emitted in ambient air are the product of fast ionization waves that are guided within a channel of a gas flow, such as helium. This guided ionization wave can be transmitted through a dielectric material and under some conditions can ignite a discharge behind the dielectric material. Here we present a novel way to produce large volume diffuse low pressure plasma inside a Pyrex chamber that does not have any electrodes or electrical energy directly applied to it. The diffuse plasma is ignited inside the chamber by a plasma jet located externally to the chamber and that is physically and electrically unconnected to the chamber. Instead, the plasma jet is just brought in close proximity to the external wall/surface of the chamber or to a dielectric tubing connected to the chamber. The plasma thus generated is diffuse, large volume and with physical and chemical characteristics that are different than the external plasma jet that ignited it. So by using a plasma jet we are able to ``remotely'' ignite volumetric plasma under controlled conditions. This novel method of ``remote'' generation of a low pressure, low temperature diffuse plasma can be useful for various applications including material processing and biomedicine.

  1. The Dynamical Generation of Current Sheets in Astrophysical Plasma Turbulence

    NASA Astrophysics Data System (ADS)

    Howes, Gregory G.

    2016-08-01

    Turbulence profoundly affects particle transport and plasma heating in many astrophysical plasma environments, from galaxy clusters to the solar corona and solar wind to Earth's magnetosphere. Both fluid and kinetic simulations of plasma turbulence ubiquitously generate coherent structures, in the form of current sheets, at small scales, and the locations of these current sheets appear to be associated with enhanced rates of dissipation of the turbulent energy. Therefore, illuminating the origin and nature of these current sheets is critical to identifying the dominant physical mechanisms of dissipation, a primary aim at the forefront of plasma turbulence research. Here, we present evidence from nonlinear gyrokinetic simulations that strong nonlinear interactions between counterpropagating Alfvén waves, or strong Alfvén wave collisions, are a natural mechanism for the generation of current sheets in plasma turbulence. Furthermore, we conceptually explain this current sheet development in terms of the nonlinear dynamics of Alfvén wave collisions, showing that these current sheets arise through constructive interference among the initial Alfvén waves and nonlinearly generated modes. The properties of current sheets generated by strong Alfvén wave collisions are compared to published observations of current sheets in the Earth's magnetosheath and the solar wind, and the nature of these current sheets leads to the expectation that Landau damping of the constituent Alfvén waves plays a dominant role in the damping of turbulently generated current sheets.

  2. Thomson parabola spectrometry for gold laser-generated plasmas

    SciTech Connect

    Torrisi, L.; Cutroneo, M.; Ando, L.; Ullschmied, J.

    2013-02-15

    The plasma generated from thin gold films irradiated in high vacuum at high intensity ({approx}10{sup 15} W/cm{sup 2}) laser shot is characterized in terms of ion generation through time-of-flight techniques and Thomson parabola spectrometry. Gold ions and protons, accelerated in forward direction by the electric field developed in non-equilibrium plasma, have been investigated. Measurements, performed at PALS laboratory, give information about the gold charge states distributions, the ion energy distributions and the proton acceleration driven as a function of film thickness, laser parameters, and angular emission. The ion diagnostics of produced plasma in forward direction permits to understand some mechanisms developed during its expansion kinetics. The role of the focal position of a laser beam with respect to the target surface, plasma properties, and the possibility to accelerate protons up to energies above 3 MeV has been presented and discussed.

  3. Electrode assemblies, plasma apparatuses and systems including electrode assemblies, and methods for generating plasma

    DOEpatents

    Kong, Peter C; Grandy, Jon D; Detering, Brent A; Zuck, Larry D

    2013-09-17

    Electrode assemblies for plasma reactors include a structure or device for constraining an arc endpoint to a selected area or region on an electrode. In some embodiments, the structure or device may comprise one or more insulating members covering a portion of an electrode. In additional embodiments, the structure or device may provide a magnetic field configured to control a location of an arc endpoint on the electrode. Plasma generating modules, apparatus, and systems include such electrode assemblies. Methods for generating a plasma include covering at least a portion of a surface of an electrode with an electrically insulating member to constrain a location of an arc endpoint on the electrode. Additional methods for generating a plasma include generating a magnetic field to constrain a location of an arc endpoint on an electrode.

  4. Charge-exchange plasma generated by an ion thruster

    NASA Technical Reports Server (NTRS)

    Kaufman, H. R.

    1977-01-01

    The charge exchange plasma generated by an ion thruster was investigated experimentally using both 5 cm and 15 cm thrusters. Results are shown for wide ranges of radial distance from the thruster and angle from the beam direction. Considerations of test environment, as well as distance from the thruster, indicate that a valid simulation of a thruster on a spacecraft was obtained. A calculation procedure and a sample calculation of charge exchange plasma density and saturation electron current density are included.

  5. Spontaneous generation of rotation in tokamak plasmas

    SciTech Connect

    Parra Diaz, Felix

    2013-12-24

    Three different aspects of intrinsic rotation have been treated. i) A new, first principles model for intrinsic rotation [F.I. Parra, M. Barnes and P.J. Catto, Nucl. Fusion 51, 113001 (2011)] has been implemented in the gyrokinetic code GS2. The results obtained with the code are consistent with several experimental observations, namely the rotation peaking observed after an L-H transition, the rotation reversal observed in Ohmic plasmas, and the change in rotation that follows Lower Hybrid wave injection. ii) The model in [F.I. Parra, M. Barnes and P.J. Catto, Nucl. Fusion 51, 113001 (2011)] has several simplifying assumptions that seem to be satisfied in most tokamaks. To check the importance of these hypotheses, first principles equations that do not rely on these simplifying assumptions have been derived, and a version of these new equations has been implemented in GS2 as well. iii) A tokamak cross-section that drives large intrinsic rotation has been proposed for future large tokamaks. In large tokamaks, intrinsic rotation is expected to be very small unless some up-down asymmetry is introduced. The research conducted under this contract indicates that tilted ellipticity is the most efficient way to drive intrinsic rotation.

  6. Edge Plasma Boundary Layer Generated By Kink Modes in Tokamaks

    SciTech Connect

    L.E. Zakharov

    2010-11-22

    This paper describes the structure of the electric current generated by external kink modes at the plasma edge using the ideally conducting plasma model. It is found that the edge current layer is created by both wall touching and free boundary kink modes. Near marginal stability, the total edge current has a universal expression as a result of partial compensation of the δ-functional surface current by the bulk current at the edge. The resolution of an apparent paradox with the pressure balance across the plasma boundary in the presence of the surface currents is provided.

  7. Magnetic Cusp Configuration of the SPL Plasma Generator

    SciTech Connect

    Kronberger, Matthias; Chaudet, Elodie; Favre, Gilles; Lettry, Jacques; Kuechler, Detlef; Moyret, Pierre; Paoluzzi, Mauro; Prever-Loiri, Laurent; Schmitzer, Claus; Scrivens, Richard; Steyaert, Didier

    2011-09-26

    The Superconducting Proton Linac (SPL) is a novel linear accelerator concept currently studied at CERN. As part of this study, a new Cs-free, RF-driven external antenna H{sup -} plasma generator has been developed to withstand an average thermal load of 6 kW. The magnetic configuration of the new plasma generator includes a dodecapole cusp field and a filter field separating the plasma heating and H{sup -} production regions. Ferrites surrounding the RF antenna serve in enhancing the coupling of the RF to the plasma. Due to the space requirements of the plasma chamber cooling circuit, the cusp magnets are pushed outwards compared to Linac4 and the cusp field strength in the plasma region is reduced by 40% when N-S magnetized magnets are used. The cusp field strength and plasma confinement can be improved by replacing the N-S magnets with offset Halbach elements of which each consists of three magnetic sub-elements with different magnetization direction. A design challenge is the dissipation of RF power induced by eddy currents in the cusp and filter magnets which may lead to overheating and demagnetization. In view of this, a copper magnet cage has been developed that shields the cusp magnets from the radiation of the RF antenna.

  8. A study of single and binary ion plasma expansion into laboratory-generated plasma wakes

    NASA Technical Reports Server (NTRS)

    Wright, Kenneth Herbert, Jr.

    1988-01-01

    Plasma expansion into the wake of a large rectangular plate immersed in a collisionless, supersonic plasma was investigated in laboratory experiments. The experimental conditions address both single ion and binary ion plasma flows for the case of a body whose size is large in comparison with the Debye length, when the potential difference between the body and the plasma is relatively small. A new plasma source was developed to generate equi-velocity, binary ion plasma flows, which allows access to new parameter space that have previously been unavailable for laboratory studies. Specifically, the new parameters are the ionic mass ratio and the ionic component density ratio. In a series of experiments, a krypton-neon plasma is employed where the ambient density ratio of neon to krypton is varied more than an order of magnitude. The expansion in both the single ion and binary ion plasma cases is limited to early times, i.e., a few ion plasma periods, by the combination of plasma density, plasma drift speed, and vacuum chamber size, which prevented detailed comparison with self-similar theory.

  9. Generation of low-temperature air plasma for food processing

    NASA Astrophysics Data System (ADS)

    Stepanova, Olga; Demidova, Maria; Astafiev, Alexander; Pinchuk, Mikhail; Balkir, Pinar; Turantas, Fulya

    2015-11-01

    The project is aimed at developing a physical and technical foundation of generating plasma with low gas temperature at atmospheric pressure for food industry needs. As known, plasma has an antimicrobial effect on the numerous types of microorganisms, including those that cause food spoilage. In this work an original experimental setup has been developed for the treatment of different foods. It is based on initiating corona or dielectric-barrier discharge in a chamber filled with ambient air in combination with a certain helium admixture. The experimental setup provides various conditions of discharge generation (including discharge gap geometry, supply voltage, velocity of gas flow, content of helium admixture in air and working pressure) and allows for the measurement of the electrical discharge parameters. Some recommendations on choosing optimal conditions of discharge generation for experiments on plasma food processing are developed.

  10. Analyses of the plasma generated by laser irradiation on sputtered target for determination of the thickness used for plasma generation

    SciTech Connect

    Kumaki, Masafumi; Ikeda, Shunsuke; Sekine, Megumi; Munemoto, Naoya; Fuwa, Yasuhiro; Cinquegrani, David; Kanesue, Takeshi; Okamura, Masahiro; Washio, Masakazu

    2014-02-15

    In Brookhaven National Laboratory, laser ion source has been developed to provide heavy ion beams by using plasma generation with 1064 nm Nd:YAG laser irradiation onto solid targets. The laser energy is transferred to the target material and creates a crater on the surface. However, only the partial material can be turned into plasma state and the other portion is considered to be just vaporized. Since heat propagation in the target material requires more than typical laser irradiation period, which is typically several ns, only the certain depth of the layers may contribute to form the plasma. As a result, the depth is more than 500 nm because the base material Al ions were detected. On the other hand, the result of comparing each carbon thickness case suggests that the surface carbon layer is not contributed to generate plasma.

  11. Harmonic generation by circularly polarized laser beams propagating in plasma

    SciTech Connect

    Agrawal, Ekta; Hemlata,; Jha, Pallavi

    2015-04-15

    An analytical theory is developed for studying the phenomenon of generation of harmonics by the propagation of an obliquely incident, circularly polarized laser beam in homogeneous, underdense plasma. The amplitudes of second and third harmonic radiation as well as detuning distance have been obtained and their variation with the angle of incidence is analyzed. The amplitude of harmonic radiation increases with the angle of incidence while the detuning distance decreases, for a given plasma electron density. It is observed that the generated second and third harmonic radiation is linearly and elliptically polarized, respectively. The harmonic radiation vanishes at normal incidence of the circularly polarized laser beam.

  12. High-Quality Ion Beam Generation in Laser Plasma Interaction

    NASA Astrophysics Data System (ADS)

    Nagashima, Toshihiro; Takano, Masahiro; Izumiyzma, Takeshi; Barada, Daisuke; Kawata, Shigeo; Gu, Yan Jun; Kong, Qing; Xiao Wang, Ping; Ma, Yan Yun; Wang, Wei Min

    We focus on a control of generation of high-quality ion beam. In this study, near-critical density plasmas are employed and are illuminated by high intensity short laser pulses; we have successfully generated high-energy ions by multiple-stages acceleration. We performed particle-in-cell simulations in this paper. Near-critical density plasmas are employed at the proton source and also in the post acceleration. A beam bunching method is also proposed to control the ion beam length.

  13. Thrombostatin FM compounds: direct thrombin inhibitors - mechanism of action in vitro and in vivo

    SciTech Connect

    Nieman, M T; Burke, F; Warnock, M; Zhou, Y; Sweigart, J; Chen, A; Ricketts, D; Lucchesi, B R; Chen, Z; Cera, E Di; Hilfinger, J; Kim, J S; Mosberg, H I; Schmaier, A H

    2008-04-29

    Novel pentapeptides called Thrombostatin FM compounds consisting mostly of D-isomers and unusual amino acids were prepared based upon the stable angiotensin converting enzyme breakdown product of bradykinin - RPPGF. These peptides are direct thrombin inhibitors prolonging the thrombin clotting time, activated partial thromboplastin time, and prothrombin time at ≥0.78, 1.6, and 1.6 μm, respectively. They competitively inhibit α-thrombin-induced cleavage of a chromogenic substrate at 4.4--8.2 μm. They do not significantly inhibit plasma kallikrein, factor (F) XIIa, FXIa, FIXa, FVIIa-TF, FXa, plasmin or cathepsin G. One form, FM19 [rOicPaF(p-Me)], blocks α-thrombin-induced calcium flux in fibroblasts with an IC50 of 6.9 ± 1.2 μm. FM19 achieved 100% inhibition of threshold α- or γ-thrombin-induced platelet aggregation at 8.4 ± 4.7 μm and 16 ± 4 μm, respectively. The crystal structure of thrombin in complex with FM19 shows that the N-terminal D-Arg retrobinds into the S1 pocket, its second residue Oic interacts with His-57, Tyr-60a and Trp-60d, and its C-terminal p-methyl Phe engages thrombin's aryl binding site composed of Ile-174, Trp-215, and Leu-99. When administered intraperitoneal, intraduodenal, or orally to mice, FM19 prolongs thrombin clotting times and delays carotid artery thrombosis. FM19, a low affinity reversible direct thrombin inhibitor, might be useful as an add-on agent to address an unmet need in platelet inhibition in acute coronary syndromes in diabetics and others who with all current antiplatelet therapy still have reactive platelets.

  14. Zinc modulates thrombin adsorption to fibrin

    SciTech Connect

    Hopmeier, P.; Halbmayer, M.; Fischer, M.; Marx, G. )

    1990-05-01

    Human thrombin with high affinity to Sepharose insolubilized fibrin monomers (high-affinity thrombin) was used to investigate the effect of Zn(II) on the thrombin adsorption to fibrin. Results showed that at Zn(II) concentrations exceeding 100 mumols/l, thrombin binding to fibrin was decreased concomitant with the Zn(II) concentration and time; at lower Zn(II) concentrations, thrombin adsorption was enhanced. Experimental results were identical by using 125I-labelled high-affinity alpha-thrombin or by measuring the thrombin activity either by chromogenic substrate or by a clotting time method. In contrast, Ca(II) alone (final conc. 3 mmol/l) or in combination with Zn(II) was not effective. However, at higher Ca(II) concentrations (7.5-15 mmol/l), thrombin adsorption was apparently decreased. Control experiments revealed that Zn(II) had no impact on the clottability of fibrinogen, and that the results of the experiments with Ca(II) were not altered by possible cross-linking of fibrin. We conclude that unlike Ca(II), Zn(II) is highly effective in modulating thrombin adsorption to fibrin.

  15. Generation of radiation by intense plasma and electromagnetic undulators

    SciTech Connect

    Joshi, C.

    1991-10-01

    We examine the characteristics of the classical radiation emission resulting from the interaction of a relativistic electron beam that propagates perpendicularly through a large amplitude relativistic plasma wave. Such a study is useful for evaluating the feasibility of using relativistic plasma waves as extremely short wavelength undulators for generating short wavelength radiation. The electron trajectories in a plasma wave undulator and in an ac FEL undulator are obtained using perturbation techniques. The spontaneous radiation frequency spectrum and angular distribution emitted by a single electron oscillating in these two undulators are then calculated. The radiation gain of a copropagating electromagnetic wave is calculated. The approximate analytic results for the trajectories, spontaneous radiation and gain are compared with 3-D simulation results. The characteristics of the plasma wave undulator are compared with the ac FEL undulator and linearly polarized magnetic undulator. 50 refs., 26 figs., 3 tabs.

  16. Development of rf plasma generators for neutral beams

    SciTech Connect

    Vella, M.C.; Ehlers, K.W.; Kippenhan, D.; Pincosy, P.A.; Pyle, R.V.; DiVergilio, W.F.; Fosnight, V.V.

    1984-10-01

    The development of low frequency (1-2 MHz) rf plasma generators for high power neutral beam applications is summarized. Immersed couplers from one to three turns were used. Acceptable plasma profiles, less than or equal to 15% max/min, were obtained in a variety of field-free magnetic bucket and magnetic filter-bucket sources, with 10 x 10 cm or 10 x 40 cm extraction areas. Hydrogen beam properties were measured with a 7 x 10 cm accelerator operated at 80 kV. Atomic fraction and power efficiency were at least as high as with arc plasmas in similar chambers. The potential advantages of an rf plasma source are: ease of operation; reliability; and extended service lifetime.

  17. Development of rf plasma generators for neutral beams

    SciTech Connect

    Vella, M.C.; Ehlers, K.W.; Kippenhan, D.; Pincosy, P.A.; Pyle, R.V.; DiVergilio, W.F.; Fosnight, V.V.

    1985-05-01

    The development of low frequency (1--2 MHz) rf plasma generators for high power neutral beam applications is summarized. Immersed couplers from one to three turns were used. Acceptable plasma profiles, < or =15% max/min, were obtained in a variety of field-free, magnetic bucket and magnetic filter-bucket sources, with 10 x 10 or 10 x 40 cm extraction areas. Hydrogen beam properties were measured with a 7 x 10 cm accelerator operated at 80 kV. Atomic fraction and power efficiency were at least as high as with arc plasmas in similar chambers. The potential advantages of an rf plasma source are: ease of operation; reliability; and extended service lifetime.

  18. Preliminary characterization of a laser-generated plasma sheet

    NASA Astrophysics Data System (ADS)

    Keiter, P. A.; Malamud, G.; Trantham, M.; Fein, J.; Davis, J.; Klein, S. R.; Drake, R. P.

    2015-12-01

    We present the results from recent experiments to create a flowing plasma sheet. Two groups of three laser beams with nominally 1.5 kJ of energy per group were focused to separate pointing locations, driving a shock into a wedge target. As the shock breaks out of the wedge, the plasma is focused on center, creating a sheet of plasma. Measurements at 60 ns indicate the plasma sheet has propagated 2825 microns with an average velocity of 49 microns/ns. These experiments follow previous experiments [Krauland et al. 2013], which are aimed at studying similar physics as that found in the hot spot region of cataclysmic variables. Krauland et al. created a flowing plasma, which represents the flowing plasma from the secondary star. This flow interacted with a stationary object, which represented the disk around the white dwarf. A reverse shock is a shock formed when a freely expanding plasma encounters an obstacle. Reverse shocks can be generated by a blast wave propagating through a medium. They can also be found in binary star systems where the flowing gas from a companion star interacts with the accretion disk of the primary star.

  19. 27.12 MHz plasma generation in supercritical carbon dioxide

    SciTech Connect

    Kawashima, Ayato; Toyota, Hiromichi; Nomura, Shinfuku; Takemori, Toshihiko; Mukasa, Shinobu; Maehara, Tsunehiro; Yamashita, Hiroshi

    2007-05-01

    An experiment was conducted for generating high-frequency plasma in supercritical carbon dioxide; it is expected to have the potential for applications in various types of practical processes. It was successfully generated at 6-20 MPa using electrodes mounted in a supercritical cell with a gap of 1 mm. Emission spectra were then measured to investigate the physical properties of supercritical carbon dioxide plasma. The results indicated that while the emission spectra for carbon dioxide and carbon monoxide could be mainly obtained at a low pressure, the emission spectra for atomic oxygen could be obtained in the supercritical state, which increased with the pressure. The temperature of the plasma in supercritical state was estimated to be approximately 6000-7000 K on the assumption of local thermodynamic equilibrium and the calculation results of thermal equilibrium composition in this state showed the increase of atomic oxygen by the decomposition of CO{sub 2}.

  20. Air spark-like plasma source for antimicrobial NOx generation

    NASA Astrophysics Data System (ADS)

    Pavlovich, M. J.; Ono, T.; Galleher, C.; Curtis, B.; Clark, D. S.; Machala, Z.; Graves, D. B.

    2014-12-01

    We demonstrate and analyse the generation of nitrogen oxides and their antimicrobial efficacy using atmospheric air spark-like plasmas. Spark-like discharges in air in a 1 L confined volume are shown to generate NOx at an initial rate of about 1.5  ×  1016 NOx molecules/J dissipated in the plasma. Such a discharge operating in this confined volume generates on the order of 6000 ppm NOx in 10 min. Around 90% of the NOx is in the form of NO2 after several minutes of operation in the confined volume, suggesting that NO2 is the dominant antimicrobial component. The strong antimicrobial action of the NOx mixture after several minutes of plasma operation is demonstrated by measuring rates of E. coli disinfection on surfaces and in water exposed to the NOx mixture. Some possible applications of plasma generation of NOx (perhaps followed by dissolution in water) include disinfection of surfaces, skin or wound antisepsis, and sterilization of medical instruments at or near room temperature.

  1. Use of Plasma Actuators as a Moving-Wake Generator

    NASA Technical Reports Server (NTRS)

    Corke, Thomas C.; Thomas, Flint O.; Klapetzky Michael J.

    2007-01-01

    The work documented in this report tests the concept of using plasma actuators as a simple and easy way to generate a simulated moving-wake and the disturbances associated with it in turbines. This wake is caused by the blades of the upstream stages of the turbine. Two types of devices, one constructed of arrays of NACA 0018 airfoils, and the one constructed of flat plates were studied. The airfoils or plates were equipped with surface mounted dielectric barrier discharge (DBD) plasma actuators, which were used to generate flow disturbances resembling moving-wakes. CTA hot-wire anemometry and flow visualization using a smoke-wire were used to investigate the wake independence at various spacings and downstream locations. The flat plates were found to produce better results than the airfoils in creating large velocity fluctuations in the free-stream flow. Different dielectric materials, plasma actuator locations, leading edge contours, angles of attack and plate spacings were investigated, some with positive results. The magnitudes of the velocity fluctuations were found to be comparable to existing mechanical moving-wake generators, thus proving the feasibility of using plasma actuators as a moving-wake generator.

  2. Thrombin-Inhibiting Anticoagulant Liposomes: Development and Characterization.

    PubMed

    Endreas, Wegderes; Brüßler, Jana; Vornicescu, Doru; Keusgen, Michael; Bakowsky, Udo; Steinmetzer, Torsten

    2016-02-01

    Many peptides and peptidomimetic drugs suffer from rapid clearance in vivo; this can be reduced by increasing their size through oligomerization or covalent conjugation with polymers. As proof of principle, an alternative strategy for drug oligomerization is described, in which peptidomimetic thrombin inhibitors are incorporated into the liposome surface. For this purpose, the inhibitor moieties were covalently coupled to a palmitic acid residue through a short bifunctionalized ethylene glycol spacer. These molecules were directly added to the lipid mixture used for liposome preparation. The obtained liposomes possess strong thrombin inhibitory potency in enzyme kinetic measurements and anticoagulant activity in plasma. Their strong potency and positive ζ potential indicate that large amounts of the benzamidine-derived inhibitors are located on the surface of the liposomes. This concept should be applicable to other drug molecules that suffer from rapid elimination and allow covalent modification with a suitable fatty acid residue. PMID:26662675

  3. Measurement of optical emission from the hydrogen plasma of the Linac4 ion source and the SPL plasma generator

    NASA Astrophysics Data System (ADS)

    Lettry, J.; Bertolo, S.; Castel, A.; Chaudet, E.; Ecarnot, J.-F.; Favre, G.; Fayet, F.; Geisser, J.-M.; Haase, M.; Habert, A.; Hansen, J.; Joffe, S.; Kronberger, M.; Lombard, D.; Marmillon, A.; Balula, J. Marques; Mathot, S.; Midttun, O.; Moyret, P.; Nisbet, D.; O'Neil, M.; Paoluzzi, M.; Prever-Loiri, L.; Arias, J. Sanchez; Schmitzer, C.; Steyaert, R. Scrivens D.; Vestergard, H.; Wilhelmsson, M.

    2011-09-01

    At CERN, a non caesiated H- ion volume source derived from the DESY ion source is being commissioned. For a proposed High Power Superconducting Proton Linac (HP-SPL), a non caesiated plasma generator was designed to operate at the two orders of magnitude larger duty factor required by the SPL. The commissioning of the plasma generator test stand and the plasma generator prototype are completed and briefly described. The 2 MHz RF generators (100 kW, 50 Hz repetition rate) was successfully commissioned; its frequency and power will be controlled by arbitrary function generators during the 1 ms plasma pulse. In order to characterize the plasma, RF-coupling, optical spectrometer, rest gas analyzer and Langmuir probe measurements will be used. Optical spectrometry allows direct comparison with the currently commissioned Linac4 H- ion source plasma. The first measurements of the optical emission of the Linac4 ion source and of the SPL plasma generator plasmas are presented.

  4. Effects of argatroban, danaparoid, and fondaparinux on trombin generation in heparin-induced thrombocytopenia.

    PubMed

    Tardy-Poncet, Brigitte; Combe, Marion; Piot, Michèle; Chapelle, Céline; Akrour, Majid; Tardy, Bernard

    2013-03-01

    There is no in vitro data on the comparison of the effects of danaparoid, argatroban and fondaparinux on thrombin generation in patients with heparin-induced thrombocytopenia. It was the study objective to compare the in vitro anticoagulant potential of argatroban, danaparoid and fondaparinux using a thrombin generation assay TGA on a mixture of control platelet-rich plasma (PRP) and HIT patient platelet-poor plasma (PPP). The plasma of seven patients with a clear HIT diagnosed at our institution was selected. Mixtures of donor PRP and patient PPP were incubated with unfractionated heparin 0.2 U.mL⁻¹, argatroban at 600 ng.mL⁻¹, argatroban at 400 ng.mL⁻¹, danaparoid at 0.65 IU.mL⁻¹ and fondaparinux at 1 μg.mL⁻¹. Thrombin generation was assessed by calibrated thrombinography. The percentage of inhibition of the endogenous thrombin potential observed with argatroban at 600 ng.mL⁻¹ was statistically significantly higher compared with those observed with fondaparinux (median: 53.6% vs. 3.9%; p=0.031) but not compared with argatroban at 400 ng.mL⁻¹ and danaparoid. The percentage of inhibition of the thrombin peak observed with argatroban at 600 ng.mL⁻¹ was statistically significantly higher compared with those observed with danaparoid (median: 71.2 vs. 56.8; p=0.031) and fondaparinux (mean: 71.2 vs. 30; p=0.031) but not with argatroban at 400 ng.mL⁻¹. In conclusion, the in vitro effect of argatroban and danaparoid on thrombin generation seems to corroborate the results of clinical studies of these drugs in the treatment of HIT in term of efficiency. Fondaparinux showed a very small effect on thrombin generation evaluated by calibrated thrombinography. PMID:23328916

  5. Generation of magnetic fields by a gravitomagnetic plasma battery

    NASA Astrophysics Data System (ADS)

    Khanna, Ramon

    1998-03-01

    The generation of magnetic fields by a battery, operating in an ion-electron plasma around a Kerr black hole, is studied in the 3 + 1 split of the Kerr metric. It is found that the gravitomagnetic contributions to the electron partial pressure are able to drive currents. The strength of the equilibrium magnetic field should be higher than for the classical Biermann battery, which is found to operate in this relativistic context as well, since the gravitomagnetic driving terms can less easily be quenched than the classical ones. In axisymmetry the battery can induce only toroidal magnetic fields. Once a toroidal magnetic field is present, however, the coupling of gravitomagnetic and electromagnetic fields generates a poloidal magnetic field even in axisymmetry. A rotating black hole, embedded in plasma, will therefore always generate toroidal and poloidal magnetic fields.

  6. Effect of rabbit thrombomodulin on thrombin inhibition by antithrombin in the presence of heparin.

    PubMed

    Bourin, M C

    1989-04-01

    Thrombomodulin acts as a cofactor for protein C activation by thrombin (PC activation cofactor activity) and inhibits thrombin-induced fibrinogen clotting (direct anticoagulant activity). In addition, rabbit thrombomodulin has been shown to promote thrombin inactivation by antithrombin (AT-dependent anticoagulant activity). However, a non-acidic form (i.e. non-retarded on ion-exchange chromatography) of thrombomodulin generated by limited proteolysis retained only the PC activation cofactor activity. The acidic form (retarded on ion-exchange chromatography) of thrombomodulin is now shown to prevent the rapid inactivation of thrombin by antithrombin in the presence of heparin, presumably by preventing the formation of the ternary thrombin-AT-heparin complex. This effect was not observed with non-acidic thrombomodulin. When submitted to chondroitinase digestion, thrombomodulin was converted into an essentially non-acidic form that lacked both the AT-dependent and the direct anticoagulant activities but showed a PC activation cofactor function indistinguishable from that of native thrombomodulin. This chondroitinase-digested form did not prevent the catalytic effect of heparin on the inhibition of thrombin by AT. It is concluded that the acidic domain of rabbit thrombomodulin, a chondroitin (dermatan) sulfate glycosaminoglycan, interacts with a site of the thrombin molecule that is not involved in the protein C activation cofactor function, but is essential to the cleavage of fibrinogen or binding of heparin.

  7. Quantitative phosphoproteomics unveils temporal dynamics of thrombin signaling in human endothelial cells

    PubMed Central

    van den Biggelaar, Maartje; Hernández-Fernaud, Juan Ramon; van den Eshof, Bart L.; Neilson, Lisa J.; Meijer, Alexander B.; Mertens, Koen

    2014-01-01

    Thrombin is the key serine protease of the coagulation cascade and a potent trigger of protease-activated receptor 1 (PAR1)-mediated platelet aggregation. In recent years, PAR1 has become an appealing target for anticoagulant therapies. However, the inhibitors that have been developed so far increase bleeding risk in patients, likely because they interfere with endogenous PAR1 signaling in the endothelium. Because of its complexity, thrombin-induced signaling in endothelial cells has remained incompletely understood. Here, we have combined stable isotope amino acids in cell culture, affinity-based phosphopeptide enrichment, and high-resolution mass spectrometry and performed a time-resolved analysis of the thrombin-induced signaling in human primary endothelial cells. We identified 2224 thrombin-regulated phosphorylation sites, the majority of which have not been previously related to thrombin. Those sites were localized on proteins that are novel to thrombin signaling, but also on well-known players such as PAR1, Rho-associated kinase 2, phospholipase C, and proteins related to actin cytoskeleton, cell-cell junctions, and Weibel-Palade body release. Our study provides a unique resource of phosphoproteins and phosphorylation sites that may generate novel insights into an intimate understanding of thrombin-mediated PAR signaling and the development of improved PAR1 antagonists that affect platelet but not endothelial cell function. PMID:24501219

  8. Quantitative phosphoproteomics unveils temporal dynamics of thrombin signaling in human endothelial cells.

    PubMed

    van den Biggelaar, Maartje; Hernández-Fernaud, Juan Ramon; van den Eshof, Bart L; Neilson, Lisa J; Meijer, Alexander B; Mertens, Koen; Zanivan, Sara

    2014-03-20

    Thrombin is the key serine protease of the coagulation cascade and a potent trigger of protease-activated receptor 1 (PAR1)-mediated platelet aggregation. In recent years, PAR1 has become an appealing target for anticoagulant therapies. However, the inhibitors that have been developed so far increase bleeding risk in patients, likely because they interfere with endogenous PAR1 signaling in the endothelium. Because of its complexity, thrombin-induced signaling in endothelial cells has remained incompletely understood. Here, we have combined stable isotope amino acids in cell culture, affinity-based phosphopeptide enrichment, and high-resolution mass spectrometry and performed a time-resolved analysis of the thrombin-induced signaling in human primary endothelial cells. We identified 2224 thrombin-regulated phosphorylation sites, the majority of which have not been previously related to thrombin. Those sites were localized on proteins that are novel to thrombin signaling, but also on well-known players such as PAR1, Rho-associated kinase 2, phospholipase C, and proteins related to actin cytoskeleton, cell-cell junctions, and Weibel-Palade body release. Our study provides a unique resource of phosphoproteins and phosphorylation sites that may generate novel insights into an intimate understanding of thrombin-mediated PAR signaling and the development of improved PAR1 antagonists that affect platelet but not endothelial cell function. PMID:24501219

  9. STIM1 and Orai1 mediate thrombin-induced Ca(2+) influx in rat cortical astrocytes.

    PubMed

    Moreno, Claudia; Sampieri, Alicia; Vivas, Oscar; Peña-Segura, Claudia; Vaca, Luis

    2012-12-01

    In astrocytes, thrombin leads to cytoplasmic Ca(2+) elevations modulating a variety of cytoprotective and cytotoxic responses. Astrocytes respond to thrombin stimulation with a biphasic Ca(2+) increase generated by an interplay between ER-Ca(2+) release and store-operated Ca(2+) entry (SOCE). In many cell types, STIM1 and Orai1 have been demonstrated to be central components of SOCE. STIM1 senses the ER-Ca(2+) depletion and binds Orai1 to activate Ca(2+) influx. Here we used immunocytochemistry, overexpression and siRNA assays to investigate the role of STIM1 and Orai1 in the thrombin-induced Ca(2+) response in primary cultures of rat cortical astrocytes. We found that STIM1 and Orai1 are endogenously expressed in cortical astrocytes and distribute accordingly with other mammalian cells. Importantly, native and overexpressed STIM1 reorganized in puncta under thrombin stimulation and this reorganization was reversible. In addition, the overexpression of STIM1 and Orai1 increased by twofold the Ca(2+) influx evoked by thrombin, while knockdown of endogenous STIM1 and Orai1 significantly decreased this Ca(2+) influx. These results indicate that STIM1 and Orai1 underlie an important fraction of the Ca(2+) response that astrocytes exhibit in the presence of thrombin. Thrombin stimulation in astrocytes leads to ER-Ca(2+) release which causes STIM1 reorganization allowing the activation of Orai1 and the subsequent Ca(2+) influx.

  10. Electron-beam generated plasmas for processing applications

    NASA Astrophysics Data System (ADS)

    Meger, Robert; Leonhardt, Darrin; Murphy, Donald; Walton, Scott; Blackwell, David; Fernsler, Richard; Lampe, Martin; Manheimer, Wallace

    2001-10-01

    NRL's Large Area Plasma Processing System (LAPPS) utilizes a 5-10 mA/cm^2, 2-4 kV, 1 cm x 30-60 cm cross section beam of electrons guided by a magnetic field to ionize a low density (10-100 mTorr) gas.[1] Beam ionization allows large area, high density, low temperature plasmas to be generated in an arbitrary gas mixture at a well defined location. Energy and composition of particle fluxes to surfaces on both sides of the plasma can be controlled by gas mixture, location, rf bias, and other factors. Experiments have been performed using both pulsed and cw beams. Extensive diagnostics (Langmuir probes, mass and ion energy analyzers, optical emissions, microwave interferometry, etc.) have been fielded to measure the plasma properties and neutral particle fluxes (ions, neutrals, free radicals) with and without rf bias on nearby surfaces both with the beam on and off. Uniform, cold (Te < 1eV), dense (ne 10^13 cm-3) plasmas in molecular and atomic gases and mixtures thereof have been produced in agreement with theoretical expectations. Initial tests of LAPPS application such as ashing, etching, sputtering, and diamond growth have been performed. Program status will be presented. [1]R.A. Meger, et al, Phys. of Plasmas 8(5), p. 2558 (2001)

  11. Generation of filamentary structures by beam-plasma interaction

    SciTech Connect

    Wang, X.Y.; Lin, Y.

    2006-05-15

    The previous simulations by Wang and Lin [Phys. Plasmas. 10, 3528 (2003)] showed that filaments, frequently observed in space plasmas, can form via the interaction between an ion beam and a background plasma. In this study, the physical mechanism for the generation of the filaments is investigated by a two-dimensional hybrid simulation, in which a field-aligned ion beam with relative beam density n{sub b}=0.1 and beam velocity V{sub b}=10V{sub A} is initiated in a uniform plasma. Right-hand nonresonant ion beam modes, consistent with the linear theory, are found to be dominant in the linear stage of the beam-plasma interaction. In the later nonlinear stage, the nonresonant modes decay and the resonant modes grow through a nonlinear wave coupling. The interaction among the resonant modes leads to the formation of filamentary structures, which are the field-aligned structures (k perpendicular B) of magnetic field B, density, and temperature in the final stage. The filaments are nonlinearly generated in a prey-predator fashion by the parallel and oblique resonant ion beam modes, which meanwhile evolve into two types of shear Alfven modes, with one mainly propagating along the background field B{sub 0} and the other obliquely propagating. The filamentary structures are found to be phase standing in the plasma frame, but their amplitude oscillates with time. In the dominant filament mode, fluctuations in the background ion density, background ion temperature, and beam density are in phase with the fluctuations in B, whereas the significantly enhanced beam temperature is antiphase with B. It is found that the filaments are produced by the interaction of at least two ion beam modes with comparable amplitudes, not by only one single mode, thus their generation mechanism is different from other mechanisms such as the stimulated excitation by the decay of an Alfven wave.

  12. Syngas Generation from Organic Waste with Plasma Steam Reforming

    NASA Astrophysics Data System (ADS)

    Diaz, G.; Leal-Quiros, E.; Smith, R. A.; Elliott, J.; Unruh, D.

    2014-05-01

    A plasma steam reforming system to process waste is in the process of being set up at the University of California, Merced. The proposed concept will use two different plasma regimes, i.e. glow discharge and arc torches to process a percentage of the total liquid waste stream generated at the campus together with shredded local organic solid waste. One of the main advantages of the plasma technology to be utilized is that it uses graphite electrodes that can be fed to the reactor to achieve continuous operation, thus, electrode or nozzle life is not a concern. The waste to energy conversion process consists of two stages, one where a mixture of steam and hydrogen is generated from the liquid in a glow-discharge cell, and a second stage where the mixture of exhaust gases coming out of the first device are mixed with solid waste in a reactor operating in steam reforming mode interacting with a plasma torch to generate high-quality syngas. In this paper, the results of a thermodynamic model developed for the two stages are shown. The syngas composition obtained indicates that the fraction of CO2 present decreases with increasing temperature and the molar fractions of hydrogen and carbon monoxide become dominant. The fraction of water vapour present in the product gases coming out of the second stage needs to be condensed before the syngas can be utilized in a prime mover.

  13. Dynamics and interactions of pulsed laser generated plasma bubbles in dusty plasma liquids

    SciTech Connect

    Chu Hongyu; Liao Chenting; I Lin

    2005-10-31

    The plasma bubble with dust particle depletion can be generated by a nano-second laser pulse focused on one of the dust particles suspended in a strongly coupled dusty plasma liquid. The bubble dynamics at different time scales, including the initial forming and later traveling stages are investigated. In the first stage, dust particles are pushed outward by the outward ion flow associated with the plume generated by the more intensed plasma. The bubble then travels downward at a speed about 60 mm/s associated with a surrounding dipole-like dust flow field. Two bubbles can also be simultaneously generated at different locations by separated laser pulses to study their interactions. Strong coupling is observed between two vertical bubbles. However, two horizontal bubbles are weakly coupled. The possible mechanism is discussed.

  14. A novel, all-dielectric, microwave plasma generator towards development of plasma metamaterials

    NASA Astrophysics Data System (ADS)

    Cohick, Zane; Luo, Wei; Perini, Steven; Baker, Amanda; Wolfe, Douglas; Lanagan, Michael

    2016-11-01

    A proof of concept for a microwave microplasma generator that consists of a halved dielectric resonator is presented. The generator functions via leaking electric fields of the resonant modes — TE01δ and HEM12δ modes are explored. Computational results illustrate the electric fields, whereas the stability of resonance and coupling are studied experimentally. Finally, a working device is presented. This generator promises potentially wireless and low-loss operation. This device may find relevance in plasma metamaterials; each resonator may generate the plasma structures necessary to manipulate electromagnetic radiation. In particular, the all-dielectric nature of the generator will allow low-loss interaction with high-frequency (GHz–THz) waves.

  15. Generation of pulsed discharge plasma in water with fine bubbles

    NASA Astrophysics Data System (ADS)

    Hayashi, Yui; Takada, Noriharu; Kanda, Hideki; Goto, Motonobu; Goto laboratory Team

    2015-09-01

    Recently, some researchers have proposed electric discharge methods with bubbles in water because the discharge plasma inside bubble was easy to be generated compared to that in water. Almost all of these methods introduced bubbles in the order of millimeter size from a nozzle placed in water. In these methods, bubbles rose one after another owing to high rising speed of millibubble, leading to inefficient gas consumption. We proposed fine bubbles introduction at the discharge area in water. A fine bubble is determined a bubble with less than 100 μm in a diameter. Fine bubbles exhibit extremely slow rising speed. Fine bubbles decrease in size during bubble rising and subsequently collapse in water with OH radical generation. Therefore, combining the discharge plasma with fine bubbles is expected to generate more active species with small amount of gas consumption. In this work, fine bubbles were introduced in water and pulsed discharge plasma was generated between two cylindrical electrodes which placed in water. We examined effects of fine bubbles on electric discharge in water when argon or oxygen gas was utilized as feed gas. Fine bubbles enhanced optical emission of hydrogen and oxygen atoms from H2O molecules, but that of feed gas was not observed. The formation mechanism of H2O2 by electric discharge was supposed to be different from that with no bubbling. Dissolved oxygen in water played a role in H2O2 formation by the discharge with fine bubbles.

  16. Electric probe investigations of microwave generated, atmospheric pressure, plasma jets

    SciTech Connect

    Porteanu, H. E.; Kuehn, S.; Gesche, R.

    2010-07-15

    We examine the applicability of the Langmuir-type of characterization for atmospheric pressure plasma jets generated in a millimeter-size cavity microwave resonator at 2.45 GHz. Wide range I-V characteristics of helium, argon, nitrogen, air and oxygen are presented for different gas fluxes, distances probe-resonator, and microwave powers. A detailed analysis is performed for the fine variation in the current around the floating potential. A simplified theory specially developed for this case is presented, considering the ionic and electronic saturation currents and the floating potential. Based on this theory, we conclude that, while the charge carrier density depends on gas flow, distance to plasma source, and microwave absorbed power, the electron temperature is quite independent of these parameters. The resulting plasma parameters for helium, argon, and nitrogen are presented.

  17. Aptamer-based detection of plasma proteins by an electrochemical assay coupled to magnetic beads.

    PubMed

    Centi, Sonia; Tombelli, Sara; Minunni, Maria; Mascini, Marco

    2007-02-15

    The DNA thrombin aptamer has been extensively investigated, and the coupling of this aptamer to different transduction principles has demonstrated the wide applicability of aptamers as bioreceptors in bioanalytical assays. The goal of this work was to design an aptamer-based sandwich assay with electrochemical detection for thrombin analysis in complex matrixes, using a simple target capturing step by aptamer-functionalized magnetic beads. The conditions for the aptamer immobilization and for the protein binding have been first optimized by surface plasmon resonance, and then transferred to the electrochemical-based assay performed onto screen-printed electrodes. The assay was then applied to the analysis of thrombin in buffer, spiked serum, and plasma and high sensitivity and specificity were found. Moreover, thrombin was generated in situ in plasma by the conversion of its precursor prothrombin, and the formation of thrombin was followed at different times. The concentrations detected by the electrochemical assay were in agreement with a simulation software that mimics the formation of thrombin over time (thrombogram). The proposed work demonstrates that the high specificity of aptamers together with the use of magnetic beads are the key features for aptamer-based analysis in complex matrixes, opening the possibility of a real application to diagnostics or medical investigation.

  18. Plasma-generated reactive oxygen species for biomedical applications

    NASA Astrophysics Data System (ADS)

    Sousa, J. S.; Hammer, M. U.; Winter, J.; Tresp, H.; Duennbier, M.; Iseni, S.; Martin, V.; Puech, V.; Weltmann, K. D.; Reuter, S.

    2012-10-01

    To get a better insight into the effects of reactive oxygen species (ROS) on cellular components, fundamental studies are essential to determine the nature and concentration of plasma-generated ROS, and the chemistry induced in biological liquids by those ROS. In this context, we have measured the absolute density of the main ROS created in three different atmospheric pressure plasma sources: two geometrically distinct RF-driven microplasma jets (μ-APPJ [1] and kinpen [2]), and an array of microcathode sustained discharges [3]. Optical diagnostics of the plasma volumes and effluent regions have been performed: UV absorption for O3 and IR emission for O2(a^1δ) [4]. High concentrations of both ROS have been obtained (10^14--10^17cm-3). The effect of different parameters, such as gas flows and mixtures and power coupled to the plasmas, has been studied. For plasma biomedicine, the determination of the reactive species present in plasma-treated liquids is of great importance. In this work, we focused on the measurement of the concentration of H2O2 and NOX radicals, generated in physiological solutions like NaCl and PBS.[4pt] [1] N. Knake et al., J. Phys. D: App. Phys. 41, 194006 (2008)[0pt] [2] K.D. Weltmann et al., Pure Appl. Chem. 82, 1223 (2010)[0pt] [3] J.S. Sousa et al., Appl. Phys. Lett. 97, 141502 (2010)[0pt] [4] J.S. Sousa et al., Appl. Phys. Lett. 93, 011502 (2008)

  19. Electromagnetic radiation generated by arcing in low density plasma

    NASA Technical Reports Server (NTRS)

    Vayner, Boris V.; Ferguson, Dale C.; Snyder, David B.; Doreswamy, C. V.

    1996-01-01

    An unavoidable step in the process of space exploration is to use high-power, very large spacecraft launched into Earth orbit. Obviously, the spacecraft will need powerful energy sources. Previous experience has shown that electrical discharges occur on the surfaces of a high-voltage array, and these discharges (arcs) are undesirable in many respects. Moreover, any high voltage conductor will interact with the surrounding plasma, and that interaction may result in electrical discharges between the conductor and plasma (or between two conductors with different potentials, for example, during docking and extravehicular activity). One very important aspect is the generation of electromagnetic radiation by arcing. To prevent the negative influence of electromagnetic noise on the operation of spacecraft systems, it seems necessary to determine the spectra and absolute levels of the radiation, and to determine limitations on the solar array bias voltage that depend on the parameters of LEO plasma and the technical requirements of the spacecraft equipment. This report describes the results of an experimental study and computer simulation of the electromagnetic radiation generated by arcing on spacecraft surfaces. A large set of high quality data was obtained during the Solar Array Module Plasma Interaction Experiment (SAMPIE, flight STS-62) and ground test. These data include the amplitudes of current, pulse forms, duration of each arc, and spectra of plasma waves. A theoretical explanation of the observed features is presented in this report too. The elaborated model allows us to determine the parameters of the electromagnetic noise for different frequency ranges, distances from the arcing site, and distinct kinds of plasma waves.

  20. The influence of magnetic field on electron beam generated plasmas

    NASA Astrophysics Data System (ADS)

    Petrov, G. M.; Boris, D. R.; Lock, E. H.; Petrova, Tz B.; Fernsler, R. F.; Walton, S. G.

    2015-06-01

    Magnetically confined argon plasma in a long cylindrical tube driven by an electron beam is studied experimentally and theoretically. Langmuir probes are used to measure the electron energy distribution function, electron density and temperature in plasmas generated by 2 keV, 10 mA electron beams in a 25 mTorr argon background for magnetic field strengths of up to 200 Gauss. The experimental results agree with simulations done using a spatially averaged Boltzmann model adapted to treat an electron beam generated plasma immersed in a constant magnetic field. The confining effect of the magnetic field is studied theoretically using fluid and kinetic approaches. The fluid approach leads to two regimes of operation: weakly and strongly magnetized. The former is similar to the magnetic field-free case, while in the latter the ambipolar diffusion coefficient and electron density depend quadratically on the magnetic field strength. Finally, a more rigorous kinetic treatment, which accounts for the impact of the magnetic field over the whole distribution of electrons, is used for accurate description of the plasma.

