bluuebunny/crossref_metadata_2025 huggingface dataset:
Tissue Factor Expression during Monocyte-Macrophage Differentiation
Authors: van den Eijnden Mark M E D , Steenhauer Sari-lrina , Reitsma Pieter H , Bertina Rogier M
Published: July 2018

Tissue factor (TF), the high affinity receptor and cofactor of factor VII, is considered as the main procoagulant in stimulated monocytes and macrophages. We studied the effect of longterm culture (differentiation) on “spontaneous” and induced (LPS) expression of TF (mRNA, antigen, cell surface associated Vlla-cofactor activity) in isolated human monocytes.

TF was expressed transiently in monocytes cultured on Teflon membranes (suspension monocytes, Mo-S) and on plastic dishes (adherent monocytes, Mo-A), reaching maximal levels between days 3 and 5. Increased expression of TF was accompanied by increased stable expression of macrophage specific markers (CD71, the mannose receptor, the scavenger receptor).

Bacterial lipopolysaccharide (LPS) induced (additional) TF mRNA, antigen, and activity in both Mo-S and Mo-A. In Mo-S and Mo-A of days 3 to 5, the period in which there was “spontaneous” expression of TF, TF response to LPS was considerably lower.

It is concluded that during monocyte-macrophage transition, TF is “spontaneously” and transiently expressed and that with respect to TF induction the responsiveness of the cells to LPS is maintained.
Transient Interruption of Arterial Thrombosis by Inhibition of Factor Xa Results in Long-term Antithrombotic Effects in Baboons
Authors: Kotzé H F , Lamprecht S , Badenhorst P N , Roodt J P , van Wyk V
Published: July 2018

Recombinant tick anticoagulant peptide (r-TAP) is a potent and specific inhibitor of activated coagulation factor X which effectively interrupts in vivo arterial thrombosis during treatment. It is, however, uncertain if it also affects thrombosis after treatment is stopped. This was tested in a baboon model of arterial thrombosis where platelet deposition onto Dacron vascular graft segments, inserted as extensions into permanent femoral arteriovenous shunts, was measured. The baboons were intravenously treated with 10 μg/kg/min (low dose, aPTT = 39 ± 1 s) and 25 μg/kg/min (high dose, aPTT = 58 ± 2 s) r-TAP for two hours. During treatment the r-TAP inhibited thrombin formation and dose-dependently interrupted platelet deposition onto the graft segment. This effect lasted for up to two hours after treatment with the low dose. Following treatment with the high dose, the graft segments were kept in place for 53 h. After treatment was stopped, platelets again deposited, but at a much lower rate than in control studies. Maximum deposition was approximately 38% lower than in the control studies. Total platelet deposition over 55 h, calculated as the area under the deposition curve, was approximately 40% (p <0.05) less than in the control studies. A significant shortening in the mean platelet life span and an approximately 15-fold increase in thrombin-antithrombin III complexes during the first 31 h indicated that the thrombus surface remained thrombogenic and that the effect of r-TAP was transient. We have shown that 2 h of treatment with a full antithrombotic dose of r-TAP markedly reduced both the rate of platelet deposition after treatment was stopped and the total number of platelets deposited over 55 h. This was in spite of the finding that the antithrombotic effect of r-TAP was transient.
Relative Efficacy of Active Site-Blocked Factors IXa, Xa in Models of Rabbit Venous and Arterio-Venous Thrombosis
Authors: Wong Arnold G , Gunn Alice C , Ku Paul , Hollenbach Stanley J , Sinha Uma
Published: July 2018

In order to investigate the respective roles of prothrombinase and intrinsic tenase (IXa/VIIIa) in venous thrombosis, we compared the antithrombotic efficacy of inhibitors of these two coagulation complexes. The agents tested were dansyl-Glu-Gly-Arg chloromethyl ketone-inactivated bovine factor IXa (IXai) and Glu-Gly-Arg chloromethyl ketone- inactivated human factor Xa (Xai). In vitro formation of active complexes (prothrombinase or tenase) was inhibited by Xai and IXai resulting in IC50 values of 3 nM and 5 nM, respectively. Antithrombotic activity was measured by inhibition of clot accretion on cotton threads placed in the abdominal vena cava of anesthetized rabbits. Intravenous bolus dosing followed by infusion of Xai during the experimental protocol resulted in a dose dependent reduction of clot weight, a dosage of 16.0 μg/kg + 0.28 μg/kg/min being sufficient to produce a 96% inhibition of thrombosis. A much higher dose of IXai (1.0 mg/kg + 17.3 |ig/kg/min) resulted in a 39% reduction of clot weight. In a rabbit arterio-venous shunt model mimicking arterial thrombosis, the relative efficacy of the two agents was found to be more comparable. The doses required for optimum antithrombotic activity were 128.0 μg/kg + 2.2 μg/kg/min for Xai and 1.0 mg/kg+ 17.3 μg/kg/min for IXai. We conclude that, in this study, prothrombinase rather than tenase inhibition was more effective in reducing venous thrombosis and that these effects can be achieved without disruption of extravascular hemostasis.
Angiotensin II Increases Plasminogen Activator Inhibitor-1 and Tissue Factor mRNA Expression without Changing that of Tissue Type Plasminogen Activator or Tissue Factor Pathway Inhibitor in Cultured Rat Aortic Endothelial Cells
Authors: Nishimura Hiromi , Tsuji Hajime , Masuda Haruchika , Nakagawa Katsumi , Nakahara Yoshihumi , Kitamura Hidetsugu , Kasahara Teruhisa , Sugano Tatsuya , Yoshizumi Masami , Sawada Shohei , Nakagawa Masao
Published: July 2018

