bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of the effect of vegetation on the transition of the flood wave using hydraulic 2D models
Authors: Wolski Krzysztof , Tyminski Tomasz , Dabek Pawel B.
Published: July 2018

In the paper an impact of vegetation accumulation on flood wave transition is presented. The research was conducted with use of the MIKE FLOOD model which combines elements of 1D and 2D numerical models. The study area included a 5.5 km long section of the Bystrzyca River near Wroclaw, Poland. A hydraulic model was constructed, on which the simulation of water transition with the probability of occurrencep= 1% andp= 0.2% was conducted. The simulation was carried out for current bank vegetation conditions determined on the basis of precise LIDAR data and for conditions with no vegetation. In this way, the direct impact of vegetation on flood wave transition was obtained. Acquired results, a decrease in maximum water levels and a reduction of flooded area, show that the hydraulic influence of vegetation on high water bed should not be underestimated.
Decay processes of AOB in ASM including protozoa grazing
Authors: Zięba Bartosz , Janiak Kamil , Kokurewicz Łukasz
Published: July 2018

Protozoa grazing of nitrifiers is important process in activated sludge process that leads to decrease of mass of active bacteria. In classical models this process is included in decay processes. Such approach makes modelling of influence of protozoa grazing on nitrifiers impossible. In cases when maximization of nitrifiers growth is important (such as nitrifiers cultivation for bioaugmentation) this simplification becomes major drawback. This paper presents extended version of ASM3 model that includes protozoa grazing as well as results of calibration of protozoa grazing process on experimental data. Additionally new approach for analysis of decay rate is proposed. This approach includes calculation of new parameters: substitute decay rate which is sum of ASM3 base decay rate and excluded predation process.
Center Body Airfoil Design for Blended Wing Body Configuration
Authors: Li Peifeng , Zhang Binqian , Tao Yujin , Chen Zhenli , Li Dong
Published: July 2018

To design the center-body airfoil of a blended wing body configuration, the aerodynamic effects of the symmetrical airfoil, trailing-edge reflexed airfoil, leading-edge loaded airfoil and leading-edge loaded plus trailing-edge reflexed airfoil are investigated based on the constraints of system arrangement. A 150-passenger BWB configuration is studied; for a center-body with symmetrical airfoil, the larger outer-wing geometrical twist should be used to fulfill the positive zero-lift pitching moment according to the design requirements of longitudinal static stability, however, lift to drag ratio shows a big decrease. For leading-edge loaded airfoil, it is difficult to achieve a positive zero-lift pitching moment because of the platform limitation. For trailing-edge reflexed airfoil or leading-edge loaded plus trailing-edge reflexed airfoil, it is easy to achieve ideal design results when reasonably designing the leading-edge loading and trailing-edge unloading. The application of a blended wing body UAV shows that the loss of aerodynamic characteristics is small when adopting the "eagle hook" stealth leading edge that has the characteristics of leading edge loading.
Vibration Mitigation of the Barge-Type Offshore Wind Turbine with a Tuned Mass Damper on Floating Platform
Authors: Yang Jiajia , He Erming , Hu Yaqi
Published: July 2018

This paper evaluates the application of a passive control technique with a tuned mass damper on platform for the barge-type offshore wind turbine. First of all, the three degrees of freedom mathematical model for the floating wind turbine is established based on Lagrange's equations, and the Levenberg-Marquardt algorithm is adopted to estimate the parameters of the wind turbine. Then, the method of frequency tuning which is utilized in engineering projects and genetic algorithm are employed respectively to simulate the optimum parameters of the tuned mass damper. The vibration mechanism about the phase-angle difference between tuned mass damper and floating platform is analyzed. Finally, the dynamic responses of floating wind turbine with/without tuned mass damper are calculated under five typical wind and wave load cases, and the vibration mitigation effects are researched in marine environment. Partial ballast is substituted by the equal mass of tuned mass damper due to the mass of floating platform with tuned mass damper would increase obviously, which would change the design of the wind turbine, and the vibration mitigation is also simulated in five typical load cases. The results show that the suppression rate of standard deviation of platform pitch is up to 47.95%, after substituting the partial mass of ballast, the suppression rate is 50%. Therefore, the dynamic responses of the barge-type floating wind turbine would be reduced significantly when the ballast is replaced by the equal mass of the tuned mass damper on floating platform.
Research on Flight Collision Avoidance Control on The Sun-Earth Libration Points Based on Barrier Theory
Authors: Zhang Ke , He Zhenqi , Lü Meibo , Wang Jingyu
Published: July 2018

In the spacecraft formation task, a spacecraft failure or formation of the mission to change the need for reconstruction of the formation. In the process of reconstruction, how to carry out spacecraft anti-collision has been widespread concern. In this paper, barrier theory is adopted. By establishing Hamilton function, the optimal control law is obtained. According to the theory of barrier construction, the corresponding barrier trajectory is constructed. Then, the barrier is divided into collision area and non-collision area, so as to realize the formation flight anti-collision design. The simulation results show that the method can avoid the perturbation effect and has a certain theoretical value for the anti-collision between the spacecrafts during the formation process.
Vibration Characteristics Analysis of Integrally Shrouded Turbine Blade Considering Separation and Reattachment
Authors: He Bingbing , Ren Xingmin , He Shangwen , Qin Weiyang , Ma Yingang
Published: July 2018