  1. Method for generating a plasma wave to accelerate electrons

    DOEpatents

    Umstadter, D.; Esarey, E.; Kim, J.K.

    1997-06-10

    The invention provides a method and apparatus for generating large amplitude nonlinear plasma waves, driven by an optimized train of independently adjustable, intense laser pulses. In the method, optimal pulse widths, interpulse spacing, and intensity profiles of each pulse are determined for each pulse in a series of pulses. A resonant region of the plasma wave phase space is found where the plasma wave is driven most efficiently by the laser pulses. The accelerator system of the invention comprises several parts: the laser system, with its pulse-shaping subsystem; the electron gun system, also called beam source, which preferably comprises photo cathode electron source and RF-LINAC accelerator; electron photo-cathode triggering system; the electron diagnostics; and the feedback system between the electron diagnostics and the laser system. The system also includes plasma source including vacuum chamber, magnetic lens, and magnetic field means. The laser system produces a train of pulses that has been optimized to maximize the axial electric field amplitude of the plasma wave, and thus the electron acceleration, using the method of the invention. 21 figs.

  2. Method for generating a plasma wave to accelerate electrons

    DOEpatents

    Umstadter, Donald; Esarey, Eric; Kim, Joon K.

    1997-01-01

    The invention provides a method and apparatus for generating large amplitude nonlinear plasma waves, driven by an optimized train of independently adjustable, intense laser pulses. In the method, optimal pulse widths, interpulse spacing, and intensity profiles of each pulse are determined for each pulse in a series of pulses. A resonant region of the plasma wave phase space is found where the plasma wave is driven most efficiently by the laser pulses. The accelerator system of the invention comprises several parts: the laser system, with its pulse-shaping subsystem; the electron gun system, also called beam source, which preferably comprises photo cathode electron source and RF-LINAC accelerator; electron photo-cathode triggering system; the electron diagnostics; and the feedback system between the electron diagnostics and the laser system. The system also includes plasma source including vacuum chamber, magnetic lens, and magnetic field means. The laser system produces a train of pulses that has been optimized to maximize the axial electric field amplitude of the plasma wave, and thus the electron acceleration, using the method of the invention.

  3. Proposed generation and compression of a target plasma for MTF

    SciTech Connect

    Kirkpatrick, R.C.; Thurston, R.S.; Chrien, R.E.

    1995-09-01

    Magnetized target fusion (MTF), in which a magnetothermally insulated plasma is hydrodynamically compressed to fusion conditions, represents an approach to controlled fusion which avoids difficulties of both traditional inertial confinement and magnetic confinement approaches. The authors are proposing to demonstrate the feasibility of magnetized target fusion by: (1) creating a suitable magnetized target plasma, (2) performing preliminary liner compression experiments using existing pulsed power facilities and demonstrated liner performance. Once the target plasma and the means for its generation have been optimized, the authors plan to conduct preliminary liner compression experiments aimed at demonstrating the near-adiabatic compression of the target plasma desired for MTF. Relevant liner compression experiments have been performed at Los Alamos in the Scyllac Fast Liner Program and, more recently, in the Pegasus facility and the Procyon explosive pulsed power program. In a series of liner experiments they plan to map out the dependence of temperature and neutron production as functions of the initial plasma conditions and the liner compression achieved. With the above research program, they intend to demonstrate most of the key principles involved in magnetized target fusion, and develop the experimental and theoretical tools needed to design and execute fully integrated MTF ignition experiments.

  4. Thrombin use in surgery: an evidence-based review of its clinical use

    PubMed Central

    Ham, Sung W; Lew, Wesley K; Weaver, Fred A

    2010-01-01

    When surgical ligation of bleeding fails, or is not possible, surgeons rely on a number of hemostatic aids, including thrombin. This review discusses the history, pharmacology and clinical application of thrombin as a surgical hemostat. The initial thrombin was bovine in origin, but its use has been complicated by the formation of antibodies that cross-react with human coagulation factors. This has been associated with life-threatening bleeding and in some circumstances anaphylaxis and death. Human thrombin, isolated from pooled plasma of donors, was developed in an effort to minimize these risks, but its downsides are its limited availability and the potential for transmitting blood-borne pathogens. Recently a recombinant thrombin has been developed, and approved for use by the FDA. It has the advantage of being minimally antigenic and devoid of the risk of viral transmission. Thrombin is often used in conjunction with other hemostatic aids, including absorbable agents such as Gelfoam, and with fibrinogen in fibrin glues. The last part of this review will discuss these agents in detail, and review their clinical applications. PMID:22282693

  5. Thrombin Production and Human Neutrophil Elastase Sequestration by Modified Cellulosic Dressings and Their Electrokinetic Analysis

    PubMed Central

    Edwards, Judson Vincent; Prevost, Nicolette

    2011-01-01

    Wound healing is a complex series of biochemical and cellular events. Optimally, functional material design addresses the overlapping acute and inflammatory stages of wound healing based on molecular, cellular, and bio-compatibility issues. In this paper the issues addressed are uncontrolled hemostasis and inflammation which can interfere with the orderly flow of wound healing. In this regard, we review the serine proteases thrombin and elastase relative to dressing functionality that improves wound healing and examine the effects of charge in cotton/cellulosic dressing design on thrombin production and elastase sequestration (uptake by the wound dressing). Thrombin is central to the initiation and propagation of coagulation, and elastase is released from neutrophils that can function detrimentally in a stalled inflammatory phase characteristic of chronic wounds. Electrokinetic fiber surface properties of the biomaterials of this study were determined to correlate material charge and polarity with function relative to thrombin production and elastase sequestration. Human neutrophil elastase sequestration was assessed with an assay representative of chronic wound concentration with cotton gauze cross-linked with three types of polycarboxylic acids and one phosphorylation finish; thrombin production, which was assessed in a plasma-based assay via a fluorogenic peptide substrate, was determined for cotton, cotton-grafted chitosan, chitosan, rayon/polyester, and two kaolin-treated materials including a commercial hemorrhage control dressing (QuickClot Combat Gauze). A correlation in thrombin production to zeta potential was found. Two polycarboxylic acid cross linked and a phosphorylated cotton dressing gave high elastase sequestration. PMID:24956451

  6. Thrombin production and human neutrophil elastase sequestration by modified cellulosic dressings and their electrokinetic analysis.

    PubMed

    Edwards, Judson Vincent; Prevost, Nicolette

    2011-12-15

    Wound healing is a complex series of biochemical and cellular events. Optimally, functional material design addresses the overlapping acute and inflammatory stages of wound healing based on molecular, cellular, and bio-compatibility issues. In this paper the issues addressed are uncontrolled hemostasis and inflammation which can interfere with the orderly flow of wound healing. In this regard, we review the serine proteases thrombin and elastase relative to dressing functionality that improves wound healing and examine the effects of charge in cotton/cellulosic dressing design on thrombin production and elastase sequestration (uptake by the wound dressing). Thrombin is central to the initiation and propagation of coagulation, and elastase is released from neutrophils that can function detrimentally in a stalled inflammatory phase characteristic of chronic wounds. Electrokinetic fiber surface properties of the biomaterials of this study were determined to correlate material charge and polarity with function relative to thrombin production and elastase sequestration. Human neutrophil elastase sequestration was assessed with an assay representative of chronic wound concentration with cotton gauze cross-linked with three types of polycarboxylic acids and one phosphorylation finish; thrombin production, which was assessed in a plasma-based assay via a fluorogenic peptide substrate, was determined for cotton, cotton-grafted chitosan, chitosan, rayon/polyester, and two kaolin-treated materials including a commercial hemorrhage control dressing (QuickClot Combat Gauze). A correlation in thrombin production to zeta potential was found. Two polycarboxylic acid cross linked and a phosphorylated cotton dressing gave high elastase sequestration.

  7. Generation of attosecond electron bunches in a laser-plasma accelerator using a plasma density upramp

    NASA Astrophysics Data System (ADS)

    Weikum, M. K.; Li, F. Y.; Assmann, R. W.; Sheng, Z. M.; Jaroszynski, D.

    2016-09-01

    Attosecond electron bunches and attosecond radiation pulses enable the study of ultrafast dynamics of matter in an unprecedented regime. In this paper, the suitability for the experimental realization of a novel scheme producing sub-femtosecond duration electron bunches from laser-wakefield acceleration in plasma with self-injection in a plasma upramp profile has been investigated. While it has previously been predicted that this requires laser power above a few hundred terawatts typically, here we show that the scheme can be extended with reduced driving laser powers down to tens of terawatts, generating accelerated electron pulses with minimum length of around 166 attoseconds and picocoulombs charge. Using particle-in-cell simulations and theoretical models, the evolution of the accelerated electron bunch within the plasma as well as simple scalings of the bunch properties with initial laser and plasma parameters are presented.

  8. Nonthermal Argon Plasma Generator and Some Potential Applications

    NASA Astrophysics Data System (ADS)

    Bunoiu, M.; Jugunaru, I.; Bica, I.; Balasoiu, M.

    2015-12-01

    A laboratory - made nonthermal plasma generator is presented. It has a diameter of 0.020 m and length of 0.155 m and contains two electrodes. The first electrode is a 2% Th-W alloy, 0.002 m in diameter bar, centred inside the generator's body by means of a four channel teflon piece; the other three channels, 0.003 m in diameter, are used for Ar supply. The second electrode is a nozzle of 0.002 m - 0.008 m diameter and 0.005m length. A ~500 kV/m electric field is generated between the two electrodes by a high frequency source (13.56 MHz ±5%), equipped with a OT-1000 (Tungsram) power triode. For Ar flows ranging from 0.00008 m3/s to 0.00056 m3/s, a plasma jet of length not exceeding 0.015 m and temperature below 315 K is obtained. Anthurium andraeanumis sample , blood matrix, human hair and textile fibers may be introduced in the plasma jet. For time periods of 30 s and 60 s, various effects like, cell detexturization, fast blood coagulation or textile fiber or hair cleaning and smoothing are obtained. These effects are presented and discussed in the paper.

  9. Apparatus for recording emissions from a rapidly generated plasma from a single plasma producing event

    DOEpatents

    Tan, T.H.; Williams, A.H.

    An optical fiber-coupled detector visible streak camera plasma diagnostic apparatus. Arrays of optical fiber-coupled detectors are placed on the film plane of several types of particle, x-ray and visible spectrometers or directly in the path of the emissions to be measured and the output is imaged by a visible streak camera. Time and spatial dependence of the emission from plasma generated from a single pulse of electromagnetic radiation or from a single particle beam burst can be recorded.

  10. Apparatus for recording emissions from a rapidly generated plasma from a single plasma producing event

    DOEpatents

    Tan, Tai Ho; Williams, Arthur H.

    1985-01-01

    An optical fiber-coupled detector visible streak camera plasma diagnostic apparatus. Arrays of optical fiber-coupled detectors are placed on the film plane of several types of particle, x-ray and visible spectrometers or directly in the path of the emissions to be measured and the output is imaged by a visible streak camera. Time and spatial dependence of the emission from plasmas generated from a single pulse of electromagnetic radiation or from a single particle beam burst can be recorded.

  11. Theoretical and numerical predictions of hypervelocity impact-generated plasma

    SciTech Connect

    Li, Jianqiao; Song, Weidong Ning, Jianguo

    2014-08-15

    The hypervelocity impact generated plasmas (HVIGP) in thermodynamic non-equilibrium state were theoretically analyzed, and a physical model was presented to explore the relationship between plasma ionization degree and internal energy of the system by a group of equations including a chemical reaction equilibrium equation, a chemical reaction rate equation, and an energy conservation equation. A series of AUTODYN 3D (a widely used software in dynamic numerical simulations and developed by Century Dynamic Inc.) numerical simulations of the impacts of hypervelocity Al projectile on its targets at different incident angles were performed. The internal energy and the material density obtained from the numerical simulations were then used to calculate the ionization degree and the electron temperature. Based on a self-developed 2D smooth particle hydrodynamic (SPH) code and the theoretical model, the plasmas generated by 6 hypervelocity impacts were directly simulated and their total charges were calculated. The numerical results are in good agreements with the experimental results as well as the empirical formulas, demonstrating that the theoretical model is justified by the AUTODYN 3D and self-developed 2D SPH simulations and applicable to predict HVIGPs. The study is of significance for astrophysical and cosmonautic researches and safety.

  12. Plasma and Shock Generation by Indirect Laser Pulse Action

    SciTech Connect

    Kasperczuk, A.; Borodziuk, S.; Pisarczyk, T.; Demchenko, N. N.; Gus'kov, S. Yu.; Jungwirth, K.; Kralikova, B.; Krousky, E.; Masek, K.; Pfeifer, M.; Rohlena, K.; Rozanov, V. B.; Skala, J.; Ullschmied, J.; Kalal, M.; Limpouch, J.; Pisarczyk, P.

    2006-01-15

    In the paper the results of our experiment with flyer disks, accelerated to high velocities by the PALS iodine laser and subsequently creating craters when hitting massive targets , are presented. We have carried out experiments with the double targets consisted of a disk placed in front of a massive target part at distances of either 200 or 500 {mu}m. Both elements of the targets were made of Al. The following disk irradiation conditions were used: laser energy of 130 J, laser wavelength of 1.315 {mu}m, pulse duration of 0.4 ns, and laser spot diameter of 250 {mu}m. To measure some plasma parameters and accelerated disk velocity a three frame interferometric system was used. Efficiency of crater creation by a disk impact was determined from the crater parameters, which were obtained by means of a crater replica technique. The experimental results concern two main stages: (a) ablative plasma generation and disk acceleration and (b) disk impact and crater creation. Spatial density distributions at different moments of plasma generation and expansion are shown. Discussion of the experimental results on the basis of a 2-D theoretical model of the laser -- solid target interaction is carried out.

  13. Material for electrodes of low temperature plasma generators

    DOEpatents

    Caplan, Malcolm; Vinogradov, Sergel Evge'evich; Ribin, Valeri Vasil'evich; Shekalov, Valentin Ivanovich; Rutberg, Philip Grigor'evich; Safronov, Alexi Anatol'evich

    2008-12-09

    Material for electrodes of low temperature plasma generators. The material contains a porous metal matrix impregnated with a material emitting electrons. The material uses a mixture of copper and iron powders as a porous metal matrix and a Group IIIB metal component such as Y.sub.2O.sub.3 is used as a material emitting electrons at, for example, the proportion of the components, mass %: iron: 3-30; Y.sub.2O.sub.3:0.05-1; copper: the remainder. Copper provides a high level of heat conduction and electric conductance, iron decreases intensity of copper evaporation in the process of plasma creation providing increased strength and lifetime, Y.sub.2O.sub.3 provides decreasing of electronic work function and stability of arc burning. The material can be used for producing the electrodes of low temperature AC plasma generators used for destruction of liquid organic wastes, medical wastes, and municipal wastes as well as for decontamination of low level radioactive waste, the destruction of chemical weapons, warfare toxic agents, etc.

  14. Material for electrodes of low temperature plasma generators

    DOEpatents

    Caplan, Malcolm; Vinogradov, Sergel Evge'evich; Ribin, Valeri Vasil'evich; Shekalov, Valentin Ivanovich; Rutberg, Philip Grigor'evich; Safronov, Alexi Anatol'evich; Shiryaev, Vasili Nikolaevich

    2010-03-02

    Material for electrodes of low temperature plasma generators. The material contains a porous metal matrix impregnated with a material emitting electrons. The material uses a mixture of copper and iron powders as a porous metal matrix and a Group IIIB metal component such as Y.sub.2O.sub.3 is used as a material emitting electrons at, for example, the proportion of the components, mass %: iron:3-30; Y.sub.2O.sub.3:0.05-1; copper: the remainder. Copper provides a high level of heat conduction and electric conductance, iron decreases intensity of copper evaporation in the process of plasma creation providing increased strength and lifetime, Y.sub.2O.sub.3 provides decreasing of electronic work function and stability of arc burning. The material can be used for producing the electrodes of low temperature AC plasma generators used for destruction of liquid organic wastes, medical wastes, municipal wastes as well as for decontamination of low level radioactive waste, the destruction of chemical weapons, warfare toxic agents, etc.

  15. Nonideal Plasma Under Exreme Conditions Generated by Intense Shock Waves

    NASA Astrophysics Data System (ADS)

    Fortov, Vladimir

    2004-05-01

    Physical properties of hot dense matter at megabar pressures are the physical basis for astrophysics, planetary physics, energetics, ICF target design, beam-matter interaction, and for many other applications. The new experimental results of pressure ionization investigation of the hot dense matter generated by multiple shock compression of metals, H2, He, noble gases, S, I, fullerene C60, and H2O in the megabar pressure range are presented. High energy plasma states were generated by single and multiple shock compression and adiabatic expansion of initially warm and cryogenic solid, liquid, porous and low-density foams (aerogels) samples. These data in combination with exploding wire conductivity measurements demonstrate an ionization rate increase up to ten orders of magnitude as a result of compression of dense matter. Multiple shock compression of H2, Ar, He, Kr, Ne, Xe, and fullerene C60 in initially gaseous and cryogenic liquid state allows to measure the electrical conductivity, equation of state, and laser beam reflectivity. Thermal and pressure ionization of strongly coupled states of matter is the most prominent effects under the experimental conditions. It was shown that plasma compression strongly deforms the ionization potentials, emission spectra and scattering cross-sections of the neutrals and ions in the strongly coupled matter. Comparison of the data obtained with theoretical models (percolation, Mott transition, Zeeman and Lorenz approach etc.) is presented. In contrast to the plasma compression experiments the multiple shock compression of solid Li, Na, and Ca shows dielectrization of these elements.

  16. Solar Wind Strahl Broadening by Self-Generated Plasma Waves

    NASA Technical Reports Server (NTRS)

    Pavan, J.; Vinas, A. F.; Yoon, P. H.; Ziebell, L. F.; Gaelzer, R.

    2013-01-01

    This Letter reports on the results of numerical simulations which may provide a possible explanation for the strahl broadening during quiet solar conditions. The relevant processes involved in the broadening are due to kinetic quasi-linear wave-particle interaction. Making use of static analytical electron distribution in an inhomogeneous field, it is found that self-generated electrostatic waves at the plasma frequency, i.e., Langmuir waves, are capable of scattering the strahl component, resulting in energy and pitch-angle diffusion that broadens its velocity distribution significantly. The present theoretical results provide an alternative or complementary explanation to the usual whistler diffusion scenario, suggesting that self-induced electrostatic waves at the plasma frequency might play a key role in broadening the solar wind strahl during quiet solar conditions.

  17. On the generation of plasma waves in Saturn's inner magnetosphere

    NASA Technical Reports Server (NTRS)

    Barbosa, D. D.; Kurth, W. S.

    1993-01-01

    Voyager 1 plasma wave measurements of Saturn's inner magnetosphere are reviewed with regard to interpretative aspects of the wave spectrum. A comparison of the wave emission profile with the electron plasma frequency obtained from in situ measurements of the thermal ion density shows good agreement with various features in the wave data identified as electrostatic modes and electromagnetic radio waves. Theoretical calculations of the critical flux of superthermal electrons able to generate whistler-mode waves and electrostatic electron cyclotron harmonic waves through a loss-cone instability are presented. The comparison of model results with electron measurements shows excellent agreement, thereby lending support to the conclusion that a moderate perpendicular anisotropy in the hot electron distribution is present in the equatorial region of L = 5-8.

  18. SOLAR WIND STRAHL BROADENING BY SELF-GENERATED PLASMA WAVES

    SciTech Connect

    Pavan, J.; Gaelzer, R.; Vinas, A. F.; Yoon, P. H.; Ziebell, L. F. E-mail: rudi@ufpel.edu.br E-mail: yoonp@umd.edu

    2013-06-01

    This Letter reports on the results of numerical simulations which may provide a possible explanation for the strahl broadening during quiet solar conditions. The relevant processes involved in the broadening are due to kinetic quasi-linear wave-particle interaction. Making use of static analytical electron distribution in an inhomogeneous field, it is found that self-generated electrostatic waves at the plasma frequency, i.e., Langmuir waves, are capable of scattering the strahl component, resulting in energy and pitch-angle diffusion that broadens its velocity distribution significantly. The present theoretical results provide an alternative or complementary explanation to the usual whistler diffusion scenario, suggesting that self-induced electrostatic waves at the plasma frequency might play a key role in broadening the solar wind strahl during quiet solar conditions.

  19. Standing waves along a microwave generated surface wave plasma

    NASA Technical Reports Server (NTRS)

    Rogers, J.; Asmussen, J.

    1982-01-01

    Two surface wave plasma columns, generated by microwave power in argon at gas pressures of 0.05 torr to 330 torr, interact in the same discharge tube to form standing surface waves. Radial electric field and azimuthal magnetic field outside the discharge tube are measured to be 90 deg out of phase with respect to axial position and to decay exponentially with radial distance from the tube axis. Maximum light emission occurs at the position of maximum azimuthal magnetic field and minimum radial electric field. Electron temperature and density are measured at low pressures with double probes inserted into the plasma at a null of radial electric field. Measured electron densities compare well with those predicted by Gould-Trivelpiece surface wave theory.

  20. On the generation of plasma waves in Saturn's inner magnetosphere

    NASA Astrophysics Data System (ADS)

    Barbosa, D. D.; Kurth, W. S.

    1993-06-01

    Voyager 1 plasma wave measurements of Saturn's inner magnetosphere are reviewed with regard to interpretative aspects of the wave spectrum. A comparison of the wave emission profile with the electron plasma frequency obtained from in situ measurements of the thermal ion density shows good agreement with various features in the wave data identified as electrostatic modes and electromagnetic radio waves. Theoretical calculations of the critical flux of superthermal electrons able to generate whistler-mode waves and electrostatic electron cyclotron harmonic waves through a loss-cone instability are presented. The comparison of model results with electron measurements shows excellent agreement, thereby lending support to the conclusion that a moderate perpendicular anisotropy in the hot electron distribution is present in the equatorial region of L = 5-8.

  1. Electromagnetic Properties of Impact-Generated Plasma, Vapor and Debris

    SciTech Connect

    Crawford, D.A.; Schultz, P.H.

    1998-11-02

    Plasma, vapor and debris associated with an impact or explosive event have been demonstrated in the laboratory to produce radiofrequency and optical electromagnetic emissions that can be diagnostic of the event. Such effects could potentially interfere with communications or remote sensing equipment if an impact occurred, for example, on a satellite. More seriously, impact generated plasma could end the life of a satellite by mechanisms that are not well understood and not normally taken into account in satellite design. For example, arc/discharge phenomena resulting from highly conductive plasma acting as a current path across normally shielded circuits may have contributed to the loss of the Olympus experimental communications satellite on August 11, 1993. The possibility of significant storm activity during the Leonid meteor showers of November 1998, 1999 and 2000 (impact velocity, 72 km/s) has heightened awareness of potential vulnerabilities from hypervelocity electromagnetic effects to orbital assets. The concern is justified. The amount of plasma, electrostatic charge and the magnitude of the resulting currents and electric fields scale nearly as the cube of the impact velocity. Even for microscopic Leonid impacts, the amount of plasma approaches levels that could be dangerous to spacecraft electronics. The degree of charge separation that occurs during hypervelocity impacts scales linearly with impactor mass. The resulting magnetic fields increase linearly with impactor radius and could play a significant role in our understanding of the paleomagnetism of planetary surfaces. The electromagnetic properties of plasma produced by hypervelocity impact have been exploited by researchers as a diagnostic tool, invoked to potentially explain the magnetically jumbled state of the lunar surface and blamed for the loss of the Olympus experimental communications satellite. The production of plasma in and around an impact event can lead to several effects: (1) the

  2. Nonequilibrium dynamics of laser-generated plasma channels

    NASA Astrophysics Data System (ADS)

    Petrova, Tz. B.; Ladouceur, H. D.; Baronavski, A. P.

    2008-05-01

    A time-dependent nonequilibrium kinetics model based upon the time-dependent electron Boltzmann equation coupled with an extensive air chemistry model accounting for gas heating and vibrational kinetics is developed. The model is applied to the temporal evolution of femtosecond laser-generated air plasma channels at atmospheric pressure in an external electric field. The plasma channel dynamics depend upon the initial free electron density, the initial electron energy of the plasma, and upon the externally applied electric field strength. The model predicts an electric breakdown field strength of 5-10kV/cm with a delay time of hundreds of nanoseconds when the electron density drops to the optimum value of ˜1012-1013cm-3. The experimentally observed breakdown field is ˜5.7kV/cm with a statistical breakdown delay time of ˜200ns. The reduction in the breakdown field strength in natural air from ˜30to5kV/cm is attributed to a combination of processes such as enhanced ionization due to relaxation of the initial electron energy distribution function toward a Maxwellian distribution, strong electron detachment, and gas heating. The calculated electron density decay of the laser-generated plasma channel in both pure nitrogen and dry air is in good agreement with the NRL experiments. The derived rate constant for recombination in dry air is bBair=3.9×10-8cm3s-1 and in pure nitrogen it is bBN2=4.4×10-8cm3s-1. The attachment rate coefficient in dry air is ηBair=7.5×106s-1.

  3. Shock Generation and Control Using DBD Plasma Actuators

    NASA Technical Reports Server (NTRS)

    Patel, Mehul P.; Cain, Alan B.; Nelson, Christopher C.; Corke, Thomas C.; Matlis, Eric H.

    2012-01-01

    This report is the final report of a NASA Phase I SBIR contract, with some revisions to remove company proprietary data. The Shock Boundary Layer Interaction (SBLI) phenomena in a supersonic inlet involve mutual interaction of oblique shocks with boundary layers, forcing the boundary layer to separate from the inlet wall. To improve the inlet efficiency, it is desired to prevent or delay shock-induced boundary layer separation. In this effort, Innovative Technology Applications Company (ITAC), LLC and the University of Notre Dame (UND) jointly investigated the use of dielectric-barrier-discharge (DBD) plasma actuators for control of SBLI in a supersonic inlet. The research investigated the potential for DBD plasma actuators to suppress flow separation caused by a shock in a turbulent boundary layer. The research involved both numerical and experimental investigations of plasma flow control for a few different SBLI configurations: (a) a 12 wedge flow test case at Mach 1.5 (numerical and experimental), (b) an impinging shock test case at Mach 1.5 using an airfoil as a shock generator (numerical and experimental), and (c) a Mach 2.0 nozzle flow case in a simulated 15 X 15 cm wind tunnel with a shock generator (numerical). Numerical studies were performed for all three test cases to examine the feasibility of plasma flow control concepts. These results were used to guide the wind tunnel experiments conducted on the Mach 1.5 12 degree wedge flow (case a) and the Mach 1.5 impinging shock test case (case b) which were at similar flow conditions as the corresponding numerical studies to obtain experimental evidence of plasma control effects for SBLI control. The experiments also generated data that were used in validating the numerical studies for the baseline cases (without plasma actuators). The experiments were conducted in a Mach 1.5 test section in the University of Notre Dame Hessert Laboratory. The simulation results from cases a and b indicated that multiple

  4. Generation of kinetic Alfven waves by beam-plasma interaction in non-uniform plasma

    SciTech Connect

    Hong, M. H.; Lin, Y.; Wang, X. Y.

    2012-07-15

    This work reports a novel mechanism of the generation of kinetic Alfven waves (KAWs) using a two-dimensional hybrid simulation: the KAWs are generated by ion beam-plasma interaction in a non-uniform plasma boundary layer, in which the bulk velocity of the ion beam is assumed to be parallel to the ambient magnetic field. As a result of the beam-plasma interaction, strong shear Alfven waves as well as fast mode compressional waves are first generated on the side of the boundary layer with a high density and thus a low Alfven speed, propagating along the background magnetic field. Later, Alfven waves also form inside the boundary layer with a continuous spectrum. As the perpendicular wave number k{sub Up-Tack} of these unstably excited waves increases with time, large-amplitude, short wavelength KAWs with k{sub Up-Tack } Much-Greater-Than k{sub ||} clearly form in the boundary layer. The physics for the generation of KAWs is discussed.

  5. Reversal of trauma-induced amnesia in mice by a thrombin receptor antagonist.

    PubMed

    Itzekson, Zeev; Maggio, Nicola; Milman, Anat; Shavit, Efrat; Pick, Chaim G; Chapman, Joab

    2014-05-01

    Minimal traumatic brain injury (mTBI) is associated with the existence of retrograde amnesia and microscopic bleeds containing activated coagulation factors. In an mTBI model, we report that thrombin induces amnesia through its receptor protease-activated receptor 1 (PAR-1). Thrombin activity was significantly elevated (32 %, p < 0.05) 5 min following mTBI compared to controls. Amnesia was assessed by the novel object recognition test in mTBI animals and in animals injected intracerebroventricularly (ICV) with either thrombin or a PAR-1 agonist 1 h after the acquisition phase. Saline-injected controls had a preference index of over 0.3 while mTBI animals and those injected with thrombin or the PAR-1 agonist spent equal time with both objects indicating no recall of the object presented to them 24 h previously (p < 0.05). Co-injecting a PAR-1 antagonist (SCH79797) completely blocked the amnestic effects of mTBI, thrombin, and the PAR-1 agonist. Long-term potentiation, measured in hippocampal slices 24 h after mTBI, ICV thrombin or the PAR-1 agonist, was significantly impaired and this effect was completely reversed by the PAR-1 antagonist. The results support a crucial role for PAR-1 in the generation of amnesia following mTBI, revealing a novel therapeutic target for the cognitive effects of brain trauma.

  6. Magnetic field generation during intense laser channelling in underdense plasma

    NASA Astrophysics Data System (ADS)

    Smyth, A. G.; Sarri, G.; Vranic, M.; Amano, Y.; Doria, D.; Guillaume, E.; Habara, H.; Heathcote, R.; Hicks, G.; Najmudin, Z.; Nakamura, H.; Norreys, P. A.; Kar, S.; Silva, L. O.; Tanaka, K. A.; Vieira, J.; Borghesi, M.

    2016-06-01

    Channel formation during the propagation of a high-energy (120 J) and long duration (30 ps) laser pulse through an underdense deuterium plasma has been spatially and temporally resolved via means of a proton imaging technique, with intrinsic resolutions of a few μm and a few ps, respectively. Conclusive proof is provided that strong azimuthally symmetric magnetic fields with a strength of around 0.5 MG are created inside the channel, consistent with the generation of a collimated beam of relativistic electrons. The inferred electron beam characteristics may have implications for the cone-free fast-ignition scheme of inertial confinement fusion.

  7. An electrochemical aptasensor electrocatalyst for detection of thrombin.

    PubMed

    Tian, Rong; Chen, Xiaojun; Li, Qingwen; Yao, Cheng

    2016-05-01

    This work reports a novel signal amplification strategy based on three-dimensional ordered macroporous C60-poly(3,4-ethylenedioxythiophene)-1-butyl-3-methylimidazolium hexafluorophosphate (3DOM C60-PEDOT-[BMIm][BF6]) for ultrasensitive detection of thrombin by cascade catalysis of Au-PEDOT@SiO2 microspheres and alcohol dehydrogenase (ADH). Au-PEDOT@SiO2 microspheres were constructed not only as nanocarriers to anchor the large amounts of secondary thrombin aptamers but also as nanocatalysts to catalyze the oxidation of ethanol efficiently. Significantly, the electrochemical signal was greatly enhanced based on cascade catalysis: First, ADH catalyzed the oxidation of ethanol to acetaldehyde with the concomitant generation of NADH in the presence of β-nicotinamide adenine dinucleotide hydrate (NAD(+)). Then, gold nanoparticles (AuNPs) as nanocatalysts could effectively catalyze NADH to produce NAD(+) with the help of PEDOT as redox probe. Under the optimal conditions, the proposed aptasensor exhibits a linear range of 2 × 10(-13) to 2 × 10(-8) M with a low detection limit of 2 × 10(-14) M for thrombin detection and shows high sensitivity and good specificity. PMID:26869084

  8. Protein C inhibits endocytosis of thrombin-thrombomodulin complexes in A549 lung cancer cells and human umbilical vein endothelial cells

    SciTech Connect

    Maruyama, I.; Majerus, P.W.

    1987-05-01

    We investigated the effect of protein C on the endocytosis of thrombin-thrombomodulin complexes. We previously showed that exposure of umbilical vein endothelial cells to thrombin stimulated the internalization and degradation of thrombin. A similar internalization was stimulated by a monoclonal antithrombomodulin antibody. We have repeated these studies in the presence of protein C and found that endocytosis of /sup 125/I-thrombin-thrombomodulin complexes, but not /sup 125/I-antithrombomodulin-thrombomodulin complexes, is inhibited. Activated protein C did not inhibit endocytosis of thrombin-thrombomodulin complexes. Protein C inhibited both internalization and degradation of /sup 125/I-thrombin and diisopropylphosphoryl (DIP) /sup 125/I-thrombin in human lung cancer cells (A549). These effects were observed at protein C concentrations found in human plasma. Protein S had no effect on the inhibition of endocytosis of thrombin-thrombomodulin complexes by protein C. We propose that protein C may regulate the rate of endocytosis of thrombin-thrombomodulin complexes in vivo and thereby control the capacity for endothelium to activate protein C.

  9. Micro-plasmas as efficient generators of singlet delta oxygen

    NASA Astrophysics Data System (ADS)

    Puech, Vincent; Bauville, Gerard; Lacour, Bernard; Santos Sousa, Joao; Pitchford, Leanne C.; Touzeau, Michel

    2008-05-01

    This paper discusses the possibility of producing high concentrations of O2(a1Δg) states at pressures up to atmospheric in rare-gas/oxygen/NO mixtures by using micro-plasmas. Micro-plasmas refer to electric discharges created in very small geometries which have been proven able to operate in DC mode at high pressure and high power loading without undergoing any glow to arc transition. The so-called Micro Cathode Sustained Discharge (MCSD), which is a three-electrode configuration using a Micro Hollow Cathode Discharge (MHCD) as a plasma cathode, can be operated as a non-self-sustained discharge with low values of the reduced electric field and of the gas temperature. As a result, these MCSDs can efficiently generate large amounts of singlet delta oxygen. In Ar/O2/NO mixtures, at an oxygen partial pressure of 10 mbar, high values of O2(a1Δg) number density (1.5 1016 cm-3) and of the production yield (6.7 %) can be simultaneously obtained. For lower O2 partial pressure, yields higher than 10 % have been measured. In He/O2/NO mixtures, O2(a1Δg) number densities around 1016 cm-3 were achieved at atmospheric pressure for flow rates in the range 5-30 ln/mn, which could give rise to new applications.

  10. Cleavage of the thrombin receptor: identification of potential activators and inactivators.

    PubMed Central

    Parry, M A; Myles, T; Tschopp, J; Stone, S R

    1996-01-01

    The kinetic parameters were determined for the hydrolysis of a peptide based on the activation site of the thrombin receptor (residues 38-60) by thrombin and 12 other proteases. The kcat and Km values for the cleavage of this peptide (TR39-40) by thrombin were 107 s-1 and 1.3 microM; the kcat/Km of TR39-40 is among the highest observed for thrombin. A model is presented that reconciles the parameters for cleavage of the peptide with the concentration dependence of cellular responses to thrombin. Cleavage of TR39-40 was not specific for thrombin. The pancreatic proteases trypsin and chymotrypsin hydrolysed TR39-40 efficiently (kcat/Km > 10(6) M-1.s-1). Whereas trypsin cleaved TR39-40 at the thrombin activation site (Arg41-Ser42), chymotrypsin hydrolysed the peptide after Phe43. This chymotryptic cleavage would result in inactivation of the receptor. The efficient cleavage of TR39-40 by chymotrypsin (kcat/Km approximately 10(6) M-1.s-1) was predominantly due to a low Km value (2.8 microM). The proteases factor Xa, plasmin, plasma kallikrein, activated protein C and granzyme A also hydrolysed TR39-40 at the Arg41-Ser43 bond, but exhibited kcat/Km values that were at least 10(3)-fold lower than that observed with thrombin. Both tissue and urokinase plasminogen activators as well as granzyme B and neutrophil elastase were unable to cleave TR39-60 at appreciable rates. However, neutrophil cathepsin G hydrolysed the receptor peptide after Phe55. Like the chymotryptic cleavage, this cleavage would lead to inactivation of the receptor, but the cathepsin G reaction was markedly less efficient; the kcat/K(m) value was almost four orders of magnitude lower than that for thrombin. In addition to the above cleavage sites, a secondary site for thrombin and other arginine-specific proteases was identified at Arg46, but the cleavage at this site only occurred at very low rates and is unlikely to be significant in vivo. PMID:8947506

  11. Generation of strongly coupled plasmas by high power excimer laser

    NASA Astrophysics Data System (ADS)

    Zhu, Yongxiang; Liu, Jingru; Zhang, Yongsheng; Hu, Yun; Zhang, Jiyan; Zheng, Zhijian; Ye, Xisheng

    2013-05-01

    (ultraviolet). To generate strongly coupled plasmas (SCP) by high power excimer laser, an Au-CH-Al-CH target is used to make the Al sample reach the state of SCP, in which the Au layer transforms laser energy to X-ray that heating the sample by volume and the CH layers provides necessary constraints. With aid of the MULTI-1D code, we calculate the state of the Al sample and its relationship with peak intensity, width and wavelength of laser pulses. The calculated results suggest that an excimer laser with peak intensity of the magnitude of 1013W/cm2 and pulse width being 5ns - 10ns is suitable to generate SCP with the temperature being tens of eV and the density of electron being of the order of 1022/cm-3. Lasers with shorter wavelength, such as KrF laser, are preferable.

  12. Antiplatelet therapy: thrombin receptor antagonists

    PubMed Central

    Tello-Montoliu, Antonio; Tomasello, Salvatore D; Ueno, Masafumi; Angiolillo, Dominick J

    2011-01-01

    Activated platelets stimulate thrombus formation in response to rupture of an atherosclerotic plaque or endothelial cell erosion, promoting atherothrombotic disease. Multiple pathways contribute to platelet activation. Aspirin, an irreversible inhibitor of thromboxane A2 synthesis, in combination with clopidogrel, an inhibitor of P2Y12 adenosine diphosphate platelet receptors, represent the current standard-of-care of antiplatelet therapy for patients with acute coronary syndrome and for those undergoing percutaneous coronary intervention. Although these agents have demonstrated significant clinical benefit, the increased risk of bleeding and the recurrence of thrombotic events represent substantial limitations. Thrombin is one of the most important platelet activators. The inhibition of protease-activated receptor 1 showed a good safety profile in preclinical studies. In fact, phase II studies with vorapaxar (SCH530348) and atopaxar (E5555) showed no increase of bleeding events in addition to the current standard-of-care of antiplatelet therapy. Although the results of phase III trials for both drugs are awaited, this family is a promising new addition to the current clinical practice for patients with atherothrombotic disease, not only as an alternative, but also as additional therapy. PMID:21906120

  13. Adenosine regulates the proinflammatory signaling function of thrombin in endothelial cells

    PubMed Central

    Hassanian, Seyed Mahdi; Dinarvand, Peyman; Rezaie, Alireza R.

    2014-01-01

    The plasma level of the regulatory metabolite adenosine increases during the activation of coagulation and inflammation. Here we investigated the effect of adenosine on modulation of thrombin-mediated proinflammatory responses in HUVECs. We found that adenosine inhibits the barrier-disruptive effect of thrombin in HUVECs by a concentration-dependent manner. Analysis of cell surface expression of adenosine receptors revealed that A2A and A2B are expressed at the highest level among the four receptor subtypes (A2B>A2A>A1>A3) on HUVECs. The barrier-protective effect of adenosine in response to thrombin was recapitulated by the A2A specific agonist, CGS 21680, and abrogated both by the siRNA knockdown of the A2A receptor and by the A2A-specific antagonists, ZM-241385 and SCH-58261. The thrombin-induced RhoA activation and its membrane translocation were both inhibited by adenosine in a cAMP-dependent manner, providing a molecular mechanism through which adenosine exerts a barrier-protective function. Adenosine also inhibited thrombin-mediated activation of NF-κB and decreased adhesion of monocytic THP-1 cells to stimulated HUVECs via down-regulation of expression of cell surface adhesion molecules, VCAM-1, ICAM-1 and E-selectin. Moreover, adenosine inhibited thrombin-induced elevated expression of proinflammatory cytokines, IL-6 and HMGB-1; and chemokines, MCP-1, CXCL-1 and CXCL-3. Taken together, these results suggest that adenosine may inhibit thrombin-mediated proinflammatory signaling responses, thereby protecting the endothelium from injury during activation of coagulation and inflammation. PMID:24477600

  14. Ion Beam Analysis applied to laser-generated plasmas

    NASA Astrophysics Data System (ADS)

    Cutroneo, M.; Macková, A.; Havranek, V.; Malinsky, P.; Torrisi, L.; Kormunda, M.; Barchuk, M.; Ullschmied, J.; Dudzak, R.

    2016-04-01

    This paper presents the research activity on Ion Beam Analysis methods performed at Tandetron Laboratory (LT) of the Institute of Nuclear Physics AS CR, Rez, Czech Republic. Recently, many groups are paying attention to implantation by laser generated plasma. This process allows to insert a controllable amount of energetic ions into the surface layers of different materials modifying the physical and chemical properties of the surface material. Different substrates are implanted by accelerated ions from plasma through terawatt iodine laser, at nominal intensity of 1015 W/cm2, at the PALS Research Infrastructure AS CR, in the Czech Republic. This regime of the laser matter interaction generates, multi-MeV proton beams, and multi-charged ions that are tightly confined in time (hundreds ps) and space (source radius of a few microns). These ion beams have a much lower transverse temperature, a much shorter duration and a much higher current than those obtainable from conventional accelerators. The implementation of protons and ions acceleration driven by ultra-short high intensity lasers is exhibited by adopting suitable irradiation conditions as well as tailored targets. An overview of implanted targets and their morphological and structural characterizations is presented and discussed.

  15. Bernstein wave aided laser third harmonic generation in a plasma

    NASA Astrophysics Data System (ADS)

    Tyagi, Yachna; Tripathi, Deepak; Kumar, Ashok

    2016-09-01

    The process of Bernstein wave aided resonant third harmonic generation of laser in a magnetized plasma is investigated. The extra-ordinary mode (X-mode) laser of frequency ω 0 and wave number k → 0 , travelling across the magnetic field in a plasma, exerts a second harmonic ponderomotive force on the electrons imparting them an oscillatory velocity v → 2 ω0 , 2 k → 0 . This velocity beats with the density perturbation due to the Bernstein wave to produce a density perturbation at cyclotron frequency shifted second harmonic. The density perturbation couples with the oscillatory velocity v → ω0 , k → 0 of X-mode of the laser to produce the cyclotron frequency shifted third harmonic current density leading to harmonic radiation. The phase matching condition for the up shifted frequency is satisfied when the Bernstein wave is nearly counter-propagating to the laser. As the transverse wave number of the Bernstein wave is large, it is effective in the phase matched third harmonic generation, when the laser frequency is not too far from the upper hybrid frequency.

  16. Dense plasma focus powered by flux compression generators

    SciTech Connect

    Fowler, C.M.; Freeman, B.L.; Caird, R.S.; Erickson, D.J.; Garn, W.B.

    1992-12-01

    A short summary is given of earlier Los Alamos work in which a Dense Plasma Focus was powered by Flux Compression Generators. Neutron yields obtained in the shot series scaled well with the fifth power of the current. The shot parameters were modeled surprisingly well through the plasma rundown phase by a simple snowplow model. It is shown, with the use of this model, that DPF currents in excess of 10 MA should be obtained with existing generators and initial energy sources. One new element is needed -- a high energy opening switch such as a fuse. Much more is known about fuse operation since the Los Alamos program was stopped, so development of this component should be relatively straightforward. If the yield-current scaling relation holds to this current level, then D-T neutron yields in excess of 10{sup 16} per burst would result, sufficient for some interesting pulsed radiography applications that involve rapidly moving components. Finally, in a sheer flight of fancy, it is shown that D-T yields approaching 10{sup 20} could be obtained, using FCGs not too much beyond the state of the art, provided the simple modeling and neutron-current scaling relations continue to hold, a rather unlikely supposition.

  17. Dense plasma focus powered by flux compression generators

    NASA Astrophysics Data System (ADS)

    Fowler, C. M.; Freeman, B. L.; Caird, R. S.; Erickson, D. J.; Garn, W. B.

    A short summary is given of earlier Los Alamos work in which a Dense Plasma Focus was powered by Flux Compression Generators. Neutron yields obtained in the shot series scaled well with the fifth power of the current. The shot parameters were modeled surprisingly well through the plasma rundown phase by a simple snowplow model. It is shown, with the use of this model, that DPF currents in excess of 10 MA should be obtained with existing generators and initial energy sources. One new element is needed--a high energy opening switch such as a fuse. Much more is known about fuse operation since the Los Alamos program was stopped, so development of this component should be relatively straightforward. If the yield-current scaling relation holds to this current level, then D-T neutron yields in excess of 10(exp 16) per burst would result, sufficient for some interesting pulsed radiography applications that involve rapidly moving components. Finally, in a sheer flight of fancy, it is shown that D-T yields approaching 10(exp 20) could be obtained, using FCG's not too much beyond the state of the art, provided the simple modeling and neutron-current scaling relations continue to hold, a rather unlikely supposition.

  18. Dense plasma focus powered by flux compression generators

    SciTech Connect

    Fowler, C.M.; Freeman, B.L.; Caird, R.S.; Erickson, D.J.; Garn, W.B.

    1992-01-01

    A short summary is given of earlier Los Alamos work in which a Dense Plasma Focus was powered by Flux Compression Generators. Neutron yields obtained in the shot series scaled well with the fifth power of the current. The shot parameters were modeled surprisingly well through the plasma rundown phase by a simple snowplow model. It is shown, with the use of this model, that DPF currents in excess of 10 MA should be obtained with existing generators and initial energy sources. One new element is needed -- a high energy opening switch such as a fuse. Much more is known about fuse operation since the Los Alamos program was stopped, so development of this component should be relatively straightforward. If the yield-current scaling relation holds to this current level, then D-T neutron yields in excess of 10[sup 16] per burst would result, sufficient for some interesting pulsed radiography applications that involve rapidly moving components. Finally, in a sheer flight of fancy, it is shown that D-T yields approaching 10[sup 20] could be obtained, using FCGs not too much beyond the state of the art, provided the simple modeling and neutron-current scaling relations continue to hold, a rather unlikely supposition.

  19. PREFACE: Acceleration and radiation generation in space and laboratory plasmas

    NASA Astrophysics Data System (ADS)

    Bingham, R.; Katsouleas, T.; Dawson, J. M.; Stenflo, L.