Angiotensin converting enzyme inhibitors (ACE-I) have been reported to prevent the recurrence of cardiovascular events. The mechanism of this decrease, however, can not be completely explained by anti-hypertensive and anti-hypertrophic effects of ACE-I. To investigate the mechanism of this decrease, we studied the regulation of plasminogen activator inhibitor-1 (PAI-1), tissue type plasminogen activator (TPA), tissue factor (TF), and tissue factor pathway inhibitor (TFPI) by angiotensin II (Ang II) in cultured rat aortic endothelial cells. Ang II increased PAI-1 and TF mRNA expression without affecting that of TPA or TFPI. These inductions were accompanied by increases in PAI-1 and TF activities and were inhibited by a type 1 Ang II receptor antagonist. The results suggest that Ang II decreases the antithrombotic properties of endothelial cells which increases the chance of thrombosis. Thus, inhibition of the renin-angiotensin system may be beneficial to prevent thrombus formation in treatment of ischemic heart disease.
A Comparison of Thromboelastography with Heparinase or Protamine Sulfate Added In Vitro during Heparinized Cardiopulmonary Bypass
Authors: Spiess Bruce D , Wall Michael H , Gillies Bruce S , Fitch Jane C K , Soltow Louise O , Chandler Wayne L
Published: July 2018

Thromboelastography (TEG) has been used after cardiopulmonary bypass (CPB) to diagnose excessive postoperative hemorrhage. Conventional TEG during CPB is not possible due to the sensitivity of the TEG to even small amounts of heparin, which produces a nondiagnostic tracing. The purpose of this study was to compare heparin neutralization using heparinase or protamine in TEG blood samples obtained during CPB. TEG testing was performed on 48 patients before, during and after CPB. Tissue plasminogen activator activity and antigen were measured on a subset of 32 patients. We found: 1) heparinase neutralized at least 10 IU/ml heparin while 1.6 ug/ml protamine neutralized up to 7 IU/ml heparin, 2) in samples with complete heparin neutralization by both methods, there was no significant difference in the R values, 3) while there was good correlation for other TEG parameters between heparinase and protamine treated samples, heparinase treatment produced shorter K values and higher angle, MA and A60, 4) while fibrinolysis was detected using both methods, heparinase treatment suppressed fibrinolysis in the TEG in both samples from patients and after in vitro addition of tissue plasminogen activator, 5) TEG was not a sensitive indicator of t-PA activity, detecting only 21% of samples with increased t-PA activity during bypass, and 5) heparinase was at least 100 times more expensive than protamine. We conclude that while both heparinase and protamine can be used to neutralize heparin in TEG samples obtained during CPB, protamine neutralization is more sensitive to fibrinolysis and less expensive, but the protamine dose must be carefully selected to match the heparin level used at individual institutions.
Effect of Strenuous Exercise on Fibrinogen and Fibrinolysis in Healthy Elderly Men and Women
Authors: Schuit Albertine J , Schouten Evert G , Kluft Cornelis , de Maat Moniek , Menheere Paul P C A , Kok Frans J
Published: July 2018

The elevated incidence of thrombotic disease in elderly people may be associated with an increase in PAI-1 and fibrinogen with ageing. Cross-sectional studies report an inverse relation of PAI-1 and fibrinogen with physical activity, but training studies show inconsistent results. In a controlled intervention study among elderly subjects (aged 60-80 years) we observed a moderate decrease in PAI-1 antigen (4%, -2.1 ± 2.4 ng/ml), a significant increase in t-PA activity (11%, 0.07 ± 0.04 IU/ml) and an unexpected significant increase in fibrinogen (6%, 0.18 ± 0.07 g/1) in subjects following a 6-month intensive training program as compared to controls. Reduction in PAI-1 antigen was significantly associated with a decrease in triglycerides (β = 10.3 ng/ml per 1 mM, p <0.01) and insulin (β = 2.37 ng/ml per 1 mU/1, p = 0.07). Increase in fibrinogen coincided with a rise in C-reactive protein (p <0.001). These data suggest that regular intensive activity may increase fibrinolytic activity in a moderate way, but also may cause chronically elevated plasma levels of acute phase proteins in elderly persons.
Determination of the International Sensitivity Index of a New Near-Patient Testing Device to Monitor Oral Anticoagulant Therapy
Authors: Tripodi Armando , Chantarangkul Veena , Clerici Marigrazia , Negri Barbara , Mannucci Pier Mannuccio
Published: July 2018

A key issue for the reliable use of new devices for the laboratory control of oral anticoagulant therapy with the INR is their conformity to the calibration model. In the past, their adequacy has mostly been assessed empirically without reference to the calibration model and the use of International Reference Preparations (IRP) for thromboplastin. In this study we reviewed the requirements to be fulfilled and applied them to the calibration of a new near-patient testing device (TAS, Cardiovascular Diagnostics) which uses thromboplastin-containing test cards for determination of the INR. On each of 10 working days citrat- ed whole blood and plasma samples were obtained from 2 healthy subjects and 6 patients on oral anticoagulants. PT testing on whole blood and plasma was done with the TAS and parallel testing for plasma by the manual technique with the IRP CRM 149S. Conformity to the calibration model was judged satisfactory if the following requirements were met: (i) there was a linear relationship between paired log-PTs (TAS vs CRM 149S); (ii) the regression line drawn through patients data points, passed through those of normals; (iii) the precision of the calibration expressed as the CV of the slope was <3%. A good linear relationship was observed for calibration plots for plasma and whole blood (r = 0.98). Regression lines drawn through patients data points, passed through those of normals. The CVs of the slope were in both cases 2.2% and the ISIs were 0.965 and 1.000 for whole blood and plasma. In conclusion, our study shows that near-patient testing devices can be considered reliable tools to measure INR in patients on oral anticoagulants and provides guidelines for their evaluation.
The 20210 A Allele of the Prothrombin Gene Is a Common Risk Factor among Swedish Outpatients with Verified Deep Venous Thrombosis
Authors: Hillarp Andreas , Zӧller Bengt , Svensson Peter J , Dahlbäck Bjӧrn
Published: July 2018