The nonlinear forced vibration responses of integrally shrouded turbine blade considering different contact state are investigated in this paper. A lumped mass model of integrally shrouded turbine blade considering separation and reattachment of adjacent shrouds and centrifugal stiffening effects is established and its dynamic equation is deduced. Collision force is approximated by linear and cubic springs together which is more realistic, and friction force is approximated by an exponential-type velocity-dependent model. Numerical results indicate that integrally shrouded turbine blade displays very complex nonlinear phenomena and it can experience periodic 1, periodic 2, periodic 3, periodic 4 and chaotic vibration. Gap asymmetry leads to more complicated motions of the shrouded blade.
Simulation of Nose Landing Gear Shimmy with Flexible Airframe Considered
Authors: Chen Yi , Cui Rongyao , Ju Rongbo , Dou Qingbo
Published: July 2018

Shimmy stability of the nose landing gear of an aircraft is studied in this paper. Firstly, Shimmy model was built considering the dynamic characteristics of the airframe. Then the critical damping, critical velocity and frequency range of the shimmy are obtained by introducing relevant parameters into the shimmy model. The research shows that the problem of shimmy is a tire type shimmy caused by insufficient damping of dampers and brings coupled resonance with the vibration mode of the airframe, which can be avoided by increasing the damping of the shimmy. At the same time, the influence of airframe dynamics and tire stiffness on the shimmy characteristics of the landing gear is also studied. With the increase of tire torsion and lateral stiffness, the critical velocity, maximum critical damping value and shimmy frequency of the landing gear increase. However, the elasticity of the airframe makes the frequency of the aircraft landing gear lower and the stable region of the shimmy smaller, so that the phenomenon of shimmy is more likely to occur. Therefore, the influence of airframe dynamic characteristics can not be ignored when studying the shimmy stability of the landing gear of a modern large passenger aircraft.
Combined Navigation MethodGPS
Authors: Gao Yang , Gao Li , Wu Meng , Wang Chengbin
Published: July 2018

According to the characteristics of DMI with high-precision position information, a navigation method combines DMIs with GPS and IMU is proposed in this paper. Firstly, the prototype system architecture is presented and its operational principle is discussed. Secondly, some key technologies are studied, which include integrated organization method of DMIs and road net data, the position method based on DMI matching with real-time image and the federal Kalman filter model with DMI, GPS and IMU. Finally, experimental results show that the proposed method can counteract GPS signal's unlocking problem and the inertial component's divergence for its error accumulation with time in a vehicle navigation system, whose positioning accuracy and robustness are improved in complex environment.
Glück trotz psychischer Erkrankung?
Authors: Prins Sibylle
Published: July 2018

Das Wort „trotz“ und das Fragezeichen im Titel des Beitrags legen nahe, dass eine psychische Erkrankung dem Glück entgegensteht. Tatsächlich ist eine psychische Erkrankung zunächst etwas, was unglücklich macht. Das liegt nicht zuletzt an den mit der Krankheit verbundenen psychosozialen Konsequenzen. Psychiatrieerfahrene sind bei den klassischen Glücksquellen häufig benachteiligt. Doch zum einen ist es gar nicht klar, ob es im Leben immer nur darauf ankommt, glücklich zu sein. Unglückliche Menschen haben der Welt viel gegeben (z. B. als Philosophen und Künstler). Und zum anderen kann man auch das Glück haben, nicht nur trotz, sondern wegen einer psychischen Erkrankung glücklich zu werden. Der Beitrag endet mit einer illustrativen Geschichte vom unverhofften Besuch des Glücks.
Universitätspsychiatrie, Heilanstalt, Wehrmachtslazarett: Der Heidelberger Psychiater Hans W. Gruhle (1880 – 1958) in der württembergischen Anstaltspsychiatrie 1935 – 1945
Authors: Reichelt Bernd , Müller Thomas
Published: July 2018

Wegen seiner Vorbehalte gegenüber dem Nationalsozialismus konnte der Heidelberger Psychiater Hans W. Gruhle 1934 seine Universitätslaufbahn nicht fortsetzen. Er wurde im württembergischen Innenministerium tätig und leitete später die Heilanstalten Zwiefalten und Weissenau bei Ravensburg. Von 1940 – 1945 leitete er das Reservelazarett in Winnenden. Anhand archivalischer Quellen wird Gruhles Biografie auf Handlungsspielräume des ärztlichen Personals in der Psychiatrie während der Zeit des Nationalsozialismus hin untersucht.
γ-Dimerization, α-Polymerization, and Plasmin Degradation of Human Fibrin
Authors: Carsten Feddersen J , Gormsen Johs
Published: July 2018

The effect of different factor XIII inhibitors (competetive inhibition, interference with active center SH-groups in different ways, Ca2+ depletion) on the sequence of the γ-dimerization and α-polymerization of fibrin is examined by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAE) (reduced material). They all inhibit either γ-dimerization and a-polymerization or a-polymerization alone irrespective of the factor XIII inhibitory mechanism.

Non-crosslinked fibrin and fibrin clots of different degrees of crosslinking are digested with plasmin and the lysate tested in SDS-PAE (non-reduced material) and crossed agarose gel Immunoelectrophoresis (CAIE). The digests contain Fragment D and Fragment D-D respectively and Fragment E. An additional Fragment E with less anodic mobility in CAIE, and not demonstrable in SDS-PAE, is seen in increasing amounts with increasing γ-dimerization, α-polymerization does not further change the CAIE patterns.
Analysis of the Disappearance Curve of Labelled Fibrinogen at the Time of Hyperfibrinogenemia in Rabbits with Acute or Chronic Intravascular Coagulation
Authors: Hasegawa H , Watanabe N , Nagata H , Murao M
Published: July 2018

In order to study fibrinogen metabolism, the disappearance curve of 125I-labelled homologous fibrinogen was investigated in the rabbits with experimentally induced acute or chronic intravascular coagulation by injection of Lycopodium spores or thromboplastin. The results obtained were as follows.