    1994-01-01

    Sixty-six leading researchers from ten nations gathered in the Homeric village of Kardamyli, on the southern coast of mainland Greece, from August 29-September 4, 1993 for the International Workshop on Acceleration and Radiation Generation in Space and Laboratory Plasmas. This Special Issue represents a cross-section of the presentations made at and the research stimulated by that meeting. According to the Iliad, King Agamemnon used Kardamyli as a dowry offering in order to draw a sulking Achilles into the Trojan War. 3000 years later, Kardamyli is no less seductive. Its remoteness and tranquility made it an ideal venue for promoting the free exchange of ideas between various disciplines that do not normally interact. Through invited presen tations, informal poster discussions and working group sessions, the Workshop brought together leaders from the laboratory and space/astrophysics communities working on common problems of acceleration and radiation generation in plasmas. It was clear from the presentation and discussion sessions that there is a great deal of common ground between these disciplines which is not at first obvious due to the differing terminologies and types of observations available to each community. All of the papers in this Special Issue highlight the role collective plasma processes play in accelerating particles or generating radiation. Some are state-of-the-art presentations of the latest research in a single discipline, while others investi gate the applicability of known laboratory mechanisms to explain observations in natural plasmas. Notable among the latter are the papers by Marshall et al. on kHz radiation in the magnetosphere ; Barletta et al. on collective acceleration in solar flares; and by Dendy et al. on ion cyclotron emission. The papers in this Issue are organized as follows: In Section 1 are four general papers by Dawson, Galeev, Bingham et al. and Mon which serves as an introduction to the physical mechanisms of acceleration

  20. High duty factor plasma generator for CERN's Superconducting Proton Linac.

    PubMed

    Lettry, J; Kronberger, M; Scrivens, R; Chaudet, E; Faircloth, D; Favre, G; Geisser, J-M; Küchler, D; Mathot, S; Midttun, O; Paoluzzi, M; Schmitzer, C; Steyaert, D

    2010-02-01

    CERN's Linac4 is a 160 MeV linear accelerator currently under construction. It will inject negatively charged hydrogen ions into CERN's PS-Booster. Its ion source is a noncesiated rf driven H(-) volume source directly inspired from the one of DESY and is aimed to deliver pulses of 80 mA of H(-) during 0.4 ms at a 2 Hz repetition rate. The Superconducting Proton Linac (SPL) project is part of the luminosity upgrade of the Large Hadron Collider. It consists of an extension of Linac4 up to 5 GeV and is foreseen to deliver protons to a future 50 GeV synchrotron (PS2). For the SPL high power option (HP-SPL), the ion source would deliver pulses of 80 mA of H(-) during 1.2 ms and operate at a 50 Hz repetition rate. This significant upgrade motivates the design of the new water cooled plasma generator presented in this paper. Its engineering is based on the results of a finite element thermal study of the Linac4 H(-) plasma generator that identified critical components and thermal barriers. A cooling system is proposed which achieves the required heat dissipation and maintains the original functionality. Materials with higher thermal conductivity are selected and, wherever possible, thermal barriers resulting from low pressure contacts are removed by brazing metals on insulators. The AlN plasma chamber cooling circuit is inspired from the approach chosen for the cesiated high duty factor rf H(-) source operating at SNS. PMID:20192392

  1. High duty factor plasma generator for CERN's Superconducting Proton Linac.

    PubMed

    Lettry, J; Kronberger, M; Scrivens, R; Chaudet, E; Faircloth, D; Favre, G; Geisser, J-M; Küchler, D; Mathot, S; Midttun, O; Paoluzzi, M; Schmitzer, C; Steyaert, D

    2010-02-01

    CERN's Linac4 is a 160 MeV linear accelerator currently under construction. It will inject negatively charged hydrogen ions into CERN's PS-Booster. Its ion source is a noncesiated rf driven H(-) volume source directly inspired from the one of DESY and is aimed to deliver pulses of 80 mA of H(-) during 0.4 ms at a 2 Hz repetition rate. The Superconducting Proton Linac (SPL) project is part of the luminosity upgrade of the Large Hadron Collider. It consists of an extension of Linac4 up to 5 GeV and is foreseen to deliver protons to a future 50 GeV synchrotron (PS2). For the SPL high power option (HP-SPL), the ion source would deliver pulses of 80 mA of H(-) during 1.2 ms and operate at a 50 Hz repetition rate. This significant upgrade motivates the design of the new water cooled plasma generator presented in this paper. Its engineering is based on the results of a finite element thermal study of the Linac4 H(-) plasma generator that identified critical components and thermal barriers. A cooling system is proposed which achieves the required heat dissipation and maintains the original functionality. Materials with higher thermal conductivity are selected and, wherever possible, thermal barriers resulting from low pressure contacts are removed by brazing metals on insulators. The AlN plasma chamber cooling circuit is inspired from the approach chosen for the cesiated high duty factor rf H(-) source operating at SNS.

  2. Promoting Plasma Physics as a Career: A Generational Approach

    NASA Astrophysics Data System (ADS)

    Morgan, James

    2005-10-01

    A paradigm shift is occurring in education physics programs. Educators are shifting from the traditional teaching focus to concentrate on student learning. Students are unaware of physics as a career, plasma physics or the job opportunities afforded to them with a physics degree. The physics profession needs to promote itself to the younger generations, or specifically the millennial generation (Born in the 1980's-2000's). Learning styles preferred by ``Millennials'' include a technological environment that promotes learning through active task performance rather than passive attendance at lectures. Millennials respond well to anything experiential and will be motivated by opportunities for creativity and challenging learning environments. The open-ended access to information, the ability to tailor learning paths, and continuous and instantaneous performance assessment offer flexibility in the design of curricula as well as in the method of delivery. Educators need to understand the millennial generation, appeal to their motivations and offer a learning environment designed for their learning style. This poster suggests promoting a physics career by focusing on generational learning styles and preferences.

  3. Two-color high-harmonic generation in plasmas: efficiency dependence on the generating particle properties.

    PubMed

    Emelina, Anna S; Emelin, Mikhail Yu; Ganeev, Rashid A; Suzuki, Masayuki; Kuroda, Hiroto; Strelkov, Vasily V

    2016-06-27

    The high-order harmonic generation (HHG) in silver, gold, and zinc plasma plumes irradiated by orthogonally polarized two-color field is studied theoretically and experimentally. We find an increase of the HHG efficiency in comparison with the single-color case, which essentially depends on the plasma species and harmonic order. An increase of more than an order of magnitude is observed for silver plasma, whereas for gold and zinc it is lower; these results are reproduced in our calculations that include both propagation and microscopic response studies. We show that the widely used theoretical approach assuming the 1s ground state of the generating particle fails to reproduce the experimental results; the agreement is achieved in our theory using the actual quantum numbers of the outer electron of the generating particles. Moreover, our theoretical studies highlight the redistribution of the electronic density in the continuum wave packet as an important aspect of the HHG enhancement in the two-color orthogonally polarized fields with comparable intensities: in the single-color field the electronic trajectories with almost zero return energy are the most populated ones; in the two-color case the total field maximum can be shifted in time so that the trajectories with high return energies (in particular, the cut-off trajectory) become the most populated ones. PMID:27410560

  4. Correlated Motions and Residual Frustration in Thrombin

    PubMed Central

    2013-01-01

    Thrombin is the central protease in the cascade of blood coagulation proteases. The structure of thrombin consists of a double β-barrel core surrounded by connecting loops and helices. Compared to chymotrypsin, thrombin has more extended loops that are thought to have arisen from insertions in the serine protease that evolved to impart greater specificity. Previous experiments showed thermodynamic coupling between ligand binding at the active site and distal exosites. We present a combined approach of molecular dynamics (MD), accelerated molecular dynamics (AMD), and analysis of the residual local frustration of apo-thrombin and active-site-bound (PPACK-thrombin). Community analysis of the MD ensembles identified changes upon active site occupation in groups of residues linked through correlated motions and physical contacts. AMD simulations, calibrated on measured residual dipolar couplings, reveal that upon active site ligation, correlated loop motions are quenched, but new ones connecting the active site with distal sites where allosteric regulators bind emerge. Residual local frustration analysis reveals a striking correlation between frustrated contacts and regions undergoing slow time scale dynamics. The results elucidate a motional network that probably evolved through retention of frustrated contacts to provide facile conversion between ensembles of states. PMID:23621631

  5. Magnetohydrodynamic Power Generation in the Laboratory Simulated Martian Entry Plasma

    NASA Technical Reports Server (NTRS)

    Vuskovic, L.; Popovic, S.; Drake, J.; Moses, R. W.

    2005-01-01

    This paper addresses the magnetohydrodynamic (MHD) conversion of the energy released during the planetary entry phase of an interplanetary vehicle trajectory. The effect of MHD conversion is multi-fold. It reduces and redirects heat transferred to the vehicle, and regenerates the dissipated energy in reusable and transportable form. A vehicle on an interplanetary mission carries about 10,000 kWh of kinetic energy per ton of its mass. This energy is dissipated into heat during the planetary atmospheric entry phase. For instance, the kinetic energy of Mars Pathfinder was about 4220 kWh. Based on the loss in velocity, Mars Pathfinder lost about 92.5% of that energy during the plasma-sustaining entry phase that is approximately 3900 kWh. An ideal MHD generator, distributed over the probe surface of Mars Pathfinder could convert more than 2000 kWh of this energy loss into electrical energy, which correspond to more than 50% of the kinetic energy loss. That means that the heat transferred to the probe surface can be reduced by at least 50% if the converted energy is adequately stored, or re-radiated, or directly used. Therefore, MHD conversion could act not only as the power generating, but also as the cooling process. In this paper we describe results of preliminary experiments with light and microwave emitters powered by model magnetohydrodynamic generators and discuss method for direct use of converted energy.

  6. Measurement of optical emission from the hydrogen plasma of the Linac4 ion source and the SPL plasma generator

    SciTech Connect

    Lettry, J.; Bertolo, S.; Castel, A.; Chaudet, E.; Ecarnot, J.-F.; Favre, G.; Fayet, F.; Geisser, J.-M.; Haase, M.; Habert, A.; Hansen, J.; Joffe, S.; Kronberger, M.; Lombard, D.; Marmillon, A.; Balula, J. Marques; Mathot, S.; Midttun, O.; Moyret, P.; Nisbet, D.

    2011-09-26

    At CERN, a non caesiated H{sup -} ion volume source derived from the DESY ion source is being commissioned. For a proposed High Power Superconducting Proton Linac (HP-SPL), a non caesiated plasma generator was designed to operate at the two orders of magnitude larger duty factor required by the SPL. The commissioning of the plasma generator test stand and the plasma generator prototype are completed and briefly described. The 2 MHz RF generators (100 kW, 50 Hz repetition rate) was successfully commissioned; its frequency and power will be controlled by arbitrary function generators during the 1 ms plasma pulse. In order to characterize the plasma, RF-coupling, optical spectrometer, rest gas analyzer and Langmuir probe measurements will be used. Optical spectrometry allows direct comparison with the currently commissioned Linac4 H{sup -} ion source plasma. The first measurements of the optical emission of the Linac4 ion source and of the SPL plasma generator plasmas are presented.

  7. Rotorcraft Fuselage Flow Control Using Plasma Streamwise Vortex Generators

    NASA Astrophysics Data System (ADS)

    Coleman, Dustin; Thomas, Flint

    2012-11-01

    Active flow control, in the form of dielectric barrier discharge (DBD) plasma actuators, is applied to a NASA ROBIN-mod7 generic rotorcraft fuselage model. The model is considered in what would be a typical cruise position i.e. a nose down position at α = -5° . This configuration gives rise to a massive 3-D flow separation over the aft ramp section of the fuselage, characterized by two counter-rotating, streamwise vortices. The control objective is to minimize these concentrated vortices by means of flush fuselage-mounted plasma streamwise vortex generators (PSVGs), and consequently, reduce the form drag of the vehicle. Experiments were conducted at freestream Mach and Reynolds numbers of M∞ = 0 . 12 and ReL = 2 . 65 million, respectively. Aerodynamic loads under both natural and controlled conditions were acquired through use of an ATI Mini40 6-component force sensor. The pressure field on the ramp section was monitored by a 128 count static pressure array. Likewise, the flow field was captured by time-resolved PIV wake surveys. Results are compared with previous studies that utilized active flow control by way of pulsed jets or combustion actuators. This work is supported under NASA Cooperative Agreement NNX10AM32G.

  8. Numerical Model of the Plasma Sheath Generated by the Plasma Source Instrument Aboard the Polar Satellite

    NASA Technical Reports Server (NTRS)

    Leung, Wing C.; Singh, Nagendra; Moore, Thomas E.; Craven, Paul D.

    2000-01-01

    The plasma sheath generated by the operation of the Plasma Source Instrument (PSI) aboard the POLAR satellite is studied by using a 3-dimensional Particle-In-Cell (PIC) code. When the satellite passes through the region of low density plasma, the satellite charges to positive potentials as high as 4050Volts due to the photoelectrons emission. In such a case, ambient core ions cannot accurately be measured or detected. The goal of the onboard PSI is to reduce the floating potential of the satellite to a sufficiently low value so that the ions in the polar wind become detectable. When the PSI is operated, an ion-rich Xenon plasma is ejected from the satellite, such that the floating potential of the satellite is reduced and is maintained at about 2Volts. Accordingly, in our 3-dimensional PIC simulation, we considered that the potential of the satellite is 2Volts as a fixed bias. Considering the relatively high density of the Xenon plasma in the sheath (approx. 10 - 10(exp 3)/cc), the ambient plasma of low density (less than 1/cc) is neglected. In the simulations, the electric fields and plasma dynamics are calculated self-consistently. We found that an "Apple" shape positive potential sheath forms surrounding the satellite. In the region near the PSI emission, a high positive potential hill develops. Near the Thermal Ion Detection Experiment (TIDE) detector away from the PSI, the potentials are sufficiently low for the ambient polar wind ions to reach it. In the simulations, it takes about a hundred electron gyroperiods for the sheath to reach a quasi-steady state. This time is approximately the time taken by the heavy Xe(+) ions to expand up to about one average Larmor radius of electrons from the satellite surface. Using the steady state sheath, we performed trajectory calculations to characterize the detector response to a highly supersonic polar wind flow. The detected ions' velocity distribution shows significant deviations from a shifted Maxwellian in the

  9. Numerical Model of the Plasma Sheath Generated by the Plasma Source Instrument Aboard the Polar Satellite

    NASA Technical Reports Server (NTRS)

    Singh, N.; Leung, W. C.; Moore, T. E.; Craven, P. D.

    2001-01-01

    The plasma sheath generated by the operation of the Plasma Source Instrument (PSI) aboard the Polar satellite is studied by using a three-dimensional particle-in-cell (PIC) code. When the satellite passes through the region of low-density plasma, the satellite charges to positive potentials as high as 40-50 V, owing to the photoelectron emission. In such a case, ambient core ions cannot accurately be measured or detected. The goal of the onboard PSI is to reduce the floating potential of the satellite to a sufficiently low value so that the ions in the polar wind become detectable. When the PSI is operated, ion-rich xenon plasma is ejected from the satellite, such that the floating potential of the satellite is reduced and is maintained at approximately 2 V. Accordingly, in our three-dimensional PIC simulation we considered that the potential of the satellite is 2 V as a fixed bias. Considering the relatively high density of the xenon plasma in the sheath (10-10(exp 3)/cc), the ambient plasma of low density (<1/cc) is neglected. In the simulations the electric fields and plasma dynamics are calculated self-consistently. We found that an 'apple'-shape positive potential sheath forms surrounding the satellite. In the region near the PSI emission a high positive potential hill develops. Near the Thermal Ion Dynamics Experiment detector away from the PSI, the potentials are sufficiently low for the ambient polar wind ions to reach it. In the simulations it takes only about a couple of tens of electron gyroperiods for the sheath to reach a quasi steady state. This time is approximately the time taken by the heavy Xe(+) ions to expand up to about one average Larmor radius of electrons from the satellite surface. After this time the expansion of the sheath in directions transverse to the ambient magnetic field slows down because the electrons are magnetized. Using the quasi steady sheath, we performed trajectory calculations to characterize the detector response to a

  10. Mechanisms of polymer degradation using an oxygen plasma generator

    NASA Technical Reports Server (NTRS)

    Colony, Joe A.; Sanford, Edward L.

    1987-01-01

    An RF oxygen plasma generator was used to produce polymer degradation which appears to be similar to that which has been observed in low Earth orbit. Mechanisms of this type of degradation were studied by collecting the reaction products in a cryogenic trap and identifying the molecular species using infrared, mass spectral, and X-ray diffraction techniques. No structurally dependent species were found from Kapton, Teflon, or Saran polymers. However, very reactive free radical entities are produced during the polymer degradation, as well as carbon dioxide and water. Reactions of the free radicals with the glass reaction vessel, with copper metal in the cold trap, and with a triphenyl phosphate scavenger in the cold trap, demonstrated the reactivity of the primary products.

  11. Numerical studies of third-harmonic generation in laser filament in air perturbed by plasma spot

    SciTech Connect

    Feng Liubin; Lu Xin; Liu Xiaolong; Li Yutong; Chen Liming; Ma Jinglong; Dong Quanli; Wang Weimin; Xi Tingting; Sheng Zhengming; Zhang Jie; He Duanwei

    2012-07-15

    Third-harmonic emission from laser filament intercepted by plasma spot is studied by numerical simulations. Significant enhancement of the third-harmonic generation is obtained due to the disturbance of the additional plasma. The contribution of the pure plasma effect and the possible plasma-enhanced third-order susceptibility on the third-harmonic generation enhancement are compared. It is shown that the plasma induced cancellation of destructive interference [Y. Liu et al., Opt. Commun. 284, 4706 (2011)] of two-colored filament is the dominant mechanism of the enhancement of third-harmonic generation.

  12. Osteopontin Fragments with Intact Thrombin-Sensitive Site Circulate in Cervical Cancer Patients

    PubMed Central

    Lim, Pak-Leong; Cheung, Tak-Hong; Wong, Raymond R. Y.; Yim, So-Fan; Ng, Margaret H. L.; Tam, Frankie C. H.; Chung, Tony K. H.; Wong, Yick-Fu

    2016-01-01

    We investigated whether circulating osteopontin (OPN) could be used as a biomarker for cervical cancer. We employed a monoclonal antibody (mAb 659) specific for the unique and intact thrombin-sensitive site in OPN using an inhibition ELISA. We found significantly higher levels of OPN in 33 cervical cancer patients in both the plasma (mean +/- SD, 612 +/- 106 ng/mL) and serum (424 +/- 121 ng/mL) compared to healthy subjects [409 +/- 56 ng/mL, from 31 plasma samples (P < 0.0001), and 314 +/- 98 ng/mL, from 32 serum samples (P = 0.0002), respectively]. Similar results were obtained when the plasma from a bigger group (147 individuals) of cervical cancer patients (560 +/- 211 ng/mL) were compared with the same plasma samples of the healthy individuals (P = 0.0014). More significantly, the OPN level was highest in stage III-IV disease (614 +/- 210 ng/mL, from 52 individuals; P = 0.0001) and least and non-discriminatory in stage I (473 +/- 110 ng/mL, from 40 individuals; P = 0.5318). No such discrimination was found when a mAb of a different specificity (mAb 446) was used in a similar inhibition ELISA to compare the two groups in the first study; a commercial capture ELISA also failed. The possibility that the target epitope recognized by the antibody probe in these assays was absent from the circulating OPN due to protein truncation was supported by gel fractionation of the OPN found in patients’ plasma: 60–64 kDa fragments were found instead of the presumably full-length OPN (68 kDa) seen in healthy people. How these fragments are generated and what possible role they play in cancer biology remain interesting questions. PMID:27494141

  13. Oxidation of human alpha-thrombin by the myeloperoxidase-H2O2-chloride system: structural and functional effects.

    PubMed

    De Cristofaro, R; Landolfi, R

    2000-02-01

    The myeloperoxidase-H2O2-chloride system (MPOS) is exploited by white blood cells to generate reactive oxygen species in many processes involved in the pathogenesis of inflammation and atherothrombosis. This, study investigated the biochemical and functional effects of alpha-thrombin oxidation by MPOS. This system, in the presence of 100 microM L-tyrosine, caused in the thrombin molecule loss of tryptophan and lysine residues and formation of dityrosine, chloramine and carbonyl groups. The same changes could be directly induced by thrombin incubation with reagent HOCI, but not with H2O2 alone. Exposure to either MPOS or HOCl caused major functional abnormalities in human alpha-thrombin. The interaction of oxidized (ox-)thrombin with Protein C and antithrombin III-heparin complex were most sensitive to oxidation, being the kcat/Km value for Protein C hydrolysis roughly reduced 13-fold and the affinity for the antithrombin III-heparin complex decreased approximately 15-fold. Ox-thrombin interaction with small synthetic peptides showed several changes, arising from a perturbation of the S2-S3 specificity of the enzyme. Ox-thrombin was also characterized by a 5-fold decrease of the kcat/Km value for both fibrinopeptide A and B release from fibrinogen, a 5.8-fold increase of the EC50 value for platelet activation and a 2-fold decrease of binding affinity for thrombomodulin. The above results indicate a high sensitivity of thrombin to oxidative modifications by myeloperoxidase. Perturbed interactions with Protein C and the heparin-ATIII complex were the most relevant functional abnormalities of ox-thrombin. PMID:10739383

  14. Terahertz generation by beating two Langmuir waves in a warm and collisional plasma

    SciTech Connect

    Zhang, Xiao-Bo; Qiao, Xin; Cheng, Li-Hong; Tang, Rong-An; Zhang, Ai-Xia; Xue, Ju-Kui

    2015-09-15

    Terahertz (THz) radiation generated by beating of two Langmuir waves in a warm and collisional plasma is discussed theoretically. The critical angle between the two Langmuir waves and the critical wave-length (wave vector) of Langmuir waves for generating THz radiation are obtained analytically. Furthermore, the maximum radiation energy is obtained. We find that the critical angle, the critical wave-length, and the generated radiation energy strongly depend on plasma temperature and wave-length of the Langmuir waves. That is, the THz radiation generated by beating of two Langmuir waves in a warm and collisional plasma can be controlled by adjusting the plasma temperature and the Langmuir wave-length.

  15. Microwave plasmas generated in bubbles immersed in liquids for hydrocarbons reforming

    NASA Astrophysics Data System (ADS)

    Levko, Dmitry; Sharma, Ashish; Raja, Laxminarayan L.

    2016-06-01

    We present a computational modeling study of microwave plasma generated in cluster of atmospheric-pressure argon bubbles immersed in a liquid. We demonstrate that the use of microwaves allows the generation of a dense chemically active non-equilibrium plasma along the gas-liquid interface. Also, microwaves allow generation of overdense plasma in all the bubbles considered in the cluster which is possible because the collisional skin depth of the wave exceeds the bubble dimension. These features of microwave plasma generation in bubbles immersed in liquids are highly desirable for the large-scale liquid hydrocarbon reforming technologies.

  16. Highly sensitive thermal detection of thrombin using aptamer-functionalized phase change nanoparticles.

    PubMed

    Wang, Chaoming; Hossain, Mainul; Ma, Liyuan; Ma, Zeyu; Hickman, James J; Su, Ming

    2010-10-15

    This paper describes a novel thermal biosensing technique for the highly sensitive and selective detection of thrombin using RNA aptamer-functionalized phase change nanoparticles as thermal probes. The presence of thrombin in solution leads to attachment of nanoparticles onto a substrate modified with the same aptamer by forming sandwiched complexes. The phase changes of nanoparticles from solid to liquid adsorb heat energy and generate sharp melting peaks during linear temperature scans, where the positions and areas of the melting peaks reflect the presence and the amount of thrombin, respectively. A detection sensitivity of 22 nM is achieved on flat aluminum surfaces, and the sensitivity can be enhanced by four times using silicon nanopillar substrates that have higher surface area. The thermal detection is immune to colored species in solution and has been used directly to detect thrombin in serum samples. By combining the high specificity of aptamers and the large surface area of silicon nanostructures, the thermal signals obtained during phase change of nanoparticles provide a highly sensitive, selective and low-cost method for thrombin detection.

  17. Influence of ionic strength, pH and aptamer configuration for binding affinity to thrombin.

    PubMed

    Hianik, Tibor; Ostatná, Veronika; Sonlajtnerova, Michaela; Grman, Igor

    2007-01-01

    We used the methods of electrochemical indicators and the quartz crystal microbalance (QCM) for detection of thrombin-aptamer interactions. We analyzed how the method of immobilization of aptamer to a solid support, the aptamer configuration as well as variation in ionic strength and pH will affect the binding of thrombin to the aptamer. The immobilization of aptamer by means of avidin-biotin technology revealed best results in sensitivity in comparison with immobilization utilizing dendrimers of first generation and in comparison with chemisorption of aptamer to a gold surface. Linear and molecular beacon aptamers of similar structure of binding site revealed similar binding properties to thrombin. Increased concentration of NaCl resulted in weakening of the binding of thrombin to the aptamers, probably due to shielding effect of Na(+) ions. The binding of the thrombin to the aptamer depends on electrolyte pH, which is presumably connected with maintaining the three dimensional aptamer configuration, optimal for binding the protein.

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

    PubMed

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

    2010-05-01

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

  19. Wakefields generated by collisional neutrinos in neutral-electron-positron plasma

    SciTech Connect

    Tinakiche, Nouara

    2013-02-15

    A classical fluid description is adopted to investigate nonlinear interaction between an electron-type neutrino beam and a relativistic collisionless unmagnetized neutral-electron-positron plasma. In this work, we consider the collisions of the neutrinos with neutrals in the plasma and study their effect on the generation of wakefields in this plasma.

  20. The thrombin receptor extracellular domain contains sites crucial for peptide ligand-induced activation.

    PubMed Central

    Bahou, W F; Coller, B S; Potter, C L; Norton, K J; Kutok, J L; Goligorsky, M S

    1993-01-01

    A thrombin receptor (TR) demonstrating a unique activation mechanism has recently been isolated from a megakaryocytic (Dami) cell line. To further study determinants of peptide ligand-mediated activation phenomenon, we have isolated, cloned, and stably expressed the identical receptor from a human umbilical vein endothelial cell (HUVEC) library. Chinese hamster ovary (CHO) cells expressing a functional TR (CHO-TR), platelets, and HUVECs were then used to specifically characterize alpha-thrombin- and peptide ligand-induced activation responses using two different antibodies: anti-TR34-52 directed against a 20-amino acid peptide spanning the thrombin cleavage site, and anti-TR1-160 generated against the NH2-terminal 160 amino acids of the TR expressed as a chimeric protein in Escherichia coli. Activation-dependent responses to both alpha-thrombin (10 nM) and peptide ligand (20 microM) were studied using fura 2-loaded cells and microspectrofluorimetry. Whereas preincubation of CHO-TR with anti-TR34-52 abolished only alpha-thrombin-induced [Ca2+]i transients, preincubation with anti-TR1-160 abrogated both alpha-thrombin- and peptide ligand-induced responses. This latter inhibitory effect was dose dependent and similar for both agonists, with an EC50 of approximately 90 micrograms/ml. Anti-TR1-160 similarly abolished peptide ligand-induced [Ca2+]i transients in platelets and HUVECs, whereas qualitatively different responses characterized by delayed but sustained elevations in [Ca2+]i transients were evident using alpha-thrombin. Platelet aggregation to low concentrations of both ligands was nearly abolished by anti-TR1-160, although some shape change remained; anti-TR34-52 only inhibited alpha-thrombin-induced aggregation. These data establish that a critical recognition sequence for peptide ligand-mediated receptor activation is contained on the NH2-terminal portion of the receptor, upstream from the first transmembrane domain. Furthermore, alpha-thrombin

  1. Thrombin-Mediated Direct Activation of Proteinase-Activated Receptor-2: Another Target for Thrombin Signaling.

    PubMed

    Mihara, Koichiro; Ramachandran, Rithwik; Saifeddine, Mahmoud; Hansen, Kristina K; Renaux, Bernard; Polley, Danny; Gibson, Stacy; Vanderboor, Christina; Hollenberg, Morley D

    2016-05-01

    Thrombin is known to signal to cells by cleaving/activating a G-protein-coupled family of proteinase-activated receptors (PARs). The signaling mechanism involves the proteolytic unmasking of an N-terminal receptor sequence that acts as a tethered receptor-activating ligand. To date, the recognized targets of thrombin cleavage and activation for signaling are PAR1 and PAR4, in which thrombin cleaves at a conserved target arginine to reveal a tethered ligand. PAR2, which like PAR1 is also cleaved at an N-terminal arginine to unmask its tethered ligand, is generally regarded as a target for trypsin but not for thrombin signaling. We now show that thrombin, at concentrations that can be achieved at sites of acute injury or in a tumor microenvironment, can directly activate PAR2 vasorelaxation and signaling, stimulating calcium and mitogen-activated protein kinase responses along with triggeringβ-arrestin recruitment. Thus, PAR2 can be added alongside PAR1 and PAR4 to the targets, whereby thrombin can affect tissue function.

  2. Recombination and population inversion in plasmas generated by tunneling ionization.

    PubMed

    Pert, G J

    2006-06-01

    Above-threshold ionization (ATI) ionization by linearly polarized light has been proposed by several authors as a means of driving recombination lasers in the soft x-ray spectral region. The pump radiation generates a cold electron plasma with ions in a single ionization stage, which is an ideal starting condition for strong recombination. Population inversions form during the recombination cascade to the ground state of the next ionization stage. In the absence of any relaxation the electron distribution is strongly peaked near zero energy. However, a number of different processes all heat the cold electrons towards Maxwellian, and may thereby reduce the recombination rate in the higher levels. Using numerical models we investigate these relaxation processes and their effect on recombination. We show that the recombination can be well described by the standard cascade model, provided an appropriate temperature is used. We examine two cases in detail, hydrogen-like lithium where the inversion is with respect to the ground state, and lithium-like nitrogen where it is with the first excited state. The two cases differ markedly in the degree of relaxation achieved, and in the duration of the population inversion.

  3. Naphthalene and acenaphthene decomposition by electron beam generated plasma application

    SciTech Connect

    Ostapczuk, A.; Hakoda, T.; Shimada, A.; Kojima, T.

    2008-08-15

    The application of non-thermal plasma generated by electron beam (EB) was investigated in laboratory scale to study decomposition of polycyclic aromatic hydrocarbons like naphthalene and acenaphthene in flue gas. PAH compounds were treated by EB with the dose up to 8 kGy in dry and humid base gas mixtures. Experimentally established G-values gained 1.66 and 3.72 mol/100 eV for NL and AC at the dose of 1 kGy. NL and AC removal was observed in dry base gas mixtures showing that the reaction with OH radical is not exclusive pathway to initialize PAH decomposition; however in the presence of water remarkably higher decomposition efficiency was observed. As by-products of NL decomposition were identified compounds containing one aromatic ring and oxygen atoms besides CO and CO{sub 2}. It led to the conclusion that PAH decomposition process in humid flue gas can be regarded as multi-step oxidative de-aromatization analogical to its atmospheric chemistry.

  4. Generation of uniform electron beam plasma in a dielectric flask at fore-vacuum pressures

    NASA Astrophysics Data System (ADS)

    Zolotukhin, D. B.; Burdovitsin, V. A.; Oks, E. M.

    2016-02-01

    We describe a system for the generation of spatially uniform and homogeneous dense plasma in a dielectric flask using a forevacuum-pressure plasma-cathode electron beam source. At optimum beam energy and gas pressure, the non-uniformity in plasma density distribution along the length of the flask is less than 10%, and the plasma density and electron temperature in the flask are greater than for the plasma produced in the vacuum chamber with no flask. The measured parameters of the beam plasma in the flask are compared to the predictions of a model based on balance equations.

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

    PubMed

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

    2014-01-01

    Dabigatran and rivaroxaban are novel oral anticoagulants that specifically inhibit thrombin and factor Xa, respectively. The aim of this study is to elucidate antithrombotic properties of these anticoagulant agents under arterial and venous shear conditions. Whole blood samples treated with dabigatran or rivaroxaban at 250, 500, and 1000 nM, with/without aspirin and AR-C66096, a P2Y12 antagonist, were perfused over a microchip coated with collagen and tissue thromboplastin at shear rates of 240 and 600 s(-1). Fibrin-rich platelet thrombus formation was quantified by monitoring flow pressure changes. Dabigatran at higher concentrations (500 and 1000 nM) potently inhibited thrombus formation at both shear rates, whereas 1000 nM of rivaroxaban delayed, but did not completely inhibit, thrombus formation. Dual antiplatelet agents weakly suppressed thrombus formation at both shear rates, but intensified the anticoagulant effects of dabigatran and rivaroxaban. The anticoagulant effects of dabigatran and rivaroxaban were also evaluated under static conditions using thrombin generation (TG) assay. In platelet-poor plasma, dabigatran at 250 and 500 nM efficiently prolonged the lag time (LT) and moderately reduce peak height (PH) of TG, whereas rivaroxaban at 250 nM efficiently prolonged LT and reduced PH of TG. In platelet-rich plasma, however, both anticoagulants efficiently delayed LT and reduced PH of TG. Our results suggest that dabigatran and rivaroxaban may exert distinct antithrombotic effects under flow conditions, particularly in combination with dual antiplatelet therapy. PMID:24497951

  6. Dabigatran and Argatroban Diametrically Modulate Thrombin Exosite Function

    PubMed Central

    Yeh, Calvin H.; Stafford, Alan R.; Leslie, Beverly A.; Fredenburgh, James C.; Weitz, Jeffrey I.

    2016-01-01

    Thrombin is a highly plastic molecule whose activity and specificity are regulated by exosites 1 and 2, positively-charged domains that flank the active site. Exosite binding by substrates and cofactors regulates thrombin activity by localizing thrombin, guiding substrates, and by inducing allosteric changes at the active site. Although inter-exosite and exosite-to-active-site allostery have been demonstrated, the impact of active site ligation on exosite function has not been examined. To address this gap, we used surface plasmon resonance to determine the effects of dabigatran and argatroban, active site-directed inhibitors, on thrombin binding to immobilized γA/γA-fibrin or glycoprotein Ibα peptide via exosite 1 and 2, respectively, and thrombin binding to γA/γ′-fibrin or factor Va, which is mediated by both exosites. Whereas dabigatran attenuated binding, argatroban increased thrombin binding to γA/γA- and γA/γ′-fibrin and to factor Va. The results with immobilized fibrin were confirmed by examining the binding of radiolabeled thrombin to fibrin clots. Thus, dabigatran modestly accelerated the dissociation of thrombin from γA/γA-fibrin clots, whereas argatroban attenuated dissociation. Dabigatran had no effect on thrombin binding to glycoprotein Ibα peptide, whereas argatroban promoted binding. These findings not only highlight functional effects of thrombin allostery, but also suggest that individual active site-directed thrombin inhibitors uniquely modulate exosite function, thereby identifying potential novel mechanisms of action. PMID:27305147

  7. Radiofrequency plasma antenna generated by femtosecond laser filaments in air

    SciTech Connect

    Brelet, Y.; Houard, A.; Point, G.; Prade, B.; Carbonnel, J.; Andre, Y.-B.; Mysyrowicz, A.; Arantchouk, L.; Pellet, M.

    2012-12-24

    We demonstrate tunable radiofrequency emission from a meter-long linear plasma column produced in air at atmospheric pressure. A short-lived plasma column is initially produced by femtosecond filamentation and subsequently converted into a long-lived discharge column by application of an external high voltage field. Radiofrequency excitation is fed to the plasma by induction and detected remotely as electromagnetic radiation by a classical antenna.

  8. Control of disruption-generated runaway plasmas in TFTR

    NASA Astrophysics Data System (ADS)

    Fredrickson, E. D.; Bell, M. G.; Taylor, G.; Medley, S. S.

    2015-01-01

    Many disruptions in the Tokamak Fusion Test Reactor (TFTR) (Meade and the TFTR Group 1991 Proc. Int. Conf. on Plasma Physics and Controlled Nuclear Fusion (Washington, DC, 1990) vol 1 (Vienna: IAEA) pp 9-24) produced populations of runaway electrons which carried a significant fraction of the original plasma current. In this paper, we describe experiments where, following a disruption of a low-beta, reversed-shear plasma, currents of up to 1 MA carried mainly by runaway electrons were controlled and then ramped down to near zero using the ohmic transformer. In the longer lasting runaway plasmas, events resembling Parail-Pogutse instabilities were observed.

  9. Cylindrical plasmas generated by an annular beam of ultraviolet light

    SciTech Connect

    Thomas, D. M.; Allen, J. E.

    2015-07-15

    We investigate a cylindrical plasma system with ionization, by an annular beam of ultraviolet light, taking place only in the cylinder's outer region. In the steady state, both the outer and inner regions contain a plasma, with that in the inner region being uniform and field-free. At the interface between the two regions, there is an infinitesimal jump in ion density, the magnitude approaching zero in the quasi-neutral (λ{sub D} → 0) limit. The system offers the possibility of producing a uniform stationary plasma in the laboratory, hitherto obtained only with thermally produced alkali plasmas.

  10. Pencil lead plasma for generating multimicrojoule high-order harmonics with a broad spectrum

    SciTech Connect

    Pertot, Y.; Elouga Bom, L. B.; Ozaki, T.; Bhardwaj, V. R.

    2011-03-07

    Using the plasma harmonic method, we show the generation of efficient and intense high-order harmonics from plasma of pencil lead. We demonstrate multimicrojoule energy in each harmonic order for the 11th to the 17th order of a Ti:sapphire laser. By analyzing the target morphology and the plasma composition, we conclude that these intense harmonics are generated from nanoparticles of graphitic carbon.

  11. Thomson scattering measurement of a collimated plasma jet generated by a high-power laser system

    NASA Astrophysics Data System (ADS)

    Ishikawa, T.; Sakawa, Y.; Morita, T.; Yamaura, Y.; Kuramitsu, Y.; Moritaka, T.; Sano, T.; Shimoda, R.; Tomita, K.; Uchino, K.; Matsukiyo, S.; Mizuta, A.; Ohnishi, N.; Crowston, R.; Woolsey, N.; Doyle, H.; Gregori, G.; Koenig, M.; Michaut, C.; Pelka, A.; Yuan, D.; Li, Y.; Zhang, K.; Zhong, J.; Wang, F.; Takabe, H.

    2016-03-01

    One of the important and interesting problems in astrophysics and plasma physics is collimation of plasma jets. The collimation mechanism, which causes a plasma flow to propagate a long distance, has not been understood in detail. We have been investigating a model experiment to simulate astrophysical plasma jets with an external magnetic field [Nishio et al., EPJ. Web of Conferences 59, 15005 (2013)]. The experiment was performed by using Gekko XII HIPER laser system at Institute of Laser Engineering, Osaka University. We shot CH plane targets (3 mm × 3 mm × 10 μm) and observed rear-side plasma flows. A collimated plasma flow or plasma jet was generated by separating focal spots of laser beams. In this report, we measured plasma jet structure without an external magnetic field with shadowgraphy, and simultaneously measured the local parameters of the plasma jet, i.e., electron density, electron and ion temperatures, charge state, and drift velocity, with collective Thomson scattering.

  12. Beam-plasma generators of stochastic microwave oscillations used for plasma heating in fusion and plasma-chemistry devices and ionospheric investigations

    NASA Astrophysics Data System (ADS)

    Mitin, Leonid A.; Perevodchikov, Vladimir I.; Shapiro, A. L.; Zavjalov, M. A.; Bliokh, Yury P.; Fainberg, Ya. B.

    1996-10-01

    The results of theoretical and experimental investigations of generator of stochastic microwave power based on beam- plasma inertial feedback amplifier is discussed to use stochastic oscillation for heating of plasma. The efficiency of heating of plasma in the region of low-frequency resonance in the geometry of `Tokomak' is considered theoretically. It is shown, that the temp of heating is proportional the power multiplied by spectra width of noiselike signal.

  13. Heparin enhances the catalytic activity of des-ETW-thrombin.

    PubMed

    Goodwin, C A; Deadman, J J; Le Bonniec, B F; Elgendy, S; Kakkar, V V; Scully, M F

    1996-04-01

    The thrombin mutant, des-ETW-thrombin, lacking Glu(146), Thr(147), and Trp(148) within a unique insertion loop located at the extreme end of the primary specificity pocket, has been shown previously to exhibit reduced catalytic activity with respect to macromolecular and synthetic thrombin substrates and reduced or enhanced susceptibility to inhibition. Investigation of the hydrolysis of peptidyl p-nitroanilide substrates by des-ETW-thrombin showed increased activity in the presence of heparin and other sulphated glycosaminoglycans. No effect was observed upon the activity of wild-type thrombin. Heparin was found to decrease the K(m) for cleavage of four thrombin-specific substrates by des-ETW-thrombin by 3-4-fold. Similarly, pentosan polysulphate (PPS) decreased the K(m) with these substrates by 8-10-fold. Heparin also increased the rate of inhibition of des-ETW-thrombin by antithrombin III and D-phenylalanyl-prolyl-arginylchloromethane (PPACK). The inhibition of des-ETW-thrombin by a number of thrombin-specific peptide boronic acids also showed significant reduction in the final K(i) in the presence of heparin, due to reduction in the off-rate. A peptide analogue of a sequence of hirudin which binds thrombin tightly to exosite I (fibrinogen recognition site) potentiated the activity of des-ETW-thrombin against peptide p-nitroanilide substrates in a manner similar to heparin. The K(i) for the inhibition of des-ETW-thrombin by p-aminobenzamidine was decreased by these ligands from 9.7 mM to 7.5 mM, 5.1 mM, and 2.5 mM in the presence of heparin, hirudin peptide and PPS respectively, suggesting the increased catalytic activity is due to enhanced access to the primary specificity pocket. The positive influence of these ligands on des-ETW-thrombin was reversed in the presence of ATP or ADP; the latter has previously been shown to inhibit thrombin activity by blocking initial interaction with fibrinogen at exosite 1. Because the effect of heparin and PPS is similar to

  14. Cavitational Iron Microparticles Generation By Plasma Procedures For Medical Applications

    NASA Astrophysics Data System (ADS)

    Bica, Ioan; Bunoiu, Madalin; Chirigiu, Liviu; Spunei, Marius; Juganaru, Iulius

    2012-12-01

    The paper presents the experimental installation for the production, in argon plasma, of cavitational iron microparticles (pore microspheres, microtubes and octopus-shaped microparticles). Experimental results are presented and discussed and it is shown that absorbant particles with a minimum iron content are obtained by the plasma procedures

  15. A plasma generator utilizing the high intensity ASTROMAG magnets

    NASA Technical Reports Server (NTRS)

    Sullivan, James D.; Post, R. S.; Lane, B. G.; Tarrh, J. M.

    1986-01-01

    The magnet configuration for the proposed particle astrophysics magnet facility (ASTROMAG) on the space station includes a cusp magnetic field with an intensity of a few tesla. With these large magnets (or others) located in the outer ionosphere, many quite interesting and unique plasma physics experiments become possible. First there are studies utilizing the magnet alone to examine the supersonic, sub-Alfvenic interaction with the ambient medium; the scale length for the magnet perturbation is approx. 20 m. The magnetic field geometry when combined with the Earth's and their relative motion will give rise to a host of plasma phenomena: ring nulls, x-points, ion-acoustic and lower-hybrid shocks, electron heating (possible shuttle glow without a surface) launching of Alfvenwaves, etc. Second, active experiments are possible for a controlled study of fundamental plasma phenomena. A controlled variable species plasma can be made by using an RF ion source; use of two soft iron rings placed about the line cusp would give an adequate resonance zone (ECH or ICH) and a confining volume suitable for gas efficiency. The emanating plasma can be used to study free expansion of plasma along and across field lines (polar wind), plasma flows around the space platform, turbulent mixing in the wake region, long wavelength spectrum of convecting modes, plasma-dust interactions, etc.

  16. Generation of reactive species by an atmospheric pressure plasma jet

    NASA Astrophysics Data System (ADS)

    Kelly, S.; Turner, M. M.

    2014-12-01

    The role of gas mixing in reactive species delivery to treatment surfaces for an atmospheric pressure capacitively coupled plasma helium jet is investigated by numerical modelling. Atomic oxygen in the jet effluent is shown to quickly convert to ozone for increasing device to surface separation due to the molecular oxygen present in the gas mixture. Surface profiles of reactive oxygen species show narrow peaks for atomic oxygen and broader surface distributions for ozone and metastable species. Production efficiency of atomic oxygen to the helium plasma jet by molecular oxygen admixture is shown to be dependent on electro-negativity. Excessive molecular oxygen admixture results in negative ion dominance over electrons which eventually quenches the plasma. Interaction of the plasma jet with an aqueous surface showed hydrogen peroxide as the dominant species at this interface. Gas heating by the plasma is found to be dominated by elastic electron collisions and positive ion heating. Comparison with experimental measurements for atomic oxygen shows good agreement.

  17. Microwave plasma generation of hydrogen atoms for rocket propulsion

    NASA Technical Reports Server (NTRS)

    Chapman, R.; Filpus, J.; Morin, T.; Snellenberger, R.; Asmussen, J.; Hawley, M.; Kerber, R.

    1981-01-01

    A flow microwave plasma reaction system is used to study the conversion of hydrogen to hydrogen atoms as a function of pressure, power density, cavity tuning, cavity mode, and time in the plasma zone. Hydrogen atom concentration is measured down-stream from the plasma by NOCl titration. Extensive modeling of the plasma and recombination zones is performed with the plasma zone treated as a backmix reaction system and the recombination zone treated as a plug flow. The thermodynamics and kinetics of the recombination process are examined in detail to provide an understanding of the conversion of recombination energy to gas kinetic energy. It is found that cavity tuning, discharge stability, and optimum power coupling are critically dependent on the system pressure, but nearly independent of the flow rate.

  18. Theoretical model for plasma expansion generated by hypervelocity impact

    SciTech Connect

    Ju, Yuanyuan; Zhang, Qingming Zhang, Dongjiang; Long, Renrong; Chen, Li; Huang, Fenglei; Gong, Zizheng

    2014-09-15

    The hypervelocity impact experiments of spherical LY12 aluminum projectile diameter of 6.4 mm on LY12 aluminum target thickness of 23 mm have been conducted using a two-stage light gas gun. The impact velocity of the projectile is 5.2, 5.7, and 6.3 km/s, respectively. The experimental results show that the plasma phase transition appears under the current experiment conditions, and the plasma expansion consists of accumulation, equilibrium, and attenuation. The plasma characteristic parameters decrease as the plasma expands outward and are proportional with the third power of the impact velocity, i.e., (T{sub e}, n{sub e}) ∝ v{sub p}{sup 3}. Based on the experimental results, a theoretical model on the plasma expansion is developed and the theoretical results are consistent with the experimental data.

  19. Lupus anticoagulants form immune complexes with prothrombin and phospholipid that can augment thrombin production in flow.

    PubMed

    Field, S L; Hogg, P J; Daly, E B; Dai, Y P; Murray, B; Owens, D; Chesterman, C N

    1999-11-15

    Lupus anticoagulants (LA) are a family of autoantibodies that are associated with in vitro anticoagulant activity but a strong predisposition to in vivo thrombosis. They are directed against plasma phospholipid binding proteins, including prothrombin. We found that a murine monoclonal antiprothrombin antibody and 7 of 7 LA IgGs tested enhanced binding of prothrombin to 25:75 phosphatidyl serine:phosphatidyl choline vesicles in a concentration-dependent manner. We hypothesized that enhanced binding of prothrombin to phospholipid in the presence of LA IgG might result in increased thrombin production when reactions are performed in flow. Thrombin production by purified prothrombinase components was measured in a phospholipid-coated flow reactor. The flow reactor was incubated with prothrombin, calcium ions, and the IgGs and then perfused with prothrombin, calcium ions, the IgGs, factor Va, and factor Xa. A murine monoclonal antiprothrombin antibody and 4 of 6 LA IgGs from patients with a history of thrombosis increased thrombin production up to 100% over control in the first 15 minutes. In summary, LA IgGs concentrate prothrombin on a phospholipid surface that can augment thrombin production by prothrombinase in flow. These observations suggest that LA might propagate coagulation in flowing blood by facilitating prothrombin interaction with the damaged blood vessel wall.

  20. System and method for generating steady state confining current for a toroidal plasma fusion reactor

    DOEpatents

    Bers, Abraham

    1981-01-01

    A system for generating steady state confining current for a toroidal plasma fusion reactor providing steady-state generation of the thermonuclear power. A dense, hot toroidal plasma is initially prepared with a confining magnetic field with toroidal and poloidal components. Continuous wave RF energy is injected into said plasma to estalish a spectrum of traveling waves in the plasma, where the traveling waves have momentum components substantially either all parallel, or all anti-parallel to the confining magnetic field. The injected RF energy is phased to couple to said traveling waves with both a phase velocity component and a wave momentum component in the direction of the plasma traveling wave components. The injected RF energy has a predetermined spectrum selected so that said traveling waves couple to plasma electrons having velocities in a predetermined range .DELTA.. The velocities in the range are substantially greater than the thermal electron velocity of the plasma. In addition, the range is sufficiently broad to produce a raised plateau having width .DELTA. in the plasma electron velocity distribution so that the plateau electrons provide steady-state current to generate a poloidal magnetic field component sufficient for confining the plasma. In steady state operation of the fusion reactor, the fusion power density in the plasma exceeds the power dissipated inthe plasma.

  1. System and method for generating steady state confining current for a toroidal plasma fusion reactor

    DOEpatents

    Fisch, Nathaniel J.

    1981-01-01

    A system for generating steady state confining current for a toroidal plasma fusion reactor providing steady-state generation of the thermonuclear power. A dense, hot toroidal plasma is initially prepared with a confining magnetic field with toroidal and poloidal components. Continuous wave RF energy is injected into said plasma to establish a spectrum of traveling waves in the plasma, where the traveling waves have momentum components substantially either all parallel, or all anti-parallel to the confining magnetic field. The injected RF energy is phased to couple to said traveling waves with both a phase velocity component and a wave momentum component in the direction of the plasma traveling wave components. The injected RF energy has a predetermined spectrum selected so that said traveling waves couple to plasma electrons having velocities in a predetermined range .DELTA.. The velocities in the range are substantially greater than the thermal electron velocity of the plasma. In addition, the range is sufficiently broad to produce a raised plateau having width .DELTA. in the plasma electron velocity distribution so that the plateau electrons provide steady-state current to generate a poloidal magnetic field component sufficient for confining the plasma. In steady state operation of the fusion reactor, the fusion power density in the plasma exceeds the power dissipated in the plasma.