A dimorphism in the 3’-untranslated region of the prothrombin gene (G to A transition at position 20210) has recently been reported to be associated with increases in plasma prothrombin levels and in the risk of venous thrombosis (1). We have examined the prothrombin dimorphism among 99 unselected outpatients with phlebography verified deep venous thrombosis, and in 282 healthy controls. The prevalence of the 20210 A allele was 7.1% (7/99) in the patient group, and 1.8% (5/282) in the healthy control group (p = 0.0095). The relative risk of venous thrombosis was calculated to be 4.2 (95% Cl, 1.3 to 13.6), and was still significant when adjustment was made for age, sex and the factor V:R506Q mutation causing APC resistance [odds ratio 3.8 (95% Cl, 1.1 13.2)]. As previously reported, 28% of the patients were carriers of the factor V:R506Q mutation. Thus, 34% (one patient carried both traits) of unselected patients with deep venous thrombosis were carriers of an inherited prothrombotic disorder. To sum up, our results confirm the 20210 A allele of the prothrombin gene to be an important risk factor for venous thrombosis.
An Exploratory Trial of Two Dosages of a Novel Synthetic Thrombin Inhibitor (Napsagatran, Ro 46-6240) Compared with Unfractionated Heparin for Treatment of Proximal Deep-vein Thrombosis
Authors: Bounameaux Henri , Ehringer Herbert , Hulting Johan , Rasche Herbert , Rapold Hans J , Zultak Maurice ,   ADVENT Investigators
Published: July 2018

One hundred and ten patients with acute proximal deep-vein thrombosis were randomized in a sequential dose-finding design, to receive continuous intravenous infusion of napsagatran, a novel synthetic thrombin-inhibitor, at a fixed dose of 5 mg/h (n = 37) or 9 mg/h (n = 26), or APTT-adjusted unfractionated heparin (n = 47). Oral anticoagulants were started on the 2nd day and the study drug was discontinued from the 5th treatment day, as soon as the International Normalized Ratio was above 2.

Control venogram (97 venogram pairs evaluable) after 5-8 days of treatment showed improvement in 3 napsagatran-treated patients (versus none in heparin-treated patients) and worsening in 4 napsagatran- treated patients (versus 2 in heparin-treated patients). The venographic Marder’s score did not change among the treatment groups. New lung scan perfusion defects (99 scintigram pairs evaluable) occurred in 4 (11%), 4 (21%), and 4 (10%) patients in the napsagatran (5 mg/h) group, in the napsagatran (9 mg/h) group, and in the heparin control group, respectively. There was no statistically significant difference in any of these endpoints between the 3 groups. No major bleeding was observed and the rare minor bleedings occurred at a similar rate in the three treatment groups.

In conclusion, the ADVENT trial has shown data that suggest comparable efficacy and safety of a synthetic, direct thrombin inhibitor (napsagatran) and conventional heparin therapy for treatment of proximal DVT. These results suggest that synthetic direct thrombin inhibitors are a promising class of antithrombotic agents which deserves further development in this field.
New Coagulation Factor V Gene Polymorphisms Define a Single and Infrequent Haplotype Underlying the Factor V Leiden Mutation in Mediterranean Populations and Indians
Authors: Castoldi E , Lunghi B , Mingozzi F , Loannou P , Marchetti G , Bernardi F
Published: July 2018

Two novel polymorphisms were identified in the factor V gene by direct sequencing of intronic areas. One of them, located in intron 9, is the marker closest to the Leiden mutation ever described, whereas the other, in intron 16, displays a rare allele invariantly associated to the mutation. Allele-specific amplification protocols were designed to perform extensive screenings for both polymorphic sites. The new markers were used in combination with six previously described polymorphisms to define specific factor V gene haplotypes. Haplotype investigations in 506Q homozygous thrombotic patients and normal controls showed the presence of a single haplotype underlying the factor V Leiden mutation in Mediterranean populations (among which Greek Cypriots, where the R506Q mutation is particularly frequent) and Indians. When traced in the absence of the Leiden mutation, the background haplotype was found to be present and roughly as frequent as the mutation itself in these populations. These findings indicate a single mutational event, that probably occurred outside Europe, as the cause of the Leiden mutation and provide a powerful tool to investigate its evolutionary history.
An Experimental Multiple-Organ Model for the Study of Regional Net Release/Uptake Rates of Tissue-type Plasminogen Activator in the Intact Pig
Authors: Jern Christina , Seeman-Lodding Heléne , Biber Bjӧrn , Winsӧ Ola , Jern Sverker
Published: July 2018