1. Using haemolysate, an intermediate phase with upward convexity was clearly recognized between the early rapid-decay phase and the late slow phase in each radioactivity decay curve obtained in groups of rabbits. This convexity was most marked with acute intravascular coagulation induced by injection of Lycopodium spores, and was less marked, although higher, with chronic intravascular coagulation induced by injection of thromboplastin than that in the normal control.

2. The disappearance curve with the intermediate phase could be expressed, in approximation, as a sum of 2 equations - the initial exponential decay equation and the late parabolic one.

3. From the results obtained by separate examinations of the disappearance curve of plasma, fibrin clots and serum in rabbits with acute intravascular coagulation induced by injection of Lycopodium spores, the intermediate phase appears to be influenced more by the secondary increase of labelled non-clottable part than recirculation of the labelled fibrinogen.

4. The half time (27.4 hours) of the radioactivity in fibrin clots at the late phase observed in the group of rabbits with acute intravascular coagulation induced by injection of Lycopodium spores was shorter than that in the normal rabbits (50.2 hours). This fact may indicate that the increase of fibrinogen in the group of rabbits with acute intravascular coagulation induced by the injection of Lycopodium spores is due to overproduction of fibrinogen.

5. The half time of labelled fibrinogen should be calculated from disappearance curve of fibrin clots, instead from that of haemolysate or plasma.
Platelet Adhesiveness and Fibrinolysis after Recent Cerebro-Vascular Accidents and their Relationship with Subsequent Deep Venous Thrombosis of the Legs
Authors: Warlow C. P , Rennie J. A. N , Ogston D , Douglas A. S
Published: July 2018

In fifteen patients with a cerebro-vascular accident resulting in an acute hemiplegia there was a subsequent rise in the platelet count and plasma fibrinogen level. There were no significant alterations in platelet adhesiveness, plasminogen activator, plasminogen, FR-antigen and haematocrit. Patients diagnosed as developing deep venous thrombosis with the 125I-fibrinogen technique had a significantly lower platelet adhesiveness and plasminogen level than those who were not.
Microvascular Haemostasis and the Effect of Local Stimulation and inhibition of Platelet Function. An Experimental Study in Rabbits
Authors: Bergqvist D , Arfors K.-E
Published: July 2018

The local stimulation and inhibition of haemostatic plug formation was studied by local infusion and superfusion of different agents – ADP, thrombin, adenosine, heparin, prostaglandin E1 (PGE1) and laser injury. ADP and laser injury shortened venular haemostatic plug formation time whereas adenosine in the superfusate and PGE1 prolonged it. Thrombin infusion had no effect but thrombin in the superfusate significantly stabilised the haemostatic plugs. It is suggested that ADP released from red cells is the most potent stimulator for haemostatic plug formation in the rabbit mesenteric microcirculation.
Venous Thrombosis in Suspected Pulmonary Embolism: Incidence Detectable by Doppler Ultrasound
Authors: Barnes Robert W. , Kinkead Lewis R. , Wu Kenneth K. , Hoak John C.
Published: July 2018

Doppler ultrasound has been used to screen patients for venous thrombosis with an accuracy of 94% compared to venography. Of 168 patients with suspected pulmonary embolism, only 48 (28%) had a source of venous thrombosis detectable by Doppler examination. The calf and iliofemoral venous segments were the two most common sites of involvement. When compared to Doppler examination, clinical assessment of the legs was falsely negative in 15% and falsely positive in 54% of patients. The highest incidence of venous thrombosis detected by Doppler examination (49%) was in the group of patients with a positive lung scan and a normal chest film. Doppler evidence of venous thrombosis was present in only 21% of patients with both a positive scan and an abnormal chest film. One-third of the patients with suspected pulmonary embolism had a negative lung scan. The most common conditions mimicking pulmonary embolism were congestive heart failure, pneumonia, chronic lung disease and atelectasis. Patients with suspected pulmonary emboli frequently have no demonstrable source of thrombosis and may deserve more thorough angiographic evaluation for proper diagnosis and therapy.
Platelet Preservation. III. The Influence of Dimethylsulfoxide and Cooling Conditions on Serotonin Uptake Velocity and Response to Hypotonic Stress of Human Platelets
Authors: Odink J , Sprokholt R
Published: July 2018

1. Serotonin uptake velocity of human platelets was found to be reversibly inhibited by the presence of dimethylsulfoxide (DMSO).

2. Incubation of platelet concentrates in the presence of DMSO for 90 minutes at room temperature decreased serotonin uptake velocity and response to hypotonic stress.

3. The serotonin uptake velocity was not substantially influenced by the temperature of incubation with DMSO.

4. The best recovery of serotonin uptake velocity after cryopreservation in the presence of DMSO was observed when DMSO was added quickly before cooling and removed quickly after thawing.