  2. Measurement of plasma-generated RONS in the cancer cells exposed by atmospheric pressure helium plasma jet

    NASA Astrophysics Data System (ADS)

    Joh, Hea Min; Baek, Eun Jeong; Kim, Sun Ja; Chung, Tae Hun

    2015-09-01

    The plasma-induced reactive oxygen and nitrogen species (RONS) could result in cellular responses including DNA damages and apoptotic cell death. These chemical species, O, O2-,OH, NO, and NO2-,exhibit strong oxidative stress and/or trigger signaling pathways in biological cells. Each plasma-generated chemical species having biological implication should be identified and quantitatively measured. For quantitative measurement of RONS, this study is divided into three stages; plasma diagnostics, plasma-liquid interactions, plasma-liquid-cell interactions. First, the optical characteristics of the discharges were obtained by optical emission spectroscopy to identify various excited plasma species. And the characteristics of voltage-current waveforms, gas temperature, and plume length with varying control parameters were measured. Next, atmospheric pressure plasma jet was applied on the liquid. The estimated OH radical densities were obtained by ultraviolet absorption spectroscopy at the liquid surface. And NO2-is detected by Griess test and compared between the pure liquid and the cell-containing liquid. Finally, bio-assays were performed on plasma treated human lung cancer cells (A549). Intracellular ROS production was measured using DCF-DA. Among these RONS, productions of NO and OH within cells were measured by DAF-2DA and APF, respectively. The data are very suggestive that there is a strong correlation among the production of RONS in the plasmas, liquids, and cells.

  3. Magnetic field distribution in the plasma flow generated by a plasma focus discharge

    SciTech Connect

    Mitrofanov, K. N.; Krauz, V. I. Myalton, V. V.; Velikhov, E. P.; Vinogradov, V. P.; Vinogradova, Yu. V.

    2014-11-15

    The magnetic field in the plasma jet propagating from the plasma pinch region along the axis of the chamber in a megajoule PF-3 plasma focus facility is studied. The dynamics of plasma with a trapped magnetic flow is analyzed. The spatial sizes of the plasma jet region in which the magnetic field concentrates are determined in the radial and axial directions. The magnetic field configuration in the plasma jet is investigated: the radial distribution of the azimuthal component of the magnetic field inside the jet is determined. It is shown that the magnetic induction vector at a given point in space can change its direction during the plasma flight. Conclusions regarding the symmetry of the plasma flow propagation relative to the chamber axis are drawn.

  4. Dust generation at interaction of plasma jet with surfaces

    NASA Astrophysics Data System (ADS)

    Ticos, Catalin; Toader, Dorina; Banu, Nicoleta; Scurtu, Adrian; Oane, Mihai

    2013-10-01

    Coatings of W and C with widths of a few microns will be exposed to plasma jet for studying the erosion of the surface and detachment of micron size dust particles. A coaxial plasma gun has been built inside a vacuum chamber for producing supersonic plasma jets. Its design is based on a 50 kJ coaxial plasma gun which has been successfully used for accelerating hypervelocity dust. Initial shots were carried out for a capacitor bank with C = 12 μF and charged up to 2 kV. Currents of tens of amps were measured with a Rogowsky coil and plasma flow speeds of 4 km/s were inferred from high-speed images of jet propagation. An upgrade consisting in adding capacitors in parallel will be performed in order to increase the energy up to 2 kJ. A coil will be installed at the gun muzzle to compress the plasma flow and increase the energy density of the jet on the sample surface. A CCD camera with a maximum recording speed of 100 k fps and a maximum resolution of 1024 × 1024 pixels was set for image acquisition of the plasma and dust. A laser system used to illuminate the ejected dust from the surface includes a laser diode emitting at 650 nm with a beam power of 25 mW. The authors acknowledge support from EURATOM WP13-IPH-A03-P2-02-BS22.

  5. Reactive species in non-equilibrium atmospheric-pressure plasmas: Generation, transport, and biological effects

    NASA Astrophysics Data System (ADS)

    Lu, X.; Naidis, G. V.; Laroussi, M.; Reuter, S.; Graves, D. B.; Ostrikov, K.

    2016-05-01

    Non-equilibrium atmospheric-pressure plasmas have recently become a topical area of research owing to their diverse applications in health care and medicine, environmental remediation and pollution control, materials processing, electrochemistry, nanotechnology and other fields. This review focuses on the reactive electrons and ionic, atomic, molecular, and radical species that are produced in these plasmas and then transported from the point of generation to the point of interaction with the material, medium, living cells or tissues being processed. The most important mechanisms of generation and transport of the key species in the plasmas of atmospheric-pressure plasma jets and other non-equilibrium atmospheric-pressure plasmas are introduced and examined from the viewpoint of their applications in plasma hygiene and medicine and other relevant fields. Sophisticated high-precision, time-resolved plasma diagnostics approaches and techniques are presented and their applications to monitor the reactive species and plasma dynamics in the plasma jets and other discharges, both in the gas phase and during the plasma interaction with liquid media, are critically reviewed. The large amount of experimental data is supported by the theoretical models of reactive species generation and transport in the plasmas, surrounding gaseous environments, and plasma interaction with liquid media. These models are presented and their limitations are discussed. Special attention is paid to biological effects of the plasma-generated reactive oxygen and nitrogen (and some other) species in basic biological processes such as cell metabolism, proliferation, survival, etc. as well as plasma applications in bacterial inactivation, wound healing, cancer treatment and some others. Challenges and opportunities for theoretical and experimental research are discussed and the authors' vision for the emerging convergence trends across several disciplines and application domains is presented to

  6. High density plasma gun generates plasmas at 190 kilometers per second

    NASA Technical Reports Server (NTRS)

    Espy, P. N.

    1971-01-01

    Gun has thin metal foil disc which positions or localizes gas to be ionized during electrical discharge cycle, overcoming major limiting factor in obtaining such plasmas. Expanding plasma front travels at 190 km/sec, compared to plasmas of 50 to 60 km/sec previously achieved.

  7. Liquid crystal-based detection of thrombin coupled to interactions between a polyelectrolyte and a phospholipid monolayer.

    PubMed

    Zhang, Minmin; Jang, Chang-Hyun

    2014-06-15

    Herein, we describe a real-time, label-free biosensing strategy for thrombin detection that uses the orientational properties of nematic liquid crystals (LCs) and the interactions between a polyelectrolyte and a phospholipid monolayer. The imaging principle is based on the disruption of the orientation of 4-cyano-4'-pentylbiphenyl by reorganized 1,2-dioleoyl-sn-glycero-3-phospho-rac-(1-glycerol) sodium salt (DOPG) at the aqueous/LC interface. Positively charged, multiple arginine peptides (poly-l-arginine hydrochloride) interacted with negatively charged DOPG at the aqueous/LC interface, which caused reorganization of the phospholipid layer and induced an orientational transition of LCs from a homeotropic to a planar state. As a result, a dark to bright shift in the optical response was observed. Thrombin cleaves poly-l-arginine hydrochloride into peptides. Thus, when thrombin was added, the optical signals generated by the LCs reverted from bright to dark because of the weakened ability of the fragments to induce electrostatic interactions. The limit of detection of the LC-based sensor was 0.25ng/mL (6.7pM) thrombin, and the sensor was fully reusable. The detection limit of our LC-based interface sensor is 600 times lower than that of a previously reported enzyme-linked aptamer assay for the detection of thrombin. Thus, we have established a new, simple thrombin biosensor with high sensitivity and low interference. PMID:24708935

  8. Response to "Comment on `A large volume uniform plasma generator for the experiments of electromagnetic wave propagation in plasma'" [Phys. Plasmas 23, 094701 (2016)

    NASA Astrophysics Data System (ADS)

    Yang, Min; Li, Xiaoping; Xie, Kai; Liu, yanming; Liu, Donglin

    2016-09-01

    We respond to the issues raised in the comment by Eliseev and Kudryavtsev [Phys. Plasmas 23, 094701 (2016)]. We re-examine the principle of plasma generation and the operating situations in our plasma device, and some simplified models are founded to illustrate the qualitative relations between the pressure and the magnitude and uniformity of ne. We stand by our original conclusions in our plasma device that the magnitude and uniformity of ne are in roughly reverse proportion to the gas pressure in the chamber, as observed in the experiment.

  9. Low-order harmonic generation in metal ablation plasmas in nanosecond and picosecond laser regimes

    SciTech Connect

    Lopez-Arias, M.; Oujja, M.; Sanz, M.; Castillejo, M.; Ganeev, R. A.; Boltaev, G. S.; Satlikov, N. Kh.; Tugushev, R. I.; Usmanov, T.

    2012-02-15

    Low-order harmonics, third and fifth, of IR (1064 nm) laser emission have been produced in laser ablation plasmas of the metals manganese, copper and silver. The harmonics were generated in a process triggered by laser ablation followed by frequency up-conversion of a fundamental laser beam that propagates parallel to the target surface. These studies were carried out in two temporal regimes by creating the ablation plasma using either nanosecond or picosecond pulses and then probing the plasma plume with pulses of the same duration. The spatiotemporal behavior of the generated harmonics was characterized and reveals the distinct composition and dynamics of the plasma species that act as nonlinear media, allowing the comparison of different processes that control the generation efficiency. These results serve to guide the choice of laser ablation plasmas to be used for efficient high harmonic generation of laser radiation.

  10. Generation of magnetoacoustic zonal flows by Alfven waves in a rotating plasma

    SciTech Connect

    Mikhailovskii, A. B.; Lominadze, J. G.; Churikov, A. P.; Erokhin, N. N.; Tsypin, V. S.; Smolyakov, A. I.; Galvao, R. M. O.

    2007-08-15

    Analytical theory of nonlinear generation of magnetoacoustic zonal flows in a rotating plasma is developed. As the primary modes causing such a generation, a totality of the Alfven waves are considered, along with the kinetic, inertial, and rotational. It is shown that in all these cases of the Alfven waves the generation is possible if the double plasma rotation frequency exceeds the zonal flow frequency.

  11. Numerical Simulation of Flow in the Chamber of the Water-Argon Plasma Generator

    NASA Astrophysics Data System (ADS)

    Hlbočan, Peter; Varchola, Michal; Knížat, Branislav; Mlkvik, Marek; Olšiak, Róbert

    2012-12-01

    The paper describes the CFD simulation of the flow of gas and plasma in a plasma generator with a hybrid stabilization of the electric arc. The momentum equations of the model also take Lorentz forces into account. In the energy equation, Joule heat is introduced as an energy source. The introduction of boundary conditions is also explained, as along with plasma transport properties and a method of solution. The paper presents selected results of pressure and velocity fields in the chamber of the plasma generator.

  12. The functionalization of graphene using electron-beam generated plasmas

    SciTech Connect

    Baraket, M.; Walton, S. G.; Lock, E. H.; Robinson, J. T.; Perkins, F. K.

    2010-06-07

    A plasmas-based, reversible functionalization of graphene is discussed. Using electron-beam produced plasmas, oxygen and fluorine functionalities have been added by changing the processing gas mixtures from Ar/O{sub 2} to Ar/SF{sub 6}, respectively. The reversibility of the functionalization was investigated by annealing the samples. The chemical composition and structural changes were studied by x-ray photoelectron spectroscopy and Raman spectroscopy.

  13. Diagnostic evaluations of microwave generated helium and nitrogen plasma mixtures

    NASA Technical Reports Server (NTRS)

    Haraburda, Scott S.; Hawley, Martin C.; Dinkel, Duane W.

    1990-01-01

    The goal of this work is to continue the development to fundamentally understand the plasma processes as applied to spacecraft propulsion. The diagnostic experiments used are calorimetric, dimensional, and spectroscopic measurements using the TM 011 and TM 012 modes in the resonance cavity. These experimental techniques are highly important in furthering the understanding of plasma phenomena and of designing rocket thrusters. Several experimental results are included using nitrogen and helium gas mixtures.

  14. Microwave guiding and intense plasma generation at subcutoff dimensions for focused ion beams

    SciTech Connect

    Mathew, Jose V.; Dey, Indranuj; Bhattacharjee, Sudeep

    2007-07-23

    The mechanism of microwave guiding and plasma generation is investigated in a circular waveguide with a subcutoff dimension using pulsed microwaves of 3 GHz. During the initial phase, gaseous breakdown is induced by the exponentially decaying wave. Upon breakdown, the refractive index of the plasma medium varies radially, with the plasma density reaching close to cutoff values in the central region. At lower pressures, the waves can propagate through the peripheral plasma with a reduced wavelength, due to the collisionally broadened upper hybrid resonance region. The intense narrow cross sectional plasma bears promise for multielemental focused ion beams.

  15. Theory of Generation of Alfvenic Non-Propagating Electromagnetic Plasma Structures and Acceleration of Charged Particles in Cosmic Plasmas

    NASA Astrophysics Data System (ADS)

    Song, Yan; Lysak, Robert

    2015-04-01

    In Earth's auroral acceleration regions, the nonlinear interaction of incident and reflected Alfven wave packets can collectively create non-propagating electromagnetic plasma structures, such as the Transverse Alfvenic Double Layer (TA-DL) and Charge Hole (TA-CH). These structures, such as TA-DL, encompass localized strong electrostatic electric fields, nested in low density cavities and surrounded by a local dynamo. Such structures constitute powerful high energy particle accelerators causing auroral particle acceleration and creating both Alfvenic and quasi-static discrete auroras. Similar electromagnetic plasma structures should also be generated by Alfvenic interaction in other inhomogenous cosmic plasma regions, and would constitute effective high energy particle accelerators.

  16. Generation and diagnostics of atmospheric pressure CO{sub 2} plasma by laser driven plasma wind tunnel

    SciTech Connect

    Matsui, Makoto; Yamagiwa, Yoshiki; Tanaka, Kensaku; Arakawa, Yoshihiro; Nomura, Satoshi; Komurasaki, Kimiya

    2012-08-01

    Atmospheric pressure CO{sub 2} plasma was generated by a laser driven plasma wind tunnel. At an ambient pressure of 0.38 MPa, a stable plasma was maintained by a laser power of 1000 W for more than 20 min. The translational temperature was measured using laser absorption spectroscopy with the atomic oxygen line at 777.19 nm. The measured absorption profiles were analyzed by a Voigt function considering Doppler, Stark, and pressure-broadening effects. Under the assumption of thermochemical equilibrium, all broadening effects were consistent with each other. The measured temperature ranged from 8500 K to 8900 K.

  17. Ground-Based Simulation of Low-Earth Orbit Plasma Conditions: Plasma Generation and Characterization

    NASA Technical Reports Server (NTRS)

    Williams, John D.; Farnell, Casey C.; Shoemaker, Paul B.; Vaughn, Jason A.; Schneider, Todd A.

    2004-01-01

    A 16-cm diameter plasma source operated on argon is described that is capable of producing a plasma environment that closely simulates the low Earth orbit (LEO) conditions experienced by satellites in the altitude range between 300 to 500 km. The plasma source uses a transverse-field magnetic filter, and has been successful in producing low electron temperature plasmas that contain streaming ion populations. Both of these characteristics are important because the plasma in LEO is relatively cold (e.g., Te approx. 0.1 eV) and the ram energy of the ions due to the motion of the satellite relative to the LEO plasma is high (e.g., 7,800 m/s which corresponds to approx. 5 eV for O+ ions). Plasma source operational conditions of flow rate and discharge power are presented that allow the electron temperature to be adjusted over a range from 0.14 to 0.4 eV. The expanding plasma flow field downstream of the source contains both low-energy, charge-exchange ions and streaming ions with energies that are adjustable over a range from 4 eV to 6 eV. At low flow rates and low facility pressures, the streaming ion component of the ion population comprises over 90% of the total plasma density. In the work described herein, a large area retarding potential analyzer was used to measure both electron and ion energy distribution functions in the low density, expanding plasma produced downstream of the plasma source. The benefits of using this type of plasma diagnostic tool in easily perturbed, low-density plasma are identified, and techniques are also discussed that can be used to perform real-time measurements of electron temperature. Finally, recommendations are made that may enable lower electron temperatures to be produced while simultaneously decreasing the plasma source flow rate below 1 to 2 sccm.

  18. Inhibition of thrombin-mediated cellular effects by triabin, a highly potent anion-binding exosite thrombin inhibitor.

    PubMed

    Glusa, E; Bretschneider, E; Daum, J; Noeske-Jungblut, C

    1997-06-01

    Triabin, a 17 kDa protein from the saliva of the assassin bug Triatoma pallidipennis is a potent thrombin inhibitor interfering with the anion-binding exosite of the enzyme. The recombinant protein, produced by the baculovirus/insect cell system, was used to study the inhibitory effect on thrombin-mediated cellular responses. The thrombin (1 nM)-stimulated aggregation of washed human platelets and the rise in cytoplasmic calcium in platelets were inhibited by triabin at nanomolar concentrations. In contrast, the rise in calcium induced by the thrombin receptor-activating peptide (10 microM) was not suppressed by triabin. In isolated porcine pulmonary arteries, preconstricted with PGF 2 alpha thrombin (2 nM) elicited an endothelium-dependent relaxation which was inhibited by triabin in the same concentration range as found for the inhibition of platelet aggregation. Higher concentrations of triabin were required to diminish the contractile response of endotheliumdenuded pulmonary vessels to thrombin (10 nM). In cultured bovine coronary smooth muscle cells, the mitogenic activity of thrombin (3 nM), measured by [3H]thymidine incorporation, was also suppressed by triabin. In all these assays, the inhibitory effect of triabin was dependent on the thrombin concentration used. These studies suggest that the new anion-binding exosite thrombin inhibitor triabin is one of the most potent inhibitors of thrombin-mediated cellular effects. PMID:9241757

  19. Forced KLF4 expression increases the generation of mature plasma cells and uncovers a network linked with plasma cell stage.

    PubMed

    Schoenhals, Matthieu; Jourdan, Michel; Seckinger, Anja; Pantesco, Véronique; Hose, Dirk; Kassambara, Alboukadel; Moreaux, Jérôme; Klein, Bernard

    2016-07-17

    A role of the transcription factor Krüppel-like factor 4 (KLF4) in the generation of mature plasma cells (PC) is unknown. Indeed, KLF4 is critical in controlling the differentiation of various cell linages, particularly monocytes and epithelial cells. KLF4 is expressed at low levels in pro-B cells and its expression increases as they mature into pre-B cells, resting naïve B cells and memory B cells. We show here that KLF4 is expressed in human bone marrow plasma cells and its function was studied using an in vitro model of differentiation of memory B cells into long lived plasma cells. KLF4 is rapidly lost when memory B cells differentiate into highly cell cycling plasmablasts, poorly cycling early plasma cells and then quiescent long-lived plasma cells. A forced expression of KLF4 in plasmablasts enhances the yield of their differentiation into early plasma cell and long lived plasma cells, by inhibiting apoptosis and upregulating previously unknown plasma cell pathways.

  20. Chemically reactive species in liquids generated by atmospheric-pressure plasmas and their roles in plasma medicine

    NASA Astrophysics Data System (ADS)

    Hamaguchi, Satoshi

    2013-07-01

    Plasmas whose gas temperatures are close to room temperature may be generated in ambient air or a gas at atmospheric pressure with the use of low-frequency high voltage or low-power radio-frequency (RF) or microwave power applied to electrodes. Such plasmas can serve as a powerful source of free radicals and/or chemically reactive species that arise from atoms and molecules of the ambient gas. Recently use of such plasmas for medical purposes has attracted much attention as they can be implemented in possible medical devices that can cause blood coagulation, heal wounds, facilitate angiogenesis, sterilize surgical devices as well as living tissues without harming healthy cells, and selectively inactivate cancer cells. Especially of interest among reactive species generated by atmospheric-pressure plasmas (APP) are reactive oxygen species (ROS) and reactive nitrogen species (RNS) that are generated in liquid phase. Since most living tissues and cells are immersed in liquids (such as blood or culture media), reactive species generated by APPs in the gas phase are transported to the liquid phase and possibly converted to different types of reactive species therein before causing some influence on the tissues or cells. In this study, the rate equations are solved to evaluate concentrations of various reactive species in pure water that are originated by plasma reactions in atmosphere and possible effects of such species (including ROS/RNS) on living tissues and cells are discussed.

  1. Chemically reactive species in liquids generated by atmospheric-pressure plasmas and their roles in plasma medicine

    SciTech Connect

    Hamaguchi, Satoshi

    2013-07-11

    Plasmas whose gas temperatures are close to room temperature may be generated in ambient air or a gas at atmospheric pressure with the use of low-frequency high voltage or low-power radio-frequency (RF) or microwave power applied to electrodes. Such plasmas can serve as a powerful source of free radicals and/or chemically reactive species that arise from atoms and molecules of the ambient gas. Recently use of such plasmas for medical purposes has attracted much attention as they can be implemented in possible medical devices that can cause blood coagulation, heal wounds, facilitate angiogenesis, sterilize surgical devices as well as living tissues without harming healthy cells, and selectively inactivate cancer cells. Especially of interest among reactive species generated by atmospheric-pressure plasmas (APP) are reactive oxygen species (ROS) and reactive nitrogen species (RNS) that are generated in liquid phase. Since most living tissues and cells are immersed in liquids (such as blood or culture media), reactive species generated by APPs in the gas phase are transported to the liquid phase and possibly converted to different types of reactive species therein before causing some influence on the tissues or cells. In this study, the rate equations are solved to evaluate concentrations of various reactive species in pure water that are originated by plasma reactions in atmosphere and possible effects of such species (including ROS/RNS) on living tissues and cells are discussed.

  2. Arc plasma generator of atomic driver for steady-state negative ion source

    NASA Astrophysics Data System (ADS)

    Ivanov, A. A.; Belchenko, Yu. I.; Davydenko, V. I.; Ivanov, I. A.; Kolmogorov, V. V.; Listopad, A. A.; Mishagin, V. V.; Putvinsky, S. V.; Shulzhenko, G. I.; Smirnov, A.

    2014-02-01

    The paper reviews the results of development of steady-state arc-discharge plasma generator with directly heated LaB6 cathode. This arc-discharge plasma generator produces a plasma jet which is to be converted into an atomic one after recombination on a metallic plate. The plate is electrically biased relative to the plasma in order to control the atom energies. Such an intensive jet of hydrogen atoms can be used in negative ion sources for effective production of negative ions on a cesiated surface of plasma grid. All elements of the plasma generator have an augmented water cooling to operate in long pulse mode or in steady state. The thermo-mechanical stresses and deformations of the most critical elements of the plasma generator were determined by simulations. Magnetic field inside the discharge chamber was optimized to reduce the local power loads. The first tests of the steady-state arc plasma generator prototype have performed in long-pulse mode.

  3. Arc plasma generator of atomic driver for steady-state negative ion source

    SciTech Connect

    Ivanov, A. A.; Belchenko, Yu. I.; Davydenko, V. I.; Ivanov, I. A.; Kolmogorov, V. V.; Listopad, A. A. Mishagin, V. V.; Shulzhenko, G. I.; Putvinsky, S. V.; Smirnov, A.

    2014-02-15

    The paper reviews the results of development of steady-state arc-discharge plasma generator with directly heated LaB{sub 6} cathode. This arc-discharge plasma generator produces a plasma jet which is to be converted into an atomic one after recombination on a metallic plate. The plate is electrically biased relative to the plasma in order to control the atom energies. Such an intensive jet of hydrogen atoms can be used in negative ion sources for effective production of negative ions on a cesiated surface of plasma grid. All elements of the plasma generator have an augmented water cooling to operate in long pulse mode or in steady state. The thermo-mechanical stresses and deformations of the most critical elements of the plasma generator were determined by simulations. Magnetic field inside the discharge chamber was optimized to reduce the local power loads. The first tests of the steady-state arc plasma generator prototype have performed in long-pulse mode.

  4. Arc plasma generator of atomic driver for steady-state negative ion source.

    PubMed

    Ivanov, A A; Belchenko, Yu I; Davydenko, V I; Ivanov, I A; Kolmogorov, V V; Listopad, A A; Mishagin, V V; Putvinsky, S V; Shulzhenko, G I; Smirnov, A

    2014-02-01

    The paper reviews the results of development of steady-state arc-discharge plasma generator with directly heated LaB6 cathode. This arc-discharge plasma generator produces a plasma jet which is to be converted into an atomic one after recombination on a metallic plate. The plate is electrically biased relative to the plasma in order to control the atom energies. Such an intensive jet of hydrogen atoms can be used in negative ion sources for effective production of negative ions on a cesiated surface of plasma grid. All elements of the plasma generator have an augmented water cooling to operate in long pulse mode or in steady state. The thermo-mechanical stresses and deformations of the most critical elements of the plasma generator were determined by simulations. Magnetic field inside the discharge chamber was optimized to reduce the local power loads. The first tests of the steady-state arc plasma generator prototype have performed in long-pulse mode.

  5. Thrombin exacerbates brain edema in focal cerebral ischemia.

    PubMed

    Hua, Y; Wu, J; Keep, R F; Hoff, J T; Xi, G

    2003-01-01

    Thrombin contributes to edema formation after intracerebral hemorrhage. Recent studies suggest that thrombin may also play a role in ischemic brain damage. In the present study, adult male Sprague-Dawley rats were anesthetized with pentobarbital. Middle cerebral artery (MCA) was occluded using the suture method. We found that brain thrombin activity was elevated after permanent MCA occlusion as was prothrombin messenger RNA expression. Intracerebral injection of a thrombin inhibitor, hirudin, reduced neurological deficits following cerebral ischemia. In contrast, intracerebral administration of exogenous thrombin (at a dose that is non-toxic to normal brain), markedly exacerbated brain edema after transient focal cerebral ischemia. These results indicate that extravascular thrombin inhibition may be a new therapeutic target for cerebral ischemia.

  6. Laser-induced plasma generation and evolution in a transient spray.

    PubMed

    Kawahara, Nobuyuki; Tsuboi, Kazuya; Tomita, Eiji

    2014-01-13

    The behaviors of laser-induced plasma and fuel spray were investigated by visualizing images with an ultra-high-speed camera. Time-series images of laser-induced plasma in a transient spray were visualized using a high-speed color camera. The effects of a shockwave generated from the laser-induced plasma on the evaporated spray behavior were investigated. The interaction between a single droplet and the laser-induced plasma was investigated using a single droplet levitated by an ultrasonic levitator. Two main conclusions were drawn from these experiments: (1) the fuel droplets in the spray were dispersed by the shockwave generated from the laser-induced plasma; and (2) the plasma position may have shifted due to breakdown of the droplet surface and the lens effect of droplets.

  7. Generation of high-power electromagnetic radiation by a beam-driven plasma antenna

    NASA Astrophysics Data System (ADS)

    Annenkov, V. V.; Volchok, E. P.; Timofeev, I. V.

    2016-04-01

    In this paper we study how efficiently electromagnetic radiation can be generated by a relativistic electron beam with a gigawatt power level during its injection into a thin magnetized plasma. It is shown that, if the transverse beam and plasma size is compared with the radiation wavelength and the plasma density is modulated along the magnetic field, such a beam-plasma system can radiate electromagnetic waves via the antenna mechanism. We propose a theoretical model describing generation of electromagnetic waves by this plasma antenna and calculate its main radiation characteristics. In the two-dimensional case theoretical predictions on the radiation efficiency are shown to be confirmed by the results of particle-in-cell simulations, and the three-dimensional variant of this theory is used to estimate the peak power of sub-terahertz radiation that can be achieved in beam-plasma experiments in mirror traps.

  8. Magnetic field generation from Self-Consistent collective neutrino-plasma interactions

    SciTech Connect

    Brizard, A.J.; Murayama H.; Wurtele, J.S.

    1999-11-24

    A new Lagrangian formalism for self-consistent collective neutrino-plasma interactions is presented in which each neutrino species is described as a classical ideal fluid. The neutrino-plasma fluid equations are derived from a covariant relativistic variational principle in which finite-temperature effects are retained. This new formalism is then used to investigate the generation of magnetic fields and the production of magnetic helicity as a result of collective neutrino-plasma interactions.

  9. Wakefields generated by collisional neutrinos in neutral-electron-positron-ion plasma

    SciTech Connect

    Tinakiche, Nouara

    2015-12-15

    A classical fluid description is adopted to investigate nonlinear interaction between an electron-type neutrino beam and a relativistic collisionless unmagnetized neutral-electron-positron-ion plasma. In this work, we consider the collisions of the neutrinos with neutrals in the plasma and study their effect on the generation of wakefields in presence of a fraction of ions in a neutral-electron-positron plasma. The results obtained in the present work are interpreted and compared with previous studies.

  10. Laser driven terahertz generation in hot plasma with step density profile

    SciTech Connect

    Kumar, Manoj Jeong, Young Uk; Tripathi, Vipin Kumar

    2015-06-15

    An analytical formalism of terahertz (THz) radiation generation by beating of two lasers in a hot plasma with step density profile is developed. The lasers propagate obliquely to plasma surface normal, and the nonlinearity arises through the ponderomotive force. The THz is emitted in the specular reflection direction, and the yield is enhanced due to coupling with the Langmuir wave when the plasma frequency is close to THz frequency. The power conversion efficiency maximizes at an optimum angle of incidence.

  11. Microwave diagnostics of femtosecond laser-generated plasma filaments

    SciTech Connect

    Papeer, J.; Ehrlich, Y.; Zigler, A.; Mitchell, C.; Penano, J.; Sprangle, P.

    2011-10-03

    We present a simple non-intrusive experimental method allowing a complete single shot temporal measurement of laser produced plasma filament conductivity. The method is based on filament interaction with low intensity microwave radiation in a rectangular waveguide. The suggested diagnostics allow a complete single shot temporal analysis of filament plasma decay with resolution better than 0.3 ns and high spatial resolution along the filament. The experimental results are compared to numerical simulations, and an initial electron density of 7 x 10{sup 16 }cm{sup -3} and decay time of 3 ns are obtained.

  12. Generation of collisionless shock in laser-produced plasmas

    NASA Astrophysics Data System (ADS)

    Fiuza, Frederico

    2015-08-01

    Collisionless shocks are ubiquitous in astrophysical environments and are tightly connected with magnetic-field amplification and particle acceleration. The fast progress in high-power laser technology is bringing the study of high Mach number shocks into the realm of laboratory plasmas, where in situ measurements can be made helping us understand the fundamental kinetic processes behind shocks. I will discuss the recent progress in laser-driven shock experiments at state-of-the-art facilities like NIF and Omega and how these results, together with ab initio massively parallel simulations, can impact our understanding of magnetic field amplification and particle acceleration in astrophysical plasmas.

  13. Generation of anomalously energetic suprathermal electrons by an electron beam interacting with a nonuniform plasma

    SciTech Connect

    Sydorenko, D.; Kaganovich, I. D.; Chen, L.; Ventzek, P. L. G.

    2015-12-15

    Generation of anomalously energetic suprathermal electrons was observed in simulation of a high-voltage dc discharge with electron emission from the cathode. An electron beam produced by the emission interacts with the nonuniform plasma in the discharge via a two-stream instability. The energy transfer from the beam to the plasma electrons is ensured by the plasma nonuniformity. The electron beam excites plasma waves whose wavelength and phase speed gradually decrease towards anode. The waves with short wavelength near the anode accelerate plasma bulk electrons to suprathermal energies. The sheath near the anode reflects some of the accelerated electrons back into the plasma. These electrons travel through the plasma, reflect near the cathode, and enter the accelerating area again but with a higher energy than before. Such particles are accelerated to energies much higher than after the first acceleration. This mechanism plays a role in explaining earlier experimental observations of energetic suprathermal electrons in similar discharges.

  14. Characteristics of pulsed internal inductively coupled plasma for next generation display processing.

    PubMed

    Kim, Tae Hyung; Lee, Seung Min; Lee, Chul Hee; Bae, Jeong Oun; Yeom, Geun Young; Kim, Kyong Nam

    2014-12-01

    RF pulsed plasma characteristics of inductively coupled plasma (ICP) sources operated with internal linear type antennas for the next generation display processing were investigated. By applying the rf pulse mode in the ICP source, with decreasing the rf pulse duty percentage, the average electron temperature was decreased and the plasma non-uniformity was improved with decreasing the rf pulse duty percentage. In the case of plasma uniformity, for the same time average rf power of 3 kW to the ICP source, the plasma non-uniformity was improved from 8.4% at 100% of rf duty percentage to 6.4% at 60% of rf duty percentage due to the increased diffusion of the plasma during the pulse-off time. When SiO2 was etched using CF4, the etch rate uniformity was also improved due to the improvement of plasma uniformity. PMID:25971107

  15. Cold atmospheric plasma jet-generated RONS and their selective effects on normal and carcinoma cells.

    PubMed

    Kim, Sun Ja; Chung, T H

    2016-01-01

    Cold atmospheric helium plasma jets were fabricated and utilized for plasma-cell interactions. The effect of operating parameters and jet design on the generation of specific reactive oxygen and nitrogen species (RONS) within cells and cellular response were investigated. It was found that plasma treatment induced the overproduction of RONS in various cancer cell lines selectively. The plasma under a relatively low applied voltage induced the detachment of cells, a reduction in cell viability, and apoptosis, while the plasma under higher applied voltage led to cellular necrosis in our case. To determine whether plasma-induced reactive oxygen species (ROS) generation occurs through interfering with mitochondria-related cellular response, we examined the plasma effects on ROS generation in both parental A549 cells and A549 ρ(0) cells. It was observed that cancer cells were more susceptible to plasma-induced RONS (especially nitric oxide (NO) and nitrogen dioxide (NO2(-)) radicals) than normal cells, and consequently, plasma induced apoptotic cell responses mainly in cancer cells.

  16. Hypersensitivity to thrombin of platelets from hypercholesterolemic rats

    SciTech Connect

    Winocour, P.D.; Rand, M.L.; Kinlough-Rathbone, R.L.; Mustard, J.F.

    1986-03-01

    Hypersensitivity of platelets to thrombin has been associated with hypercholesterolemia. The authors have examined the mechanisms involved in this hypersensitivity. Rats were given diets rich in milk fat and containing added cholesterol and taurocholate to produce hypercholesterolemia (HC) (262 +/- 25 mg%) or added sitosterol as a normocholesterolemic control (NC) (89 +/- 6 mg%). Washed platelets were prelabelled with /sup 14/C-serotonin. In the presence of acetylsalicyclic acid (ASA) (to inhibit thromboxane A/sub 2/ (TXA/sub 2/) formation) and creatine phosphate/creatine phosphokinase (CP/CPK) (to remove released ADP), HC platelets aggregated more (26 +/- 1%) and released more /sup 14/C (9.1 +/- 2.0%) than NC platelets (aggregation: 0%, p < 0.001; /sup 14/C release: 1.5 +/- 0.5%, p < 0.002) in response to thrombin (0.075 U/ml). Thus, a pathway independent of released ADP or TXA/sub 2/ formation is involved in the hypersensitivity of HC platelets to thrombin. Total binding of /sup 125/I-thrombin to HC platelets was less than that to NC platelets but HC platelets were smaller and had less protein than NC platelets; the thrombin binding per mg platelet protein was the same for HC and NC platelets, indicating that hypersensitivity to thrombin of HC platelets does not result from increased thrombin binding. Thus, hypersensitivity of HC platelets to thrombin is not due to TXA/sub 2/ formation, the action of released ADP or increased thrombin binding.

  17. Specificity and selectivity profile of EP217609: a new neutralizable dual-action anticoagulant that targets thrombin and factor Xa

    PubMed Central

    Swanson, Richard; Petitou, Maurice

    2012-01-01

    EP217609 is a new dual-action parenteral anticoagulant that combines an indirect factor Xa inhibitor (fondaparinux analog) and a direct thrombin inhibitor (α-NAPAP analog) in a single molecule together with a biotin tag to allow avidin neutralization. EP217609 exhibits an unprecedented pharmacologic profile in showing high bioavailability, long plasma half-life, and potent antithrombotic activity in animals without the complications of thrombin rebound. Here we report the exceptional specificity and selectivity profile of EP217609. EP217609 inhibited thrombin with rapid kinetics (kon > 107M−1s−1), a high affinity (KI = 30-40pM), and more than 1000-fold selectivity over other coagulation and fibrinolytic protease targets, comparing favorably with the best direct thrombin inhibitors known. EP217609 bound antithrombin with high affinity (KD = 30nM) and activated the serpin to rapidly (kass ∼ 106M−1s−1) and selectively (> 20-fold) inhibit factor Xa. The dual inhibitor moieties of EP217609 acted largely independently with only modest linkage effects of ligand occupancy of one inhibitor moiety on the potency of the other (∼ 5-fold). In contrast, avidin binding effectively neutralized the potency of both inhibitor moieties (20- to 100-fold). These findings demonstrate the superior anticoagulant efficacy and rapid avidin neutralizability of EP217609 compared with anticoagulants that target thrombin or factor Xa alone. PMID:22144183

  18. A brief exposure to tryptase or thrombin potentiates fibrocyte differentiation in the presence of serum or SAP

    PubMed Central

    White, Michael J.V.; Galvis-Carvajal, Elkin; Gomer, Richard H.

    2014-01-01

    A key question in both wound healing and fibrosis is the trigger for the initial formation of scar tissue. To help form scar tissue, circulating monocytes enter the tissue and differentiate into fibroblast-like cells called fibrocytes, but fibrocyte differentiation is strongly inhibited by the plasma protein Serum Amyloid P (SAP), and healthy tissues contain very few fibrocytes. In wounds and fibrotic lesions, mast cells degranulate to release tryptase, and in early wounds thrombin mediates blood clotting. Tryptase and thrombin are upregulated in wound healing and fibrotic lesions, and inhibition of these proteases attenuates fibrosis. Here we report that tryptase and thrombin potentiate human fibrocyte differentiation at biologically relevant concentrations and exposure times, even in the presence of concentrations of serum and SAP that normally completely inhibit fibrocyte differentiation. The fibrocyte potentiation by thrombin and tryptase is mediated by protease-activated receptors 1 and 2, respectively. Together, these results suggest that tryptase and thrombin may be an initial trigger to override SAP inhibition of fibrocyte differentiation to initiate scar tissue formation. PMID:25429068

  19. The role of laser wavelength on plasma generation and expansion of ablation plumes in air

    SciTech Connect

    Hussein, A. E.; Diwakar, P. K.; Harilal, S. S.; Hassanein, A.

    2013-04-14

    We investigated the role of excitation laser wavelength on plasma generation and the expansion and confinement of ablation plumes at early times (0-500 ns) in the presence of atmospheric pressure. Fundamental, second, and fourth harmonic radiation from Nd:YAG laser was focused on Al target to produce plasma. Shadowgraphy, fast photography, and optical emission spectroscopy were employed to analyze the plasma plumes, and white light interferometry was used to characterize the laser ablation craters. Our results indicated that excitation wavelength plays a crucial role in laser-target and laser-plasma coupling, which in turn affects plasma plume morphology and radiation emission. Fast photography and shadowgraphy images showed that plasmas generated by 1064 nm are more cylindrical compared to plasmas generated by shorter wavelengths, indicating the role of inverse bremsstrahlung absorption at longer laser wavelength excitation. Electron density estimates using Stark broadening showed higher densities for shorter wavelength laser generated plasmas, demonstrating the significance of absorption caused by photoionization. Crater depth analysis showed that ablated mass is significantly higher for UV wavelengths compared to IR laser radiation. In this experimental study, the use of multiple diagnostic tools provided a comprehensive picture of the differing roles of laser absorption mechanisms during ablation.

  20. Generation of terahertz radiation by focusing femtosecond bichromatic laser pulses in a gas or plasma

    SciTech Connect

    Chizhov, P A; Volkov, Roman V; Bukin, V V; Ushakov, A A; Garnov, Sergei V; Savel'ev-Trofimov, Andrei B

    2013-04-30

    The generation of terahertz radiation by focusing two-frequency femtosecond laser pulses is studied. Focusing is carried out both in an undisturbed gas and in a pre-formed plasma. The energy of the terahertz radiation pulses is shown to reduce significantly in the case of focusing in a plasma. (extreme light fields and their applications)

  1. Generation and characterization of atmospheric plasma torch array

    SciTech Connect

    Koretzky, E.; Kuo, S.P.

    1997-12-31

    Using a capacitively coupled electrical discharge, an array of plasma torches can be produced simultaneously by using a common 60 cycle power source (i.e. a simple wall plug) at atmospheric pressure. The size of each torch depends on the geometry of the electrode pair and the streaming speed of the air flow. Such a flat panel plasma torch array can be made into the desired volume and plasma density. A laser beam is used to measure the dimensions of the torch. It is found that each torch has a radius of about 1 cm and a height of about 6.5 cm. Surprisingly, it is shown that the torch can cause up to 80% modulation of the laser beam intensity. From the voltage and current measurements, the average power consumption of each torch is estimated to be 0.6 kW. The electron density can also be estimated and is found to exceed 10{sup 13}cm{sup {minus}3}. The discharge may be represented by a lump circuit. Thus, a computer simulation of the discharge is performed. The results are found to be in good agreement with experimental measurements. Simulations have also been performed to study the dependence of average electron density, with the electron-ion recombination coefficient as a parameter. The study is aimed at developing an efficient large volume dense plasma for industrial applications.

  2. On uniform plasma generation for the large area plasma processing in intermediate pressures

    SciTech Connect

    Kim, Hyun Jun; Hwang, Hye-Ju; Cho, Jeong Hee; Chae, Hee Sun; Kim, Dong Hwan; Chung, Chin-Wook

    2015-04-21

    Radial plasma discharge characteristics in the range of 450 mm were studied in a dual inductively coupled plasma (ICP) source, which consisted of a helical ICP and the side type ferrite ICPs. Since the energy relaxation length is shorter than the distance between each of the ferrite ICPs in an intermediate pressure (600 mTorr), local difference in the plasma ignition along the antenna position were observed. In addition, large voltage drop in the discharge of the ferrite ICPs causes an increase in the displacement current to the plasma, and separate discharge mode (E and H mode) according to the antenna position was observed. This results in non-uniform plasma distribution. For the improvement in the discharge of the ferrite ICPs, a capacitor which is placed between the ends of antenna and the ground is adjusted to minimize the displacement current to the plasma. As a result, coincident transitions from E to H mode were observed along the antenna position, and radially concave density profile (edge focused) was measured. For the uniform density distribution, a helical ICP, which located at the center of the discharge chamber, was simultaneously discharged with the ferrite ICPs. Due to the plasma potential variation through the simultaneous discharge of helical ICP and ferrite ICPs, uniform radial distribution in both plasma density and electron temperature are achieved.

  3. On uniform plasma generation for the large area plasma processing in intermediate pressures

    NASA Astrophysics Data System (ADS)

    Kim, Hyun Jun; Hwang, Hye-Ju; Kim, Dong Hwan; Cho, Jeong Hee; Chae, Hee Sun; Chung, Chin-Wook

    2015-04-01

    Radial plasma discharge characteristics in the range of 450 mm were studied in a dual inductively coupled plasma (ICP) source, which consisted of a helical ICP and the side type ferrite ICPs. Since the energy relaxation length is shorter than the distance between each of the ferrite ICPs in an intermediate pressure (600 mTorr), local difference in the plasma ignition along the antenna position were observed. In addition, large voltage drop in the discharge of the ferrite ICPs causes an increase in the displacement current to the plasma, and separate discharge mode (E and H mode) according to the antenna position was observed. This results in non-uniform plasma distribution. For the improvement in the discharge of the ferrite ICPs, a capacitor which is placed between the ends of antenna and the ground is adjusted to minimize the displacement current to the plasma. As a result, coincident transitions from E to H mode were observed along the antenna position, and radially concave density profile (edge focused) was measured. For the uniform density distribution, a helical ICP, which located at the center of the discharge chamber, was simultaneously discharged with the ferrite ICPs. Due to the plasma potential variation through the simultaneous discharge of helical ICP and ferrite ICPs, uniform radial distribution in both plasma density and electron temperature are achieved.

  4. Modelling of plasma generation and thin film deposition by a non-thermal plasma jet at atmospheric pressure

    NASA Astrophysics Data System (ADS)

    Sigeneger, F.; Becker, M. M.; Foest, R.; Loffhagen, D.

    2016-09-01

    The gas flow and plasma in a miniaturized non-thermal atmospheric pressure plasma jet for plasma enhanced chemical vapour deposition has been investigated by means of hydrodynamic modelling. The investigation focuses on the interplay between the plasma generation in the active zone where the power is supplied by an rf voltage to the filaments, the transport of active plasma particles due to the gas flow into the effluent, their reactions with the thin film precursor molecules and the transport of precursor fragments towards the substrate. The main features of the spatially two-dimensional model used are given. The results of the numerical modelling show that most active particles of the argon plasma are mainly confined within the active volume in the outer capillary of the plasma jet, with the exception of molecular argon ions which are transported remarkably into the effluent together with slow electrons. A simplified model of the precursor kinetics yields radial profiles of precursor fragment fluxes onto the substrate, which agree qualitatively with the measured profiles of thin films obtained by static film deposition experiments.

  5. Flow and delta-P dictate where thrombin, fibrin, and von Willebrand Factor will be found.

    PubMed

    Diamond, Scott L

    2016-05-01

    Hemostasis occurs in two different topological scenarios: complete severing of a vessel or disruption of the vessel wall. Either to meet the daily rigors of active life or during an acute trauma, hemostasis involves the regulated and self-limiting production of thrombin to stop bleeding. In contrast, arterial and venous thrombosis typically involves the unregulated, intraluminal growth of a clot, in the absence of bleeding. For either hemostasis or thrombosis, the presence of flow and pressure gradients (delta-P, ΔP) dictates when and where thrombin and fibrin are located and in what quantity. For hemostatic clots, fibrin formation helped limit clot growth. We found that γ'-fibrinogen had a role in limiting clot growth via anti-thrombin activity at venous, but not arterial conditions. For hemophilic blood, severe factor deficiency (<1% healthy) led to a defect in both platelet and fibrin deposition under flow. However, moderate deficiency, which is associated with a less severe bleeding phenotype, had normalized platelet function but still lacked fibrin production. We conclude signaling levels of thrombin can be generated during moderate hemophilia to sufficiently activate platelets to achieve primary hemostasis, even if fibrin formation remains defective. Finally, as a clot grows, shear stresses can become sufficiently extreme in diseased arteries to drive von Willebrand Factor self-association into massive fibers, potentially the final burst of clot growth towards full thrombotic occlusion. PMID:27207416

  6. Flow and delta-P dictate where thrombin, fibrin, and von Willebrand Factor will be found.

    PubMed

    Diamond, Scott L

    2016-05-01

    Hemostasis occurs in two different topological scenarios: complete severing of a vessel or disruption of the vessel wall. Either to meet the daily rigors of active life or during an acute trauma, hemostasis involves the regulated and self-limiting production of thrombin to stop bleeding. In contrast, arterial and venous thrombosis typically involves the unregulated, intraluminal growth of a clot, in the absence of bleeding. For either hemostasis or thrombosis, the presence of flow and pressure gradients (delta-P, ΔP) dictates when and where thrombin and fibrin are located and in what quantity. For hemostatic clots, fibrin formation helped limit clot growth. We found that γ'-fibrinogen had a role in limiting clot growth via anti-thrombin activity at venous, but not arterial conditions. For hemophilic blood, severe factor deficiency (<1% healthy) led to a defect in both platelet and fibrin deposition under flow. However, moderate deficiency, which is associated with a less severe bleeding phenotype, had normalized platelet function but still lacked fibrin production. We conclude signaling levels of thrombin can be generated during moderate hemophilia to sufficiently activate platelets to achieve primary hemostasis, even if fibrin formation remains defective. Finally, as a clot grows, shear stresses can become sufficiently extreme in diseased arteries to drive von Willebrand Factor self-association into massive fibers, potentially the final burst of clot growth towards full thrombotic occlusion.

  7. Plasma generation for controlled microwave-reflecting surfaces in plasma antennas

    SciTech Connect

    Bliokh, Yury P.; Felsteiner, Joshua; Slutsker, Yakov Z.