Experimental data indicate large between-organs variations in rates of synthesis of tissue-type plasminogen activator (t-PA), which may reflect important differences in the capacity for constitutive and stimulated t-PA release from the vascular endothelium. In this report we describe a new multiple-organ experimental in vivo model for simultaneous determinations of net release/uptake rates of t-PA across the coronary, splanchnic, pulmonary, and hepatic vascular beds. In eleven intact anesthetized pigs, blood samples were obtained simultaneously from the proximal aorta, coronary sinus, pulmonary artery, and portal and hepatic veins. Plasma flows were monitored separately for each vascular region. Total plasma t-PA was determined by ELISA with a porcine t-PA standard. Regional net release/uptake rates were defined as the product of arteriovenous concentration gradients and local plasma flows. The net release of t-PA across the splanchnic vascular bed was very high, with a mean output of 1,919 ng total t-PA X min-1 (corresponding to 90 ng per min and 100 g tissue). The net coronary t-PA release was 68 ng X min-1 (30 ng X min-1 X 100 g"1)- Pulmonary net fluxes of t-PA were variable without any significant net t-PA release. The net hepatic uptake rate was 4,855 ng X min-1 (436 ng X min-1 X 100 g-1). Net trans-organ changes of active t-PA mirrored those of total t-PA. The results demonstrate marked regional differences in net release rates of t-PA in vivo. The experimental model we present offers new possibilities for evaluation of regional secretion patterns in the intact animal.
The Effect of Active Site-inhibited Factor VIIa on Tissue Factor-initiated Coagulation Using Platelets before and after Aspirin Administration
Authors: Kjalke Marianne , Oliver Julie A , Monroe Dougald M , Hoffman Maureane , Ezban Mirella , Hedner Ulla , Roberts Harold R
Published: July 2018

Active site-inactivated factor VIIa has potential as an antithrombotic agent. The effects of D-Phe-L-Phe-L-Arg-chloromethyl ketone-treated factor VIla (FFR-FVIIa) were evaluated in a cell-based system mimicking in vivo initiation of coagulation. FFR-FVIIa inhibited platelet activation (as measured by expression of P-selectin) and subsequent large-scale thrombin generation in a dose-dependent manner with IC50 values of 1.4 ± 0.8 nM (n = 8) and 0.9 ± 0.7 nM (n = 7), respectively. Kd for factor VIIa binding to monocytes ki for FFR-FVIIa competing with factor VIIa were similar (11.4 ± 0.8 pM and 10.6 ± 1.1 pM, respectively), showing that FFR-FVIIa binds to tissue factor in the tenase complex with the same affinity as factor VIIa. Using platelets from volunteers before and after ingestion of aspirin (1.3 g), there were no significant differences in the IC50 values of FFR-FVIIa [after aspirin ingestion, the IC50 values were 1.7 ± 0.9 nM (n = 8) for P-selectin expression, p = 0.37, and 1.4 ± 1.3 nM (n = 7) for thrombin generation, p = 0.38]. This shows that aspirin treatment of platelets does not influence the inhibition of tissue factor-initiated coagulation by FFR-FVIIa, probably because thrombin activation of platelets is not entirely dependent upon expression of thromboxane A2.
Inhibition of Mannose Receptor-mediated Clearance of Tissue-type Plasminogen Activator (t-PA) by Dextran: a New Explanation for Its Antithrombotic Effect
Authors: Noorman F , Barrett-Bergshoeff M M , Bekkers M , Emeis J J , Rijken D C
Published: July 2018

Dextran is used during surgery as a prophylactic agent to prevent deep venous thrombosis. Recently it has been shown that dextran increases t-PA plasma concentrations in patients. As dextran is a potential ligand for the mannose receptor, we studied whether this glucose-polymer would be able to inhibit mannose receptor-mediated clearance of t-PA.

In this report we show that dextran 40 and dextran 70 were able to inhibit t-PA binding to the isolated human mannose receptor (IC5014 and 4 mg/ml, respectively). Both glucose-polymers inhibited mannose receptor-mediated t-PA degradation by human monocyte-derived macrophages in vitro (IC50 7 and 2 mg/ml, respectively). The α2-macroglobulin receptor/low density lipoprotein receptor-related protein (LRP)-mediated t-PA degradation by the macrophages was not affected by dextran. During and after a 45 min infusion of dextran 70 (Macrodex) in rats, in plasma endogenous t-PA concentrations increased to 162 ± 33% and 122 ± 35% respectively. The plasma clearance of a bolus injection of exogenous t-PA was decreased by 33 ± 9% in the same rats.

We conclude that dextran inhibits mannose receptor-mediated t-PA clearance. The inhibition of t-PA clearance during dextran infusion results in increased endogenous t-PA plasma concentrations. Increased t-PA concentrations present during thrombus formation are known to increase thrombus lysability. Thus the inhibition of t-PA clearance can contribute to the antithrombotic effect of dextran.
Partial Blockade of Nitric Oxide Synthase Blunts the Exercise-induced Increase of von Willebrand Factor Antigen and of Factor VIII in Man
Authors: Jilma Bernd , Dirnberger Eva , Eichler Hans-Georg , Matulla Bettina , Schmetterer Leopold , Kapiotis Stylianos , Speiser Wolfgang , Wagner Oswald F
Published: July 2018

Background: Until now the effects of β-adrenergic agonists have largely been ascribed to their ability to induce intracellular formation of cyclic adenosine monophosphate. Recently evidence has been accumulating that at least some β1 and β2-adrenoceptor effects may be mediated by nitric oxide (NO). Based on these studies, we hypothesized that the β-adrenoceptor mediated increase of von Willebrand factor and factor VIII-activity (FVIII:C) in plasma during exercise, is caused by an NO-dependent mechanism. Methods: Thirteen young healthy subjects finished an exhaustive bicycle exercise protocol while they were infused placebo or the NO-synthase inhibitor N-monomethyl-L-arginine (L-NMMA) on two separate days in a randomized, double blind cross-over design. Findings: During exercise systemic haemo-dynamic changes were parallel in both treatment periods, but L-NMMA caused a partial inhibition of NO-synthase as evidenced by a 30% decrease in exhaled NO. The workload capacities were not different during L-NMMA or placebo infusion. However, under placebo treatment exercise increased vWF-Ag by a maximum of 61% (CI: 43-84; p = 0.002) and FVIII:C by 44% (CI: 31-59; p = 0.001), which was significantly attenuated when subjects were treated with L-NMMA (p <0.05): under L-NMMA treatment vWF-Ag increased by only 25% (CI: 5-51; p = 0.001) and FVIII:C by 12% (CI: 6-39; p = 0.001). Interpretation: Partial blockade of NO-synthase with L-NMMA blunts the exercise-induced increase in vWF-Ag and FVIII:C. Our trial points to a role of endogenous NO-generation in the β2-adrenergic increase in vWF/FVIII. Thus, we propose that physiologic processes which are induced by systemic β2-adrenoceptor stimulation may at least partly be mediated by NO.
Occult Cancer in Patients with Venous Thromboembolism: which Patients, which Cancers
Authors: Monreal Manuel , Fernandez-Llamazares Jaume , Perandreu Joan , Urrutia Agustin , Sahuquillo Joan Carles , Contel Elena
Published: July 2018