5. No significant differences were observed in serotonin uptake velocity and response to hypotonic stress after cryopreservation in the presence of DMSO when cooling rates were varied from 2 to 10° C/min.
Newborn Platelet Dysfunction: a Storage Pool and Release Defect
Authors: Corby Donald G. , Zuck Thomas F.
Published: July 2018

Per cent aggregation, release and content of adenine nucleotides, and specific radioactivity were evaluated in citrated platelet-rich plasma (PRP) prepared from paired samples of maternal and cord blood. Platelets of newborn infants aggregated normally in response to high dose ADP (20 μM), strong collagen suspensions, and thrombin; however, when compared with PRP from the mothers or from normal adults, per cent aggregation in response to lower concentrations of ADP (2 μM), weak collagen, and part particularly epinephrine was markedly reduced. Nucleotide release after stimulation of the newborns’ PRP with the latter two inducers was also impaired. ATP and ADP content of the newborns’ platelets was also significantly less than that of their mothers or of normal adults, but specific activity was normal. The data suggest that the impairment of ADP release in the platelets of newborn infants is due to decreased sensitivity to external stimuli. Since metabolic ATP is necessary for the platelet release reaction, it is postulated that the platelet dysfunction results from a lack of metabolic ATP.
The Use of a Chelating Ion-Exchange Resin to Evaluate the Effects of the Extracellular Calcium Concentration on Adenosine Diphosphate Induced Aggregation of Human Blood Platelets
Authors: Heptinstall Stanley
Published: July 2018

1. An ion-exchange resin, Chelex 100, has been used to prepare suspensions of human blood platelets in calcium and magnesium depleted plasma.

2. Extracellular calcium is required for platelet aggregation when induced by adenosine diphosphate (ADP). Magnesium only supports aggregation provided that a small amount of calcium is present in the plasma.

3. The extent of platelet aggregation depends upon the concentration of calcium in the plasma. There is an optimum concentration of calcium with which the maximum amount of aggregation is obtained in response to any single concentration of ADP. This optimum calcium concentration is below the physiological level. Higher calcium concentrations reduce the extent of aggregation by enhancing the rate of disaggregation and high magnesium concentrations have the same effect. It is possible that free ADP levels are reduced as a result of ADP-divalent cation complex formation.

4. Platelets were found to contain 18.6 (S.D. ±1.1) × 10–6 mol Ca and 9.3 (S.D. ±1.0) × 10–6 mol Mg per 1011 cells.
Effect of Platelet Age on Adhesiveness to Collagen and Platelet Surface Charge
Authors: Castellan Robert M. , Steiner Manfred
Published: July 2018

Adhesion to collagen was investigated as a function of platelet age in rat platelets. Platelet adherence was measured using EDTA-containing platelet- rich plasma which was added to preparations of collagen fibers clamped between magnetic stirrers by recording changes in light transmission. The plot of light transmission versus logarithm of time was linear and allowed calculation of a slope factor which related to the rate of adherence. Neither the amount of collagen nor the platelet count were limiting in the test. Young platelet populations (≤ 1 day old) were obtained during the recovery phase from immune induced thrombocytopenia. Old platelet populations were prepared by blocking thrombopoiesis with cyclophosphamide. Young platelets showed a moderate but statistically significant increase in adhesivity to collagen but old platelets did not differ significantly from randomly aged platelets in this function. The electrophoretic mobility of platelets was not affected by their age.
Inhibition of Human and Animal Platelet Adhesiveness to Glass Bead Columns by Adenosine, Dipyridamole, Chlorpromazine and Acetylsalicylic Acid
Authors: Fujttani Buichi , Tsuboi Toshimichi , Takeno Kazuko , Yoshida Kouichi , Shimizu Masanao
Published: July 2018

The differences among human, rabbit and guinea-pig platelet adhesiveness as for inhibitions by adenosine, dipyridamole, chlorpromazine and acetylsalicylic acid are described, and the influence of measurement conditions on platelet adhesiveness is also reported. Platelet adhesiveness of human and animal species decreased with an increase of heparin concentrations and an increase of flow rate of blood passing through a glass bead column. Human and rabbit platelet adhesiveness was inhibited in vitro by adenosine, dipyridamole and chlorpromazine, but not by acetylsalicylic acid. On the other hand, guinea-pig platelet adhesiveness was inhibited by the four drugs including acetylsalicylic acid. In in vivo study, adenosine, dipyridamole and chlorpromazine inhibited platelet adhesiveness in rabbits and guinea-pigs. Acetylsalicylic acid showed the inhibitory effect in guinea-pigs, but not in rabbits.
Studies of an Inhibitor of the Thrombin-Fibrinogen Reaction Localized in Rat Liver Microsomes. Interference with the Polymerization Step
Authors: Helgeland L
Published: July 2018

A heat-stable, macromolecular inhibitor of the thrombin-fibrinogen reaction localized in rat liver microsomes has been shown to interfere with the polymerization step in the fibrinogen-fibrin conversion. The inhibitor had no effect on thrombin activity as measured with the synthetic, chromogenic substrate Bz-Phe-Val-Arg-pNA. The amount of fibrin formed and the release of fibrinopeptide A were not affected by the inhibitor. Recording of turbidity at 350 nm and 600 nm indicated an inhibition of the lateral aggregation of the end-to-end fibrin polymers. The inhibitor was localized in both the luminal and membrane fractions of the microsomes. The inhibitor activity was not affected by warfarin treatment of the rats.
Thrombin Elaboration in Endotoxin-Induced intravascular Fibrin Deposition
Authors: Lipinski Boguslaw , Gurewich Victor , Hyde Elisabeth
Published: July 2018