    2014-04-28

    The idea of replacing metal antenna elements with equivalent plasma objects has long been of interest because of the possibility of switching the antenna on and off. In general, two kinds of designs have so far been reported: (a) Separate plasma “wires” which are thin glass tubes filled with gas, where plasma appears due to discharge inside. (b) Reflecting surfaces, consisting of tightly held plasma wires or specially designed large discharge devices with magnetic confinement. The main disadvantages of these antennas are either large weight and size or too irregular surfaces for proper reflection. To design a microwave plasma antenna in the most common radar wavelength range of 1–3 cm with a typical gain of 30 dB, a smooth plasma mirror having a 10–30 cm diameter and a proper curvature is required. The plasma density must be 10{sup 12}–10{sup 14} cm{sup −3} in order to exceed the critical density for the frequency of the electromagnetic wave. To achieve this we have used a ferromagnetic inductively coupled plasma (FICP) source, where a thin magnetic core of a large diameter is fully immersed in the plasma. In the present paper, we show a way to adapt the FICP source for creating a flat switchable microwave plasma mirror with an effective diameter of 30 cm. This mirror was tested as a microwave reflector and there was found no significant difference when compared with a copper plate having the same diameter.

  8. Method for generating a highly reactive plasma for exhaust gas aftertreatment and enhanced catalyst reactivity

    DOEpatents

    Whealton, John H.; Hanson, Gregory R.; Storey, John M.; Raridon, Richard J.; Armfield, Jeffrey S.; Bigelow, Timothy S.; Graves, Ronald L.

    2001-01-01

    A method for non-thermal plasma aftertreatment of exhaust gases the method comprising the steps of providing short risetime (about 40 ps), high frequency (about 5G hz), high power bursts of low-duty factor microwaves sufficient to generate a dielectric barrier discharge and passing a gas to treated through the discharge so as to cause dissociative reduction of the exhaust gases. The invention also includes a reactor for generating the non-thermal plasma.

  9. A reflex electron beam discharge as a plasma source for electron beam generation

    SciTech Connect

    Murray, C.S.; Rocca, J.J.; Szapiro, B. )

    1988-10-01

    A reflex electron beam glow discharge has been used as a plasma source for the generation of broad-area electron beams. An electron current of 120 A (12 A/cm/sup 2/) was extracted from the plasma in 10 ..mu..s pulses and accelerated to energies greater than 1 keV in the gap between two grids. The scaling of the scheme for the generation of multikiloamp high-energy beams is discussed.

  10. Elevated Cytokines, Thrombin and PAI-1 in Severe HCPS Patients Due to Sin Nombre Virus

    PubMed Central

    Bondu, Virginie; Schrader, Ron; Gawinowicz, Mary Ann; McGuire, Paul; Lawrence, Daniel A.; Hjelle, Brian; Buranda, Tione

    2015-01-01

    Sin Nombre Hantavirus (SNV, Bunyaviridae Hantavirus) is a Category A pathogen that causes Hantavirus Cardiopulmonary Syndrome (HCPS) with case fatality ratios generally ranging from 30% to 50%. HCPS is characterized by vascular leakage due to dysregulation of the endothelial barrier function. The loss of vascular integrity results in non-cardiogenic pulmonary edema, shock, multi-organ failure and death. Using Electric Cell-substrate Impedance Sensing (ECIS) measurements, we found that plasma samples drawn from University of New Mexico Hospital patients with serologically-confirmed HCPS, induce loss of cell-cell adhesion in confluent epithelial and endothelial cell monolayers grown in ECIS cultureware. We show that the loss of cell-cell adhesion is sensitive to both thrombin and plasmin inhibitors in mild cases, and to thrombin only inhibition in severe cases, suggesting an increasing prothrombotic state with disease severity. A proteomic profile (2D gel electrophoresis and mass spectrometry) of HCPS plasma samples in our cohort revealed robust antifibrinolytic activity among terminal case patients. The prothrombotic activity is highlighted by acute ≥30 to >100 fold increases in active plasminogen activator inhibitor (PAI-1) which, preceded death of the subjects within 48 h. Taken together, this suggests that PAI-1 might be a response to the severe pathology as it is expected to reduce plasmin activity and possibly thrombin activity in the terminal patients. PMID:25674766

  11. Optical Characterization of Plasma Generated in a Commercial Grade Plasma Etching System

    NASA Astrophysics Data System (ADS)

    Hardy, Ashley; Drake, Dereth

    2015-11-01

    The use of plasma for etching and cleaning of many types of metal surfaces is becoming more prominent in industry. This is primarily due to the fact that plasma etching can reduce the amount of time necessary to clean/etch the surface and does not require large amounts of environmentally hazardous chemicals. Most plasma etching systems are designed and built in academic institutions. These systems provide reasonable etching rates and easy accessibility for monitoring plasma parameters. The downside is that the cost is typically high. Recently a number of commercial grade plasma etchers have been introduced on the market. These etching systems cost near a fraction of the price, making them a more economical choice for researchers in the field. However, very few academics use these devices because their effectiveness has not yet been adequately verified in the current literature. We will present the results from experiments performed in a commercial grade plasma etching system, including analysis of the pulse characteristics observed by a photo diode and the plasma parameters obtained with optical emission spectroscopy.

  12. Characterization of Plasma Generated in a Commercial Grade Plasma Etching system

    NASA Astrophysics Data System (ADS)

    Bessinger, Gabriella; Drake, Dereth; Popovic, Svetozar; Vuskovic, Leposava

    2014-10-01

    The use of plasma for etching and cleaning of many types of metal surfaces is becoming more prominent in industry. This is primarily due to the fact that plasma etching can reduce the amount of time necessary to clean/etch the surface and does not require large amounts of environmentally hazardous chemicals. Most plasma etching systems are designed and built in academic institutions. These systems provide reasonable etching rates and easy accessibility for monitoring plasma parameters. The downside is that the cost is typically high. Recently a number of commercial grade plasma etchers have been introduced on the market. These etching systems cost near a fraction of the price, making them a more economical choice for researchers in the field. However, very few academicians use these devices because their effectiveness has not yet been adequately verified in the current literature. We will present the results from experiments performed in a commercial grade plasma etching system, including analysis of the pulse characteristics observed by a photo diode and the plasma parameters obtained with optical emission spectroscopy.

  13. Magnetic-Field Generation and Amplification in an Expanding Plasma

    NASA Astrophysics Data System (ADS)

    Schoeffler, K. M.; Loureiro, N. F.; Fonseca, R. A.; Silva, L. O.

    2014-05-01

    Particle-in-cell simulations are used to investigate the formation of magnetic fields B in plasmas with perpendicular electron density and temperature gradients. For system sizes L comparable to the ion skin depth di, it is shown that B˜di/L, consistent with the Biermann battery effect. However, for large L/di, it is found that the Weibel instability (due to electron temperature anisotropy) supersedes the Biermann battery as the main producer of B. The Weibel-produced fields saturate at a finite amplitude (plasma β≈100), independent of L. The magnetic energy spectra below the electron Larmor radius scale are well fitted by the power law with slope -16/3, as predicted by Schekochihin et al. [Astrophys. J. Suppl. Ser. 182, 310 (2009)].

  14. Plasma-wave Generation in a Dynamic Spacetime

    NASA Astrophysics Data System (ADS)

    Yang, Huan; Zhang, Fan

    2016-02-01

    We propose a new electromagnetic (EM)-emission mechanism in magnetized, force-free plasma, which is driven by the evolution of the underlying dynamic spacetime. In particular, the emission power and angular distribution of the emitted fast-magnetosonic and Alfvén waves are separately determined. Previous numerical simulations of binary black hole mergers occurring within magnetized plasma have recorded copious amounts of EM radiation that, in addition to collimated jets, include an unexplained, isotropic component that becomes dominant close to the merger. This raises the possibility of multimessenger gravitational-wave and EM observations on binary black hole systems. The mechanism proposed here provides a candidate analytical characterization of the numerical results, and when combined with previously understood mechanisms such as the Blandford-Znajek process and kinetic-motion-driven radiation, it allows us to construct a classification of different EM radiation components seen in the inspiral stage of compact-binary coalescences.

  15. Magnetic filter apparatus and method for generating cold plasma in semicoductor processing

    DOEpatents

    Vella, Michael C.

    1996-01-01

    Disclosed herein is a system and method for providing a plasma flood having a low electron temperature to a semiconductor target region during an ion implantation process. The plasma generator providing the plasma is coupled to a magnetic filter which allows ions and low energy electrons to pass therethrough while retaining captive the primary or high energy electrons. The ions and low energy electrons form a "cold plasma" which is diffused in the region of the process surface while the ion implantation process takes place.

  16. Magnetic filter apparatus and method for generating cold plasma in semiconductor processing

    DOEpatents

    Vella, M.C.

    1996-08-13

    Disclosed herein is a system and method for providing a plasma flood having a low electron temperature to a semiconductor target region during an ion implantation process. The plasma generator providing the plasma is coupled to a magnetic filter which allows ions and low energy electrons to pass therethrough while retaining captive the primary or high energy electrons. The ions and low energy electrons form a ``cold plasma`` which is diffused in the region of the process surface while the ion implantation process takes place. 15 figs.

  17. Terahertz generation by two cross focused laser beams in collisional plasmas

    SciTech Connect

    Sharma, R. P. Singh, Ram Kishor

    2014-07-15

    The role of two cross-focused spatial-Gaussian laser beams has been studied for the high power and efficient terahertz (THz) radiation generation in the collisional plasma. The nonlinear current at THz frequency arises on account of temperature dependent collision frequency of electrons with ions in the plasma and the presence of a static electric field (applied externally in the plasma) and density ripple. Optimisation of laser-plasma parameters gives the radiated THz power of the order of 0.23  MW.

  18. Higher-Order Harmonic Generation from Fullerene by Means of the Plasma Harmonic Method

    SciTech Connect

    Ganeev, R. A.; Bom, L. B. Elouga; Abdul-Hadi, J.; Ozaki, T.; Wong, M. C. H.; Brichta, J. P.; Bhardwaj, V. R.

    2009-01-09

    We demonstrate, for the first time, high-order harmonic generation from C{sub 60} by an intense femtosecond Ti:sapphire laser. Laser-produced plasmas from C{sub 60}-rich epoxy and C{sub 60} films were used as the nonlinear media. Harmonics up to the 19th order were observed. The harmonic yield from fullerene-rich plasma is about 25 times larger compared with those produced from a bulk carbon target. Structural studies of plasma debris confirm the presence and integrity of fullerenes within the plasma plume, indicating fullerenes as the source of high-order harmonics.

  19. High-temperature coal-syngas plasma characteristics for advanced MHD power generation

    SciTech Connect

    Mikheev, A.V.; Kayukawa, N.; Okinaka, N.; Kamada, Y.; Yatsu, S.

    2006-03-15

    Properties of magnetohydrodynamic (MHD) plasma based on syngas (CO, H{sub 2}) combustion products were investigated experimentally with shock tube facility. The experiments were carried out under various MHD generator load and shock tube operation conditions. Important characteristics of syngas plasma such as temperature, electric field, conductivity, and total output power were directly measured and evaluated. Special attention was paid to the influence of syngas composition (CO : H{sub 2} : O{sub 2} ratio). The results show that syngas combustion can provide high plasma ionization and attainable plasma electrical conductivity has an order of 60-80 S/m at gas temperature 3100-3300 K.

  20. Development of a stable dielectric-barrier discharge enhanced laminar plasma jet generated at atmospheric pressure

    SciTech Connect

    Tang Jie; Li Shibo; Zhao Wei; Wang Yishan; Duan Yixiang

    2012-06-18

    A stable nonthermal laminar atmospheric-pressure plasma source equipped with dielectric-barrier discharge was developed to realize more efficient plasma generation, with the total energy consumption reduced to nearly 25% of the original. Temperature and emission spectra monitoring indicates that this plasma is uniform in the lateral direction of the jet core region. It is also found that this plasma contains not only abundant excited argon atoms but also sufficient excited N{sub 2} and OH. This is mainly resulted from the escape of abundant electrons from the exit, due to the sharp decrease of sustaining voltage and the coupling between ions and electrons.

  1. High Magnetic field generation for laser-plasma experiments

    SciTech Connect

    Pollock, B B; Froula, D H; Davis, P F; Ross, J S; Fulkerson, S; Bower, J; Satariano, J; Price, D; Glenzer, S H

    2006-05-01

    An electromagnetic solenoid was developed to study the effect of magnetic fields on electron thermal transport in laser plasmas. The solenoid, which is driven by a pulsed power system suppling 30 kJ, achieves magnetic fields of 13 T. The field strength was measured on the solenoid axis with a magnetic probe and optical Zeeman splitting. The measurements agree well with analytical estimates. A method for optimizing the solenoid design to achieve magnetic fields exceeding 20 T is presented.

  2. Structure of the bipolar plasma sheath generated by SPEAR I

    SciTech Connect

    Katz, I.; Jongeward, G.A.; Davis, V.A.; Mandell, M.J.; Kuharski, R.A.; Lilley, J.R. Jr. ); Raitt, W.J. ); Cooke, D.L. ); Torbert, R.B.; Larson, G.; Rau, D. )

    1989-02-01

    The Space Power Experiment Aboard Rockets I (SPEAR I) biased two 10-cm radius spheres as high as 46,000 V positive with respect to an aluminum rocket body. The experiment measured the steady state current to the spheres and the floating potential of the rocket body. Three-dimensional calculations performed using NASCAP/LEO and POLAR 2.0 show that both ion-collecting and electron-collecting sheaths were formed. The rocket body potential with respect to the ionospheric plasma adjusted to achieve a balance between the electron current collected by the spheres and the secondary electron-enhanced ion current to the rocket body. This current balance was obtained with a large ion-collecting sheath that enveloped most of the electron-collecting sheath and reduced the area for collection of ionospheric electrons. The calculated current is in agreement with the flight measurement of a steady state current of less than 1/10 A. The calculations show that the rocket body was driven thousands of volts negative with respect to the ionospheric plasma. The calculated rocket potential is within the uncertainty of that inferred from ion spectrometer data. The current flowed through the space plasma. There was almost no direct charge transport between the spheres and the rocket body.

  3. Laser produced plasma soft x-ray generation

    SciTech Connect

    Cerjan, C.; Rosen, M.D.

    1991-05-20

    The efficiency of soft x-ray production from laser-irradiated plasmas is simulated for two different spectral regions. These two regions, 14{Angstrom} {plus minus} 15% and 130{Angstrom} {plus minus} 1%, were chosen for proximity mask or point-projection technological applications. Relatively large conversion efficiencies were obtained from irradiation of a stainless steel target using the conditions suggested by recent Hampshire Instruments' experiments for proximity masking. Pulse-width and laser frequency parameter studies were performed for point-projection applications which suggest that the conversion applications which suggest that the conversion efficiency is sensitive to pulse-width but not to laser frequency. One of the critical components of any x-ray lithographic scheme is of course the x-ray laser source. There are two primary contenders for a reliable, efficient source currently: synchrotron radiation and spectral emission from laser produced plasma. The dominant issue for laser-plasma emission is the conversion efficiency -- output in the intended operating spectral region relative the required incident laser energy. Simulations are described in the following for both high and low energy spectral regions which have been suggested by either the proximity masking or point-projection technology.

  4. Cold atmospheric plasma jet-generated RONS and their selective effects on normal and carcinoma cells

    PubMed Central

    Kim, Sun Ja; Chung, T. H.

    2016-01-01

    Cold atmospheric helium plasma jets were fabricated and utilized for plasma–cell interactions. The effect of operating parameters and jet design on the generation of specific reactive oxygen and nitrogen species (RONS) within cells and cellular response were investigated. It was found that plasma treatment induced the overproduction of RONS in various cancer cell lines selectively. The plasma under a relatively low applied voltage induced the detachment of cells, a reduction in cell viability, and apoptosis, while the plasma under higher applied voltage led to cellular necrosis in our case. To determine whether plasma-induced reactive oxygen species (ROS) generation occurs through interfering with mitochondria-related cellular response, we examined the plasma effects on ROS generation in both parental A549 cells and A549 ρ0 cells. It was observed that cancer cells were more susceptible to plasma-induced RONS (especially nitric oxide (NO) and nitrogen dioxide (NO2−) radicals) than normal cells, and consequently, plasma induced apoptotic cell responses mainly in cancer cells. PMID:26838306

  5. Targeting cancer cells with reactive oxygen and nitrogen species generated by atmospheric-pressure air plasma.

    PubMed

    Ahn, Hak Jun; Kim, Kang Il; Hoan, Nguyen Ngoc; Kim, Churl Ho; Moon, Eunpyo; Choi, Kyeong Sook; Yang, Sang Sik; Lee, Jong-Soo

    2014-01-01

    The plasma jet has been proposed as a novel therapeutic method for cancer. Anticancer activity of plasma has been reported to involve mitochondrial dysfunction. However, what constituents generated by plasma is linked to this anticancer process and its mechanism of action remain unclear. Here, we report that the therapeutic effects of air plasma result from generation of reactive oxygen/nitrogen species (ROS/RNS) including H2O2, Ox, OH-, •O2, NOx, leading to depolarization of mitochondrial membrane potential and mitochondrial ROS accumulation. Simultaneously, ROS/RNS activate c-Jun NH2-terminal kinase (JNK) and p38 kinase. As a consequence, treatment with air plasma jets induces apoptotic death in human cervical cancer HeLa cells. Pretreatment of the cells with antioxidants, JNK and p38 inhibitors, or JNK and p38 siRNA abrogates the depolarization of mitochondrial membrane potential and impairs the air plasma-induced apoptotic cell death, suggesting that the ROS/RNS generated by plasma trigger signaling pathways involving JNK and p38 and promote mitochondrial perturbation, leading to apoptosis. Therefore, administration of air plasma may be a feasible strategy to eliminate cancer cells.

  6. Decomposition of chlorinated ethylenes and ethanes in an electron beam generated plasma reactor

    SciTech Connect

    Vitale, S.A.

    1996-02-01

    An electron beam generated plasma reactor (EBGPR) is used to determine the plasma chemistry kinetics, energetics and decomposition pathways of six chlorinated ethylenes and ethanes: 1,1,1-trichloroethane, 1,1-dichloroethane, ethyl chloride, trichloroethylene, 1,1-dichloroethylene, and vinyl chloride. A traditional chemical kinetic and chemical engineering analysis of the data from the EBGPR is performed, and the following hypothesis was verified: The specific energy required for chlorinated VOC decomposition in the electron beam generated plasma reactor is determined by the electron attachment coefficient of the VOC and the susceptibility of the molecule to radical attack. The technology was demonstrated at the Hanford Reservation to remove VOCs from soils.

  7. Simulation study of wakefield generation by two color laser pulses propagating in homogeneous plasma

    SciTech Connect

    Kumar Mishra, Rohit; Saroch, Akanksha; Jha, Pallavi

    2013-09-15

    This paper deals with a two-dimensional simulation of electric wakefields generated by two color laser pulses propagating in homogeneous plasma, using VORPAL simulation code. The laser pulses are assumed to have a frequency difference equal to the plasma frequency. Simulation studies are performed for two similarly as well as oppositely polarized laser pulses and the respective amplitudes of the generated longitudinal wakefields for the two cases are compared. Enhancement of wake amplitude for the latter case is reported. This simulation study validates the analytical results presented by Jha et al.[Phys. Plasmas 20, 053102 (2013)].

  8. High-order harmonic generation of picosecond radiation of moderate intensity in laser plasma

    SciTech Connect

    Boltaev, G S; Ganeev, Rashid A; Kulagin, I A; Satlikov, N Kh; Usmanov, T

    2012-10-31

    The results of investigations into the generation of highorder harmonics (up to the 21st order) of picosecond ({tau} = 38 ps) Nd : YAG laser radiation in the plasma produced by laser ablation of metal and carbon-containing material surfaces are presented. We demonstrate the feasibility of generating high-order harmonics in the vacuum ultraviolet spectral range (with radiation wavelengths shorter than 120 nm) in plasmas with an efficiency of {approx}0.7 Multiplication-Sign 10{sup -4}. In carbon-containing plasma, the 7th harmonic intensity exceeded that of the 5th one by a factor of seven. (nonlinear optical phenomena)

  9. High-order harmonic generation of picosecond radiation of moderate intensity in laser plasma

    NASA Astrophysics Data System (ADS)

    Boltaev, G. S.; Ganeev, Rashid A.; Kulagin, I. A.; Satlikov, N. Kh; Usmanov, T.

    2012-10-01

    The results of investigations into the generation of highorder harmonics (up to the 21st order) of picosecond (τ = 38 ps) Nd : YAG laser radiation in the plasma produced by laser ablation of metal and carbon-containing material surfaces are presented. We demonstrate the feasibility of generating high-order harmonics in the vacuum ultraviolet spectral range (with radiation wavelengths shorter than 120 nm) in plasmas with an efficiency of ~0.7 × 10-4. In carbon-containing plasma, the 7th harmonic intensity exceeded that of the 5th one by a factor of seven.

  10. Negative-permittivity plasma generation in negative-permeability space with high-energy metamaterials

    NASA Astrophysics Data System (ADS)

    Sakai, Osamu; Nakamura, Yoshihiro; Iwai, Akinori; Iio, Satoshi

    2016-10-01

    Plasma generation by electromagnetic waves in negative-permeability space is analyzed using experimental results and theoretical models. Installation of negative-permeability metamaterials triggers drastic changes to the propagation of electromagnetic waves. Unlike usual cases in which permeability is  +1, negative permeability induces evanescent modes in a space without plasma. However, if permittivity becomes negative due to high-electron-density or overdense plasma, electromagnetic waves can propagate because negative-refractive-index states emerge. In this study, reviewing our previous experimental data, we study the underlying physical processes in plasma generation in terms of wave propagation and parameters of wave media. We confirm nonlinear (transition) processes in the phase of density evolution up to the negative permittivity state and negative-refractive-index states in the quasi-steady phase. We also note that such energetic metamaterials are built up when we use plasma, unlike conventional metamaterials composed of solid-state materials.

  11. Turbulent jet flow generated downstream of a low temperature dielectric barrier atmospheric pressure plasma device.

    PubMed

    Whalley, Richard D; Walsh, James L

    2016-01-01

    Flowing low temperature atmospheric pressure plasma devices have been used in many technological applications ranging from energy efficient combustion through to wound healing and cancer therapy. The generation of the plasma causes a sudden onset of turbulence in the inhomogeneous axisymmetric jet flow downstream of the plasma plume. The mean turbulent velocity fields are shown to be self-similar and independent of the applied voltage used to generate the plasma. It is proposed that the production of turbulence is related to a combination of the small-amplitude plasma induced body forces and gas heating causing perturbations in the unstable shear layers at the jet exit which grow as they move downstream, creating turbulence. PMID:27561246

  12. Turbulent jet flow generated downstream of a low temperature dielectric barrier atmospheric pressure plasma device

    PubMed Central

    Whalley, Richard D.; Walsh, James L.

    2016-01-01

    Flowing low temperature atmospheric pressure plasma devices have been used in many technological applications ranging from energy efficient combustion through to wound healing and cancer therapy. The generation of the plasma causes a sudden onset of turbulence in the inhomogeneous axisymmetric jet flow downstream of the plasma plume. The mean turbulent velocity fields are shown to be self-similar and independent of the applied voltage used to generate the plasma. It is proposed that the production of turbulence is related to a combination of the small-amplitude plasma induced body forces and gas heating causing perturbations in the unstable shear layers at the jet exit which grow as they move downstream, creating turbulence. PMID:27561246

  13. Computer Model for Electrode Plasma Generation by Electron and Ion Flows

    NASA Astrophysics Data System (ADS)

    Ryzhov, Victor V.; Bespalov, Valeri I.; Kirikov, Alexander V.; Turchanovskii, Igor. Yu.; Tarakanov, Vladimir P.

    2002-12-01

    A model is proposed for computer simulation of the electrode plasma generation by electron and ion flows. The distribution of the absorbed energy of particles in the electrode material is calculated by the Monte-Carlo codes. This provides a possibility to control the electrode temperature by solving the heat conductivity equation for specified distributions of thermal sources and to calculate the rate of plasma generation. The behavior of the plasma in the gap can be modeled based on simple model where the velocity, the density, and the temperature of the plasma can be given by some dependence. Within the framework of the model proposed, numerical study is performed on the effect of the plasma flows in Rod Pinch Diodes and in the Insulator Stack of the Z-accelerator.

  14. Turbulent jet flow generated downstream of a low temperature dielectric barrier atmospheric pressure plasma device

    NASA Astrophysics Data System (ADS)

    Whalley, Richard D.; Walsh, James L.

    2016-08-01

    Flowing low temperature atmospheric pressure plasma devices have been used in many technological applications ranging from energy efficient combustion through to wound healing and cancer therapy. The generation of the plasma causes a sudden onset of turbulence in the inhomogeneous axisymmetric jet flow downstream of the plasma plume. The mean turbulent velocity fields are shown to be self-similar and independent of the applied voltage used to generate the plasma. It is proposed that the production of turbulence is related to a combination of the small-amplitude plasma induced body forces and gas heating causing perturbations in the unstable shear layers at the jet exit which grow as they move downstream, creating turbulence.

  15. In vitro pharmacological characterization of vorapaxar, a novel platelet thrombin receptor antagonist.

    PubMed

    Hawes, Brian E; Zhai, Ying; Hesk, David; Wirth, Mark; Wei, Huijun; Chintala, Madhu; Seiffert, Dietmar

    2015-09-01

    Vorapaxar is a novel protease-activated receptor-1 (PAR1) antagonist recently approved for the reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction or with peripheral arterial disease. The present study provides a comprehensive in vitro pharmacological characterization of vorapaxar interaction with the PAR1 receptor on human platelets. Similar studies were performed with a metabolite of vorapaxar (M20). Vorapaxar and M20 were competitive PAR1 antagonists that demonstrated concentration-dependent, saturable, specific, and slowly reversible binding to the receptor present on intact human platelets. The affinities of vorapaxar and M20 for the PAR1 receptor were in the low nanomolar range, as determined by saturation-, kinetic- and competitive binding studies. The calculated Kd and Ki values for vorapaxar increased in the presence of plasma, indicating a decrease in the free fraction available for binding to the PAR1 receptor on human platelets. Vorapaxar was also evaluated in functional assays using thrombin or a PAR1 agonist peptide (SFLLRN). Vorapaxar and M20 completely blocked thrombin-stimulated PAR1/β-arrestin association in recombinant cells and abolished thrombin-stimulated calcium influx in washed human platelets and vascular smooth muscle cells. Moreover, vorapaxar and M20 inhibited PAR1 agonist peptide-mediated platelet aggregation in human platelet rich plasma with a steep concentration response relationship. Vorapaxar exhibited high selectivity for inhibition of PAR1 over other platelet GPCRs. In conclusion, vorapaxar is a potent PAR1 antagonist exhibiting saturable, reversible, selective binding with slow off-rate kinetics and effectively inhibits thrombin's PAR1-mediated actions on human platelets. PMID:26022529

  16. Advanced properties of extended plasmas for efficient high-order harmonic generation

    SciTech Connect

    Ganeev, R. A.; Suzuki, M.; Kuroda, H.

    2014-05-15

    We demonstrate the advanced properties of extended plasma plumes (5 mm) for efficient harmonic generation of laser radiation compared with the short lengths of plasmas (∼0.3–0.5 mm) used in previous studies. The harmonic conversion efficiency quadratically increased with the growth of plasma length. The studies of this process along the whole extreme ultraviolet range using the long plasma jets produced on various metal surfaces, particularly including the resonance-enhanced laser frequency conversion and two-color pump, are presented. Such plasmas could be used for the quasi-phase matching experiments by proper modulation of the spatial characteristics of extended ablating area and formation of separated plasma jets.

  17. Generation of one-cycle laser pulses by use of high-amplitude plasma waves

    PubMed

    Sheng; Sentoku; Mima; Nishihara

    2000-11-01

    The dynamics of a short laser pulse located in the density trough of a background plasma wave is investigated and a scheme is proposed to compress the pulse duration by use of a high-amplitude plasma wave. The threshold amplitude of the plasma wave, at which the compressing effect just balances the dispersive spreading of the laser pulse, is estimated for certain pulse profiles. Numerical simulations are conducted with particle-in-cell codes, where a pump pulse is used to generate a high-amplitude plasma wave and a signal pulse copropagates behind. It is shown that the signal pulse can be compressed by the plasma wave from ten laser cycles to about one cycle within a millimeter in tenuous plasma only a few percent of the critical density.

  18. Helium generated cold plasma finely regulates activation of human fibroblast-like primary cells.

    PubMed

    Brun, Paola; Pathak, Surajit; Castagliuolo, Ignazio; Palù, Giorgio; Brun, Paola; Zuin, Matteo; Cavazzana, Roberto; Martines, Emilio

    2014-01-01

    Non-thermal atmospheric pressure plasmas are being developed for a wide range of health care applications, including wound healing. However in order to exploit the potential of plasma for clinical applications, the understanding of the mechanisms involved in plasma-induced activation of fibroblasts, the cells active in the healing process, is mandatory. In this study, the role of helium generated plasma in the tissue repairing process was investigated in cultured human fibroblast-like primary cells, and specifically in hepatic stellate cells and intestinal subepithelial myofibroblasts. Five minutes after treatment, plasma induced formation of reactive oxygen species (ROS) in cultured cells, as assessed by flow cytometric analysis of fluorescence-activated 2',7'-dichlorofluorescein diacetate probe. Plasma-induced intracellular ROS were characterized by lower concentrations and shorter half-lives with respect to hydrogen peroxide-induced ROS. Moreover ROS generated by plasma treatment increased the expression of peroxisome proliferator activated receptor (PPAR)-γ, nuclear receptor that modulates the inflammatory responses. Plasma exposure promoted wound healing in an in vitro model and induced fibroblast migration and proliferation, as demonstrated, respectively, by trans-well assay and partitioning between daughter cells of carboxyfluorescein diacetate succinimidyl ester fluorescent dye. Plasma-induced fibroblast migration and proliferation were found to be ROS-dependent as cellular incubation with antioxidant agents (e.g. N-acetyl L-cysteine) cancelled the biological effects. This study provides evidence that helium generated plasma promotes proliferation and migration in liver and intestinal fibroblast-like primary cells mainly by increasing intracellular ROS levels. Since plasma-evoked ROS are time-restricted and elicit the PPAR-γ anti-inflammatory molecular pathway, this strategy ensures precise regulation of human fibroblast activation and can be considered a

  19. Time Resolved Temperature Measurement of Hypervelocity Impact Generated Plasma Using a Global Optimization Method

    NASA Astrophysics Data System (ADS)

    Hew, Y. M.; Linscott, I.; Close, S.

    2015-12-01

    Meteoroids and orbital debris, collectively referred to as hypervelocity impactors, travel between 7 and 72 km/s in free space. Upon their impact onto the spacecraft, the energy conversion from kinetic to ionization/vaporization occurs within a very brief timescale and results in a small and dense expanding plasma with a very strong optical flash. The radio frequency (RF) emission produced by this plasma can potentially lead to electrical anomalies within the spacecraft. In addition, space weather, such as solar activity and background plasma, can establish spacecraft conditions which can exaggerate the damages done by these impacts. During the impact, a very strong impact flash will be generated. Through the studying of this emission spectrum of the impact, we hope to study the impact generated gas cloud/plasma properties. The impact flash emitted from a ground-based hypervelocity impact test is long expected by many scientists to contain the characteristics of the impact generated plasma, such as plasma temperature and density. This paper presents a method for the time-resolved plasma temperature estimation using three-color visible band photometry data with a global pattern search optimization method. The equilibrium temperature of the plasma can be estimated using an optical model which accounts for both the line emission and continuum emission from the plasma. Using a global pattern search based optimizer, the model can isolate the contribution of the continuum emission versus the line emission from the plasma. The plasma temperature can thus be estimated. Prior to the optimization step, a Gaussian process is also applied to extract the optical emission signal out of the noisy background. The resultant temperature and line-to-continuum emission weighting factor are consistent with the spectrum of the impactor material and current literature.

  20. Helium generated cold plasma finely regulates activation of human fibroblast-like primary cells.

    PubMed

    Brun, Paola; Pathak, Surajit; Castagliuolo, Ignazio; Palù, Giorgio; Brun, Paola; Zuin, Matteo; Cavazzana, Roberto; Martines, Emilio

    2014-01-01

    Non-thermal atmospheric pressure plasmas are being developed for a wide range of health care applications, including wound healing. However in order to exploit the potential of plasma for clinical applications, the understanding of the mechanisms involved in plasma-induced activation of fibroblasts, the cells active in the healing process, is mandatory. In this study, the role of helium generated plasma in the tissue repairing process was investigated in cultured human fibroblast-like primary cells, and specifically in hepatic stellate cells and intestinal subepithelial myofibroblasts. Five minutes after treatment, plasma induced formation of reactive oxygen species (ROS) in cultured cells, as assessed by flow cytometric analysis of fluorescence-activated 2',7'-dichlorofluorescein diacetate probe. Plasma-induced intracellular ROS were characterized by lower concentrations and shorter half-lives with respect to hydrogen peroxide-induced ROS. Moreover ROS generated by plasma treatment increased the expression of peroxisome proliferator activated receptor (PPAR)-γ, nuclear receptor that modulates the inflammatory responses. Plasma exposure promoted wound healing in an in vitro model and induced fibroblast migration and proliferation, as demonstrated, respectively, by trans-well assay and partitioning between daughter cells of carboxyfluorescein diacetate succinimidyl ester fluorescent dye. Plasma-induced fibroblast migration and proliferation were found to be ROS-dependent as cellular incubation with antioxidant agents (e.g. N-acetyl L-cysteine) cancelled the biological effects. This study provides evidence that helium generated plasma promotes proliferation and migration in liver and intestinal fibroblast-like primary cells mainly by increasing intracellular ROS levels. Since plasma-evoked ROS are time-restricted and elicit the PPAR-γ anti-inflammatory molecular pathway, this strategy ensures precise regulation of human fibroblast activation and can be considered a

  1. Measurements of electron energy distribution in tantalum laser-generated plasma

    SciTech Connect

    Torrisi, L.; Giuffrida, L.; Mascali, D.; Miracoli, R.; Gammino, S.; Gambino, N.; Margarone, D.

    2010-06-15

    The time and space resolved characterization of laser-generated pulsed plasmas is useful not only for the comprehension of basic phenomena involved in the plasma generation and following supersonic expansion, but it also permits to control the nonequilibrium process that is useful for many applications (e.g., ion implantation). The ''on-line'' characterization can be performed by means of Langmuir probes, ion collectors, and ion energy analyzers, in order to measure the plasma temperatures and densities of atoms, ions, and electrons. The investigated plasmas were generated by means of laser pulses with intensity of the order of 10{sup 9} W/cm{sup 2}. The contemporary characterization of the electron (through the Langmuir probe) and ion energy distribution functions, EEDF and IEDF, respectively, permits to correlate the ion properties, like charge states and temperatures, with the electron properties, like the shape of the EEDF at different times and distances from the ablated target surface.

  2. EFFECTS OF LASER RADIATION ON MATTER. LASER PLASMA: Low-threshold generation of harmonics and hard x radiation in a laser plasma. 2. Multipeak generation

    NASA Astrophysics Data System (ADS)

    Apollonov, V. V.; Derzhavin, S. I.; Kazakov, K. Kh

    1993-02-01

    The conditions for the generation of hard x radiation with a multipeak structure in a plasma pumped by a long pulse from a free-running CO2 laser at a low intensity (q≲10 GW/cm2) have been studied. This x-ray generation had been observed in a previous study by the present authors. It is shown that this generation of hard x radiation with a multipeak structure leads to a more than tenfold increase in the yield of hard x radiation per laser pulse, under optimum conditions. This increase results from the additional peaks in the x-ray signal. An explanation of this effect is proposed.

  3. Coordinate activation of human platelet protease-activated receptor-1 and -4 in response to subnanomolar alpha-thrombin.

    PubMed

    Ofosu, Frederick A; Dewar, Lori; Craven, Sharon J; Song, Yingqi; Cedrone, Aisha; Freedman, John; Fenton, John W

    2008-10-01

    We previously demonstrated that human platelets activated with SFLLRN release PAR-1 activation peptide, PAR-1-(1-41), even in the presence of hirudin. This observation suggests that during their activation, platelets generate a protease that activates PAR-1. In this study, PAR-1 and -4 activation peptides were detected 10 s after thrombin, 10 microm SFLLRN, or 100 microm AYPGKF were added to platelets. When SFLLRN or AYGPKF were added to platelets, generation of PAR-1 and -4 activation peptides was complete at 10 s. Generation of both PAR-1 and -4 activation peptides in response to 1 nm alpha-thrombin was significantly inhibited by affinity-purified anti-PAR-1-(35-62) IgY, anti-PAR-4-(34-54) IgY, and by the specific PAR-1 antagonist BMS 200261, but not by the PAR-4 antagonist YD3. Effective inhibition of platelet aggregation in response to 1.0 nm alpha-thrombin occurred only in the presence of both anti-PAR span antibodies. We conclude that platelet activation initiated with thrombin proceeds via simultaneous PAR-1 and -4 activation. Inhibiting the activation of either PAR inhibits activation of the other. Both PAR-1 and -4 activation must be inhibited to prevent platelet activation subsequent to thrombin binding to platelets. The more efficient generation of PAR activation peptides by platelets activated with SFLLRN or AYGPKF, compared with alpha-thrombin, indicates that a platelet-derived serine protease that is inactivated by soybean trypsin inhibitor propagates PAR-1 and -4 activation. PMID:18682394

  4. Electron beam generated whistler emissions in a laboratory plasma

    SciTech Connect

    Van Compernolle, B. Pribyl, P.; Gekelman, W.; An, X.; Bortnik, J.; Thorne, R. M.

    2015-12-10

    Naturally occurring whistler mode emissions in the magnetosphere, are important since they are responsible for the acceleration of outer radiation belt electrons to relativistic energies and also for the scattering loss of these electrons into the atmosphere. Recently, we reported on the first laboratory experiment where whistler waves exhibiting fast frequency chirping have been artificially produced [1]. A beam of energetic electrons is launched into a cold plasma and excites both chirping whistler waves and broadband waves. Here we extend our previous analysis by comparing the properties of the broadband waves with linear theory.

  5. Electron beam generated whistler emissions in a laboratory plasma

    NASA Astrophysics Data System (ADS)

    Van Compernolle, B.; An, X.; Bortnik, J.; Thorne, R. M.; Pribyl, P.; Gekelman, W.

    2015-12-01

    Naturally occurring whistler mode emissions in the magnetosphere, are important since they are responsible for the acceleration of outer radiation belt electrons to relativistic energies and also for the scattering loss of these electrons into the atmosphere. Recently, we reported on the first laboratory experiment where whistler waves exhibiting fast frequency chirping have been artificially produced [1]. A beam of energetic electrons is launched into a cold plasma and excites both chirping whistler waves and broadband waves. Here we extend our previous analysis by comparing the properties of the broadband waves with linear theory.

  6. Generation of dusty plasmas in supercritical carbon dioxide using surface dielectric barrier discharges

    NASA Astrophysics Data System (ADS)

    Matsubayashi, Yasuhito; Urabe, Keiichiro; Stauss, Sven; Terashima, Kazuo

    2015-11-01

    Dusty plasmas are a class of plasmas that not only have repercussions for many branches of plasma science and technology, but also thermodynamics and statistical mechanics. However, in ground-based experiments, gravity influences the dynamics and formation of plasma crystals, and the realization of zero-gravity dusty plasmas in space is very costly and time-consuming. To overcome some of these limitations, we propose dusty plasmas in supercritical fluids as a means for realizing ground-based experiments under pseudo-microgravity conditions, to study the formation and self-organization of plasma crystals. Dusty plasmas were realized by using surface dielectric barrier discharges (DBDs) generated in supercritical carbon dioxide (\\text{scC}{{\\text{O}}2} ), and the motion of fine particles above the electrode surface was studied by high-speed imaging. The plasmas deposited charge on the particles, and the particles formed a self-organized structure above the surface DBD reactor. The particle charge estimated from the analysis of particle motion was on the order of  -104 to -105 e C, and the estimation of the Coulomb coupling parameter of the charged particles with a value of 102 to 104 confirmed the formation of strongly coupled plasmas.

  7. 21 CFR 864.7875 - Thrombin time test.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Thrombin time test. 864.7875 Section 864.7875 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7875 Thrombin time test....

  8. 21 CFR 864.7875 - Thrombin time test.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Thrombin time test. 864.7875 Section 864.7875 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7875 Thrombin time test....

  9. 21 CFR 864.7875 - Thrombin time test.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Thrombin time test. 864.7875 Section 864.7875 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7875 Thrombin time test....

  10. 21 CFR 864.7875 - Thrombin time test.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Thrombin time test. 864.7875 Section 864.7875 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7875 Thrombin time test....

  11. 21 CFR 864.7875 - Thrombin time test.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Thrombin time test. 864.7875 Section 864.7875 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7875 Thrombin time test....

  12. Acidosis, magnesium and acetylsalicylic acid: Effects on thrombin

    NASA Astrophysics Data System (ADS)

    Borisevich, Nikolaj; Loznikova, Svetlana; Sukhodola, Aleksandr; Halets, Inessa; Bryszewska, Maria; Shcharbin, Dzmitry

    2013-03-01

    Thrombin, an enzyme from the hydrolase family, is the main component of the blood coagulation system. In ischemic stroke it acts as a serine protease that converts soluble fibrinogen into insoluble strands of fibrin forming blood clots in the brain. It has been found to phosphoresce at room temperature in the millisecond and microsecond ranges. The phosphorescence of thrombin was studied under physiological conditions, in acidosis (decrease of pH from 8.0 to 5.0) and on the addition of salts (magnesium sulfate and sodium chloride) and of acetylsalicylic acid, and its connection with thrombin function is discussed. Acidosis significantly increased the internal dynamics of thrombin. We propose that lactate-acidosis plays a protective role in stroke, preventing the formation of clots. The addition of NaCl and MgSO4 in different concentrations increased the internal dynamics of thrombin. Also, the addition of MgSO4 decreased thrombin-induced platelet aggregation. However, magnesium sulfate and acetylsalicylic acid in the therapeutic concentrations used for treatment of ischemic stroke had no effect on thrombin internal dynamics. The data obtained will help to elucidate the conformational stability of thrombin under conditions modulating lactate-acidosis and in the presence of magnesium sulfate.

  13. Acidosis, magnesium and acetylsalicylic acid: effects on thrombin.

    PubMed

    Borisevich, Nikolaj; Loznikova, Svetlana; Sukhodola, Aleksandr; Halets, Inessa; Bryszewska, Maria; Shcharbin, Dzmitry

    2013-03-01

    Thrombin, an enzyme from the hydrolase family, is the main component of the blood coagulation system. In ischemic stroke it acts as a serine protease that converts soluble fibrinogen into insoluble strands of fibrin forming blood clots in the brain. It has been found to phosphoresce at room temperature in the millisecond and microsecond ranges. The phosphorescence of thrombin was studied under physiological conditions, in acidosis (decrease of pH from 8.0 to 5.0) and on the addition of salts (magnesium sulfate and sodium chloride) and of acetylsalicylic acid, and its connection with thrombin function is discussed. Acidosis significantly increased the internal dynamics of thrombin. We propose that lactate-acidosis plays a protective role in stroke, preventing the formation of clots. The addition of NaCl and MgSO(4) in different concentrations increased the internal dynamics of thrombin. Also, the addition of MgSO(4) decreased thrombin-induced platelet aggregation. However, magnesium sulfate and acetylsalicylic acid in the therapeutic concentrations used for treatment of ischemic stroke had no effect on thrombin internal dynamics. The data obtained will help to elucidate the conformational stability of thrombin under conditions modulating lactate-acidosis and in the presence of magnesium sulfate.

  14. Role of thrombin signalling in platelets in haemostasis and thrombosis

    NASA Astrophysics Data System (ADS)

    Sambrano, Gilberto R.; Weiss, Ethan J.; Zheng, Yao-Wu; Huang, Wei; Coughlin, Shaun R.

    2001-09-01

    Platelets are critical in haemostasis and in arterial thrombosis, which causes heart attacks and other events triggered by abnormal clotting. The coagulation protease thrombin is a potent activator of platelets ex vivo. However, because thrombin also mediates fibrin deposition and because multiple agonists can trigger platelet activation, the relative importance of platelet activation by thrombin in haemostasis and thrombosis is unknown. Thrombin triggers cellular responses at least in part through protease-activated receptors (PARs). Mouse platelets express PAR3 and PAR4 (ref. 9). Here we show that platelets from PAR4-deficient mice failed to change shape, mobilize calcium, secrete ATP or aggregate in response to thrombin. This result demonstrates that PAR signalling is necessary for mouse platelet activation by thrombin and supports the model that mouse PAR3 (mPAR3) does not by itself mediate transmembrane signalling but instead acts as a cofactor for thrombin cleavage and activation of mPAR4 (ref. 10). Importantly, PAR4-deficient mice had markedly prolonged bleeding times and were protected in a model of arteriolar thrombosis. Thus platelet activation by thrombin is necessary for normal haemostasis and may be an important target in the treatment of thrombosis.

  15. Development of a plasma generator for a long pulse ion source for neutral beam injectors

    SciTech Connect

    Watanabe, K.; Dairaku, M.; Tobari, H.; Kashiwagi, M.; Inoue, T.; Hanada, M.; Jeong, S. H.; Chang, D. H.; Kim, T. S.; Kim, B. R.; Seo, C. S.; Jin, J. T.; Lee, K. W.; In, S. R.; Oh, B. H.; Kim, J.; Bae, Y. S.

    2011-06-15

    A plasma generator for a long pulse H{sup +}/D{sup +} ion source has been developed. The plasma generator was designed to produce 65 A H{sup +}/D{sup +} beams at an energy of 120 keV from an ion extraction area of 12 cm in width and 45 cm in length. Configuration of the plasma generator is a multi-cusp bucket type with SmCo permanent magnets. Dimension of a plasma chamber is 25 cm in width, 59 cm in length, and 32.5 cm in depth. The plasma generator was designed and fabricated at Japan Atomic Energy Agency. Source plasma generation and beam extraction tests for hydrogen coupling with an accelerator of the KSTAR ion source have been performed at the KSTAR neutral beam test stand under the agreement of Japan-Korea collaborative experiment. Spatial uniformity of the source plasma at the extraction region was measured using Langmuir probes and {+-}7% of the deviation from an averaged ion saturation current density was obtained. A long pulse test of the plasma generation up to 200 s with an arc discharge power of 70 kW has been successfully demonstrated. The arc discharge power satisfies the requirement of the beam production for the KSTAR NBI. A 70 keV, 41 A, 5 s hydrogen ion beam has been extracted with a high arc efficiency of 0.9 -1.1 A/kW at a beam extraction experiment. A deuteron yield of 77% was measured even at a low beam current density of 73 mA/cm{sup 2}.

  16. Development of a plasma generator for a long pulse ion source for neutral beam injectors.

    PubMed

    Watanabe, K; Dairaku, M; Tobari, H; Kashiwagi, M; Inoue, T; Hanada, M; Jeong, S H; Chang, D H; Kim, T S; Kim, B R; Seo, C S; Jin, J T; Lee, K W; In, S R; Oh, B H; Kim, J; Bae, Y S

    2011-06-01

    A plasma generator for a long pulse H(+)/D(+) ion source has been developed. The plasma generator was designed to produce 65 A H(+)/D(+) beams at an energy of 120 keV from an ion extraction area of 12 cm in width and 45 cm in length. Configuration of the plasma generator is a multi-cusp bucket type with SmCo permanent magnets. Dimension of a plasma chamber is 25 cm in width, 59 cm in length, and 32.5 cm in depth. The plasma generator was designed and fabricated at Japan Atomic Energy Agency. Source plasma generation and beam extraction tests for hydrogen coupling with an accelerator of the KSTAR ion source have been performed at the KSTAR neutral beam test stand under the agreement of Japan-Korea collaborative experiment. Spatial uniformity of the source plasma at the extraction region was measured using Langmuir probes and ±7% of the deviation from an averaged ion saturation current density was obtained. A long pulse test of the plasma generation up to 200 s with an arc discharge power of 70 kW has been successfully demonstrated. The arc discharge power satisfies the requirement of the beam production for the KSTAR NBI. A 70 keV, 41 A, 5 s hydrogen ion beam has been extracted with a high arc efficiency of 0.9 -1.1 A/kW at a beam extraction experiment. A deuteron yield of 77% was measured even at a low beam current density of 73 mA/cm(2).