We have previously demonstrated that patients with idiopathic venous thromboembolism (VTE) have a higher frequency of underlying cancer. Now we present a retrospective analysis of our 5-year experience with a series of 674 consecutive otherwise healthy patients, and a more restricted battery of diagnostic tests. Occult cancer was found in 15 patients during admission. The diagnostic tools which led to suspect occult cancer were: abdominal CT-scan (4 patients); high carcinoembryonic levels (2 patients); and high prostate-specific antigen levels (9 patients). Eight further patients were diagnosed of cancer after discharge. Cancer was more commonly found in patients with idiopathic VTE: 13/105 patients (12%) versus 10/569 patients (2%); p <0.01; 0. R.: 7.9 (95% Cl: 3.14-20.09).

During the same period of time we diagnosed VTE in 147 patients with previously known cancer. When overall considered, VTE was the first sign of malignancy in most patients with prostatic and pancreatic carcinoma. On the contrary, most patients with breast, lung, uterine and brain cancers developed VTE as a terminal event of the disease. At variance with VTE patients and previously known cancer, most patients with occult malignancy were at an early stage. Further studies are needed to confirm whether patients with idiopathic VTE could benefit from screening for occult cancer. Meanwhile, our findings may serve as guidelines for physicians in this field.
Levels of Prothrombin Fragment F1+2 in Patients with Hyperhomocysteinemia and a History of Venous Thromboembolism
Authors: Kyrle Paul A , Stümpflen Andreas , Hirschl Mirko , Bialonczyk Christine , Herkner Kurt , Speiser Wolfgang , Weltermann Ansgar , Kaider Alexandra , Pabinger Ingrid , Lechner Klaus , Eichinger Sabine
Published: July 2018

Increased thrombin generation occurs in many individuals with inherited defects in the antithrombin or protein C anticoagulant pathways and is also seen in patients with thrombosis without a defined clotting abnormality. Hyperhomocysteinemia (H-HC) is an important risk factor of venous thromboembolism (VTE). We prospectively followed 48 patients with H-HC (median age 62 years, range 26-83; 18 males) and 183 patients (median age 50 years, range 18-85; 83 males) without H-HC for a period of up to one year. Prothrombin fragment Fl+2 (Fl+2) was determined in the patient’s plasma as a measure of thrombin generation during and at several time points after discontinuation of secondary thromboprophylaxis with oral anticoagulants. While on anticoagulants, patients with H-HC had significantly higher Fl+2 levels than patients without H-HC (mean 0.52 ± 0.49 nmol/1, median 0.4, range 0.2-2.8, versus 0.36 ± 0.2 nmol/1, median 0.3, range 0.1-2.1; p = 0.02). Three weeks and 3,6,9 and 12 months after discontinuation of oral anticoagulants, up to 20% of the patients with H-HC and 5 to 6% without H-HC had higher Fl+2 levels than a corresponding age- and sex-matched control group. 16% of the patients with H-HC and 4% of the patients without H-HC had either Fl+2 levels above the upper limit of normal controls at least at 2 occasions or (an) elevated Fl+2 level(s) followed by recurrent VTE. No statistical significant difference in the Fl+2 levels was seen between patients with and without H-HC. We conclude that a permanent hemostatic system activation is detectable in a proportion of patients with H-HC after discontinuation of oral anticoagulant therapy following VTE. Furthermore, secondary thromboprophylaxis with conventional doses of oral anticoagulants may not be sufficient to suppress hemostatic system activation in patients with H-HC.
A New Model for Quantitative In Vivo Microscopic Analysis of Thrombus Formation and Vascular Recanalisation: The Ear of the Hairless (hr/hr) Mouse
Authors: Roesken Frank , Ruecker Martin , Vollmar Brigitte , Boeckel Nicole , Morgenstern Eberhard , Menger Michael D
Published: July 2018