Intravascular coagulation was induced by two appropriately spaced doses of endotoxin and by infusion of thromboplastin. The resulting fibrin deposition was measured by a previously described quantitative technique. Evidence of thrombin elaboration was obtained indirectly by measurement of fibrin monomer (FM) and by the detection and isolation of a thrombin-induced anticlotting activity. Venous segments were isolated at intervals and examined for thrombus formation following 40 minutes of stasis. Endotoxin triggered thrombin elaboration was not detectable in the circulation for at least one hour and was not accompanied by any thrombosis in isolated venous segments. No thrombin elaboration was found in leukopenic rabbits given endotoxin. In the thromboplastin infused animals, the quantity of fibrin deposited in the organs was comparable to that found after endotoxin. However, thrombin was found in the blood immediately and was associated with thrombosis in the isolatet venous segments. Less thrombin-induced anticoagulant activity was found after thromboplastin than after endotoxin. The findings suggest that endotoxin-induced intravascular coagulation is probably not caused by a mechanism of systemic hypercoagulability due to the release of thromboplastic material into the blood stream. A focal process of thrombin elaboration involving leukocytes is postulated. The study is believed relevant to patients with disseminated intravascular coagulation in whom venous thromboembolism is rarely found despite evidence of extensive microvascular fibrin deposition.
Impairment of ADP-Induced Platelet Aggregation by Hashish Components
Authors: Levy Rachel , Schurr Avital , Nathan Ilana , Dvilanski Alexander , Livne Avinoam
Published: July 2018

ADP-induced aggregation of washed human platelets is inhibited by the hashish components Δ1-tetrahydrocannabinol (THC) and cannabidiol (CBD). The inhibition is counteracted by added ADP. When the cannabinoids are present at concentrations higher than 10−5M, the platelets aggregate non-reversibly, independently of an added inducer, apparently due to lysis and release of endogenous inducers. THC is clearly more potent than CBD in exhibiting the biphasic effect. Collagen- and thrombin-induced aggregation of washed platelets are hardly affected by the cannabinoids. THC and CBD also curtail ADP-induced reversible aggregation in platelet-rich plasma, while serotonin release and irreversible aggregation, caused by either ADP, collagen or thrombin, are not affected by the cannabinoids in platelet-rich plasma. The data point to associated sites for ADP and the cannabinoids on the platelet membrane.
Cell Shape Change and Cytosolic Ca2+ in Human Umbilical-Vein Endothelial Cells Stimulated with Thrombin
Authors: Sago Haruhiko , linuma Kazuso
Published: July 2018

We quantified thrombin-induced endothelial cells shape change and investigated the role of Ca2+ in such shape change. We used the fluorescent Ca2+ indicator, fura2, to measure both shape change as cell size and intracellular free Ca2+ ([Ca2+]i), in cultured human umbilical-vein endothelial cells (HUVEC). Thrombin induced concentration-dependent decreases in cell size (percentage of cell size at 6 min after stimulation with 0.01 U/ml, 0.1 U/ml, or 1 U/ml thrombin) was 90.1 ± 1.5%, 78.1 ± 2.4%, and 40.9 ± 2.4%, respectively. Thrombin also increased [Ca2+]i in a concentration-dependent manner. Both depletion of extracellular Ca2+, and also the addition of W5, a calmodulin antagonist, inhibited thrombin-induced size reduction. These results indicate an association between shape change and [Ca2+]i mobilization in human endothelial cells stimulated by thrombin.
The Glycosaminoglycan of Recombinant Human Soluble Thrombomodulin Affects Antithrombotic Activity in a Rat Model of Tissue Factor-Induced Disseminated Intravascular Coagulation
Authors: Nawa Katsuhiko , Itani Teru , Ono Mayumi , Sakano Katsu-ichi , Marumoto Yasumasa , Iwamoto Masahiro
Published: July 2018

Previous studies on recombinant human soluble thrombomodulin (rsTM) from Chinese hamster ovary cells revealed that rsTM was expressed as two proteins that differed functionally in vitro due to the presence (rsTMp) or absence (rsTMa) of chondroitin-4-sulfate. The current study evaluates the in vivo behavior of rsTM in rats and in a rat model of tissue factor-induced disseminated intravascular coagulation (DIC). rsTMp was more potent than rsTMa for prolongation of the activated partial thromboplastin time (APTT) and their in vivo half-lives determined by ELISA were 20 min for rsTMp and 5.0 h for rsTMa. Injection of a tissue factor suspension (5 mg/kg) resulted in DIC as judged by decreased platelet counts and fibrinogen concentrations, prolonged APTT, and increased fibrin and fibrinogen degradation products (FDP) levels. A bolus injection of either rsTM (0.2 mg/kg) 1 min before induction of DIC essentially neutralized effects on platelets, fibrinogen, and FDP levels, and had only a moderate effect on APTT prolongation. The dose of anticoagulant to inhibit the drop in platelet counts by 50% (ED50) was 0.2 mg/kg rsTMa, 0.07 mg/kg rsTMp, and 7 U/ kg heparin. The effect of increasing concentrations of rsTM and heparin on bleeding times were compared in experiments involving incision of the rat tail. Doubling of the bleeding times occurred at 5 mg/kg rsTMa, 3 mg/kg rsTMp or 90 U/kg heparin. These values represent a 25-fold increase over the ED50 for rsTMa, 43-fold for rsTMp and 13-fold for heparin. These results suggest that rsTMp is a potent anticoagulant to inhibit the platelet reduction when injected prior to the induction of DIC in rats.
Analysis of Intrinsic Fibrinolysis in Human Plasma Induced by Dextran Sulfate
Authors: Tsuda Hiroko , Miyata Toshiyuki , Iwanaga Sadaaki , Yamamoto Tetsuro
Published: July 2018