  17. Evanescent wave fields at the plasma frequency in a microwave-generated hollow-cathode plasma

    NASA Astrophysics Data System (ADS)

    Hildebrandt, J.

    2006-08-01

    The different discharge regimes of the double-plate hollow-cathode are analysed with respect to the high plasmon levels, which are measured by the spectroscopic plasma-satellite method. The high-current glow discharge at start up creates a preplasma, which lets charging half-cycles start in an alternating order from both cathodes. They follow a cylindric boundary surrounding the central plasma cylinder, which exceeds the cut-off density, and thus constitute a self sustaining microwave oscillator. The ions from anodic space are radially attracted by the scattered Hertzian electrons and approach the central plasma, where they get neutralized upon penetrating the boundary, which is steadily displacing. Below the spiking threshold these ions of a high final radial velocity are responsible for the rapidly growing plasma core, whose expansion velocity has a strong cooling effect on the radial electron kinetic energy. Then a Lorentzian line shape indicating critical damping over a single oscillation is found for the near and the far satellites to the forbidden component of the helium I 447 nm line, corresponding to a field of up to 4 kV cm-1. The rotating wave approximation allows us to derive the exponential damping of the field envelope. The other solution of the rotating wave approximation is associated with the reflection of microwaves at the plasma boundary. Above the spiking threshold the production of wave fields around the plasma frequency in the central region is continued by the 4 ns current spikes. But the boundary conditions of high-current electron-neutral scattering require a spatially evanescent Green's function, therefore within both regions 2 mm adjacent to the cathode surfaces no plasma-satellites are then found.

  18. Planar Hall magnetoresistive aptasensor for thrombin detection.

    PubMed

    Sinha, B; Ramulu, T S; Kim, K W; Venu, R; Lee, J J; Kim, C G

    2014-09-15

    The use of aptamer-based assays is an emerging and attractive approach in disease research and clinical diagnostics. A sensitive aptamer-based sandwich-type sensor is presented to detect human thrombin using a planar Hall magnetoresistive (PHR) sensor in cooperation with superparamagnetic labels. A PHR sensor has the great advantages of a high signal-to-noise ratio, a small offset voltage and linear response in the low-field region, allowing it to act as a high-resolution biosensor. In the system presented here, the sensor has an active area of 50 µm × 50 µm with a 10-nm gold layer deposited onto the sensor surface prior to the binding of thiolated DNA primary aptamer. A polydimethylsiloxane well of 600-µm radius and 1-mm height was prepared around the sensor surface to maintain the same specific area and volume for each sensor. The sensor response was traced in real time upon the addition of streptavidin-functionalized magnetic labels on the sensor. A linear response to the thrombin concentration in the range of 86 pM-8.6 µM and a lower detection limit down to 86 pM was achieved by the proposed present method with a sample volume consumption of 2 µl. The proposed aptasensor has a strong potential for application in clinical diagnosis.

  19. The Transition of Prothrombin to Thrombin

    PubMed Central

    Krishnaswamy, Sriram

    2013-01-01

    Summary The proteolytic conversion of prothrombin to thrombin catalysed by prothrombinase is one of the more extensively studied reactions of blood coagulation. Sophisticated biophysical and biochemical insights into the players of this reaction were developed in the early days of the field. Yet, many basic enzymological questions remained unanswered. I summarise new developments that uncover mechanisms by which high substrate specificity is achieved, and the impact of these strategies on enzymic function. Two principles emerge that deviate from conventional wisdom that has otherwise dominated thinking in the field. 1) Enzymic specificity is dominated by the contribution of exosite binding interactions between substrate and enzyme rather than by specific recognition of sequences flanking the scissile bond. Coupled with the regulation of substrate conformation as a result of the zymogen to proteinase transition, novel mechanistic insights result for numerous aspects of enzyme function. 2) The transition of zymogen to proteinase following cleavage is not absolute and instead, thrombin can reversibly interconvert between zymogen-like and proteinase-like forms depending on the complement of ligands bound to it. This establishes new paradigms for considering proteinase allostery and how enzyme function may be modulated by ligand binding. These insights into the action of prothrombinase on prothrombin have wide-ranging implications for the understanding of function in blood coagulation. PMID:23809130

  20. Plasma generation near an Ion thruster disharge chamber hollow cathode

    NASA Technical Reports Server (NTRS)

    Katz, Ira; Anderson, John R.; Goebel, Dan M.; Wirz, Richard; Sengupta, Anita

    2003-01-01

    In gridded electrostatic thrusters, ions are produced by electron bombardment in the discharge chamber. In most of these thrusters, a single, centrally located hollow cathode supplies the ionizing electrons. An applied magnetic field in the discharge chamber restricts the electrons leaving the hollow cathode to a very narrow channel. In this channel, the high electron current density ionizes both propellant gas flowing from the hollow cathode, and other neutrals from the main propellant flow from the plenum. The processes that occur just past the hollow cathode exit are very important. In recent engine tests, several cases of discharge cathode orifice place and keeper erosion have been reported. In this paper we present results from a new 1-D, variable area model of the plasma processes in the magnetized channel just downstream of the hollow cathode keeper. The model predicts plasma densities, and temperatures consistent with those reported in the literature for the NSTAR engine, and preliminary results from the model show a potential maximum just downstream of the cathode.

  1. Negative ion beam generation in laser plasma interactions

    NASA Astrophysics Data System (ADS)

    Jequier, Sophie; Tikhonchuk, Vladimir; Ter-Avetisyan, Sargis

    2013-10-01

    Detection of a large number of energetic negative ions and neutral atoms have been reported in recent intense laser plasma interaction experiments. These particles were produced from fast positive ions (proton, carbon, oxygen) accelerated from a laser produced plasma when they were passing through a cold spray of water or ethanol. The negative ions formation is strongly related to the fast positive ions, and it is explained by a process of a single electron capture - loss. Double charge exchange, elastic scattering and energy loss phenomena have been neglected since their cross sections are much smaller. Assuming independent atoms approximation, we study populations evolution through the interaction zone analytically and numerically by solving the rate equations using cross sections drawn from literature. Taking into account the energy distribution of the incident ions, the calculations give the final energy distribution for the different species that can be compared to experimental spectra. First results obtained for hydrogen in the water case indicate that this model can explain the main observed features. The results concerning the carbon and oxygen ions will be also presented as well as refinement of the cross sections since some cross sections are missing for these energies.

  2. Collimated fast electron beam generation in critical density plasma

    SciTech Connect

    Iwawaki, T. Habara, H.; Morita, K.; Tanaka, K. A.; Baton, S.; Fuchs, J.; Chen, S.; Nakatsutsumi, M.; Rousseaux, C.; Filippi, F.; Nazarov, W.

    2014-11-15

    Significantly collimated fast electron beam with a divergence angle 10° (FWHM) is observed when an ultra-intense laser pulse (I = 10{sup 14 }W/cm{sup 2}, 300 fs) irradiates a uniform critical density plasma. The uniform plasma is created through the ionization of an ultra-low density (5 mg/c.c.) plastic foam by X-ray burst from the interaction of intense laser (I = 10{sup 14 }W/cm{sup 2}, 600 ps) with a thin Cu foil. 2D Particle-In-Cell (PIC) simulation well reproduces the collimated electron beam with a strong magnetic field in the region of the laser pulse propagation. To understand the physical mechanism of the collimation, we calculate energetic electron motion in the magnetic field obtained from the 2D PIC simulation. As the results, the strong magnetic field (300 MG) collimates electrons with energy over a few MeV. This collimation mechanism may attract attention in many applications such as electron acceleration, electron microscope and fast ignition of laser fusion.

  3. Research progress on ionic plasmas generated in an intense hydrogen negative ion source

    SciTech Connect

    Takeiri, Y. Tsumori, K.; Nagaoka, K.; Kaneko, O.; Ikeda, K.; Nakano, H.; Kisaki, M.; Tokuzawa, T.; Osakabe, M.; Kondo, T.; Sato, M.; Shibuya, M.; Komada, S.; Sekiguchi, H.; Geng, S.

    2015-04-08

    Characteristics of ionic plasmas, observed in a high-density hydrogen negative ion source, are investigated with a multi-diagnostics system. The ionic plasma, which consists of hydrogen positive- and negative-ions with a significantly low-density of electrons, is generated in the ion extraction region, from which the negative ions are extracted through the plasma grid. The negative ion density, i.e., the ionic plasma density, as high as the order of 1×10{sup 17}m{sup −3}, is measured with cavity ring-down spectroscopy, while the electron density is lower than 1×10{sup 16}m{sup −3}, which is confirmed with millimeter-wave interferometer. Reduction of the negative ion density is observed at the negative ion extraction, and at that time the electron flow into the ionic plasma region is observed to conserve the charge neutrality. Distribution of the plasma potential is measured in the extraction region in the direction normal to the plasma grid surface with a Langmuir probe, and the results suggest that the sheath is formed at the plasma boundary to the plasma grid to which the bias voltage is applied. The beam extraction should drive the negative ion transport in the ionic plasma across the sheath formed on the extraction surface. Larger reduction of the negative ions at the beam extraction is observed in a region above the extraction aperture on the plasma grid, which is confirmed with 2D image measurement of the Hα emission and cavity ring-down spectroscopy. The electron distribution is also measured near the plasma grid surface. These various properties observed in the ionic plasma are discussed.

  4. Resistive wall tearing mode generated finite net electromagnetic torque in a static plasma

    SciTech Connect

    Hao, G. Z. Wang, A. K.; Xu, M.; Qu, H. P.; Peng, X. D.; Wang, Z. H.; Xu, J. Q.; Qiu, X. M.; Liu, Y. Q.

    2014-01-15

    The MARS-F code [Y. Q. Liu et al., Phys. Plasmas 7, 3681 (2000)] is applied to numerically investigate the effect of the plasma pressure on the tearing mode stability as well as the tearing mode-induced electromagnetic torque, in the presence of a resistive wall. The tearing mode with a complex eigenvalue, resulted from the favorable averaged curvature effect [A. H. Glasser et al., Phys. Fluids 18, 875 (1975)], leads to a re-distribution of the electromagnetic torque with multiple peaking in the immediate vicinity of the resistive layer. The multiple peaking is often caused by the sound wave resonances. In the presence of a resistive wall surrounding the plasma, a rotating tearing mode can generate a finite net electromagnetic torque acting on the static plasma column. Meanwhile, an equal but opposite torque is generated in the resistive wall, thus conserving the total momentum of the whole plasma-wall system. The direction of the net torque on the plasma is always opposite to the real frequency of the mode, agreeing with the analytic result by Pustovitov [Nucl. Fusion 47, 1583 (2007)]. When the wall time is close to the oscillating time of the tearing mode, the finite net torque reaches its maximum. Without wall or with an ideal wall, no net torque on the static plasma is generated by the tearing mode. However, re-distribution of the torque density in the resistive layer still occurs.

  5. Resistive wall tearing mode generated finite net electromagnetic torque in a static plasma

    NASA Astrophysics Data System (ADS)

    Hao, G. Z.; Liu, Y. Q.; Wang, A. K.; Xu, M.; Qu, H. P.; Peng, X. D.; Wang, Z. H.; Xu, J. Q.; Qiu, X. M.

    2014-01-01

    The MARS-F code [Y. Q. Liu et al., Phys. Plasmas 7, 3681 (2000)] is applied to numerically investigate the effect of the plasma pressure on the tearing mode stability as well as the tearing mode-induced electromagnetic torque, in the presence of a resistive wall. The tearing mode with a complex eigenvalue, resulted from the favorable averaged curvature effect [A. H. Glasser et al., Phys. Fluids 18, 875 (1975)], leads to a re-distribution of the electromagnetic torque with multiple peaking in the immediate vicinity of the resistive layer. The multiple peaking is often caused by the sound wave resonances. In the presence of a resistive wall surrounding the plasma, a rotating tearing mode can generate a finite net electromagnetic torque acting on the static plasma column. Meanwhile, an equal but opposite torque is generated in the resistive wall, thus conserving the total momentum of the whole plasma-wall system. The direction of the net torque on the plasma is always opposite to the real frequency of the mode, agreeing with the analytic result by Pustovitov [Nucl. Fusion 47, 1583 (2007)]. When the wall time is close to the oscillating time of the tearing mode, the finite net torque reaches its maximum. Without wall or with an ideal wall, no net torque on the static plasma is generated by the tearing mode. However, re-distribution of the torque density in the resistive layer still occurs.

  6. Generation of Shock-Wave Disturbances at Plasma-Vapor Bubble Oscillation

    NASA Astrophysics Data System (ADS)

    Kuznetsova, N. S.; Yudin, A. S.; Voitenko, N. V.

    2015-11-01

    The complex physical and mathematical model describing all steps of plasma-vapor bubble evolution in the system of the water-ground condensed media is presented. Discharge circuit operation, discharge plasma channel expansion, its transformation into the vapor-plasma bubble and its pulsation, pressure wave generation and propagation of the mechanical stress waves in the ground are self-consistently considered in the model. The model allows investigation of the basic laws of stored energy transformation into the discharge plasma channel, next to the plasma-vapor bubble and transformation of this energy to the energy of pressure wave compressing the surrounding ground. Power characteristics of wave disturbances generated by gas-vapor bubble oscillation in liquid depending on the circuit parameters are analyzed for the prediction of the ground boundary displacement. The dynamics of the shock-wave propagation in water-ground condensed media depending on the rate of the plasma channel energy release is investigated. Simulation of the shock-wave phenomena at a plasma-vapor bubble oscillation in condensed media consecutively describes the physical processes underlying technology for producing piles by electro-discharge stuffing. The quantitative model verified by physical experimental tests will allow optimization of pulse generator parameters and electrode system construction of high-voltage equipment.

  7. Fast camera studies at an electron cyclotron resonance table plasma generator

    SciTech Connect

    Rácz, R.; Biri, S.

    2014-02-15

    A simple table-size ECR plasma generator operates in the ATOMKI without axial magnetic trap and without any particle extraction tool. Radial plasma confinement is ensured by a NdFeB hexapole. The table-top ECR is a simplified version of the 14 GHz ATOMKI-ECRIS. Plasma diagnostics experiments are planned to be performed at this device before installing the measurement setting at the “big” ECRIS. Recently, the plasma generator has been operated in pulsed RF mode in order to investigate the time evolution of the ECR plasma in two different ways. (1) The visible light radiation emitted by the plasma was investigated by the frames of a fast camera images with 1 ms temporal resolution. Since the visible light photographs are in strong correlation with the two-dimensional spatial distribution of the cold electron components of the plasma it can be important to understand better the transient processes just after the breakdown and just after the glow. (2) The time-resolved ion current on a specially shaped electrode was measured simultaneously in order to compare it with the visible light photographs. The response of the plasma was detected by changing some external setting parameters (gas pressure and microwave power) and was described in this paper.

  8. Fast camera studies at an electron cyclotron resonance table plasma generator.

    PubMed

    Rácz, R; Biri, S; Hajdu, P; Pálinkás, J

    2014-02-01

    A simple table-size ECR plasma generator operates in the ATOMKI without axial magnetic trap and without any particle extraction tool. Radial plasma confinement is ensured by a NdFeB hexapole. The table-top ECR is a simplified version of the 14 GHz ATOMKI-ECRIS. Plasma diagnostics experiments are planned to be performed at this device before installing the measurement setting at the "big" ECRIS. Recently, the plasma generator has been operated in pulsed RF mode in order to investigate the time evolution of the ECR plasma in two different ways. (1) The visible light radiation emitted by the plasma was investigated by the frames of a fast camera images with 1 ms temporal resolution. Since the visible light photographs are in strong correlation with the two-dimensional spatial distribution of the cold electron components of the plasma it can be important to understand better the transient processes just after the breakdown and just after the glow. (2) The time-resolved ion current on a specially shaped electrode was measured simultaneously in order to compare it with the visible light photographs. The response of the plasma was detected by changing some external setting parameters (gas pressure and microwave power) and was described in this paper.

  9. Intense terahertz-pulse generation by four-wave mixing process in induced gas plasma

    NASA Astrophysics Data System (ADS)

    Wicharn, S.; Buranasiri, P.

    2015-08-01

    In this article, we have numerically investigated an intense terahertz (THz) pulses generation in gaseous plasma based on the third-order nonlinear effect, four-wave mixing rectification (FWMR). We have proposed that the fundamental fields and second-harmonic field of ultra-short pulse lasers are combined and focused into a very small gas chamber to induce a gaseous plasma, which intense THz pulse is produced. To understand the THz generation process, the first-order multiple-scale perturbation method (MSPM) has been utilized to derive a set of nonlinear coupled-mode equations for interacting fields such as two fundamental fields, a second-harmonic field, and a THz field. Then, we have simulate the intense THz-pulse generation by using split step-beam propagation method (SS-BPM) and calculated output THz intensities. Finally, the output THz intensities generated from induced air, nitrogen, and argon plasma have been compared.

  10. Optical emission spectroscopy of the Linac4 and superconducting proton Linac plasma generators

    SciTech Connect

    Lettry, J.; Kronberger, M.; Mahner, E.; Schmitzer, C.; Sanchez, J.; Scrivens, R.; Midttun, O.; O'Neil, M.; Pereira, H.; Paoluzzi, M.; Fantz, U.; Wuenderlich, D.; Kalvas, T.; Koivisto, H.; Komppula, J.; Myllyperkioe, P.; Tarvainen, O.

    2012-02-15

    CERN's superconducting proton Linac (SPL) study investigates a 50 Hz high-energy, high-power Linac for H{sup -} ions. The SPL plasma generator is an evolution of the DESY ion source plasma generator currently operated at CERN's Linac4 test stand. The plasma generator is a step towards a particle source for the SPL, it is designed to handle 100 kW peak RF-power at a 6% duty factor. While the acquisition of an integrated hydrogen plasma optical spectrum is straightforward, the measurement of a time-resolved spectrum requires dedicated amplification schemes. The experimental setup for visible light based on photomultipliers and narrow bandwidth filters and the UV spectrometer setup are described. The H{sub {alpha}}, H{sub {beta}}, and H{sub {gamma}} Balmer line intensities, the Lyman band and alpha transition were measured. A parametric study of the optical emission from the Linac4 ion source and the SPL plasma generator as a function of RF-power and gas pressure is presented. The potential of optical emission spectrometry coupled to RF-power coupling measurements for on-line monitoring of short RF heated hydrogen plasma pulses is discussed.

  11. Microcathode Sustained Discharges for the generation of DC, non-thermal plasmas at high gas pressure

    NASA Astrophysics Data System (ADS)

    Pitchford, Leanne

    2007-10-01

    It is now well known that non-thermal DC plasmas can be generated and maintained in high pressure gases in small - hundreds of micron-sized - geometries. One such configuration, a MicroHollow Cathode Discharge (MHCD), orginally investigated by Schoenbach and colleagues (KH Schoenbach, et al, Plasma Sources Sci. Technol. 6, 468 (1997)), consists of a metal/dielectric/metal sandwich through through which a central hole is pierced. The diameter of the hole and the thickness of the sandwich are each some 100's of microns. Larger volume plasmas can be generated by placing a third, positively biased electrode some distance (1 cm) away, in which case the MHCD can act as a plasma cathode. This configuration is called a MicroCathode Sustained Discharge or MCSD (RH Stark and KH Schoenbach J. Appl. Phys. 85 2075 (1999)). This talk will focus on the properties of the MCSD - its initiation and its electrical properties - and on the properties of the plasma generated in the MCSD volume. Experimental and numerical results for discharges in rare gases and in rare gas/oxygen mixtures at pressures up to atmospheric will be used to illustrate that the plasma generated in the MCSD is similar to a positive column plasma, with a low electric field and low to moderate gas temperature. The plasma conditions in the MCSD are suitable for the generation of large densities of radical species, such as oxygen molecules in the singlet delta metastable state (G. Bauville, et al, Appl. Phys. Lett. 90, 031501 (2007)).

  12. Plasma characterization of the superconducting proton linear accelerator plasma generator using a 2 MHz compensated Langmuir probe.

    PubMed

    Schmitzer, C; Kronberger, M; Lettry, J; Sanchez-Arias, J; Störi, H

    2012-02-01

    The CERN study for a superconducting proton Linac (SPL) investigates the design of a pulsed 5 GeV Linac operating at 50 Hz. As a first step towards a future SPL H(-) volume ion source, a plasma generator capable of operating at Linac4 or nominal SPL settings has been developed and operated at a dedicated test stand. The hydrogen plasma is heated by an inductively coupled RF discharge e(-) and ions are confined by a magnetic multipole cusp field similar to the currently commissioned Linac4 H(-) ion source. Time-resolved measurements of the plasma potential, temperature, and electron energy distribution function obtained by means of a RF compensated Langmuir probe along the axis of the plasma generator are presented. The influence of the main tuning parameters, such as RF power and frequency and the timing scheme is discussed with the aim to correlate them to optimum H(-) ion beam parameters measured on an ion source test stand. The effects of hydrogen injection settings which allow operation at 50 Hz repetition rate are discussed. PMID:22380224

  13. Plasma characterization of the superconducting proton linear accelerator plasma generator using a 2 MHz compensated Langmuir probe

    SciTech Connect

    Schmitzer, C.; Kronberger, M.; Lettry, J.; Sanchez-Arias, J.; Stoeri, H.

    2012-02-15

    The CERN study for a superconducting proton Linac (SPL) investigates the design of a pulsed 5 GeV Linac operating at 50 Hz. As a first step towards a future SPL H{sup -} volume ion source, a plasma generator capable of operating at Linac4 or nominal SPL settings has been developed and operated at a dedicated test stand. The hydrogen plasma is heated by an inductively coupled RF discharge e{sup -} and ions are confined by a magnetic multipole cusp field similar to the currently commissioned Linac4 H{sup -} ion source. Time-resolved measurements of the plasma potential, temperature, and electron energy distribution function obtained by means of a RF compensated Langmuir probe along the axis of the plasma generator are presented. The influence of the main tuning parameters, such as RF power and frequency and the timing scheme is discussed with the aim to correlate them to optimum H{sup -} ion beam parameters measured on an ion source test stand. The effects of hydrogen injection settings which allow operation at 50 Hz repetition rate are discussed.

  14. Plasma characterization of the superconducting proton linear accelerator plasma generator using a 2 MHz compensated Langmuir probe.

    PubMed

    Schmitzer, C; Kronberger, M; Lettry, J; Sanchez-Arias, J; Störi, H

    2012-02-01

    The CERN study for a superconducting proton Linac (SPL) investigates the design of a pulsed 5 GeV Linac operating at 50 Hz. As a first step towards a future SPL H(-) volume ion source, a plasma generator capable of operating at Linac4 or nominal SPL settings has been developed and operated at a dedicated test stand. The hydrogen plasma is heated by an inductively coupled RF discharge e(-) and ions are confined by a magnetic multipole cusp field similar to the currently commissioned Linac4 H(-) ion source. Time-resolved measurements of the plasma potential, temperature, and electron energy distribution function obtained by means of a RF compensated Langmuir probe along the axis of the plasma generator are presented. The influence of the main tuning parameters, such as RF power and frequency and the timing scheme is discussed with the aim to correlate them to optimum H(-) ion beam parameters measured on an ion source test stand. The effects of hydrogen injection settings which allow operation at 50 Hz repetition rate are discussed.

  15. Monitoring of dabigatran therapy using Hemoclot(®) Thrombin Inhibitor assay in patients with atrial fibrillation.

    PubMed

    Samoš, Matej; Stančiaková, Lucia; Ivanková, Jela; Staško, Ján; Kovář, František; Dobrotová, Miroslava; Galajda, Peter; Kubisz, Peter; Mokáň, Marián

    2015-01-01

    Dabigatran, a new direct thrombin inhibitor, achieves strong anticoagulation that is more predictable than warfarin. Nevertheless, a patient on dabigatran therapy (DT) may suffer from thrombotic or bleeding events. The routine monitoring of DT is not recommended, and standard coagulation tests are not sensitive enough for the assessment of DT activity. The aim of this study was to examine the clinical usefulness of the Hemoclot(®) Thrombin Inhibitor (HTI) assay in the assessment of dabigatran plasma levels in patients with non-valvular AF. Nineteen patients (12 men, 7 women) on DT were included in this preliminary prospective observational study. Dabigatran was administrated twice daily in a two dose regimens: 150 mg (5 patients) and 110 mg (14 patients). Blood samples were taken for the assessment of trough and peak levels of dabigatran. Dabigatran concentrations were measured with the HTI assay. The average dabigatran trough level was 69.3 ± 55.5 ng/ml and the average dabigatran peak level was 112.7 ± 66.6 ng/ml. The dabigatran trough plasma concentration was in the established reference range in 15 patients and the dabigatran peak plasma concentration was in the established reference range in 9 patients, respectively. Despite the fact that the activated partial thromboplastin and thrombin times were generally changed (prolonged), these tests failed to identify the patients with too low or too high dabigatran concentrations. The study confirmed the high sensitivity of the HTI assay for the assessment of dabigatran plasma levels. When compared to standard coagulation tests, the HTI is a more suitable assay for the monitoring of patients treated with dabigatran. Monitoring of DT may be beneficial in selected patients; however, further studies will be needed for the final clarification of this issue. PMID:25103614

  16. Trapping of electrons in troughs of self generated electromagnetic standing waves in a bounded plasma column

    SciTech Connect

    Bhattacharjee, Sudeep; Sahu, Debaprasad; Pandey, Shail; Chatterjee, Sanghomitro; Dey, Indranuj; Roy Chowdhury, Krishanu

    2014-01-15

    Observations and measurements are reported on electron trapping in troughs of self-generated electromagnetic standing waves in a bounded plasma column confined in a minimum-B field. The boundaries are smaller than the free space wavelength of the waves. Earlier work of researchers primarily focused upon electron localization effects induced by purely electrostatic perturbation. We demonstrate the possibility in the presence of electromagnetic standing waves generated in the bounded plasma column. The electron trapping is verified with electrostatic measurements of the plasma floating potential, electromagnetic measurements of the wave field profile, and optical intensity measurements of Argon ionic line at 488 nm. The experimental results show a reasonably good agreement with predictions of a Monte Carlo simulation code that takes into account all kinematical and dynamical effects in the plasma in the presence of bounded waves and external fields.

  17. Characteristics of the NASA Lewis bumpy-torus plasma generated with positive applied potentials

    NASA Technical Reports Server (NTRS)

    Roth, J. R.; Gerdin, G. A.; Richardson, R. W.

    1976-01-01

    Experimental observations were made during steady-state operation of a bumpy-torus plasma at input powers up to 150 kW in deuterium and helium gas and with positive potentials applied to the midplane electrodes. In this steady-state ion heating method a modified Penning discharge is operated such that the plasma is acted upon by a combination of strong electric and magnetic fields. Experimental investigation of a deuterium plasma revealed electron temperatures from 14 to 140 eV and ion kinetic temperatures from 160 to 1785 eV. At least two distinct modes of operation exist. Experimental data shows that the average ion residence time in the plasma is virtually independent of the magnetic field strength. Data was taken when all 12 anode rings were at high voltage, and in other symmetric configurations in which the toroidal plasma was generated by applying positive potentials to six anode rings, three anode rings, and a single anode ring.

  18. Generation of two-column helicon plasma on KAIST-TOKAMAK

    NASA Astrophysics Data System (ADS)

    Jeon, S. J.; Huh, S. W.; Kim, J.; Lee, T. S.; Moon, S. Y.; Choe, W.; Choi, D. I.

    2000-10-01

    Industrial plasma application studies reveal that helicon waves provide high ionization rate even at modest rf input power. This suggests that helicon waves be effectively used for plasma pre-ionization/startup, and plasma heating in a tokamak. The two-column helicon plasma was produced with a Nagoya type ¥2 antenna which was modified for toroidal geometry of KAIST-TOKAMAK. The observed two columns locate at the same major radius and they move outward as toroidal magnetic field increases. In addition to the 2D image captured by a CCD camera, an 8-channel Langmuir probe array is used to measure the density profile. Parallel wave number is measured by magnetic pickup probes and a phase detector in order to study wave generation and propagation inside the plasma.

  19. The membrane potential modulates thrombin-stimulated Ca²⁺ mobilization and platelet aggregation.

    PubMed

    Albarrán, Letizia; Dionisio, Natalia; López, Esther; Salido, Ginés M; Rosado, Juan A

    2013-10-15

    G protein-coupled receptors can be directly modulated by changes in transmembrane voltage in a variety of cell types. Here we show that, while changes in the membrane voltage itself do not induce detectable modifications in the cytosolic Ca(2+) concentration, platelet stimulation with thrombin or the PAR-1 and PAR-4 agonist peptides SFLLRN and AYPGKF, respectively, results in Ca(2+) release from intracellular stores that is sensitive to the membrane depolarisation. Direct activation of G proteins or phospholipase C by AlF4(-) and m-3M3FBS, respectively, leads to Ca(2+) release that is insensitive to changes in the membrane potential. Thapsigargin-, as well as OAG-induced Ca(2+) entry are affected by the membrane voltage, probably as a result of the modification in the driving force for Ca(2+) influx; however, hyperpolarisation does not enhance thrombin- or OAG-evoked Ca(2+) entry probably revealing the presence of a voltage-sensitive regulatory mechanism. Transmembrane voltage also modulates the activity of the plasma membrane Ca(2+)-ATPase (PMCA) most likely due to a decrease in the phosphotyrosine content of the pump. Thrombin-stimulated platelet aggregation is modulated by membrane depolarisation by a mechanism that is, at least partially, independent of Ca(2+). These observations indicate that PAR-1 and PAR-4 receptors are modulated by the membrane voltage in human platelets. PMID:23988350

  20. Label-free impedimetric biosensor for thrombin using the thrombin-binding aptamer as receptor

    NASA Astrophysics Data System (ADS)

    Frense, D.; Kang, S.; Schieke, K.; Reich, P.; Barthel, A.; Pliquett, U.; Nacke, T.; Brian, C.; Beckmann, D.

    2013-04-01

    This study presents the further establishment of impedimetric biosensors with aptamers as receptors. Aptamers are short single-stranded oligonucleotides which bind analytes with a specific region of their 3D structure. Electrical impedance spectroscopy is a sensitive method for analyzing changes on the electrode surface, e.g. caused by receptor-ligand-interactions. Fast and inexpensive prototyping of electrodes on the basis of commercially available compact discs having a 24 carat gold reflective layer was investigated. Electrode structures (CDtrodes [1]) in the range from few millimetres down to 100 microns were realized. The well-studied thrombin-binding aptamer (TBA) was used as receptor for characterizing these micro- and macro-electrodes. The impedance signal showed a linear correlation for concentrations of thrombin between 1.0 nM to 100 nM. This range corresponds well with most of the references and may be useful for the point-of-care testing (POCT).

  1. Improvement of the lifetime of radio frequency antenna for plasma generation

    SciTech Connect

    Reijonen, J.; Eardley, M.; Gough, R.; Keller, R.; Leung, K.; Thomae, R.; Pickard, D.; Williams, M. D.

    2000-02-01

    At Lawrence Berkeley National Laboratory different antenna protection schemes have been investigated for the radio frequency-driven multicusp ion source. It was found that the antenna lifetime can be greatly enhanced by an additional shielding, which consists of porcelain, quartz or boron nitride. Different antenna configurations and their influence on the plasma generation will be discussed. Antenna life time greater than 500 hours continuous wave operation has been demonstrated in hydrogen plasma using a novel quartz antenna design. (c)

  2. Modelling Of Generation And Growth Of Nanoparticles In Low-Pressure Plasmas

    SciTech Connect

    Gordiets, B. F.

    2008-09-07

    Theoretical kinetic models of generation and growth of clusters and nanoparticles in low-pressure plasma are briefly rewired. The relatively simple kinetic model is discussed more detail. Simple formulas and equations are given for monomer density; cluster dimension distribution; critical cluster dimension; rate of particle production; particle density and average dimension as well as plasma characteristics. The analytical formula is also obtained for the time delay of the measured LIPEE signal in the 'Laser Induced Particle Explosive Evaporation' experimental method.

  3. Thrombin induces long-term potentiation of reactivity to afferent stimulation and facilitates epileptic seizures in rat hippocampal slices: toward understanding the functional consequences of cerebrovascular insults.

    PubMed

    Maggio, Nicola; Shavit, Efrat; Chapman, Joab; Segal, Menahem

    2008-01-16

    The effects of thrombin, a blood coagulation serine protease, were studied in rat hippocampal slices, in an attempt to comprehend its devastating effects when released into the brain after stroke and head trauma. Thrombin acting through its receptor, protease-activated receptor 1 (PAR1), produced a long-lasting enhancement of the reactivity of CA1 neurons to afferent stimulation, an effect that saturated the ability of the tissue to undergo tetanus-induced long-term potentiation. This effect was mediated by activation of a PAR1 receptor, because it was shared by a PAR1 agonist, and was blocked by its selective antagonist. An independent effect of thrombin involved the lowering of the threshold for generating epileptic seizures in CA3 region of the hippocampus. Thus, the experiments in a slice mimicked epileptic and cognitive dysfunction induced by thrombin in the brain, and suggest that these effects are mediated by activation of the PAR1 receptor. PMID:18199772

  4. Characteristic measurements of silicon dioxide aerogel plasmas generated in a Planckian radiation environment

    SciTech Connect

    Dong Quanli; Wang Shoujun; Li Yutong; Zhang Yi; Zhao Jing; Wei Huigang; Shi Jianrong; Zhao Gang; Zhang Jiyan; Gu Yuqiu; Ding Yongkun; Wen Tianshu; Zhang Wenhai; Hu Xin; Liu Shenye; Zhang Lin; Tang Yongjian; Zhang Baohan; Zheng Zhijian; Nishimura, Hiroaki

    2010-01-15

    The temporally and spatially resolved characteristics of silicon dioxide aerogel plasmas were studied using x-ray spectroscopy. The plasma was generated in the near-Planckian radiation environment within gold hohlraum targets irradiated by laser pulses with a total energy of 2.4 kJ in 1 ns. The contributions of silicon ions at different charge states to the specific components of the measured absorption spectra were also investigated. It was found that each main feature in the absorption spectra of the measured silicon dioxide aerogel plasmas was contributed by two neighboring silicon ionic species.

  5. Generating vorticity and magnetic fields in plasmas in general relativity: Spacetime curvature drive

    NASA Astrophysics Data System (ADS)

    Asenjo, Felipe A.; Mahajan, Swadesh M.; Qadir, Asghar

    2013-02-01

    Using the generally covariant magnetofluid formalism for a hot plasma, a spacetime curvature driven mechanism for generating seed vorticity/magnetic field is presented. The "battery" owes its origin to the interaction between the gravity modified Lorentz factor of the fluid element and the inhomogeneous plasma thermodynamics. The general relativistic drive is evaluated for two simple cases: seed formation in a simplified model of a hot plasma accreting in stable orbits around a Schwarzschild black hole and for particles in free fall near the horizon. Some astrophysical applications are suggested.

  6. NEXT-GENERATION PLASMA CONTROL IN THE DIII-D TOKAMAK

    SciTech Connect

    WALKER, ML; FERRON, JR; HUMPHREYS, DA; JOHNSON, RD; LEUER, JA; PENAFLOR, BG; PIGLOWSKI, DA; ARIOLA, M; PIRONTI, A; SCHUSTER, E

    2002-10-01

    OAK A271 NEXT-GENERATION PLASMA CONTROL IN THE DIII-D TOKAMAK. The advanced tokamak (AT) operating mode which is the principal focus of the DIII-D tokamak requires highly integrated and complex plasma control. Simultaneous high performance regulation of the plasma boundary and internal profiles requires multivariable control techniques to account for the highly coupled influences of equilibrium shape, profile, and stability control. This paper describes progress towards the DIII-D At mission goal through both significantly improved real-time computational hardware and control algorithm capability.

  7. Generation of terahertz radiation in the reflection of a laser pulse from a dense plasma

    SciTech Connect

    Frolov, A. A.

    2007-12-15

    The generation of low-frequency (terahertz) electromagnetic radiation in the reflection of a laser pulse from the boundary of a dense plasma is considered. Low-frequency wave electromagnetic fields in vacuum are excited by a vortex electric current that is induced at the plasma boundary by the ponderomotive force of the laser pulse. The spectral, angular, and energy parameters of the low-frequency radiation, as well as the spatiotemporal structure of the emitted waves, are investigated. It is shown that for typical parameters of present-day laser plasma experiments, the power of terahertz radiation can amount to tens of megawatts.

  8. Generating vorticity and magnetic fields in plasmas in general relativity: Spacetime curvature drive

    SciTech Connect

    Asenjo, Felipe A.; Mahajan, Swadesh M.; Qadir, Asghar

    2013-02-15

    Using the generally covariant magnetofluid formalism for a hot plasma, a spacetime curvature driven mechanism for generating seed vorticity/magnetic field is presented. The 'battery' owes its origin to the interaction between the gravity modified Lorentz factor of the fluid element and the inhomogeneous plasma thermodynamics. The general relativistic drive is evaluated for two simple cases: seed formation in a simplified model of a hot plasma accreting in stable orbits around a Schwarzschild black hole and for particles in free fall near the horizon. Some astrophysical applications are suggested.

  9. Method for generating a highly reactive plasma for exhaust gas aftertreatment and enhanced catalyst reactivity

    DOEpatents

    Whealton, John H.; Hanson, Gregory R.; Storey, John M.; Raridon, Richard J.; Armfield, Jeffrey S.; Bigelow, Timothy S.; Graves, Ronald L.

    2002-01-01

    A method for non-thermal plasma aftertreatment of exhaust gases the method comprising the steps of providing short risetime, high frequency, high power bursts of low-duty factor microwaves sufficient to generate a plasma discharge and passing a gas to be treated through the discharge so as to cause dissociative reduction of the exhaust gases and enhanced catalyst reactivity through application of the pulsed microwave fields directly to the catalyst material sufficient to cause a polarizability catastrophe and enhanced heating of the metal crystallite particles of the catalyst, and in the presence or absence of the plasma. The invention also includes a reactor for aftertreatment of exhaust gases.

  10. A plasma needle for generating homogeneous discharge in atmospheric pressure air

    SciTech Connect

    Li Xuechen; Yuan Ning; Jia Pengying; Chen Junying

    2010-09-15

    Homogeneous discharge in air is often considered to be the ultimate low-temperature atmospheric pressure plasmas for industrial applications. In this paper, we present a method whereby stable homogeneous discharge in open air can be generated by a simple plasma needle. The discharge mechanism is discussed based on the spatially resolved light emission waveforms from the plasma. Optical emission spectroscopy is used to determine electron energy and rotational temperature, and results indicate that both electron energy and rotational temperature increase with increasing the applied voltage. The results are analyzed qualitatively based on the discharge mechanism.

  11. Pilot study of the efficacy of a thrombin inhibitor for use during cardiopulmonary bypass.

    PubMed

    DeAnda, A; Coutre, S E; Moon, M R; Vial, C M; Griffin, L C; Law, V S; Komeda, M; Leung, L L; Miller, D C

    1994-08-01

    Heparin is normally used for anticoagulation during cardiopulmonary bypass (CPB), but its use is contraindicated in patients with a history of heparin-induced thrombocytopenia, heparin-provoked thrombosis, or both. Heparin therapy can also be ineffective due to heparin resistance. A short-acting, oligonucleotide-based thrombin inhibitor (thrombin aptamer) may potentially serve as a substitute for heparin in these and other clinical situations. We tested a novel thrombin aptamer in a canine CPB pilot study to determine its anticoagulant efficacy, the resultant changes in coagulation variables, and the aptamer's clearance mechanisms and pharmacokinetics. Seven dogs were studied initially: Four received varied doses of the aptamer (to establish the pharmacokinetic profile) and 3 received heparin. Subsequently, 4 other dogs underwent CPB, receiving a constant infusion of the aptamer before CPB (to characterize the baseline coagulation status), with partial CPB and hemodilution, during 60 minutes of total CPB, and, finally, after a 2-hour recovery period. At a 0.5 mg.kg-1.min-1 dose, the activated clotting time rose with aptamer infusion from 106 +/- 12 seconds to 187 +/- 8 seconds (+/- 1 standard deviation) (p = 0.014), increased further with hemodilution (to 259 +/- 41 seconds; p = 0.017), and was even more prolonged during total CPB (> 1,500 seconds; p < 0.001). This later increase in the activated clotting time paralleled a rise in the plasma concentration of the thrombin aptamer during total CPB, as determined by high-performance liquid chromatography.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8067830

  12. APTAMER-BASED SERRS SENSOR FOR THROMBIN DETECTION

    SciTech Connect

    Cho, H; Baker, B R; Wachsmann-Hogiu, S; Pagba, C V; Laurence, T A; Lane, S M; Lee, L P; Tok, J B

    2008-07-02

    We describe an aptamer-based Surface Enhanced Resonance Raman Scattering (SERRS) sensor with high sensitivity, specificity, and stability for the detection of a coagulation protein, human a-thrombin. The sensor achieves high sensitivity and a limit of detection of 100 pM by monitoring the SERRS signal change upon the single step of thrombin binding to immobilized thrombin binding aptamer. The selectivity of the sensor is demonstrated by the specific discrimination of thrombin from other protein analytes. The specific recognition and binding of thrombin by the thrombin binding aptamer is essential to the mechanism of the aptamer-based sensor, as shown through measurements using negative control oligonucleotides. In addition, the sensor can detect 1 nM thrombin in the presence of complex biofluids, such as 10% fetal calf serum, demonstrating that the immobilized, 5{prime}-capped, 3{prime}-capped aptamer is sufficiently robust for clinical diagnostic applications. Furthermore, the proposed sensor may be implemented for multiplexed detection using different aptamer-Raman probe complexes.

  13. Thrombin regulation of synaptic plasticity: implications for physiology and pathology.

    PubMed

    Maggio, Nicola; Itsekson, Zeev; Dominissini, Dan; Blatt, Ilan; Amariglio, Ninette; Rechavi, Gideon; Tanne, David; Chapman, Joab

    2013-09-01

    Thrombin, a serine protease involved in the coagulation cascade has been recently shown to affect neuronal function following blood-brain barrier breakdown. Several lines of evidence have shown that thrombin may exist in the brain parenchyma under normal physiological conditions, yet its role in normal brain functions and synaptic transmission has not been established. In an attempt to shed light on the physiological functions of thrombin and Protease Activated Receptor 1 (PAR1) in the brain, we studied the effects of thrombin and a PAR1 agonist on long term potentiation (LTP) in mice hippocampal slices. Surprisingly, different concentrations of thrombin affect LTP through different molecular routes converging on PAR1. High thrombin concentrations induced an NMDA dependent, slow onset LTP, whereas low concentrations of thrombin promoted a VGCCs, mGluR-5 dependent LTP through activated Protein C (aPC). Remarkably, aPC facilitated LTP by activating PAR1 through an Endothelial Protein C Receptor (EPCR)-mediated mechanism which involves intracellular calcium stores. These findings reveal a novel mechanism by which PAR1 may regulate the threshold for synaptic plasticity in the hippocampus and provide additional insights into the role of this receptor in normal and pathological conditions.

  14. S-Duct Engine Inlet Flow Control Using SDBD Plasma Streamwise Vortex Generators

    NASA Astrophysics Data System (ADS)

    Kelley, Christopher; He, Chuan; Corke, Thomas

    2009-11-01

    The results of a numerical simulation and experiment characterizing the performance of plasma streamwise vortex generators in controlling separation and secondary flow within a serpentine, diffusing duct are presented. A no flow control case is first run to check agreement of location of separation, development of secondary flow, and total pressure recovery between the experiment and numerical results. Upon validation, passive vane-type vortex generators and plasma streamwise vortex generators are implemented to increase total pressure recovery and reduce flow distortion at the aerodynamic interface plane: the exit of the S-duct. Total pressure recovery is found experimentally with a pitot probe rake assembly at the aerodynamic interface plane. Stagnation pressure distortion descriptors are also presented to show the performance increase with plasma streamwise vortex generators in comparison to the baseline no flow control case. These performance parameters show that streamwise plasma vortex generators are an effective alternative to vane-type vortex generators in total pressure recovery and total pressure distortion reduction in S-duct inlets.

  15. Bright high-order harmonic generation with controllable polarization from a relativistic plasma mirror.

    PubMed

    Chen, Zi-Yu; Pukhov, Alexander

    2016-01-01

    Ultrafast extreme ultraviolet (XUV) sources with a controllable polarization state are powerful tools for investigating the structural and electronic as well as the magnetic properties of materials. However, such light sources are still limited to only a few free-electron laser facilities and, very recently, to high-order harmonic generation from noble gases. Here we propose and numerically demonstrate a laser-plasma scheme to generate bright XUV pulses with fully controlled polarization. In this scheme, an elliptically polarized laser pulse is obliquely incident on a plasma surface, and the reflected radiation contains pulse trains and isolated circularly or highly elliptically polarized attosecond XUV pulses. The harmonic polarization state is fully controlled by the laser-plasma parameters. The mechanism can be explained within the relativistically oscillating mirror model. This scheme opens a practical and promising route to generate bright attosecond XUV pulses with desirable ellipticities in a straightforward and efficient way for a number of applications. PMID:27531047

  16. Investigation on plasma generated during hypervelocity impact at different impact velocities and angles

    SciTech Connect

    Song, Weidong Lv, Yangtao; Wang, Cheng; Li, Jianqiao

    2015-12-15

    A 3D Smoothed Particle Hydrodynamics code was developed to investigate plasma generation by considering a chemical reaction process in hypervelocity impacts of an aluminum projectile on an aluminum target. The chemical reaction process was described by the reaction rate based on the Arrhenius equation and used to calculate the plasma generation during the impact simulation. The predicted result was verified by empirical formulas and a new empirical formula was proposed based on the comparisons and analyses. The influence of the impact angle was discussed for different impact velocities. Then, the application of both the new and original empirical formulas for protection design from plasma generated by hypervelocity impact was discussed, which demonstrated that the code and model were useful in the prediction of hypervelocity impacts on spacecraft.

  17. Bright high-order harmonic generation with controllable polarization from a relativistic plasma mirror

    PubMed Central

    Chen, Zi-Yu; Pukhov, Alexander

    2016-01-01

    Ultrafast extreme ultraviolet (XUV) sources with a controllable polarization state are powerful tools for investigating the structural and electronic as well as the magnetic properties of materials. However, such light sources are still limited to only a few free-electron laser facilities and, very recently, to high-order harmonic generation from noble gases. Here we propose and numerically demonstrate a laser–plasma scheme to generate bright XUV pulses with fully controlled polarization. In this scheme, an elliptically polarized laser pulse is obliquely incident on a plasma surface, and the reflected radiation contains pulse trains and isolated circularly or highly elliptically polarized attosecond XUV pulses. The harmonic polarization state is fully controlled by the laser–plasma parameters. The mechanism can be explained within the relativistically oscillating mirror model. This scheme opens a practical and promising route to generate bright attosecond XUV pulses with desirable ellipticities in a straightforward and efficient way for a number of applications. PMID:27531047

  18. Manganese porphyrin-double stranded DNA complex guided in situ deposition of polyaniline for electrochemical thrombin detection.

    PubMed

    Xie, Shunbi; Chai, Yaqin; Yuan, Yali; Yuan, Ruo

    2014-07-11

    In this work, we proposed a novel electrochemical strategy for sensitive detection of thrombin (TB) based on in situ generation of polyaniline (PANI) as a redox mediator by using a manganese porphyrin-double stranded DNA (MnTMPyP-dsDNA) peroxidase-like artificial enzyme mimic as a powerful catalyst and template.

  19. Picosecond strain pulses generated by a supersonically expanding electron-hole plasma in GaAs

    NASA Astrophysics Data System (ADS)

    Young, E. S. K.; Akimov, A. V.; Campion, R. P.; Kent, A. J.; Gusev, V.