The alteration of rheological blood properties as well as deterioration of vascular perfusion conditions and cell-cell interactions are major determinants of thrombus formation. Herein, we present an experimental model which allows for quantitative in vivo microscopic analysis of these determinants during both thrombus formation and vascular recanalisation. The model does not require surgical preparation procedures, and enables for repeated analysis of identical microvessels over time periods of days or months, respectively. After i.v. administration of FITC-dextran thrombus formation was induced photochemically by light exposure to individual arterioles and venules of the ear of ten anaesthetised hairless mice. In venules, epiillumination induced rapid thrombus formation with first platelet deposition after 0.59 ± 0.04 min and complete vessel occlusion within 7.48 ±1.31 min. After a 24-h time period, 75% of the thrombosed venules were found recanalised. Marked leukocyte-endothelial cell interaction in those venules indicated persistent endothelial cell activation and/or injury, even after an observation period of 7 days. In arterioles, epi-illumination provoked vasomotion, while thrombus formation was significantly (p <0.05) delayed with first platelet deposition after 2.32 ± 0.22 min and complete vessel occlusion within 20.07 ±3.84 min. Strikingly, only one of the investigated arterioles was found recanalised after 24 h, which, however, did not show leukocyte-endothelial cell interaction. Heparin (300 U/kg, i.v.) effectively counteracted the process of thrombus formation in this model, including both first platelet deposition and vessel occlusion. We conclude that the model of the ear of the hairless mouse allows for distinct in vivo analysis of arteriolar and venular thrombus formation/ recanalisation, and, thus, represents an interesting tool for the study of novel antithrombotic and thrombolytic strategies, respectively.
Fiber array coupling based multi-spectral streak tube detection imaging method
Authors: Cao Jingya , Xia Wenze , Han Shaokun , Wang Liang , Zhai Yu
Published: July 2018

The complementary advantages of the multi-spectral technique and streak tube detection imaging technique can enrich target information with high detection accuracy. In this paper, a new multi-spectral streak tube imaging method is proposed. Instead of using a set of receiving systems for each wavelength, i.e., the traditional method, we use different lengths of fiber arrays in our imaging system to produce the time difference between the echo signals of different wavelengths arriving at the detectors. The imaging process is completed by just one set of the receiving system. The contradiction between multiple wavelength information sub-area processing and large depth of field is alleviated, and the high time resolution is ensured. The mathematical model of this simplified system is established, and two simulation experiments are organized. First, the influence of the time difference on the judgment of echo signals is discussed. Second, we simulate the process of detecting and imaging a target using the traditional multi-spectral streak tube detection method and the proposed method. Finally, we compare the three-dimensional images obtained via the two methods. By observation and calculation, we find that the imaging depth of field and time resolution of the proposed method are better than those of the traditional method.
Normal and anomalous random walks of 2-d solitons
Authors: Cisternas Jaime , Albers Tony , Radons Günter
Published: July 2018

Solitons, which describe the propagation of concentrated beams of light through nonlinear media, can exhibit a variety of behaviors as a result of the intrinsic dissipation, diffraction, and the nonlinear effects. One of these phenomena, modeled by the complex Ginzburg-Landau equation, is chaotic explosions, transient enlargements of the soliton that may induce random transversal displacements, which in the long run lead to a random walk of the soliton center. As we show in this work, the transition from nonmoving to moving solitons is not a simple bifurcation but includes a sequence of normal and anomalous random walks. We analyze their statistics with the distribution of generalized diffusivities, a novel approach that has been used successfully for characterizing anomalous diffusion.
A hyphenated echelle LIBS-Raman system for multi-purpose applications
Authors: Muhammed Shameem K. M. , Dhanada V. S. , Unnikrishnan V. K. , George Sajan D. , Kartha V. B. , Santhosh C.
Published: July 2018

We have developed and standardized a novel hybrid laser-induced breakdown spectroscopy (LIBS)-Raman system using a single pulsed laser and a high-resolution intensified charge coupled device coupled echelle spectrograph. LIBS and Raman spectroscopy are highly complementary techniques which yield elemental and molecular information. Both techniques share an apparently similar instrumental configuration but need entirely different requirements like spectral range covered, resolution, and light-gathering efficiencies. There are thus many challenges to be faced in developing a combined system. In the present work, we show that an echelle spectrograph combined with a compact Q-switched Nd:YAG laser operating at 532 nm as an excitation source in a portable configuration can be efficiently used for such multi-purpose spectroscopy. Atomic and molecular emissions from the sample surface have been recorded in a gated mode using this setup. Compared to conventional spectrographs, echelle provides simultaneous broad bandpass (250–900 nm) and better spectral resolution at an extremely small fixed slit width of 10 × 50 μm without moving the dispersive elements. The echelle-based hyphenated system provides fast and reliable analysis of materials with combined atomic and molecular spectra of the same spot with better reliability. In this paper, we discuss the optimization of various instrumental parameters and optical components of this hyphenated system using a medium Raman cross section sample, CaCO3. The feasibility of single shot LIBS-Raman measurement capabilities of echelle has also been demonstrated using the developed system.
A gas cell apparatus for measuring charge exchange cross sections with multicharged ions
Authors: Bromley S. J. , Fox D. C. , Sosolik C. E. , Harriss J. E. , Marler J. P.
Published: July 2018

A gas cell apparatus to measure charge exchange cross sections for charge state- and energy-resolved ion beams with neutrals is described. The design features a short well-defined interaction region required for beams of multicharged ions with high cross sections. Our method includes measuring the beam transmission at four different neutral pressures and extracting the cross section from the slope of a beam loss vs pressure plot. The design and procedure were tested for Ar+ interacting with neutral Ar gas over the incident ion energy range of 1.0–5.0 keV. The charge exchange cross sections agree well with previous complementary measurement techniques.
A full-field crystal plasticity study on how texture and grain structure influences hydrostatic stress in thermally strained β-Sn films
Authors: Chakraborty Aritra , Eisenlohr Philip
Published: July 2018