The analysis of normal human plasma by fibrin autography revealed four species of plasminogen activator (PA) activity related to tissue-type PA, factor XII, prekallikrein and urokinase-type PA (u-PA). The u-PA activity increased significantly by incubating plasma with dextran sulfate. This increase was coincident with both the cleavage of factor XII and the complex formation of activated factor XII with its plasma inhibitors, which were determined by immunoblotting procedure. The dextran sulfate-dependent activation of u-PA required both factor XII and prekallikrein, but did not require either plasminogen or factor XI. High molecular weight kininogen was required only at a low concentration of dextran sulfate. Thus the results indicate that the factor XII and prekallikrein-mediated activation of single chain u-PA (scu-PA) operates as a major pathway of scu-PA activation in whole plasma in contact with dextran sulfate.
Expression and Characterization of Recombinant Human Protein S in Heterologous Cells - Studies of the Interaction of Amino Acid Residues Leu-608 to Glu-612 with Human C4b-Binding Protein
Authors: Chang Glenn T G , Ploos van Amstel Hans K , Hessing Martin , Reitsma Pieter H , Bertina Rogier M , Bouma Bonno N
Published: July 2018

Mouse C127 epithelioid cells were genetically engineered to produce biologically active ³-carboxylated human protein S. A full length human protein S cDNA was cloned into a bovine papilloma virus (BPV) based shuttle vector under the transcriptional control of the Moloney murine sarcoma virus enhancer and the mouse metallothionein promoter. Stable expression was obtained in transfected C127 cells. Expression of ³-carboxylated protein S was dependent on the presence of vitamin K in the culture medium. Protein sequence analysis showed that recombinant and plasma protein S have the same amino terminal sequence. Analysis of specific post-translationally modified amino acids shows that recombinant protein S is fully ³-carboxylated and fully p-hydroxylated. Immunoblotting analysis using polyclonal and monoclonal antibodies shows that recombinant protein S has a slightly higher molecular weight than plasma protein S. After N-Glycanase treatment, identical molecular weights are observed for recombinant and plasma protein S, indicating that the difference is caused by differences in the N-linked carbohydrate side chains. Recombinant protein S also demonstrates normal cofactor activity for activated protein C in a clotting assay. Binding studies with the complement component, C4b-binding protein (C4BP), shows that recombinant protein S binds to C4BP with the same apparent affinity as plasma protein S. Two variant molecules are also tested for their binding to C4BP. The first variant has a replacement of amino acid residue leu-608 by val and was designated B variant. The second variant has three alterations, at positions 609, 611 and 612 where the acidic amino acid residues asp, asp and glu were replaced by asn, asn and gin, respectively and this variant was designated C variant. The binding of these variants to C4BP was the same as wild type recombinant protein S. This suggests that amino acid residues leu-608, asp-609, asp-611 and glu-612 are not essential for binding of the intact full length protein to C4BP.
Characterization of Thromboxane A2/Prostaglandin H2 Receptors in Porcine Coronary Artery -The Inhibitory Effect of a Novel Dibenzoxepin Derivative, KW-3635
Authors: Miki Ichiro , Ishii Akio
Published: July 2018

We characterized the thromboxane A2/prostaglandin H2 receptors in porcine coronary artery. The binding of [3H]SQ 29,548, a thromboxane A2 antagonist, to coronary arterial membranes was saturable and displaceable. Scatchard analysis of equilibrium binding showed a single class of high affinity binding sites with a dissociation constant of 18.5 ±1.0 nM and the maximum binding of 80.7 ± 5.2 fmol/mg protein. [3H]SQ 29,548 binding was concentration-dependently inhibited by thromboxane A2 antagonists such as SQ 29,548, BM13505 and BM13177 or the thromboxane A2 agonists such as U46619 and U44069. KW-3635, a novel dibenzoxepin derivative, concentration-dependently inhibited the [3H]SQ 29,548 binding to thromboxane A2/prosta-glandin H2 receptors in coronary artery with an inhibition constant of 6.0 ± 0.69 nM (mean ± S.E.M.).
Thrombospondin Levels in Patients with Malignancy
Authors: Tuszynski George P , Smith Monica , Rothman Vicki L , Capuzzi David M , Joseph Rosaline R , Katz Julian , Besa Emmanuel C , Treat Joseph , Switalska Hanna I
Published: July 2018

Thrombospondin (TSP), a large glycoprotein present in platelets, and various normal and tumor tissues, has recently been shown to promote cell adhesion and platelet aggregation. Most importantly because TSP has been shown to promote metastasis of melanoma tumor cells to the lung in a murine model (1) and since thromboembolic events commonly occur in patients afflicted with metastatic tumors, we explored the role of TSP in human cancer by measuring TSP blood levels in patients with various malignant neoplasms. Blood TSP levels were measured by indirect enzyme-linked immunoadsorbent assay (ELISA) from 20 control subjects, 22 patients with gastrointestinal (GI) cancer, 18 patients with breast cancer, and 17 patients with lung cancer. Control subjects consisted both of healthy subjects and acutely ill patients with no malignancies. TSP levels of both healthy and acutely ill controls were found to range between 245-440 μg/ml with a mean of 365 μg/ml. In contrast, elevated levels of TSP greater than the mean value of 400 μg/ml for controls ranging between 590-3,650 μg/ml were found in 20/22 (91%) patients with GI malignancies, 13/18 (72%) patients with breast cancer, and 15/17 (88%) with lung cancer. Mean TSP levels of GI, breast, and lung cancer patients were 3, 2, and 3 fold greater than controls, respectively. Increased blood TSP levels in patients were not due to increased levels of platelets since both control and patient groups had platelet counts within the normal range. These results suggest that TSP may play a role in tumor cell metastasis in man and could serve as a blood marker for metastasis.
Factor Vlla/Tissue Factor-Catalyzed Activation of Factors IX and X on a Cell Surface and in Suspension: A Kinetic Study
Authors: Rao L Vijaya Mohan , Robinson Thomas , Hoang An D
Published: July 2018