    2012-10-01

    Strain pulses with picosecond duration are generated directly in GaAs by optical excitation from a femtosecond laser. The photons are absorbed in a 15-nm layer near the surface, creating the electron-hole plasma, which diffusively expands into the bulk of the GaAs. At an early time, the drift velocity of the expanding plasma exceeds the speed of longitudinal sound, and the generated strain pulses cannot escape the plasma cloud. Such supersonic generation of strain pulses results in specific temporal and spatial shapes of the generated strain pulses, where the compression part has a much lower amplitude than the tensile part. This phenomenon is studied experimentally at low temperatures and analyzed theoretically based on the wave and diffusion equations for strain and plasma density, respectively. Two mechanisms, deformation potential and thermoelasticity, are responsible for the experimental observations. The relative contributions from these mechanisms are governed by the nonradiative recombination rate in the plasma and depend on the optical excitation density, inducing such nonlinear optoacoustic effects as shortening of the leading strain front and a superlinear/quadratic increase in its amplitude with the rise of pump laser fluence.

  20. The interaction of thrombin with platelet protease nexin

    SciTech Connect

    Knupp, C.L. )

    1989-10-01

    Thrombin interacts with a platelet protein which is immunologically related to fibroblast protease nexin and has been termed platelet protease nexin I (PNI). Conflicting hypotheses about the relationship of the thrombin-PNI complex formation to platelet activation have been proposed. The studies presented here demonstrate that the platelet-associated and supernatant complexes with added 125I-thrombin are formed only under conditions which produce platelet activation in normal and chymotrypsin-modified platelets. The platelet-associated complex is formed prior to the appearance of complexes in supernatants. Appearance of the supernatant complex coincides with the appearance of thrombospondin in the reaction supernatants. Excess native thrombin, dansylarginine N-(3-ethyl-1,5-pentanediyl) amide or hirudin can prevent radiolabeled platelet-associated complex formation if added before 125I-thrombin. DAPA or hirudin can prevent or dissociate complex formation if added up to one minute after thrombin but not at later time points. The surface associated complex is accessible to trypsin although a portion remains with the cytoskeletal proteins when thrombin-activated platelets are solubilized with Triton X 100. The surface-associated complex formation parallels many aspects of the specific measurable thrombin binding, yet it does not appear to involve other identified surface glycoprotein thrombin receptors or substrates. Although the time course of appearance of the complexes in supernatants is consistent with other data which suggest that PNI may be released from platelet granules during platelet activation, other explanations for the appearance of PNI on the platelet surface and in supernatants during platelet activation are possible.

  1. High-current lanthanum-hexaboride electron emitter for a quasi-stationary arc plasma generator

    SciTech Connect

    Davydenko, V. I. Ivanov, A. A. Shul’zhenko, G. I.

    2015-11-15

    A high-current electron emitter on the basis of lanthanum hexaboride is developed for quasi-stationary arc plasma generators of ion sources. The emitter consists of a set of LaB{sub 6} washers interleaved with washers made of thermally extended graphite. The emitter is heated by the current flowing through the graphite washers. The thermal regime of emitter operation during plasma generation is considered. The emitter has been successfully used in the ion sources of the diagnostic injectors of fast hydrogen atomic beams.

  2. High-current lanthanum-hexaboride electron emitter for a quasi-stationary arc plasma generator

    NASA Astrophysics Data System (ADS)

    Davydenko, V. I.; Ivanov, A. A.; Shul'zhenko, G. I.

    2015-11-01

    A high-current electron emitter on the basis of lanthanum hexaboride is developed for quasi-stationary arc plasma generators of ion sources. The emitter consists of a set of LaB6 washers interleaved with washers made of thermally extended graphite. The emitter is heated by the current flowing through the graphite washers. The thermal regime of emitter operation during plasma generation is considered. The emitter has been successfully used in the ion sources of the diagnostic injectors of fast hydrogen atomic beams.

  3. Detailed study of the plasma-activated catalytic generation of ammonia in N2-H2 plasmas

    NASA Astrophysics Data System (ADS)

    van Helden, J. H.; Wagemans, W.; Yagci, G.; Zijlmans, R. A. B.; Schram, D. C.; Engeln, R.; Lombardi, G.; Stancu, G. D.; Röpcke, J.

    2007-02-01

    We investigated the efficiency and formation mechanism of ammonia generation in recombining plasmas generated from mixtures of N2 and H2 under various plasma conditions. In contrast to the Haber-Bosch process, in which the molecules are dissociated on a catalytic surface, under these plasma conditions the precursor molecules, N2 and H2, are already dissociated in the gas phase. Surfaces are thus exposed to large fluxes of atomic N and H radicals. The ammonia production turns out to be strongly dependent on the fluxes of atomic N and H radicals to the surface. By optimizing the atomic N and H fluxes to the surface using an atomic nitrogen and hydrogen source ammonia can be formed efficiently, i.e., more than 10% of the total background pressure is measured to be ammonia. The results obtained show a strong similarity with results reported in literature, which were explained by the production of ammonia at the surface by stepwise addition reactions between adsorbed nitrogen and hydrogen containing radicals at the surface and incoming N and H containing radicals. Furthermore, our results indicate that the ammonia production is independent of wall material. The high fluxes of N and H radicals in our experiments result in a passivated surface, and the actual chemistry, leading to the formation of ammonia, takes place in an additional layer on top of this passivated surface.

  4. Electron generation of electrostatic waves in the plasma sheet boundary layer

    NASA Technical Reports Server (NTRS)

    Onsager, T. G.; Thomsen, M. F.; Elphic, R. C.; Gosling, J. T.; Anderson, R. R.; Kettmann, G.

    1993-01-01

    Broadband electrostatic noise (BEN) has been shown to occur in conjunction with ion beams; extensive investigations of possible ion beam-related instabilities that could generate the observed wave spectra have been conducted. It has also been demonstrated that unstable electron distribution functions are sometimes measured in the plasma sheet boundary layer. We present simultaneous observations of ion and electron distribution functions and electric field wave spectra measured by ISEE 1 and ISEE 2 in the Earth's magnetotail. As the spacecraft moved from the tail lobe toward the plasma sheet, the fast indication of boundary layer plasma was seen in the electron distributions, followed some minutes later by the detection of boundary layer ions. The onset of large-amplitude electrostatic waves at frequencies up to the electron plasma frequency was coincident with the onset of the boundary layer electrons, suggesting that broadband electrostatic waves may often be generated by unstable electron distributions in the plasma sheet boundary layer, particularly the higher frequency portion of the wave spectrum. The observed changes in the electron distribution functions indicate that the plasma was not heated locally by the waves.

  5. A Multiple Z-Pinch Configuration for the Generation of High-Density, Magnetized Plasmas

    NASA Astrophysics Data System (ADS)

    Tarditi, Alfonso G.

    2015-11-01

    The z-pinch is arguably the most straightforward and economical approach for the generation and confinement of hot plasmas, with a long history of theoretical investigations and experimental developments. While most of the past studies were focused on countering the natural tendency of z-pinches to develop instabilities, this study attempts to take advantage of those unstable regimes to form a quasi-stable plasma, with higher density and temperature, possibly of interest for a fusion reactor concept. For this purpose, a configuration with four z-pinch discharges, with axis parallel to each other and symmetrically positioned, is considered. Electrodes for the generation of the discharges and magnetic coils are arranged to favor the formation of concave discharge patterns. The mutual attraction from the co-streaming discharge currents enhances this pattern, leading to bent plasma streams, all nearing towards the axis. This configuration is intended to excite and sustain a ``kink'' unstable mode for each z-pinch, eventually producing either plasmoid structures, detached from each discharge, or sustained kink patterns: both these cases appear to lead to plasmas merging in the central region. The feasibility of this approach in creating a higher density, hotter, meta-stable plasma regime is investigated computationally, addressing both the kink excitation phase and the dynamics of the converging plasma columns.

  6. Magnetic field generation in Rayleigh-Taylor unstable inertial confinement fusion plasmas.

    PubMed

    Srinivasan, Bhuvana; Dimonte, Guy; Tang, Xian-Zhu

    2012-04-20

    Rayleigh-Taylor instabilities (RTI) in inertial confinement fusion implosions are expected to generate magnetic fields. A Hall-MHD model is used to study the field generation by 2D single-mode and multimode RTI in a stratified two-fluid plasma. Self-generated magnetic fields are predicted and these fields grow as the RTI progresses via the ∇n(e)×∇T(e) term in the generalized Ohm's law. Scaling studies are performed to determine the growth of the self-generated magnetic field as a function of density, acceleration, Atwood number, and perturbation wavelength.

  7. Fast electron generation and transport in a turbulent, magnetized plasma

    SciTech Connect

    Stoneking, W.R.

    1994-05-01

    The nature of fast electron generation and transport in the Madison Symmetric Torus (MST) reversed field pinch (RFP) is investigated using two electron energy analyzer (EEA) probes and a thermocouple calorimeter. The parallel velocity distribution of the fast electron population is well fit by a drifted Maxwellian distribution with temperature of about 100 eV and drift velocity of about 2 {times} 10{sup 6} m/s. Cross-calibration of the EEA with the calorimeter provides a measurement of the fast electron perpendicular temperature of 30 eV, much lower than the parallel temperature, and is evidence that the kinetic dynamo mechanism (KDT) is not operative in MST. The fast electron current is found to match to the parallel current at the edge, and the fast electron density is about 4 {times} 10{sup 11} cm{sup {minus}3} independent of the ratio of the applied toroidal electric field to the critical electric field for runaways. First time measurements of magnetic fluctuation induced particle transport are reported. By correlating electron current fluctuations with radial magnetic fluctuations the transported flux of electrons is found to be negligible outside r/a{approximately}0.9, but rises the level of the expected total particle losses inside r/a{approximately}0.85. A comparison of the measured diffusion coefficient is made with the ausilinear stochastic diffusion coefficient. Evidence exists that the reduction of the transport is due to the presence of a radial ambipolar electric field of magnitude 500 V/m, that acts to equilibrate the ion and electron transport rates. The convective energy transport associated with the measured particle transport is large enough to account for the observed magnetic fluctuation induced energy transport in MST.

  8. Finite toroidal flow generated by unstable tearing mode in a toroidal plasma

    SciTech Connect

    Hao, G. Z. Wang, A. K.; Xu, Y. H.; He, H. D.; Xu, M.; Qu, H. P.; Peng, X. D.; Xu, J. Q.; Qiu, X. M.; Liu, Y. Q.; Sun, Y.; Cui, S. Y.

    2014-12-15

    The neoclassical toroidal plasma viscosity torque and electromagnetic torque, generated by tearing mode (TM) in a toroidal plasma, are numerically investigated using the MARS-Q code [Liu et al., Phys. Plasmas 20, 042503 (2013)]. It is found that an initially unstable tearing mode can intrinsically drive a toroidal plasma flow resulting in a steady state solution, in the absence of the external momentum input and external magnetic field perturbation. The saturated flow is in the order of 0.5%ω{sub A} at the q=2 rational surface in the considered case, with q and ω{sub A} being the safety factor and the Alfven frequency at the magnetic axis, respectively. The generation of the toroidal flow is robust, being insensitive to the given amplitude of the perturbation at initial state. On the other hand, the flow amplitude increases with increasing the plasma resistivity. Furthermore, the initially unstable tearing mode is fully stabilized by non-linear interaction with the self-generated toroidal flow.

  9. Generation and detection of whistler wave induced space plasma turbulence at Gakona, Alaska

    NASA Astrophysics Data System (ADS)

    Rooker, L. A.; Lee, M. C.; Pradipta, R.; Watkins, B. J.

    2013-07-01

    We report on high-frequency wave injection experiments using the beat wave technique to study the generation of very-low-frequency (VLF) whistler waves in the ionosphere above Gakona, Alaska. This work is aimed at investigating whistler wave interactions with ionospheric plasmas and radiation belts. The beat wave technique involves injecting two X-mode waves at a difference frequency in the VLF range using the High-frequency Active Auroral Research Program (HAARP) heating facility. A sequence of beat wave-generated whistler waves at 2, 6.5, 7.5, 8.5, 9.5, 11.5, 15.5, 22.5, 28.5 and 40.5 kHz were detected in our 2011 experiments. We present Modular Ultra-high-frequency Ionospheric Radar (MUIR) (446 MHz) measurements of ion lines as the primary diagnosis of ionospheric plasma effects caused by beat wave-generated whistler waves. A magnetometer and digisonde were used to monitor the background ionospheric plasma conditions throughout the experiments. Our theoretical and data analyses show that VLF whistler waves can effectively interact with ionospheric plasmas via two different four-wave interaction processes leading to energization of electrons and ions. These preliminary results support our Arecibo experiments to study NAU-launched 40.75 kHz whistler wave interactions with space plasmas.

  10. Efficient second- and third-harmonic radiation generation from relativistic laser-plasma interactions

    SciTech Connect

    Singh, Mamta; Gupta, D. N.; Suk, H.

    2015-06-15

    We propose an idea to enhance the efficiency of second- and third-harmonic generation by considering the amplitude-modulation of the fundamental laser pulse. A short-pulse laser of finite spot size is modeled as amplitude modulated in time. Amplitude-modulation of fundamental laser contributes in quiver velocity of the plasma electrons and produces the strong plasma-density perturbations, thereby increase in current density at second- and third-harmonic frequency. In a result, the conversion efficiency of harmonic generation increases significantly. Power conversion efficiency of harmonic generation process is the increasing function of the amplitude-modulation parameter of the fundamental laser beam. Harmonic power generated by an amplitude modulated laser is many folds higher than the power obtained in an ordinary case.

  11. A spectral study of a radio-frequency plasma-generated flux of atomic oxygen

    NASA Technical Reports Server (NTRS)

    Batten, Carmen E.; Brown, Kenneth G.; Lewis, Beverley W.

    1994-01-01

    The active environment of a radio-frequency (RF) plasma generator, with and without low-pressure oxygen, has been characterized through the identification of emission lines in the spectral region from 250 to 900 nm. The environment is shown to be dependent on the partial pressure of oxygen and the power applied to the RF generator. Atomic oxygen has been found in significant amounts as well as atomic hydrogen and the molecular oxygen species O2((sup 1)Sigma). The only charged species observed was the singly charged molecular ion O2(+). With a polymer specimen in the plasma chamber, carbon monoxide was also observed. The significance of these observations with respect to previous studies using this type of generator to stimulate material degradation in space is discussed. The possibility of using these generators as atomic oxygen sources in the development of oxygen atom fluorescence sensors is explored.

  12. A reference protocol for comparing the biocidal properties of gas plasma generating devices

    NASA Astrophysics Data System (ADS)

    Shaw, A.; Seri, P.; Borghi, C. A.; Shama, G.; Iza, F.

    2015-12-01

    Growing interest in the use of non-thermal, atmospheric pressure gas plasmas for decontamination purposes has resulted in a multiplicity of plasma-generating devices. There is currently no universally approved method of comparing the biocidal performance of such devices and in the work described here spores of the Gram positive bacterium Bacillus subtilis (ATCC 6633) are proposed as a suitable reference biological agent. In order to achieve consistency in the form in which the biological agent in question is presented to the plasma, a polycarbonate membrane loaded with a monolayer of spores is proposed. The advantages of the proposed protocol are evaluated by comparing inactivation tests in which an alternative microorganism (methicillin resistant Staphylococcus aureus—MRSA) and the widely-used sample preparation technique of directly pipetting cell suspensions onto membranes are employed. In all cases, inactivation tests with either UV irradiation or plasma exposure were more reproducible when the proposed protocol was followed.

  13. Dynamics of a pulsed laser generated tin plasma expanding in an oxygen atmosphere

    NASA Astrophysics Data System (ADS)

    Barreca, F.; Fazio, E.; Neri, F.; Barletta, E.; Trusso, S.; Fazio, B.

    2005-10-01

    Semiconducting tin oxide can be successfully deposited by means of the laser ablation technique. In particular by ablating metallic tin in a controlled oxygen atmosphere, thin films of SnOx have been deposited. The partial oxygen pressure at which the films are deposited strongly influences both the stoichiometry and the structural properties of the films. In this work, we present a study of the expansion dynamics of the plasma generated by ablating a tin target by means of a pulsed laser using time and space resolved optical emission spectroscopy and fast photography imaging of the expanding plasma. Both Sn I and Sn II optical emission lines have been observed from the time-integrated spectroscopy. Time resolved-measurements revealed the dynamics of the expanding plasma in the ambient oxygen atmosphere. Stoichiometry of the films has been determined by means of X-ray photoelectron spectroscopy and correlated to the expansion dynamics of the plasma.

  14. Radio frequency induction plasma generator 80-kV test stand operation

    SciTech Connect

    Goede, H.; DiVergilio, W.F.; Fosnight, V.V.; Vella, M.C.; Ehlers, K.W.; Kippenhan, D.; Pincosy, P.A.; Pyle, R.V.

    1986-07-01

    Beam extraction tests at energies up to 80 kV were performed using a radio frequency induction (RFI) plasma generator hydrogen ion source. A 7 x 10-cm/sup 2/, long pulse accelerator was operated with a 10 x 10-cm/sup 2/ axial magnetic cusp bucket and a magnetic-filter bucket. Atomic fractions (up to 85% H/sup +/), plasma production efficiencies (roughly-equal0.6 A of beam per kW rf power), and beam divergence were at least as good as with arc plasmas in similar chambers. Potential advantages of the RFI plasma sources for large-scale applications are ease of operation, reliability, and extended service life.

  15. Generation of bioactive peptide hydrolysates from cattle plasma using plant and fungal proteases.

    PubMed

    Bah, Clara S F; Bekhit, Alaa El-Din A; McConnell, Michelle A; Carne, Alan

    2016-12-15

    Four protease preparations from plant and fungal sources (papain, bromelain, FP400 and FPII) were used to hydrolyse plasma which was separated from slaughterhouse cattle blood. The o-phthaldialdehyde assay was used to follow the release of TCA-soluble peptides over a 24h period. Hydrolysis profiles were displayed using SDS-PAGE. The in vitro antioxidant and antimicrobial activities of the hydrolysates were determined. The results showed that hydrolysates of cattle plasma generated with fungal protease FPII had higher antioxidant activities. Overall than hydrolysates generated with papain, bromelain and FP400. None of the hydrolysates demonstrated antimicrobial activity. The FPII peptide hydrolysate was fractionated using gel permeation chromatography, OFFGEL isoelectric focusing and RP-HPLC. The RP-HPLC fraction with highest antioxidant activity contained 15 novel peptide sequences. The use of protease FPII to hydrolyse cattle plasma resulted in a hydrolysate with high antioxidant properties and unique peptide sequences. PMID:27451160

  16. Intermittent laser-plasma interactions and hot electron generation in shock ignition

    SciTech Connect

    Yan, R.; Li, J.; Ren, C.

    2014-06-15

    We study laser-plasma interactions and hot electron generation in the ignition phase of shock ignition through 1D and 2D particle-in-cell simulations in the regime of long density scale length and moderately high laser intensity. These long-term simulations show an intermittent bursting pattern of laser-plasma instabilities, resulting from a coupling of the modes near the quarter-critical-surface and those in the lower density region via plasma waves and laser pump depletion. The majority of the hot electrons are found to be from stimulated Raman scattering and of moderate energies. However, high energy electrons of preheating threat can still be generated from the two-plasmon-decay instability.

  17. Generation of bioactive peptide hydrolysates from cattle plasma using plant and fungal proteases.

    PubMed

    Bah, Clara S F; Bekhit, Alaa El-Din A; McConnell, Michelle A; Carne, Alan

    2016-12-15

    Four protease preparations from plant and fungal sources (papain, bromelain, FP400 and FPII) were used to hydrolyse plasma which was separated from slaughterhouse cattle blood. The o-phthaldialdehyde assay was used to follow the release of TCA-soluble peptides over a 24h period. Hydrolysis profiles were displayed using SDS-PAGE. The in vitro antioxidant and antimicrobial activities of the hydrolysates were determined. The results showed that hydrolysates of cattle plasma generated with fungal protease FPII had higher antioxidant activities. Overall than hydrolysates generated with papain, bromelain and FP400. None of the hydrolysates demonstrated antimicrobial activity. The FPII peptide hydrolysate was fractionated using gel permeation chromatography, OFFGEL isoelectric focusing and RP-HPLC. The RP-HPLC fraction with highest antioxidant activity contained 15 novel peptide sequences. The use of protease FPII to hydrolyse cattle plasma resulted in a hydrolysate with high antioxidant properties and unique peptide sequences.

  18. Effect of nonlinear chirped Gaussian laser pulse on plasma wake field generation

    SciTech Connect

    Afhami, Saeedeh; Eslami, Esmaeil

    2014-08-15

    An ultrashort laser pulse propagating in plasma can excite a nonlinear plasma wake field which can accelerate charged particles up to GeV energies within a compact space compared to the conventional accelerator devices. In this paper, the effect of different kinds of nonlinear chirped Gaussian laser pulse on wake field generation is investigated. The numerical analysis of our results depicts that the excitation of plasma wave with large and highly amplitude can be accomplished by nonlinear chirped pulses. The maximum amplitude of excited wake in nonlinear chirped pulse is approximately three times more than that of linear chirped pulse. In order to achieve high wake field generation, chirp parameters and functions should be set to optimal values.

  19. Theory of coherent transition radiation generated at a plasma-vacuum interface

    SciTech Connect

    Schroeder, Carl B.; Esarey, Eric; van Tilborg, Jeroen; Leemans, Wim P.

    2003-06-26

    Transition radiation generated by an electron beam, produced by a laser wakefield accelerator operating in the self-modulated regime, crossing the plasma-vacuum boundary is considered. The angular distributions and spectra are calculated for both the incoherent and coherent radiation. The effects of the longitudinal and transverse momentum distributions on the differential energy spectra are examined. Diffraction radiation from the finite transverse extent of the plasma is considered and shown to strongly modify the spectra and energy radiated for long wavelength radiation. This method of transition radiation generation has the capability of producing high peak power THz radiation, of order 100 (mu)J/pulse at the plasma-vacuum interface, which is several orders of magnitude beyond current state-of-the-art THz sources.

  20. Plasma Processing of SRF Cavities for the next Generation Of Particle Accelerators

    SciTech Connect

    Vuskovic, Leposava

    2015-11-23

    The cost-effective production of high frequency accelerating fields are the foundation for the next generation of particle accelerators. The Ar/Cl2 plasma etching technology holds the promise to yield a major reduction in cavity preparation costs. Plasma-based dry niobium surface treatment provides an excellent opportunity to remove bulk niobium, eliminate surface imperfections, increase cavity quality factor, and bring accelerating fields to higher levels. At the same time, the developed technology will be more environmentally friendly than the hydrogen fluoride-based wet etching technology. Plasma etching of inner surfaces of standard multi-cell SRF cavities is the main goal of this research in order to eliminate contaminants, including niobium oxides, in the penetration depth region. Successful plasma processing of multi-cell cavities will establish this method as a viable technique in the quest for more efficient components of next generation particle accelerators. In this project the single-cell pill box cavity plasma etching system is developed and etching conditions are determined. An actual single cell SRF cavity (1497 MHz) is plasma etched based on the pill box cavity results. The first RF test of this plasma etched cavity at cryogenic temperature is obtained. The system can also be used for other surface modifications, including tailoring niobium surface properties, surface passivation or nitriding for better performance of SRF cavities. The results of this plasma processing technology may be applied to most of the current SRF cavity fabrication projects. In the course of this project it has been demonstrated that a capacitively coupled radio-frequency discharge can be successfully used for etching curved niobium surfaces, in particular the inner walls of SRF cavities. The results could also be applicable to the inner or concave surfaces of any 3D structure other than an SRF cavity.

  1. Low-order harmonic generation in nanosecond laser ablation plasmas of carbon containing materials

    NASA Astrophysics Data System (ADS)

    Lopez-Quintas, I.; Oujja, M.; Sanz, M.; Martín, M.; Ganeev, R. A.; Castillejo, M.

    2013-08-01

    In this work we report on a systematic study of the spatiotemporal behaviour of low-order harmonics generated in nanosecond laser ablation plasmas of carbon containing materials. Plasmas were generated from targets of graphite and boron carbide ablated with a nanosecond Q-switched Nd:YAG laser at 1064 nm. Low-order harmonics (3rd and 5th) of the fundamental wavelength of a ns Nd:YAG driving laser, propagating perpendicularly to the ablation laser at variable time delays, were observed. The temporal study of the low-order harmonics generated under vacuum and atmospheres of Kr and Xe, revealed the presence of two populations that contribute to the harmonic generation (HG) at different times. It was found that under vacuum only small species contribute to the HG process, whereas under buffer gas, heavier species, such as clusters and nanoparticles, contribute to the HG at longer times. Optical emission spectroscopy, time of flight mass spectrometry and characterization of deposits collected on-line on a nearby substrate provided additional information that complemented the results of the spatiotemporal study of the generated harmonics. This approach to ablation plume analysis allows elucidating the identity of the nonlinear emitters in laser ablation plasmas and facilitates the investigation of efficient, nanoparticle-enhanced, coherent short wavelength generation processes.

  2. Development of the plasma generator for a long pulse 10 x 40 neutral beam

    SciTech Connect

    Pincosy, P.A.; Ehlers, K.W.; Lietzke, A.F.; Owren, H.M.; Paterson, J.A.; Pyle, R.V.; Vella, M.C.

    1986-11-01

    Users of fusion devices have identified heating requirements for positive ion based neutral beams to include energies of 80 or 120 kV with pulse length up to 30 s. Additional requirements are low beam divergence (0.3/sup 0/ x 1.0/sup 0/; 1/e half angles), low impurity (less than 1%), high species (over 80% atomic), and cathode lifetime exceeding 5 h of beam operation. Accelerator design remains as an engineering problem, whereas most of the performance goals have required development of the plasma generator. Problems of concern which relate to the performance goals are the heat dissipation, magnetic field configuration, and cathode placement. The plasma generator was tested on TS IIA (the plasma generator testing facility) which does not have beam extraction capability but is used to evaluate efficiency, operating conditions, arc notching characteristics, species, plasma uniformity, and cathode conditioning. The source, consisting of the plasma generator mounted on the long pulse accelerator was mounted on NBETF (Neutral Beam Engineering Test Facility) for beam testing. During beam operation the back-streaming electrons add power to the source and affect the arc operation. Source durability and stability were studied at 80 kV and 40 A of accelerator current (deuterium). The arc efficiency was higher than the value used for the design. Power loading from back-streaming electrons was much less than the design level. With feedback control, plasma density and accel current were constant to +- 2% during 30-s shots. The beam atomic fraction of 84%-88% (deuterium) was slightly higher than measured on TS IIA. Cathode durability was tested by operating over 500, 30-s full shots at 80 kV and 40 A of deuterium. Arc conditioning was found to be an important phase to avoid filament damage.

  3. Ultrasonic-Guided Percutaneous Injection of Pancreatic Pseudoaneurysm with Thrombin

    SciTech Connect

    Sparrow, Patrick Asquith, John; Chalmers, Nick

    2003-06-15

    Pancreatic pseudoaneurysm is a relatively uncommon complication of chronic pancreatitis, with an associated high mortality if rupture or hemorrhage occurs. We present a case of pancreatic pseudoaneurysm complicating pancreatitis which was successfully treated by direct percutaneous injection of thrombin into the aneurysmal sac. Follow-up at 8 weeks did not demonstrate recurrence. This case indicates that percutaneous thrombin injection offers effective treatment of visceral arterial pseudoaneurysms.

  4. Atmospheric plasma generates oxygen atoms as oxidizing species in aqueous solutions

    NASA Astrophysics Data System (ADS)

    Mokhtar Hefny, Mohamed; Pattyn, Cedric; Lukes, Petr; Benedikt, Jan

    2016-10-01

    A remote microscale atmospheric pressure plasma jet (µAPPJ) with He, He/H2O, He/O2, and He/O2/H2O gas mixtures was used to study the transport of reactive species from the gas phase into the liquid and the following aqueous phase chemistry. The effects induced by the µAPPJ in water were quantitatively studied using phenol as a chemical probe and by measuring H2O2 concentration and pH values. These results were combined with the analysis of the absolute densities of the reactive species and the modeling of convective/diffusion transport and recombination reactions in the effluent of the plasma jet. Additionally, modified plasma jets were used to show that the role of emitted photons in aqueous chemistry is negligible for these plasma sources. The fastest phenol degradation was measured for the He/O2 plasma, followed by He/H2O, He/O2/H2O, and He plasmas. The modeled quantitative flux of O atoms into the liquid in the He/O2 plasma case was highly comparable with the phenol degradation rate and showed a very high transfer efficiency of reactive species from the plasma into the liquid, where more than half of the O atoms leaving the jet nozzle entered the liquid. The results indicate that the high oxidative effect of He/O2 plasma was primarily due to solvated O atoms, whereas OH radicals dominated the oxidative effects induced in water by plasmas with other gas mixtures. These findings help to understand, in a quantitative way, the complex interaction of cold atmospheric plasmas with aqueous solutions and will allow a better understanding of the interaction of these plasmas with water or buffered solutions containing biological macromolecules, microorganisms, or even eukaryotic cells. Additionally, the µAPPJ He/O2 plasma source seems to be an ideal tool for the generation of O atoms in aqueous solutions for any future studies of their reactivity.

  5. Thrombomodulin Binding Selects the Catalytically Active Form of Thrombin.

    PubMed

    Handley, Lindsey D; Treuheit, Nicholas A; Venkatesh, Varun J; Komives, Elizabeth A

    2015-11-01

    Human α-thrombin is a serine protease with dual functions. Thrombin acts as a procoagulant, cleaving fibrinogen to make the fibrin clot, but when bound to thrombomodulin (TM), it acts as an anticoagulant, cleaving protein C. A minimal TM fragment consisting of the fourth, fifth, and most of the sixth EGF-like domain (TM456m) that has been prepared has much improved solubility, thrombin binding capacity, and anticoagulant activity versus those of previous TM456 constructs. In this work, we compare backbone amide exchange of human α-thrombin in three states: apo, D-Phe-Pro-Arg-chloromethylketone (PPACK)-bound, and TM456m-bound. Beyond causing a decreased level of amide exchange at their binding sites, TM and PPACK both cause a decreased level of amide exchange in other regions including the γ-loop and the adjacent N-terminus of the heavy chain. The decreased level of amide exchange in the N-terminus of the heavy chain is consistent with the historic model of activation of serine proteases, which involves insertion of this region into the β-barrel promoting the correct conformation of the catalytic residues. Contrary to crystal structures of thrombin, hydrogen-deuterium exchange mass spectrometry results suggest that the conformation of apo-thrombin does not yet have the N-terminus of the heavy chain properly inserted for optimal catalytic activity, and that binding of TM allosterically promotes the catalytically active conformation. PMID:26468766

  6. Effect of thrombin and endotoxin on the in vivo metabolism of antithrombin III (AT III) in dogs

    SciTech Connect

    Tanaka, H.; Kobayashi, N.; Maekawa, T.

    1985-11-01

    Effect of thrombin and endotoxin on the metabolism of I-125-labelled canine AT III was studied in mongrel dogs. Under control condition, mean total amount of intravascular AT III with standard deviation was 23.4 +/- 2.4 mg/kg, plasma half life of i.v. injected I-125-AT III was 1.7 +/- 0.2 days, and the fractional catabolic flux (j3x) was 16.3 +/- 1.6 mg/kg/day. The total amount of intra- and extra-vascular AT III was 36.0 +/- 0.34 mg/kg. Neither a 3 hour infusion of a small dose (30 units/kg/hr) of thrombin nor i.v. injection of a large amount of thrombin (5,000-15,000 units/day) with heparin significantly affected AT III metabolism except for a transient decrease in AT III concentration in the latter case, although decrease in plasma fibrinogen concentration and platelet count was observed in both cases. Two injections with 200 micrograms/kg of endotoxin resulted in an evident acceleration of AT III metabolism with significant decrease in the plasma AT III, fibrinogen concentrations and platelet count. More marked changes in AT III metabolism were induced by a single infusion with 1 mg/kg of endotoxin. Changes in hemostatic system coincided with those observed in DIC.

  7. Electromagnetic pulse reflection at self-generated plasma mirrors: Laser pulse shaping and high order harmonic generation

    NASA Astrophysics Data System (ADS)

    Bulanov, S. S.; Macchi, A.; Maksimchuk, A.; Matsuoka, T.; Nees, J.; Pegoraro, F.

    2007-09-01

    A thin layer of overdense plasma is created when an electromagnetic pulse interacts with a rapidly ionizing thin foil. This layer will reflect the incoming pulse, forming a so-called plasma mirror. A simple realistic model based on paired kinetic and wave equations is used to analytically describe the process of mirror formation and the reflection and transmission of the incident pulse. The model incorporates the exact description of the ionization process in the foil and the polarization and conduction currents that follow. The analytical description of the reflected and transmitted pulses as well as their dependence on foil parameters, and initial pulse amplitude and form are presented. Possible application and effectiveness of this process to improve laser pulse contrast are discussed. In the case of the linearly polarized incident pulse, harmonic generation occurs, that is absent in the case of the circular polarization. The spectra of the reflected pulses for different initial forms and amplitudes are studied.

  8. Molecular modeling studies, synthesis and biological evaluation of dabigatran analogues as thrombin inhibitors.

    PubMed

    Dong, Ming-Hui; Chen, Hai-Feng; Ren, Yu-Jie; Shao, Fang-Ming

    2016-01-15

    In this work, 48 thrombin inhibitors based on the structural scaffold of dabigatran were analyzed using a combination of molecular modeling techniques. We generated three-dimensional quantitative structure-activity relationship (3D-QSAR) models based on three alignments for both comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) to highlight the structural requirements for thrombin protein inhibition. In addition to the 3D-QSAR study, Topomer CoMFA model also was established with a higher leave-one-out cross-validation q(2) and a non-cross-validation r(2), which suggest that the three models have good predictive ability. The results indicated that the steric, hydrophobic and electrostatic fields play key roles in QSAR model. Furthermore, we employed molecular docking and re-docking simulation explored the binding relationship of the ligand and the receptor protein in detail. Molecular docking simulations identified several key interactions that were also indicated through 3D-QSAR analysis. On the basis of the obtained results, two compounds were designed and predicted by three models, the biological evaluation in vitro (IC50) demonstrated that these molecular models were effective for the development of novel potent thrombin inhibitors.

  9. Impact of plasma jet vacuum ultraviolet radiation on reactive oxygen species generation in bio-relevant liquids

    NASA Astrophysics Data System (ADS)

    Jablonowski, H.; Bussiahn, R.; Hammer, M. U.; Weltmann, K.-D.; von Woedtke, Th.; Reuter, S.

    2015-12-01

    Plasma medicine utilizes the combined interaction of plasma produced reactive components. These are reactive atoms, molecules, ions, metastable species, and radiation. Here, ultraviolet (UV, 100-400 nm) and, in particular, vacuum ultraviolet (VUV, 10-200 nm) radiation generated by an atmospheric pressure argon plasma jet were investigated regarding plasma emission, absorption in a humidified atmosphere and in solutions relevant for plasma medicine. The energy absorption was obtained for simple solutions like distilled water (dH2O) or ultrapure water and sodium chloride (NaCl) solution as well as for more complex ones, for example, Rosewell Park Memorial Institute (RPMI 1640) cell culture media. As moderate stable reactive oxygen species, hydrogen peroxide (H2O2) was studied. Highly reactive oxygen radicals, namely, superoxide anion (O2•-) and hydroxyl radicals (•OH), were investigated by the use of electron paramagnetic resonance spectroscopy. All species amounts were detected for three different treatment cases: Plasma jet generated VUV and UV radiation, plasma jet generated UV radiation without VUV part, and complete plasma jet including all reactive components additionally to VUV and UV radiation. It was found that a considerable amount of radicals are generated by the plasma generated photoemission. From the experiments, estimation on the low hazard potential of plasma generated VUV radiation is discussed.

  10. Impact of plasma jet vacuum ultraviolet radiation on reactive oxygen species generation in bio-relevant liquids

    SciTech Connect

    Jablonowski, H.; Hammer, M. U.; Reuter, S.; Bussiahn, R.; Weltmann, K.-D.; Woedtke, Th. von

    2015-12-15

    Plasma medicine utilizes the combined interaction of plasma produced reactive components. These are reactive atoms, molecules, ions, metastable species, and radiation. Here, ultraviolet (UV, 100–400 nm) and, in particular, vacuum ultraviolet (VUV, 10–200 nm) radiation generated by an atmospheric pressure argon plasma jet were investigated regarding plasma emission, absorption in a humidified atmosphere and in solutions relevant for plasma medicine. The energy absorption was obtained for simple solutions like distilled water (dH{sub 2}O) or ultrapure water and sodium chloride (NaCl) solution as well as for more complex ones, for example, Rosewell Park Memorial Institute (RPMI 1640) cell culture media. As moderate stable reactive oxygen species, hydrogen peroxide (H{sub 2}O{sub 2}) was studied. Highly reactive oxygen radicals, namely, superoxide anion (O{sub 2}{sup •−}) and hydroxyl radicals ({sup •}OH), were investigated by the use of electron paramagnetic resonance spectroscopy. All species amounts were detected for three different treatment cases: Plasma jet generated VUV and UV radiation, plasma jet generated UV radiation without VUV part, and complete plasma jet including all reactive components additionally to VUV and UV radiation. It was found that a considerable amount of radicals are generated by the plasma generated photoemission. From the experiments, estimation on the low hazard potential of plasma generated VUV radiation is discussed.

  11. Influence of C{sub 60} morphology on high-order harmonic generation enhancement in fullerene-containing plasma

    SciTech Connect

    Ganeev, R. A.; Singhal, H.; Naik, P. A.; Chakera, J. A.; Srivastava, A. K.; Dhami, T. S.; Joshi, M. P.; Gupta, P. D.

    2009-11-15

    The morphologies of the fullerene targets and the ablated fullerenes to determine the optimal conditions of excitation of the C{sub 60}-containing targets have been analyzed. The optimization of fullerene-containing plasma conditions allowed the enhanced harmonic generation in these plasmas using laser radiation of different wavelengths, pulse durations, and phase modulation. A comparison between the harmonic generation in single-atom/ion-containing plasmas (using bulk carbon, silver, and indium targets) and fullerene-rich plasma plumes showed better conversion efficiency for the latter medium. The influence of phase modulation of the fundamental radiation in fullerene plasmas on the spectral properties of harmonics has been studied.

  12. Method for generating extreme ultraviolet with mather-type plasma accelerators for use in Extreme Ultraviolet Lithography

    DOEpatents

    Hassanein, Ahmed; Konkashbaev, Isak

    2006-10-03

    A device and method for generating extremely short-wave ultraviolet electromagnetic wave uses two intersecting plasma beams generated by two plasma accelerators. The intersection of the two plasma beams emits electromagnetic radiation and in particular radiation in the extreme ultraviolet wavelength. In the preferred orientation two axially aligned counter streaming plasmas collide to produce an intense source of electromagnetic radiation at the 13.5 nm wavelength. The Mather type plasma accelerators can utilize tin, or lithium covered electrodes. Tin, lithium or xenon can be used as the photon emitting gas source.

  13. Effects of trypsin, thrombin and proteinase-activated receptors on guinea pig common bile duct motility.

    PubMed

    Huang, Shih-Che

    2012-11-10

    Trypsin and thrombin activate proteinase-activated receptors (PARs), which modulate gastrointestinal motility. The common bile duct is exposed to many proteinases that can activate PARs, especially during infection and stone obstruction. We investigated PAR effects on common bile duct motility in vitro. Contraction and relaxation of isolated guinea pig common bile duct strips caused by PAR(1), PAR(2) and PAR(4) agonists were measured using isometric transducers. Reverse transcription polymerase chain reaction (RT-PCR) was performed to determine the expression of PAR(1) and PAR(2). Thrombin and two PAR(1) peptide agonists, TFLLR-NH(2) and SFLLRN-NH(2), evoked moderate relaxation of the carbachol-contracted common bile duct in a concentration-dependent manner. Trypsin and three PAR(2) peptide agonists, 2-furoyl-LIGRLO-NH(2), SLIGKV-NH(2) and SLIGRL-NH(2), generated moderate to marked relaxation as well. The existence of PAR(1) and PAR(2) mRNA in the common bile duct was identified by RT-PCR. Moreover, two PAR(4)-selective agonists, AYPGKF-NH(2) and GYPGQV-NH(2), produced relaxation of the common bile duct. In contrast, all PAR(1), PAR(2) and PAR(4) inactive control peptides did not elicit relaxation. This indicates that PAR(1), PAR(2) and PAR(4) mediate common bile duct relaxation. The thrombin, TFLLR-NH(2), trypsin, and AYPGKF-NH(2)-induced responses were not affected by tetrodotoxin, implying that the PAR effects are not neurally mediated. Our findings provide the first evidence that PAR(1) and PAR(2) mediate whereas agonists of PAR(4) elicit relaxation of the guinea pig common bile duct. Trypsin and thrombin relax the common bile duct. PARs may play an important role in the control of common bile duct motility. PMID:22960409

  14. Waves in plasmas generated by a rotating magnetic field and implications to radiation belts

    NASA Astrophysics Data System (ADS)

    Karavaev, Alexey V.

    The interaction of rotating magnetic fields (RMF) with magnetized plasmas is a fundamental plasma physics problem with implications to a wide range of areas, including laboratory and space plasma physics. Despite the importance of the topic the basic physics of the phenomenon remains unexplored. An important application of a RMF is its potential use as an efficient radiation source of low frequency waves in space plasmas, including whistler and shear Alfvéen waves (SAW) for controlled remediation of energetic particles in the Earth's radiation belts. In this dissertation the RMF waves generated in magnetized plasma are studied using numerical simulations with a semi-analytical three-dimensional magneto-hydrodynamic (MHD) model and experiments on the generation of whistler and magnetohydrodynamic waves conducted in UCLA's Large Plasma Device. Comparisons of the simulation results with the experimental measurements, namely, measured spatiotemporal wave structures, dispersion relation with finite transverse wave number, wave amplitude dependence on plasma and RMF source parameters, show good agreement in both the whistler and MHD wave regimes. In both the experiments and the 3D MHD simulations a RMF source was found to be very efficient in the generation of MHD and whistler waves with arbitrary polarizations. The RMF source drives significant field aligned plasma currents confined by the ambient magnetic field for both the whistler and MHD wave regimes, resulting in efficient transport of wave energy along the ambient magnetic field. The efficient transfer of the wave energy results in slow decay rates of the wave amplitude along the ambient magnetic field. The circular polarization of the waves generated by the RMF source, slow amplitude decay rate along the ambient magnetic field and nonzero transverse wave number determined by the RMF source size lead to nonlocal gradients of the wave magnetic field in the direction perpendicular to the ambient magnetic field. A

  15. Management of anti-thrombin III deficiency during pregnancy without administration of anti-thrombin III.

    PubMed

    Leclerc, J R; Geerts, W; Panju, A; Nguyen, P; Hirsh, J

    1986-02-15

    We report a patient with hereditary antithrombin III deficiency who was successfully treated with heparin throughout pregnancy. Functional antithrombin III levels fell to 0.32 U/ml during heparin treatment, but it was possible to achieve a heparin effect, measured by the activated partial thromboplastin time, thrombin clotting time and heparin assay with subcutaneous heparin in doses of 30,000 U to 35,000 U/24 hours. This achieve an long term heparin effect was obtained without the need for antithrombin III infusions.

  16. Evaluation of Ash Toxicity Generated From the Thermal Plasma Pyrolysis of Used Automobile Tires

    NASA Astrophysics Data System (ADS)

    Chang, J. S.; Novog, D. R.; Jamal, S.

    1996-10-01

    The disposal of used tires represents a severe environmental problem. As the heat content of the rubber tires is even higher than that of coal it should be considered as a future source of alternate fuel for power generation. There have been attempts to burn old tires directly in cofired boilers for production of electricity. However, there are several environmental concerns since the combustion flue gas may contain a significant concentration heavy metals (Fe, Zn, Cd, As, etc.). One technique currently being developed is the pyrolyzation of rubber tires by a thermal plasma to produce combustible gases. In this work, ashes generated during the plasma pyrolysis of used automobile tires using a DC Argon thermal plasma were analyzed using Neutron Activation Analysis (NAA) and produced syngas composition was analyzed by FT-IR.. The gas analysis indicates a significant quantity of combustible gases (CH4, C2H2, C2H4, CO, H2 etc..) was produced from the thermal plasma pyrolysis of used tires. The results also indicate that a majority of the heavy metals present in used tires were concentrated in the ashes deposited in reaction chamber wall and in the two-stage filtering system. Furthermore the heavy metal concentration decreases significantly with increasing distance from the plasma torch. Toxic components such as Zn, As and Cl were also collected in the filtering process.

  17. Scavenging of hydroxyl radicals generated in human plasma following X-ray irradiation.

    PubMed

    Hosokawa, Yoichiro; Sano, Tomoaki

    2015-11-01

    There are various antioxidant materials that scavenge free radicals in human plasma. It is possible that the radical-scavenging function causes a radiation protective effect in humans. This study estimated the hydroxyl (OH) radical-scavenging activity induced by X-ray irradiation in human plasma. The test subjects included 111 volunteers (75 males and 36 females) ranging from 22 to 35 years old (average, 24.0). OH radicals generated in irradiated human plasma were measured by electron spin resonance (ESR). The relationships between the amount of the OH radical and chemical and biological parameters [total protein, total cholesterol, triglycerides and hepatitis B surface (HBs) antibodies] were estimated in the plasma of the 111 volunteers by a multivariate analysis. The presence of HBs antibodies had the greatest influence on OH radical-scavenging activity. One volunteer who did not have the HBs antibody was given an inoculation of the hepatitis B vaccine. There was a remarkable decrease in the amount of OH radical generated from plasma after the HBs antibody was produced. The results indicate that the HBs antibody is an important factor for the scavenging of OH radicals initiated by X-ray irradiation in the human body.

  18. Modeling of the plasma generated in a rarefied hypersonic shock layer

    SciTech Connect

    Farbar, Erin D.; Boyd, Iain D.

    2010-10-15

    In this study, a rigorous numerical model is developed to simulate the plasma generated in a rarefied, hypersonic shock layer. The model uses the direct simulation Monte Carlo (DSMC) method to treat the particle collisions and the particle-in-cell (PIC) method to simulate the plasma dynamics in a self-consistent manner. The model is applied to compute the flow along the stagnation streamline in front of a blunt body reentering the Earth's atmosphere at very high velocity. Results from the rigorous DSMC-PIC model are compared directly to the standard DSMC modeling approach that uses the ambipolar diffusion approximation to simulate the plasma dynamics. It is demonstrated that the self-consistent computation of the plasma dynamics using the rigorous DSMC-PIC model captures many physical phenomena not accurately predicted by the standard modeling approach. These computations represent the first assessment of the validity of the ambipolar diffusion approximation when predicting the rarefied plasma generated in a hypersonic shock layer.