The present study uses full-field thermo-mechanically coupled crystal plasticity to simulate the stress distribution in thermally strained β-Sn films to better understand the conditions causing the generally rare nucleation of whiskers from such films. Following the notion that stress-driven diffusion along the grain boundary network is leading to and supporting whisker formation, the goal is to identify critical factors of crystallographic and/or geometric nature that influence the hydrostatic stress in such films prior to the onset of actual whisker formation. Approximating the film as a periodic structure of around a hundred columnar grains on an isotropic substrate, the simulations reveal a strong spatial variation of hydrostatic stress over distances comparable to the grain size but without apparent long-range gradients, suggesting whisker nucleation to be a phenomenon that depends on specifics within a relatively small neighborhood of grains. Furthermore, neither the grain size distribution nor the presence of oblique surface grains alters the width of the stress distribution by much. In contrast, the variation of hydrostatic stress notably depends on the crystallographic texture of the film, where β-Sn films for which the film normal is aligned with ⟨0 0 1] show a narrower distribution than films with ⟨1 0 0] parallel to the normal. The former film texture, therefore, is predicted to be less prone to whisker formation than the latter.
Dimension effect on the in-depth phase transition of MnAs/GaAs(001): From a thin film to a nanorod
Authors: Fu X. , Ye W. , Zhou N.
Published: July 2018

We explore the dimension effect on the in-depth phase transition behavior of MnAs thin films on GaAs substrate by investigating the in-depth strain distribution with experiments and simulations. The strain distribution along the film growth direction is verified to be changed when a two-dimensional thin film is thinned into a one-dimensional nanorod as a cross-section transmission electron microscopy (TEM) specimen, thus resulting in a significantly different transition behavior. Our work brings more insights into the transition mechanism of MnAs thin films and illustrates a noteworthy issue in TEM studies of the phase transition at the interface of epitaxial thin films.
Development of a LIBS system for in situ surface measurements during plasma exposure in PISCES-A
Authors: Nishijima D. , Patino M. , Doerner R. P.
Published: July 2018

A laser-induced breakdown spectroscopy (LIBS) system has been developed with a Q-switched Nd:YAG laser (wavelength = 1064 nm and pulse width ∼5 ns) to conduct in situ surface measurements during plasma exposure in the PISCES-A linear divertor plasma simulator. The LIBS signal enhancement is obtained with both the magnetic field normal to the surface of a target and steady-state background plasma. Migration of sputtered Ta impurities onto the neighboring Cr surface is identified during He plasma exposure, only when cone structures are formed on the Cr surface. D retention in W during D plasma exposure is observed to decrease with increasing the sample temperature. The temporal evolution of D outgassing from W is measured in a time range of ∼10−420 s right after D plasma exposure. A power law fit, t−α, yields α ∼ 0.34 ± 0.09, which is nearly consistent with calculated and measured values.
On Raman scattering cross section ratio of crystalline and microcrystalline to amorphous silicon
Authors: Zhigunov D. M. , Kamaev G. N. , Kashkarov P. K. , Volodin V. A.
Published: July 2018

In this letter, we report on accurate comparative measurements of Raman scattering from bulk crystalline Si and from hydrogenated amorphous Si thin films before and after their pulse laser annealing, performed for the purpose of Si crystalline grain formation. Being accompanied by the respective optical transmittance/reflectance measurements, these data allowed us to estimate the integrated Raman scattering cross section ratios of crystalline and microcrystalline Si to hydrogenated amorphous Si and to compare the results with those known from the literature. For crystalline Si, the obtained ratio is equal to 0.75, while for microcrystalline Si, it is equal to at least 2. Our results are found to contradict the proposed earlier exponential decay dependence of the integrated Raman scattering cross section ratio of microcrystalline to amorphous Si on the crystalline grain size. The physical reasons, which support our findings, are discussed.
Thermal property engineering of InSe layer by a thin Al2O3 stress liner
Authors: Li Kuilong , Hong Yuehua , Li Zhiwen , Liu Xinke
Published: July 2018

We investigate the thermal properties of thin InSe layers with high-κ oxide Al2O3 stress liners. Temperature-dependent Raman spectroscopy demonstrated that the Al2O3 passivation layer significantly reduced the thermal variation coefficients of the in-plane E2g1 phonon mode of the InSe layer from −0.03284 cm−1/K to −0.0212 cm−1/K in comparison with the InSe sample without the Al2O3 capping layer. Combined with power-dependent Raman spectroscopy, the in-plane thermal conductivity of InSe reaches about 53.1 W/mK, ∼40% greater than that without the Al2O3 capping layer, 38.2 W/mK, which is attributed to the large thermal conductivity of Al2O3 and the electron-phonon interactions at the interface. Generally, this work will contribute to improving the performances of the InSe-based nano-devices and extending their applications profoundly.
Corpus analysis of croatian constructions with the verb doći ‘to come’
Authors: Blagus Bartolec Goranka , Matas Ivanković Ivana
Published: July 2018

This paper presents a corpus-based analysis of constructions consisting of the verb doći
‘to come’ followed by the prepositions do ‘to’ or na
‘onto’ and a noun. Croatian lexicography mainly describes the verb doći as an
intransitive verb of motion. Other uses of this verb are listed in the idioms section. This paper will address the
association between the verb-preposition constructions and nouns that follow them. The paper will take frequency data
into consideration and attempt to distinguish between primary and additional meanings of constructions doći do ‘to come to’ and doći na ‘to come onto’. The research
will be based on hrWaC 2.0 (Croatian Web Corpus, Version 2), the Croatian National Corpus and the Croatian Language Repository corpora.
Tennis serve performances at break points: Approaching practice patterns for coaching
Authors: Meffert Dominik , O'Shannessy Craig , Born Philipp , Grambow Ralph , Vogt Tobias
Published: July 2018