The kinetics of activation of factor IX and factor X by factor Vila was studied in the presence of various sources of tissue factor: (1) a surface membrane of human ovarian carcinoma cell line, OC-2008 (2) the cell lysate (of 002008) and (3) reconstituted purified human tissue factor. The rates of activation of factors IX and X were monitored in activation peptide release assays using tritiated substrates. The results indicate that the apparent K
m values for factor IX and factor X were similar for a given tissue factor, but varied with tissue factor source. The source of tissue factor greatly influenced the apparent differences in V
max for factors IX and X. When a surface of monolayer provided tissue factor, the Vmax of factor IX was only 2-3 fold lower than factor X, but when either a cell lysate or purified tissue factor was the source of cofactor activity, the difference in V
max rose to about 8-10 fold. Although, the tissue factor apoprotein in the cells was expressed entirely on the outer surface membrane, the activity of tissue factor on the intact cell surface was 50 to 100fold lower than in the lysed cell preparation.
Defibrotide Inhibits Platelet Activation by Cathepsin G Released From Stimulated Polymorphonuclear Leukocytes
Authors: Evangelista Virgilio , Piccardoni Paola , Gaetano Giovanni de , Cerletti Chiara
Published: July 2018

Defibrotide is a polydeoxyribonucleotide with antithrombotic effects in experimental animal models. Most of the actions of this drug have been observed in in vivo test models but no effects have been reported in in vitro systems. In this paper we demonstrate that defibrotide interferes with polymorphonuclear leukocyte-induced human platelet activation in vitro. This effect was not related to any direct interaction with polymorphonuclear leukocytes or platelets, but was due to the inhibition of cathepsin G, the main biochemical mediator of this cell-cell cooperation. Since cathepsin G not only induces platelet activation but also affects some endothelial cell functions, the anticathepsin G activity of defibrotide could help to explain the antithrombotic effect of this drug.
Kinetic Aspects of the Interaction of Blood Clotting Enzymes
Authors: Hemker H. C , Vermeer C , Govers-Riemslag J
Published: July 2018

The relation between clotting time and the inverse of prothrombin concentration is shown to be rectilinear.
Localization of Tissue Thromboplastin in the Human Brain
Authors: Bjørklid E , Storm-Mathisen J , Storm E , Prydz H
Published: July 2018

Monospecific antisera against the purified protein component of tissue thromboplastin (apoprotein-III) from human brain have been raised in goats and rabbits. The antisera neutralized tissue thromboplastin prepared from brain, thyroid gland and pulmonary tissue, indicating that apoproteins in the various preparations cross-reacted immunologically and therefore were similar or identical.

Comparison of the activities of tissue thromboplastin preparations from 34 different areas of the brain demonstrated a characteristic distribution pattern and a wide range of activities. White and grey matter from the same areas had similar activities. Bulbus and tractus olfac-torius, medulla oblongata, corpus pineale, hippocampus and hypothalamus contained 160–270 % of the average activity, whereas cerebellum, globus pallidus, nucleus ruber and substantia nigra contained 30–60 %. The distinct distribution pattern was unrelated to tissue vascularization, and may suggest that apoprotein-III could serve other functions, apart from the coagulation of blood. The predominance in phylogenetically older brain regions would suggest that it represents a primitive or fundamental feature.
Studies of the Effects of Estradiol, Progesterone, Cortisol, Thrombophlebitis, and Typhoid Vaccine on Synthesis and Catabolism of Antithrombin III in the Dog
Authors: Kobayashi N , Takeda Y
Published: July 2018

Effects of estradiol, progesterone, Cortisol, thrombophlebitis and typhoid vaccine on the synthesis and catabolism of antithrombin III (AT) in dogs were studied, using I-125-labeled AT (I-125-AT) as a tracer. Five dogs were used for each study. A single intramuscular injection of 20 mg estradiol caused a 20% decrease of plasma AT concentration in 6 days without appreciable changes in the plasma half-lives of I-125-AT but with a significant decrease in the fractional catabolic rate of I-125-AT (j3u). A single intramuscular injection of 250 mg progesterone did not produce any appreciable changes of plasma AT concentration, the plasma half-lives of I-125-AT or j3u. On the other hand, intravenous and intramuscular injections of a total of 750 mg Cortisol caused a 17 % increase of plasma AT concentration in a day after the injections without alterations of the plasma half-lives of I-125-AT or j3u. Next, thrombophlebitis was produced in dogs by a single intravenous injection of 1 ml 90% phenol into a leg vein occluded for 1 min by a gauze tourniquet and the effects of thrombophlebitis were studied. The results indicated that it did not cause appreciable changes of plasma AT concentration, the plasma half-lives of I-125-AT or j3u. However, studies of the effects of a single intravenous injection of 3 ml typhoid vaccine showed a 25 % decrease of plasma AT concentration in a day after the injection with a moderate acceleration of the decline rate of plasma I-125-AT and a 14% increase in j3u values. Further studies in heparinized dogs showed similar effects with typhoid vaccine. These results indicate that estradiol causes a decreased rate of AT synthesis, that progesterone has no appreciable effects on AT metabolism, that Cortisol increases the rate of AT synthesis, that localized thrombophlebitis has no appreciable effects on AT metabolism and that typhoid vaccine causes an increased j3u by unknown mechanisms which is not an accelerated coagulation process.
A New Method for the Determination of Plasma Activators of Fibrinolysis
Authors: Margalit R , Gidron E , Shalitin Y
Published: July 2018

The term “effective activator” of plasminogen is proposed, to denote the resultant of activator-antiactivator interaction, and a method for the determination of the level of these activators is described. By adding axcess plasminogen to the euglobulin fraction of plasma the influence of the level of endogenous plasminogen and of the antiplasmin is eliminated. It is shown that the level of fibrinogen has very little bearing on the results. An effective activator unit is defined as equal to 1 CTA unit of urokinase activity on a fibrinogen-plasminogen substrate.
Binding of Collagen by Canine Blood Platelets
Authors: Kay W. W , Swanson R , Chong G , Kurylo E , Bharadwaj B. B
Published: July 2018

The binding of 125I-collagen (tropocollagen) by canine blood platelets occurred in a concentration-dependent manner but no saturation effect could be observed. The binding of collagen was not entirely specific for platelets since various eucaryotic and procaryotic cells quantitatively bound collagen as well or better.