  19. Nitrogen Gas Plasma Generated by a Static Induction Thyristor as a Pulsed Power Supply Inactivates Adenovirus

    PubMed Central

    Sakudo, Akikazu; Toyokawa, Yoichi; Imanishi, Yuichiro

    2016-01-01

    Adenovirus is one of the most important causative agents of iatrogenic infections derived from contaminated medical devices or finger contact. In this study, we investigated whether nitrogen gas plasma, generated by applying a short high-voltage pulse to nitrogen using a static induction thyristor power supply (1.5 kilo pulse per second), exhibited a virucidal effect against adenoviruses. Viral titer was reduced by one log within 0.94 min. Results from detection of viral capsid proteins, hexon and penton, by Western blotting and immunochromatography were unaffected by the plasma treatment. In contrast, analysis using the polymerase chain reaction suggested that plasma treatment damages the viral genomic DNA. Reactive chemical products (hydrogen peroxide, nitrate, and nitrite), ultraviolet light (UV-A) and slight temperature elevations were observed during the operation of the gas plasma device. Viral titer versus intensity of each potential virucidal factor were used to identify the primary mechanism of disinfection of adenovirus. Although exposure to equivalent levels of UV-A or heat treatment did not inactivate adenovirus, treatment with a relatively low concentration of hydrogen peroxide efficiently inactivated the virus. Our results suggest the nitrogen gas plasma generates reactive chemical products that inactivate adenovirus by damaging the viral genomic DNA. PMID:27322066

  20. Nitrogen Gas Plasma Generated by a Static Induction Thyristor as a Pulsed Power Supply Inactivates Adenovirus.

    PubMed

    Sakudo, Akikazu; Toyokawa, Yoichi; Imanishi, Yuichiro

    2016-01-01

    Adenovirus is one of the most important causative agents of iatrogenic infections derived from contaminated medical devices or finger contact. In this study, we investigated whether nitrogen gas plasma, generated by applying a short high-voltage pulse to nitrogen using a static induction thyristor power supply (1.5 kilo pulse per second), exhibited a virucidal effect against adenoviruses. Viral titer was reduced by one log within 0.94 min. Results from detection of viral capsid proteins, hexon and penton, by Western blotting and immunochromatography were unaffected by the plasma treatment. In contrast, analysis using the polymerase chain reaction suggested that plasma treatment damages the viral genomic DNA. Reactive chemical products (hydrogen peroxide, nitrate, and nitrite), ultraviolet light (UV-A) and slight temperature elevations were observed during the operation of the gas plasma device. Viral titer versus intensity of each potential virucidal factor were used to identify the primary mechanism of disinfection of adenovirus. Although exposure to equivalent levels of UV-A or heat treatment did not inactivate adenovirus, treatment with a relatively low concentration of hydrogen peroxide efficiently inactivated the virus. Our results suggest the nitrogen gas plasma generates reactive chemical products that inactivate adenovirus by damaging the viral genomic DNA. PMID:27322066

  1. Nitrogen Gas Plasma Generated by a Static Induction Thyristor as a Pulsed Power Supply Inactivates Adenovirus.

    PubMed

    Sakudo, Akikazu; Toyokawa, Yoichi; Imanishi, Yuichiro

    2016-01-01

    Adenovirus is one of the most important causative agents of iatrogenic infections derived from contaminated medical devices or finger contact. In this study, we investigated whether nitrogen gas plasma, generated by applying a short high-voltage pulse to nitrogen using a static induction thyristor power supply (1.5 kilo pulse per second), exhibited a virucidal effect against adenoviruses. Viral titer was reduced by one log within 0.94 min. Results from detection of viral capsid proteins, hexon and penton, by Western blotting and immunochromatography were unaffected by the plasma treatment. In contrast, analysis using the polymerase chain reaction suggested that plasma treatment damages the viral genomic DNA. Reactive chemical products (hydrogen peroxide, nitrate, and nitrite), ultraviolet light (UV-A) and slight temperature elevations were observed during the operation of the gas plasma device. Viral titer versus intensity of each potential virucidal factor were used to identify the primary mechanism of disinfection of adenovirus. Although exposure to equivalent levels of UV-A or heat treatment did not inactivate adenovirus, treatment with a relatively low concentration of hydrogen peroxide efficiently inactivated the virus. Our results suggest the nitrogen gas plasma generates reactive chemical products that inactivate adenovirus by damaging the viral genomic DNA.

  2. High-order harmonic generation from C{sub 60}-rich plasma

    SciTech Connect

    Ganeev, R. A.; Elouga Bom, L. B.; Ozaki, T.; Wong, M. C. H.; Brichta, J.-P.; Bhardwaj, V. R.; Redkin, P. V.

    2009-10-15

    We performed systematic investigation of high-order harmonic generation from fullerene-rich laser-produced plasmas. We studied harmonic generation by varying several experimental parameters, such as the delay between the ablation and driving pulses, and divergence and polarization of the pump laser. Enhancement of harmonic yield is observed near 20 eV, which is attributed to the influence of a broadband plasmon resonance of C{sub 60} on the nonlinear optical response of fullerene-rich plasma. This increase in the harmonic intensity occurs despite the increased absorption by C{sub 60} at these wavelengths. Using simulations based on time-dependent density-functional theory, we confirm that this effect is due to the influence of collective excitations. We compare harmonic generation from fullerenes using lasers with 793 nm and 396 nm wavelengths, which show the influence of plasmon resonance on the conversion efficiency of high-order harmonics for different laser wavelengths.

  3. Development of plasma streamwise vortex generators for increased boundary layer control authority

    NASA Astrophysics Data System (ADS)

    Bowles, Patrick; Schatzman, David; Corke, Thomas; Thomas, Flint

    2009-11-01

    This experimental study focuses on active boundary layer flow control utilizing streamwise vorticity produced by a single dielectric barrier discharge plasma actuator. A novel plasma streamwise vortex generator (PSVG) layout is presented that mimics the passive flow control characteristics of the trapezoidal vane vortex generator. The PSVG consists of a common insulated electrode and multiple, exposed streamwise oriented electrodes used to produce counter-rotating vortical structures. Smoke and oil surface visualization of boundary layer flow over a flat plate compare the characteristics of passive control techniques and different PSVG designs. Passive and active control over a generic wall-mounted hump model, Rec = 288,000-575,000, are compared through static wall pressure measurements along the model's centerline. Different geometric effects of the PSVG electrode configuration were investigated. PSVG's with triangular exposed electrodes outperformed ordinary PSVG's under certain circumstances. The electrode arrangement produced flow control mechanisms and effectiveness similar to the passive trapezoidal vane vortex generators.

  4. Third harmonic generation in air ambient and laser ablated carbon plasma

    SciTech Connect

    Singh, Ravi Pratap Gupta, Shyam L.; Thareja, Raj K.

    2015-12-15

    We report the third harmonic generation of a nanosecond laser pulse (1.06 μm) in air ambient and in the presence of nanoparticles from laser ablated carbon plasma. Significant decrease in the threshold of third harmonic generation and multi-fold increment in the intensity of generated third harmonic is observed in presence of carbon plasma. The third harmonic in air is due to the quasi-resonant four photon process involving vibrationally excited states of molecular ion of nitrogen due to electron impact ionization and laser pulse. Following optical emission spectroscopic observations we conclude that the presence of C{sub 2} and CN in the ablated plume play a vital role in the observed third harmonic signals.

  5. Free radical generation and concentration in a plasma polymer: the effect of aromaticity.

    PubMed

    Ershov, Sergey; Khelifa, Farid; Lemaur, Vincent; Cornil, Jérôme; Cossement, Damien; Habibi, Youssef; Dubois, Philippe; Snyders, Rony

    2014-08-13

    Plasma polymer films (PPF) have increasing applications in many fields due to the unique combination of properties of this class of materials. Among notable features arising from the specifics of plasma polymerization synthesis, a high surface reactivity can be advantageously used when exploited carefully. It is related to the presence of free radicals generated during the deposition process through manifold molecular bond scissions in the energetic plasma environment. In ambient atmosphere, these radicals undergo autoxidation reactions resulting in undesired polymer aging. However, when the reactivity of surface radicals is preserved and they are put in direct contact with a chemical group of interest, a specific surface functionalization or grafting of polymeric chains can be achieved. Therefore, the control of the surface free radical density of a plasma polymer is crucially important for a successful grafting. The present investigation focuses on the influence of the hydrocarbon precursor type, aromatic vs aliphatic, on the generation and concentration of free radicals on the surface of the PPF. Benzene and cyclohexane were chosen as model precursors. First, in situ FTIR analysis of the plasma phase supplemented by density functional theory calculations allowed the main fragmentation routes of precursor molecules in the discharge to be identified as a function of energy input. Using nitric oxide (NO) chemical labeling in combination with X-ray photoelectron spectroscopy analysis, a quantitative evaluation of concentration of surface free radicals as a function of input power has been assessed for both precursors. Different evolutions of the surface free radical density for the benzene- and cyclohexane-based PPF, namely, a continuous increase versus stabilization to a plateau, are attributed to different plasma polymerization mechanisms and resulting structures as illustrated by PPF characterization findings. The control of surface free radical density can be

  6. Modeling and experiments on differential pumping in linear plasma generators operating at high gas flows

    SciTech Connect

    Eck, H. J. N. van; Koppers, W. R.; Rooij, G. J. van; Goedheer, W. J.; Cardozo, N. J. Lopes; Kleyn, A. W.; Engeln, R.; Schram, D. C.

    2009-03-15

    The direct simulation Monte Carlo (DSMC) method was used to investigate the efficiency of differential pumping in linear plasma generators operating at high gas flows. Skimmers are used to separate the neutrals from the plasma beam, which is guided from the source to the target by a strong axial magnetic field. In this way, the neutrals are prevented to reach the target region. The neutral flux to the target must be lower than the plasma flux to enable ITER relevant plasma-surface interaction (PSI) studies. It is therefore essential to control the neutral gas dynamics. The DSMC method was used to model the expansion of a hot gas in a low pressure vessel where a small discrepancy in shock position was found between the simulations and a well-established empirical formula. Two stage differential pumping was modeled and applied in the linear plasma devices Pilot-PSI and PLEXIS. In Pilot-PSI a factor of 4.5 pressure reduction for H{sub 2} has been demonstrated. Both simulations and experiments showed that the optimum skimmer position depends on the position of the shock and therefore shifts for different gas parameters. The shape of the skimmer has to be designed such that it has a minimum impact on the shock structure. A too large angle between the skimmer and the forward direction of the gas flow leads to an influence on the expansion structure. A pressure increase in front of the skimmer is formed and the flow of the plasma beam becomes obstructed. It has been shown that a skimmer with an angle around 53 deg. gives the best performance. The use of skimmers is implemented in the design of the large linear plasma generator Magnum-PSI. Here, a three stage differentially pumped vacuum system is used to reach low enough neutral pressures near the target, opening a door to PSI research in the ITER relevant regime.

  7. Nitric Oxide Studies in Low Temperature Plasmas Generated with a Nanosecond Pulse Sphere Gap Electrical Discharge

    NASA Astrophysics Data System (ADS)

    Burnette, David Dean

    This dissertation presents studies of NO kinetics in a plasma afterglow using various nanosecond pulse discharges across a sphere gap. The discharge platform is developed to produce a diffuse plasma volume large enough to allow for laser diagnostics in a plasma that is rich in vibrationally-excited molecules. This plasma is characterized by current and voltage traces as well as ICCD and NO PLIF images that are used to monitor the plasma dimensions and uniformity. Temperature and vibrational loading measurements are performed via coherent anti-Stokes Raman spectroscopy (CARS). Absolute NO concentrations are obtained by laser-induce fluorescence (LIF) measurements, and N and O densities are found using two photon absorption laser-induced fluorescence (TALIF). For all dry air conditions studied, the NO behavior is characterized by a rapid rate of formation consistent with an enhanced Zeldovich process involving electronically-excited nitrogen species that are generated within the plasma. After several microseconds, the NO evolution is entirely controlled by the reverse Zeldovich process. These results show that under the chosen range of conditions and even in extreme instances of vibrational loading, there is no formation channel beyond ~2 musec. Both the NO formation and consumption mechanisms are strongly affected by the addition of fuel species, producing much greater NO concentrations in the afterglow.

  8. Characteristics of a long and stable filamentary argon plasma jet generated in ambient atmosphere

    NASA Astrophysics Data System (ADS)

    Teodorescu, M.; Bazavan, M.; Ionita, E. R.; Dinescu, G.

    2015-04-01

    We present a study of a long (up to 60 mm) and thin (600 μm) plasma jet generated at 13.56 MHz in argon expanding in an open atmosphere from inside of a thin glass tube. The discharge is operated with one annular external electrode on the tube, in the absence of any grounded electrode in the discharge proximity. The study comprises image, spectral and electrical measurements, aiming to define and understand the operating domains of this plasma jet source. Two plasma zones were identified, which coexist: a long filament accompanied by a diffuse discharge. The coexistence of these plasma zones was studied in the power-mass flow rate parameter space. An electric model is proposed, considering the jet as a radiating antenna, which allows the determination of the main electrical parameters like capacitance, resistance and active RF power dissipated in the discharge. The specific zones on the I-V characteristics were assigned to the operating domains observed visually. The spectral emission of plasma has been used to characterize the jet in respect to the gas temperature, excitation temperature and plasma density.

  9. Formation of the compression zone in a plasma flow generated by a magnetoplasma compressor

    SciTech Connect

    Solyakov, D. G. Petrov, Yu. V.; Garkusha, I. E.; Chebotarev, V. V.; Ladygina, M. S.; Cherednichenko, T. N.; Morgal’, Ya. I.; Kulik, N. V.; Stal’tsov, V. V.; Eliseev, D. V.

    2013-12-15

    Processes occurring in a plasma flow generated by a magnetoplasma compressor (MPC) during the formation of the compression zone are discussed. The paper presents results of measurements of the spatial distribution of the electric current in the plasma flow, the temporal and spatial (along the flow) distributions of the plasma density, and the profiles of the velocity of individual flow layers along the system axis. The spatial distribution of the electromagnetic force in the flow is analyzed. It is shown that the plasma flow is decelerated when approaching the compression zone and reaccelerated after passing it. In this case, the plasma flow velocity decreases from ν = (2–3) × 10{sup 7} cm/s at the MPC output to ν < 10{sup 6} cm/s in the region of maximum compression and then again increases to 10{sup 7} cm/s at a distance of 15–17 cm from the MPC output. In some MPC operating modes, a displacement of the magnetic field from the compression zone and the formation of toroidal electric current vortices in the plasma flow after passing the compression zone were detected.

  10. Effect of Ti-Al cathode composition on plasma generation and plasma transport in direct current vacuum arc

    SciTech Connect

    Zhirkov, I. Petruhins, A.; Dahlqvist, M.; Ingason, A. S.; Rosen, J.; Eriksson, A. O.

    2014-03-28

    DC arc plasma from Ti, Al, and Ti{sub 1-x}Al{sub x} (x = 0.16, 0.25, 0.50, and 0.70) compound cathodes was characterized with respect to plasma chemistry and charge-state-resolved ion energy. Scanning electron microscopy, X-ray diffraction, and Energy-dispersive X-ray spectroscopy of the deposited films and the cathode surfaces were used for exploring the correlation between cathode-, plasma-, and film composition. Experimental work was performed at a base pressure of 10{sup −6} Torr, to exclude plasma-gas interaction. The plasma ion composition showed a reduction of Al of approximately 5 at. % compared to the cathode composition, while deposited films were in accordance with the cathode stoichiometry. This may be explained by presence of neutrals in the plasma/vapour phase. The average ion charge states (Ti = 2.2, Al = 1.65) were consistent with reference data for elemental cathodes, and approximately independent on the cathode composition. On the contrary, the width of the ion energy distributions (IEDs) were drastically reduced when comparing the elemental Ti and Al cathodes with Ti{sub 0.5}Al{sub 0.5}, going from ∼150 and ∼175 eV to ∼100 and ∼75 eV for Ti and Al ions, respectively. This may be explained by a reduction in electron temperature, commonly associated with the high energy tail of the IED. The average Ti and Al ion energies ranged between ∼50 and ∼61 eV, and ∼30 and ∼50 eV, respectively, for different cathode compositions. The attained energy trends were explained by the velocity rule for compound cathodes, which states that the most likely velocities of ions of different mass are equal. Hence, compared to elemental cathodes, the faster Al ions will be decelerated, and the slower Ti ions will be accelerated when originating from compound cathodes. The intensity of the macroparticle generation and thickness of the deposited films were also found to be dependent on the cathode composition. The presented results

  11. Influence of impact conditions on plasma generation during hypervelocity impact by aluminum projectile

    NASA Astrophysics Data System (ADS)

    Song, Weidong; Lv, Yangtao; Li, Jianqiao; Wang, Cheng; Ning, Jianguo

    2016-07-01

    For describing hypervelocity impact (relative low-speed as related to space debris and much lower than travelling speed of meteoroids) phenomenon associated with plasma generation, a self-developed 3D code was advanced to numerically simulate projectiles impacting on a rigid wall. The numerical results were combined with a new ionization model which was developed in an early study to calculate the ionized materials during the impact. The calculated results of ionization were compared with the empirical formulas concluded by experiments in references and a good agreement was obtained. Then based on the reliable 3D numerical code, a series of impacts with different projectile configurations were simulated to investigate the influence of impact conditions on hypervelocity impact generated plasma. It was found that the form of empirical formula needed to be modified. A new empirical formula with a critical impact velocity was advanced to describe the velocity dependence of plasma generation and the parameters of the modified formula were ensured by the comparison between the numerical predictions and the empirical formulas. For different projectile configurations, the changes of plasma charges with time are different but the integrals of charges on time almost stayed in the same level.

  12. Two-dimensional calculations of a continuous optical discharge in atmospheric air flow (optical plasma generator)

    NASA Astrophysics Data System (ADS)

    Raizer, Iu. P.; Silant'ev, A. Iu.; Surzhikov, S. T.

    1987-06-01

    Two-dimensional gasdynamic processes in a continuous optical discharge in subsonic flow of atmospheric air are simulated numerically with allowance for distortions of the light channel due to laser beam refraction in the generated plasma, radiative energy losses, and radiant heat transfer. It is found that instabilities and vortex structures are formed in the hot jet behind the energy release region; flow in this region is nonstationary but periodic. These effects are not observed in the main part of the discharge, which is quite stable. Depending on flow velocity, diffraction in the plasma may lead to both defocusing and focusing of the beam.

  13. Surface plasma wave assisted second harmonic generation of laser over a metal film

    SciTech Connect

    Chauhan, Santosh; Parashar, J.

    2015-01-15

    Second harmonic generation of laser mode converted surface plasma wave (SPW) over a corrugated metal film is studied. The laser, impinged on the metal film, under attenuated total reflection configuration, excites SPW over the metal–vacuum interface. The excited SPW extends over a much wider surface area than the laser spot cross-section. It exerts a second harmonic ponderomotive force on metal electrons, imparting them velocity that beats with the surface ripple to produce a nonlinear current, driving resonant second harmonic surface plasma wave.

  14. Intense isolated attosecond pulse generation from relativistic laser plasmas using few-cycle laser pulses

    SciTech Connect

    Ma, Guangjin; Dallari, William; Borot, Antonin; Tsakiris, George D.; Veisz, Laszlo; Krausz, Ferenc; Yu, Wei

    2015-03-15

    We have performed a systematic study through particle-in-cell simulations to investigate the generation of attosecond pulse from relativistic laser plasmas when laser pulse duration approaches the few-cycle regime. A significant enhancement of attosecond pulse energy has been found to depend on laser pulse duration, carrier envelope phase, and plasma scale length. Based on the results obtained in this work, the potential of attaining isolated attosecond pulses with ∼100 μJ energy for photons >16 eV using state-of-the-art laser technology appears to be within reach.

  15. Combined flux compression and plasma opening switch on the Saturn pulsed power generator.

    PubMed

    Felber, Franklin S; Waisman, Eduardo M; Mazarakis, Michael G

    2010-05-01

    A wire-array flux-compression cartridge installed on Sandia's Saturn pulsed power generator doubled the current into a 3-nH load to 6 MA and halved its rise time to 100 ns. The current into the load, however, was unexpectedly delayed by almost 1 micros. Estimates of a plasma flow switch acting as a long-conduction-time opening switch are consistent with key features of the power compression. The results suggest that microsecond-conduction-time plasma flow switches can be combined with flux compression both to amplify currents and to sharpen pulse rise times in pulsed power drivers.

  16. Combined Flux Compression and Plasma Opening Switch on the Saturn Pulsed Power Generator

    SciTech Connect

    Felber, Franklin S.; Waisman, Eduardo M.; Mazarakis, Michael G.

    2010-05-07

    A wire-array flux-compression cartridge installed on Sandia's Saturn pulsed power generator doubled the current into a 3-nH load to 6 MA and halved its rise time to 100 ns. The current into the load, however, was unexpectedly delayed by almost 1 {mu}s. Estimates of a plasma flow switch acting as a long-conduction-time opening switch are consistent with key features of the power compression. The results suggest that microsecond-conduction-time plasma flow switches can be combined with flux compression both to amplify currents and to sharpen pulse rise times in pulsed power drivers.

  17. Extremely high-pressure generation and compression with laser implosion plasmas

    SciTech Connect

    Shigemori, K.; Hironaka, Y.; Nagatomo, H.; Fujioka, S.; Azechi, H.; Sunahara, A.; Kadono, T.; Shimizu, K.

    2013-05-06

    We have tested a scheme for using laser implosion plasmas to generate pressures in the gigabar (100 TPa) regime. Cone-in-shell targets employed in fast ignition of inertial confinement fusion were irradiated to create a high-pressure source for compression of materials. The imploded plasmas pushed a foil embedded on the tip of a cone. The pressure was estimated from the shock velocity into the material; the shock velocity was obtained from an optical measurement. The measured shock velocity of the foil was above 100 km/s, corresponding to a pressure greater than 1 Gbar.

  18. Thrombin-cleaved Fragments of Osteopontin Are Overexpressed in Malignant Glial Tumors and Provide a Molecular Niche with Survival Advantage*

    PubMed Central

    Yamaguchi, Yasuto; Shao, Zhifei; Sharif, Shadi; Du, Xiao-Yan; Myles, Timothy; Merchant, Milton; Harsh, Griffith; Glantz, Michael; Recht, Lawrence; Morser, John; Leung, Lawrence L. K.

    2013-01-01

    Osteopontin (OPN), which is highly expressed in malignant glioblastoma (GBM), possesses inflammatory activity modulated by proteolytic cleavage by thrombin and plasma carboxypeptidase B2 (CPB2) at a highly conserved cleavage site. Full-length OPN (OPN-FL) was elevated in cerebrospinal fluid (CSF) samples from all cancer patients compared with noncancer patients. However, thrombin-cleaved OPN (OPN-R) and thrombin/CPB2-double-cleaved OPN (OPN-L) levels were markedly increased in GBM and non-GBM gliomas compared with systemic cancer and noncancer patients. Cleaved OPN constituted ∼23 and ∼31% of the total OPN in the GBM and non-GBM CSF samples, respectively. OPN-R was also elevated in GBM tissues. Thrombin-antithrombin levels were highly correlated with cleaved OPN, but not OPN-FL, suggesting that the cleaved OPN fragments resulted from increased thrombin and CPB2 in this extracellular compartment. Levels of VEGF and CCL4 were increased in CSF of GBM and correlated with the levels of cleaved OPN. GBM cell lines were more adherent to OPN-R and OPN-L than OPN-FL. Adhesion to OPN altered gene expression, in particular genes involved with cellular processes, cell cycle regulation, death, and inflammation. OPN and its cleaved forms promoted motility of U-87 MG cells and conferred resistance to apoptosis. Although functional mutation of the RGD motif in OPN largely abolished these functions, OPNRAA-R regained significant cell binding and signaling function, suggesting that the SVVYGLR motif in OPN-R may substitute for the RGD motif if the latter becomes inaccessible. OPN cleavage contributes to GBM development by allowing more cells to bind in niches where they acquire anti-apoptotic properties. PMID:23204518

  19. A high-power low-temperature air plasma generator with a divergent channel of the output electrode

    NASA Astrophysics Data System (ADS)

    Gadzhiev, M. Kh.; Isakaev, E. Kh.; Tyuftyaev, A. S.; Yusupov, D. I.

    2016-01-01

    We have developed and studied a powerful high-enthalpy (H ≥ 20 kJ/g) air plasma jet generator with a divergent channel of the output electrode, which belongs to the class of dc plasmatrons with a thermionic cathode. The plasma generator possesses an efficiency of about 80% and ensures the formation of slightly divergent (2± = 12°) plasma jet with diameter D = 50 mm and a mass-average temperature of 6000-9000 K.

  20. Impedance Mismatch study between the Microwave Generator and the PUPR Plasma Machine

    NASA Astrophysics Data System (ADS)

    Gaudier, Jorge R.; Castellanos, Ligeia; Encarnación, Kabir; Zavala, Natyaliz; Rivera, Ramón; Farahat, Nader; Leal, Edberto

    2006-12-01

    Impedance mismatch inside the connection from the microwave power generator to the plasma machine is studied. A magnetron power generator transmits microwaves of 2.45 GHz and variable power from 50W to 5000W, through a flexible rectangular waveguide to heat plasma inside a Mirror Cusp devise located at the Polytechnic University of Puerto Rico. Before the production of plasma, the residual gas of the devise must be extracted by a vacuum system (5Torr or better), then Argon gas is injected to the machine. The microwaves heat the Argon ions to initiate ionization and plasma is produced. A dielectric wall is used inside the rectangular waveguide to isolate the plasma machine and maintain vacuum. Even though the dielectric will not block the wave propagation, some absorption of microwaves will occur. This absorption will cause reflection, reducing the efficiency of the power transfer. Typically a thin layer of Teflon is used, but measurements using this dielectric show a significant reflection of power back to the generator. Due to the high-power nature of the generator (5KW), this mismatch is not desirable. An electromagnetic field solver based on the Finite Difference Time Domain Method(FDTD) is used to model the rectangular waveguide connection. The characteristic impedance of the simulation is compared with the analytical formula expression and a good agreement is obtain. Furthermore the Teflon-loaded guide is modeled using the above program and the input impedance is computed. The reflection coefficient is calculated based on the transmission line theory with the characteristic and input impedances. Based on the simulation results it is possible to optimize the thickness, shape and dielectric constant of the material, in order to seal the connection with a better match.

  1. Impedance Mismatch study between the Microwave Generator and the PUPR Plasma Machine

    SciTech Connect

    Gaudier, Jorge R.; Castellanos, Ligeia; Encarnacion, Kabir; Zavala, Natyaliz; Rivera, Ramon; Farahat, Nader; Leal, Edberto

    2006-12-04

    Impedance mismatch inside the connection from the microwave power generator to the plasma machine is studied. A magnetron power generator transmits microwaves of 2.45 GHz and variable power from 50W to 5000W, through a flexible rectangular waveguide to heat plasma inside a Mirror Cusp devise located at the Polytechnic University of Puerto Rico. Before the production of plasma, the residual gas of the devise must be extracted by a vacuum system (5Torr or better), then Argon gas is injected to the machine. The microwaves heat the Argon ions to initiate ionization and plasma is produced. A dielectric wall is used inside the rectangular waveguide to isolate the plasma machine and maintain vacuum. Even though the dielectric will not block the wave propagation, some absorption of microwaves will occur. This absorption will cause reflection, reducing the efficiency of the power transfer. Typically a thin layer of Teflon is used, but measurements using this dielectric show a significant reflection of power back to the generator. Due to the high-power nature of the generator (5KW), this mismatch is not desirable. An electromagnetic field solver based on the Finite Difference Time Domain Method(FDTD) is used to model the rectangular waveguide connection. The characteristic impedance of the simulation is compared with the analytical formula expression and a good agreement is obtain. Furthermore the Teflon-loaded guide is modeled using the above program and the input impedance is computed. The reflection coefficient is calculated based on the transmission line theory with the characteristic and input impedances. Based on the simulation results it is possible to optimize the thickness, shape and dielectric constant of the material, in order to seal the connection with a better match.

  2. The Effects of Thrombin on Adenyl Cyclase Activity and a Membrane Protein from Human Platelets

    PubMed Central

    Brodie, G. N.; Baenziger, Nancy Lewis; Chase, Lewis R.; Majerus, Philip W.

    1972-01-01

    Washed human platelets were incubated with 0.1-1.0 U/ml human thrombin and the effects on adenyl cyclase activity and on a platelet membrane protein (designated thrombin-sensitive protein) were studied. Adenyl cyclase activity was decreased 70-90% when intact platelets were incubated with thrombin. The T½ for loss of adenyl cyclase activity was less than 15 sec at 1 U/ml thrombin. There was no decrease of adenyl cyclase activity when sonicated platelets or isolated membranes were incubated with these concentrations of thrombin. Loss of adenyl cyclase activity was relatively specific since the activities of other platelet membrane enzymes were unaffected by thrombin. Prior incubation of platelets with dibutyryl cyclic adenosine monophosphate (AMP), prostaglandin E1, or theophylline protected adenyl cyclase from inhibition by thrombin. Incubation of intact but not disrupted platelets with thrombin resulted in the release of thrombin-sensitive protein from the platelet membrane. The rapid release of this protein (T½ < 15 sec) at low concentrations of thrombin suggested that removal of thrombin-sensitive protein from the platelet membrane is an integral part of the platelet release reaction. This hypothesis is supported by the parallel effects of thrombin on adenyl cyclase activity and thrombin-sensitive protein release in the presence of dibutyryl cyclic AMP, prostaglandin E1, and theophylline at varying concentrations of thrombin. Images PMID:4331802

  3. Megagauss field generation for high-energy-density plasma science experiments.

    SciTech Connect

    Rovang, Dean Curtis; Struve, Kenneth William; Porter, John Larry Jr.

    2008-10-01

    There is a need to generate magnetic fields both above and below 1 megagauss (100 T) with compact generators for laser-plasma experiments in the Beamlet and Petawatt test chambers for focused research on fundamental properties of high energy density magnetic plasmas. Some of the important topics that could be addressed with such a capability are magnetic field diffusion, particle confinement, plasma instabilities, spectroscopic diagnostic development, material properties, flux compression, and alternate confinement schemes, all of which could directly support experiments on Z. This report summarizes a two-month study to develop preliminary designs of magnetic field generators for three design regimes. These are, (1) a design for a relatively low-field (10 to 50 T), compact generator for modest volumes (1 to 10 cm3), (2) a high-field (50 to 200 T) design for smaller volumes (10 to 100 mm3), and (3) an extreme field (greater than 600 T) design that uses flux compression. These designs rely on existing Sandia pulsed-power expertise and equipment, and address issues of magnetic field scaling with capacitor bank design and field inductance, vacuum interface, and trade-offs between inductance and coil designs.

  4. Ultrashort laser pulses and ultrashort electron bunches generated in relativistic laser-plasma interaction

    SciTech Connect

    Faure, J.; Glinec, Y.; Gallot, G.; Malka, V.

    2006-05-15

    An experimental study of the interaction of ultrashort laser pulses with underdense plasmas in the relativistic regime is presented. A parameter regime of particular interest was found: the so-called bubble regime. In this regime, the laser pulse is focused to relativistic intensities and its pulse duration is comparable to or shorter than the plasma period. A wealth of physical phenomena occurs for such physical parameters. These phenomena have multiple signatures which have been investigated experimentally: (i) the generation of a high quality electron beam (high energy, very collimated, quasimonoenergetic energy distribution); (ii) the laser pulse temporal shortening in nonlinear plasma waves. In addition, experimental results suggest that the electron beam produced in this way has temporal structures shorter than 50 fs.

  5. Simulation studies of plasma waves in the electron foreshock - The generation of downshifted oscillations

    NASA Technical Reports Server (NTRS)

    Dum, C. T.

    1990-01-01

    The generation of waves with frequencies downshifted from the plasma frequency, as observed in the electron foreshock, is analyzed by particle simulation. Wave excitation differs fundamentally from the familiar excitation of the plasma eigenmodes by a gentle bump-on-tail electron distribution. Beam modes are destabilized by resonant interaction with bulk electrons, provided the beam velocity spread is very small. These modes are stabilized, starting with the higher frequencies, as the beam is broadened and slowed down by the interaction with the wave spectrum. Initially a very cold beam is also capable of exciting frequencies considerably above the plasma frequency, but such oscillations are quickly stabilized. Low-frequency modes persist for a long time, until the bump in the electron distribution is completely 'ironed' out. This diffusion process also is quite different from the familiar case of well-separated beam and bulk electrons. A quantitative analysis of these processes is carried out.

  6. Integral equation for electrostatic waves generated by a point source in a spatially homogeneous magnetized plasma

    SciTech Connect

    Podesta, John J.

    2012-08-15

    The electric field generated by a time varying point charge in a three-dimensional, unbounded, spatially homogeneous plasma with a uniform background magnetic field and a uniform (static) flow velocity is studied in the electrostatic approximation which is often valid in the near field. For plasmas characterized by Maxwell distribution functions with isotropic temperatures, the linearized Vlasov-Poisson equations may be formulated in terms of an equivalent integral equation in the time domain. The kernel of the integral equation has a relatively simple mathematical form consisting of elementary functions such as exponential and trigonometric functions (sines and cosines), and contains no infinite sums of Bessel functions. Consequently, the integral equation is amenable to numerical solutions and may be useful for the study of the impulse response of magnetized plasmas and, more generally, the response to arbitrary waveforms.

  7. Divertor conditions relevant for fusion reactors achieved with linear plasma generator

    SciTech Connect

    Eck, H. J. N. van; Lof, A.; Meiden, H. J. van der; Rooij, G. J. van; Scholten, J.; Zeijlmans van Emmichoven, P. A.; Kleyn, A. W.

    2012-11-26

    Intense magnetized hydrogen and deuterium plasmas have been produced with electron densities up to 3.6 Multiplication-Sign 10{sup 20} m{sup -3} and electron temperatures up to 3.7 eV with a linear plasma generator. Exposure of a W target has led to average heat and particle flux densities well in excess of 4 MW m{sup -2} and 10{sup 24} m{sup -2} s{sup -1}, respectively. We have shown that the plasma surface interactions are dominated by the incoming ions. The achieved conditions correspond very well to the projected conditions at the divertor strike zones of fusion reactors such as ITER. In addition, the machine has an unprecedented high gas efficiency.

  8. Improved plasma generator for the PLT/PDX neutral beam injectors

    SciTech Connect

    Schilling, G.

    1981-01-01

    Neutral beam injection heating of experimental plasmas confined in the PLT tokamak was initiated in the summer of 1977. Four injectors developed and fabricated by the Fusion Energy Division of the Oak Ridge National Laboratory (1)became operational by the spring of 1978, and hot plasmas were achieved in the summer of 1978. Since the total power injected into the tokamak simultaneously by all four beams fell short of that expected (3MW H/degree/) on the basis of single-beam test stand operation, and it had been quite difficult to drive some of the ion sources up to the higher power levels, injector improvement was attempted. It was possible to improve the ion source plasma generator performance by a relatively simple change in arc arc circuit.

  9. Generation of axially modulated plasma waveguides using a spatial light modulator.

    PubMed

    Hine, G A; Goers, A J; Feder, L; Elle, J A; Yoon, S J; Milchberg, H M

    2016-08-01

    We demonstrate the generation of axially modulated plasma waveguides using spatially patterned high-energy laser pulses. A spatial light modulator (SLM) imposes transverse phase front modulations on a low-energy (10 mJ) laser pulse which is interferometrically combined with a high-energy (130-450 mJ) pulse, sculpting its intensity profile. This enables dynamic and programmable shaping of the laser profile limited only by the resolution of the SLM and the intensity ratio of the two pulses. The plasma density profile formed by focusing the patterned pulse with an axicon lens is likewise dynamic and programmable. Centimeter-scale, axially modulated plasmas of varying shape and periodicity are demonstrated. PMID:27472585

  10. A 2D-DIGE-based proteomic analysis reveals differences in the platelet releasate composition when comparing thrombin and collagen stimulations

    PubMed Central

    Vélez, Paula; Izquierdo, Irene; Rosa, Isaac; García, Ángel

    2015-01-01

    Upon stimulation, platelets release a high number of proteins (the releasate). There are clear indications that these proteins are involved in the pathogenesis of several diseases, such as atherosclerosis. In the present study we compared the platelet releasate following platelet activation with two major endogenous agonists: thrombin and collagen. Proteome analysis was based on 2D-DIGE and LC-MS/MS. Firstly, we showed the primary role of thrombin and collagen receptors in platelet secretion by these agonists; moreover, we demonstrated that GPVI is the primary responsible for collagen-induced platelet activation/aggregation. Proteomic analysis allowed the detection of 122 protein spots differentially regulated between both conditions. After excluding fibrinogen spots, down-regulated in the releasate of thrombin-activated platelets, 84 differences remained. From those, we successfully identified 42, corresponding to 37 open-reading frames. Many of the differences identified correspond to post-translational modifications, primarily, proteolysis induced by thrombin. Among others, we show vitamin K-dependent protein S, an anticoagulant plasma protein, is up-regulated in thrombin samples. Our results could have pathological implications given that platelets might be playing a differential role in various diseases and biological processes through the secretion of different subsets of granule proteins and microvesicles following a predominant activation of certain receptors. PMID:25645904

  11. Iron plasma generation using a Nd:YAG laser pulse of several hundred picoseconds.

    PubMed

    Tamura, Jun; Kumaki, Masafumi; Kondo, Kotaro; Kanesue, Takeshi; Okamura, Masahiro

    2016-02-01

    We investigated the high intensity plasma generated by using a Nd:YAG laser to apply a laser-produced plasma to the direct plasma injection scheme. The capability of the source to generate high charge state ions strongly depends on the power density of the laser irradiation. Therefore, we focused on using a higher power laser with several hundred picoseconds of pulse width. The iron target was irradiated with the pulsed laser, and the ion current of the laser-produced iron plasma was measured using a Faraday cup and the charge state distribution was investigated using an electrostatic ion analyzer. We found that higher charge state iron ions (up to Fe(21+)) were obtained using a laser pulse of several hundred picoseconds in comparison to those obtained using a laser pulse of several nanoseconds (up to Fe(19+)). We also found that when the laser irradiation area was relatively large, the laser power was absorbed mainly by the contamination on the target surface. PMID:26931980

  12. PDMS/Kapton interface plasma treatment effects on the polymeric package for a wearable thermoelectric generator.

    PubMed

    Francioso, Luca; De Pascali, Chiara; Bartali, Ruben; Morganti, Elisa; Lorenzelli, Leandro; Siciliano, Pietro; Laidani, Nadhira

    2013-07-24

    The present work highlights the progress in the field of polymeric package reliability engineering for a flexible thermoelectric generator realized by thin-film technology on a Kapton substrate. The effects of different plasma treatments on the mechanical performance at the interface of a poly(dimethylsiloxane) (PDMS)/Kapton assembly were investigated. To increase the package mechanical stability of the realized wearable power source, the Kapton surface wettability after plasma exposure was investigated by static contact-angle measurements using deionized water and PDMS as test liquids. In fact, the well-known weak adhesion between PDMS and Kapton can lead to a delamination of the package with an unrecoverable damage of the generator. The plasma effect on the adhesion performances was evaluated by the scratch-test method. The best result was obtained by performing a nitrogen plasma treatment at a radio-frequency power of 20 W and a gas flow of 20 sccm, with a measured critical load of 1.45 N, which is 2.6 times greater than the value measured on an untreated Kapton substrate and 1.9 times greater than the one measured using a commercial primer.

  13. Iron plasma generation using a Nd:YAG laser pulse of several hundred picoseconds

    NASA Astrophysics Data System (ADS)

    Tamura, Jun; Kumaki, Masafumi; Kondo, Kotaro; Kanesue, Takeshi; Okamura, Masahiro

    2016-02-01

    We investigated the high intensity plasma generated by using a Nd:YAG laser to apply a laser-produced plasma to the direct plasma injection scheme. The capability of the source to generate high charge state ions strongly depends on the power density of the laser irradiation. Therefore, we focused on using a higher power laser with several hundred picoseconds of pulse width. The iron target was irradiated with the pulsed laser, and the ion current of the laser-produced iron plasma was measured using a Faraday cup and the charge state distribution was investigated using an electrostatic ion analyzer. We found that higher charge state iron ions (up to Fe21+) were obtained using a laser pulse of several hundred picoseconds in comparison to those obtained using a laser pulse of several nanoseconds (up to Fe19+). We also found that when the laser irradiation area was relatively large, the laser power was absorbed mainly by the contamination on the target surface.

  14. Future prospects for ECR plasma generators with improved charge state distributions

    SciTech Connect

    Alton, G.D.; Liu, Y.

    1997-06-01

    The growing number and variety of fundamental, applied, and industrial uses for high intensity, high charge state ion beams continues to be the driving force behind efforts to develop Electron Cyclotron Resonance (ECR) ion sources with superior performance characteristics. Incumbent with the advent of sub-micron electronic devices and their fabrication has been the demand for improved process control and optimization. These demands have led to the development of methods for cleaning, chemical etching, and deposition of thin films based on the use of plasma devices including ECR sources. Despite the steady advance in the technology, ECR plasma heating has not yet reached its full potential in terms of charge state and intensity within a particular charge state, in part, because of the narrow band width, single-frequency microwave radiation commonly used to heat the plasma electrons. This heating technique, coupled with conventional minimum-B configuration magnetic fields used for confining the electrons, resulting in the formation of the thin, ECR surfaces within the plasma volumes of these sources. This report identifies fundamentally important methods for enhancing the performances of ECR plasma generators by transforming the ECR zones from surfaces to volumes. Two methods are readily available for increasing the sizes of these zones. These techniques include: (1) a tailored magnetic field configuration in combination with single-frequency microwave radiation to create a large uniformly distributed ECR volume and; (2) the use of broadband-frequency domain techniques derived from standard TWT technology, to transform the resonant plasma surfaces of traditional ECR ion sources into resonant plasma volumes.

  15. Three-dimensional analysis of microwave generated plasmas with extended planar laser-induced fluorescence.

    PubMed

    Stopper, U; Lindner, P; Schumacher, U

    2007-04-01

    We present the development and application of a diagnostic system for the analysis of microwave generated low-pressure plasmas, which might also be used for the investigation of the edge regions in magnetically confined fusion plasmas. Our method uses planar laser-induced fluorescence, which is produced by excitation of neutral metastable atoms through a short, intense, pulsed laser. The beam expansion optics consist of an uncommon setup of four lenses. By controlled shifting of an element of the optics sideways, the location of the laser sheet in the plasma is scanned perpendicular to the excitation plane. Together with a spectrometer observing different observation volumes along the beam path, we are able to map absolute three-dimensional (3D) population density distributions of the metastable ((2)P(12) (o)) 3s[12](0) (o) state of Ne I in an electron cyclotron resonance heating (ECRH) plasma. This optical tomography system was used to study the influence of the microwave power and mode on the spatial structure of the plasma. The results show that the population density of the neutral neon in this metastable state is found to be in the range of 10(16) m(-3), and that its spatial distribution is associated with the 3D structure of the magnetic field. We also report that the spatial distribution strongly varies with the mode structure, which depends on the microwave power.

  16. Three-dimensional analysis of microwave generated plasmas with extended planar laser-induced fluorescence

    NASA Astrophysics Data System (ADS)

    Stopper, U.; Lindner, P.; Schumacher, U.

    2007-04-01

    We present the development and application of a diagnostic system for the analysis of microwave generated low-pressure plasmas, which might also be used for the investigation of the edge regions in magnetically confined fusion plasmas. Our method uses planar laser-induced fluorescence, which is produced by excitation of neutral metastable atoms through a short, intense, pulsed laser. The beam expansion optics consist of an uncommon setup of four lenses. By controlled shifting of an element of the optics sideways, the location of the laser sheet in the plasma is scanned perpendicular to the excitation plane. Together with a spectrometer observing different observation volumes along the beam path, we are able to map absolute three-dimensional (3D) population density distributions of the metastable (P21/2o)3s[1/2]0o state of Ne I in an electron cyclotron resonance heating (ECRH) plasma. This optical tomography system was used to study the influence of the microwave power and mode on the spatial structure of the plasma. The results show that the population density of the neutral neon in this metastable state is found to be in the range of 1016 m-3, and that its spatial distribution is associated with the 3D structure of the magnetic field. We also report that the spatial distribution strongly varies with the mode structure, which depends on the microwave power.

  17. Generation of longitudinal current by a transverse electromagnetic field in classical and quantum plasmas

    SciTech Connect

    Latyshev, A. V. Yushkanov, A. A.

    2015-09-15

    A distribution function for collisionless plasma is derived from the Vlasov kinetic equation in the quadratic approximation with respect to the electromagnetic field. Formulas for calculation of the electric current at an arbitrary temperature (arbitrary degree of degeneration of the electron gas) are deduced. The case of small wavenumbers is considered. It is shown that nonlinearity leads to the generation of an electric current directed along the wave vector. This longitudinal current is orthogonal to the classical transverse current, well known in the linear theory. A distribution function for collisionless quantum plasma is derived from the kinetic equation with the Wigner integral in the quadratic approximation with respect to the vector potential. Formulas for calculation of the electric current at an arbitrary temperature are deduced. The case of small wavenumbers is considered. It is shown that, at small values of the wavenumber, the value of the longitudinal current for quantum plasma coincides with that for classical plasma. The dimensionless currents in quantum and classical plasmas are compared graphically.

  18. Design of a Hollow-Anode Discharge Source for Generation of Supersonic Plasma Jets

    NASA Astrophysics Data System (ADS)

    Kang, In Je; Cho, Soon Gook; Bae, Min Keun; Joo, Sung Kiu; Kim, Jin Woo; Kim, Hyung Jin; Chung, Kyu Sun; CenterEdge Plasma Sciences Team

    2013-10-01

    A hollow-anode discharge source was developed to produce supersonic plasma jets for various astrophysics applications. It not only provides the high density of the high-energy electrons in the hollow node region due to beam-like properties of the electron stream and focusing of the concave cathode, but also is able to easily control generating power according to applied input power. We have simulated the geometry of a plasma source by considering uniform density discharge model at a simple cylindrical structure, and have estimated the plasma parameters, such as electron temperature (Te) and plasma density (ne), with source geometry, applied power and pressure. Te is determined from particle balance by equating the total surface particle loss to the total volume ionization, while ne at the central region of source is calculated from energy balance by equating the total power absorbed to the total power lost. To perform supersonic plasma flow, the nozzle of a hollow-anode discharge source has been simulated by computing the flow using the one dimensional equations for the isentropic flow of ideal gas, and the Rankine-Hugoniot relation of normal shock waves for ideal gases.

  19. Aptamer functionalized hydrophilic polymer monolith with gold nanoparticles modification for the sensitive detection of human α-thrombin.

    PubMed

    Chen, Yuanbo; Deng, Nan; Wu, Ci; Liang, Yu; Jiang, Bo; Yang, Kaiguang; Liang, Zhen; Zhang, Lihua; Zhang, Yukui

    2016-07-01

    Low abundant proteins of body fluids participate nearly all physiological processes and indicate various kinds of diseases. The development of specific enrichment techniques is the key to identify and quantify the low abundant proteins. Herein, a novel kind of aptamer functionalized hydrophilic polymer monolith was developed for the specific enrichment and detection of human α-thrombin from the human plasma. Human α-thrombin aptamer, with thiol group modified at the 5' terminal, was immobilized on the gold nanoparticles (AuNPs) modified poly(glycidyl methacrylate-co-poly(ethylene glycol) diacrylate) monolithic column, with the binding capacity of 277.1μmol/L. Due to the hydrophilic poly(ethylene glycol) diacrylate) as the cross-linking monomer, the detection recovery of the aptamer-functionalized hydrophilic polymer monolithic column could reach to 92.6±5.2% (n=3) and the dynamic range could reach 0.5-300ng/μL (S/N>10) with on-line UV detection. Meanwhile, the column could run over 100 times, because the poly(glycidyl methacrylate-co-poly(ethylene glycol) diacrylate) stability structure and the AuNPs improved the stability of the matrix material. Furthermore, this column could even capture the target α-thrombin, which was spiked in 1000 folds of original human plasma. All these results demonstrated the great potential of the prepared aptamer functionalized hydrophilic polymer monolith for the recognition of the trace proteins in the biological samples. PMID:27154714

  20. Aptamer functionalized hydrophilic polymer monolith with gold nanoparticles modification for the sensitive detection of human α-thrombin.

    PubMed

    Chen, Yuanbo; Deng, Nan; Wu, Ci; Liang, Yu; Jiang, Bo; Yang, Kaiguang; Liang, Zhen; Zhang, Lihua; Zhang, Yukui

    2016-07-01

    Low abundant proteins of body fluids participate nearly all physiological processes and indicate various kinds of diseases. The development of specific enrichment techniques is the key to identify and quantify the low abundant proteins. Herein, a novel kind of aptamer functionalized hydrophilic polymer monolith was developed for the specific enrichment and detection of human α-thrombin from the human plasma. Human α-thrombin aptamer, with thiol group modified at the 5' terminal, was immobilized on the gold nanoparticles (AuNPs) modified poly(glycidyl methacrylate-co-poly(ethylene glycol) diacrylate) monolithic column, with the binding capacity of 277.1μmol/L. Due to the hydrophilic poly(ethylene glycol) diacrylate) as the cross-linking monomer, the detection recovery of the aptamer-functionalized hydrophilic polymer monolithic column could reach to 92.6±5.2% (n=3) and the dynamic range could reach 0.5-300ng/μL (S/N>10) with on-line UV detection. Meanwhile, the column could run over 100 times, because the poly(glycidyl methacrylate-co-poly(ethylene glycol) diacrylate) stability structure and the AuNPs improved the stability of the matrix material. Furthermore, this column could even capture the target α-thrombin, which was spiked in 1000 folds of original human plasma. All these results demonstrated the great potential of the prepared aptamer functionalized hydrophilic polymer monolith for the recognition of the trace proteins in the biological samples.