Tennis comprises specific match situations when winning the next point is crucial. These big points can decide about a win or loss and, thus, reasonably arouse mental stress. Break points (BPs) are considered as big points and the outcome is influenced by, among a variety of other factors, the serve, which is well accepted being one of the dominant strokes in Men's tennis. In this study, we examined the serve behaviour for male players in the Wimbledon tournament 2016 to investigate the possible impacts of presumed mental stress within the situation of BPs, and further, if winning players perform better than losing players. A total of 28.843 points were analysed and divided into BP (n = 2.035) and non‐break points – referred to as regular points (RP; n = 26.808).
A quantitative analysis of cohesin decay in mitotic fidelity
Authors: Carvalhal Sara , Tavares Alexandra , Santos Mariana B. , Mirkovic Mihailo , Oliveira Raquel A.
Published: July 2018

Sister chromatid cohesion mediated by cohesin is essential for mitotic fidelity. It counteracts spindle forces to prevent premature chromatid individualization and random genome segregation. However, it is unclear what effects a partial decline of cohesin may have on chromosome organization. In this study, we provide a quantitative analysis of cohesin decay by inducing acute removal of defined amounts of cohesin from metaphase-arrested chromosomes. We demonstrate that sister chromatid cohesion is very resistant to cohesin loss as chromatid disjunction is only observed when chromosomes lose >80% of bound cohesin. Removal close to this threshold leads to chromosomes that are still cohered but display compromised chromosome alignment and unstable spindle attachments. Partial cohesin decay leads to increased duration of mitosis and susceptibility to errors in chromosome segregation. We propose that high cohesin density ensures centromeric chromatin rigidity necessary to maintain a force balance with the mitotic spindle. Partial cohesin loss may lead to chromosome segregation errors even when sister chromatid cohesion is fulfilled.
Bayesianism and Explanatory Unification: A Compatibilist Account
Authors: Blanchard Thomas
Published: July 2018

Proponents of IBE claim that the ability of a hypothesis to explain a range of phenomena in a unifying way contributes to the hypothesis’s credibility in light of these phenomena. I propose a Bayesian justification of this claim that reveals a hitherto unnoticed role for explanatory unification in evaluating the plausibility of a hypothesis: considerations of explanatory unification enter into the determination of a hypothesis’s prior by affecting its ‘explanatory coherence’, that is, the extent to which the hypothesis offers mutually cohesive explanations of various phenomena.
What Emotions Really Are (In the Theory of Constructed Emotions)
Authors: Pober Jeremy
Published: July 2018

Recently, Lisa Feldman Barrett and colleagues have introduced the Theory of Constructed Emotions (TCE), in which emotions are constituted by a process of categorizing the self as being in an emotional state. The view, however, has several counterintuitive implications: for instance, a person can have multiple distinct emotions at once. Further, the TCE concludes that emotions are constitutively social phenomena. In this article, I explicate the TCE*, which, while substantially similar to the TCE, makes several distinct claims aimed at avoiding the counterintuitive implications plaguing the TCE. Further, because of the changes that comprise the TCE*, emotions are not constitutively social phenomena.
Preliminary Study of Micro-hydro Power Plant (MHPP) in The Rural Area
Authors: Ratnata I W , Saputra W S , Somantri M , Mulyana E , Ardhika A
Published: July 2018

Pakenjeng village is one of the villages in the subdistrict Pamulihan, Garut. Garut regency has the potential of natural resources is quite large and varied, namely water resources, energy, and mineral resources. Energy resources available in the form of the potential of renewable energy such as geothermal energy (geothermal), micro-hydro, solar, wave, and wind. Judging from potential micro hydro, Pakenjeng village crossed by two rivers with a flow of water large enough, the river Cikondang and Cibatarua. Currently, both the river Cikondang and river Cibatarua been used for hydroelectric power plant, with a capacity> 100 kW (scale mini-hydro), ie power plants Kombongan (river Cikondang) with a capacity of 165 kW and a power plant Panyairan (river Cibatarua) with capacity of 3 x 200 kW. The result of the potential study (pre-feasibility study) showed that Sungai Cibatarua have the quality and quantity of water that is eligible to be a source of hydroelectric energy for water discharge stable and constant reaches 5100 liters / sec. Cibatarua River has a waterfall that has a head that is high enough that Niagara Panyairan with head up to 63 meters. Hydraulic power that can be generated to reach 3248 kW and a power that can be awakened by the turbine reaches 2404 kW. Potential analysis (pre- feasibility study) of the mechanical and electrical indicates that the turbines are suitable for the MHP in the River Cibatarua namely Cross Flow Turbine Type TC 15 BO 650 with power up to 1 MW.
PI(3,5)P2controls vacuole potassium transport to support cellular osmoregulation
Authors: Wilson Zachary N. , Scott Amber L. , Dowell Robin D. , Odorizzi Greg
Published: July 2018

Lysosomes are dynamic organelles with critical roles in cellular physiology. The lysosomal signaling lipid phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) is a key regulator that has been implicated to control lysosome ion homeostasis, but the scope of ion transporters targeted by PI(3,5)P2and the purpose of this regulation is not well understood. Through an unbiased screen in Saccharomyces cerevisiae, we identified loss-of-function mutations in the vacuolar H+-ATPase (V-ATPase) and in Vnx1, a vacuolar monovalent cation/proton antiporter, as suppressor mutations that relieve the growth defects and osmotic swelling of vacuoles (lysosomes) in yeast lacking PI(3,5)P2. We observed that depletion of PI(3,5)P2synthesis in yeast causes a robust accumulation of multiple cations, most notably an ∼85 mM increase in the cellular concentration of potassium, a critical ion used by cells to regulate osmolarity. The accumulation of potassium and other cations in PI(3,5)P2-deficient yeast is relieved by mutations that inactivate Vnx1 or inactivate the V-ATPase and by mutations that increase the activity of a vacuolar cation export channel, Yvc1. Collectively, our data demonstrate that PI(3,5)P2signaling orchestrates vacuole/lysosome cation transport to aid cellular osmoregulation.