The temporal response to added collagen appeared to be binding, 3H-serotonin release, and finally platelet aggregation. Non-polymerizing salt-soluble tropocollagen was bound as well as acid-soluble tropocollagen, however neither 3H-serotonin release nor platelet aggregation occurred. Furthermore, the binding activity was not destroyed by treatment with collagenase, galactose oxidase and glucose oxidase, nor by periodate oxidation.

Platelet aggregation closely paralleled acid soluble collagen polymerization and both events were equally inhibited by arginine; however, arginine did not interfere with collagen binding. Scanning electron microscopy revealed an unusual morphological platelet response to collagen and platelets appeared to be nucleation sites for collagen polymerization.
Binding of Anti-Actin Autoantibodies to Platelets
Authors: Bouvier Claude A , Gabbiani Giulio , Ryan Graeme B , Badonnel Marie-Claude , Majno Guido , Lüscher Ernst F
Published: July 2018

Normal platelets incubated with anti-actin autoantibodies (AAA) (from the serum of patients with chronic aggressive hepatitis) do not show binding of these antibodies as seen by indirect immunofluorescence. AAA serum does not inhibit thrombin-induced clot retraction, despite the binding of the antibodies to platelets in the clot. Similarly, AAA serum does not affect “reversible” or “irreversible” aggregation (induced by ADP, collagen or epinephrine), despite the binding of the antibodies to platelet actin under such circumstances. AAA also bind to platelets when aggregation is inhibited by EDTA. The incubation of “reversibly” aggregated platelet with AAA results in a small but definite binding of AAA to platelets. These findings suggest that during “irreversible” and/or “reversible” aggregation, changes take place at the surface of platelets which expose the antigen at the surface of the cell.
Cyanide Insensitive Oxidase in Platelets of Newborn Infant
Authors: Del Principe D , Menichelli A , Damiano A. M , Coppola L , Sabetta G
Published: July 2018

The authors studied the behaviour of neonate platelet O2 consumption after the addition of pyridine nucleotide compared to adult controls.

O2 consumption of neonate platelets after NADH addition was 103,2 mμmol O2/109/hr (SE = 24,74) and in adult controls 188,8 mμmol O2/109/hr (SE = 36,46).

After the addition of NADPH O2 consumption was, respectively, 233,5 mμmol (SE = 46,29) and 218,3 mμmol (SE = 30,01).
Calcium Electrode – a Method for the Continuous Monitoring of the Platelet Release Reaction
Authors: Robblee Lois S , Kornstein Laura B , Shepro David
Published: July 2018

The calcium electrode is a convenient, inexpensive, and non-traumatic method for measuring changes in the extracellular calcium which accompanies a platelet release reaction. With this instrument, the temporal pattern of release by platelets in a buffered-saline medium following thrombin stimulation was observed as follows: an initial time lag phase, followed by a maximum release phase, and finally a slow release phase.
ADPase Activity of Normal and Atherosclerotic Human Aorta intima
Authors: Heyns A. du P , Badenhorst C. J , Retief F. P
Published: July 2018

ADP plays a key role in platelet aggregation and the enzymatic removal of this nucleotide may be important in the pathogenesis of intravascular thrombosis and atherosclerosis. Aortic intima extracts have ADPase activity and is able to remove small quantities of ADP efficiently. ADPase activity was assayed by measuring the catabolism of 2 μM 14C-ADP (final concentration) by the tissue extracts. Extracts prepared from normal, moderately and severely atherosclerotic human aorta intimas showed a significant progressive decrease in ADPase activity with increasing atherosclerosis. ADPase activity of the arch, thoracic and abdominal regions of normal aortas did not vary significantly, and thus did not correlate with the anatomical distribution of atherosclerosis. Vascular ADPase activity seems relevant in thrombogenesis since it may be a link between blood platelets and blood vessel wall interaction.
Marathon Run I: Effects on Blood Coagulation and Fibrinolysis
Authors: Mandalaki T , Dessypris A , Louizou C , Bossinakou I , Panayotopoulou C , Antonopoulou A
Published: July 2018

Blood coagulation and fibrinolysis were assessed in 13 Finnish amateur runners aged 31 to 48, and one 65-year old taking part in a non-competitive marathon (42.2 km). After the run the mean values of partial thromboplastin time showed a very significant shortening, whereas the mean values of the prothrombin time and of plasma fibrinogen were not significantly altered. The mean values of euglobulin lysis time were significantly shorter and the mean values of fibrin degradation products increased highly significantly. After the run, protamine sulphate was positive or strongly positive in all subjects, whereas the ethanol gelation test was negative in all runners; no cryofibrinogen was detected in any participant. Thus, running a marathon race affects the haemostatic balance and activates the fibrinolytic mechanism. The effects of training and physical fitness on the above parameters are discussed.