bluuebunny/crossref_metadata_2025 huggingface dataset:
Benchmark on the Dynamics of Liquid Draining Inside a Tank
Authors: Mohd Sakri Fadhilah , Mat Ali Mohamed Sukri , Zaki Sheikh Ahmad
Published: May 2019

Immense information and details observation of flow physics inside a draining tank can be achieved by adopting reliable numerical simulations. Yet the accuracy of numerical results has been always debatable and it is mainly affected by the grid convergence error and computational modeling approaches. Hence, this study is divided into two stages. In the first stage, this paper determines a systematic method of refining a computational grid for a liquid draining inside a tank using OpenFOAM software. The sensitivity of the computed flow field on different mesh resolutions is also examined. In order to study the effect of grid dependency, three different grid refinements are investigated: fine, medium and coarse grids. By using a form of Richardson extrapolation and Grid Convergence Index (GCI), the level of grid independence is attained. In this paper, a monotonic convergence criteria is reached when the fine grid has the GCI value below 10% for each parameter. In the second stage, different computational modeling approaches (DNS, RANS k-ε, RANS k-ω and LES turbulence models) are investigated using the finer grid from the first stage. The results for the draining time and flow visualization of the generation of an air-core are in a good agreement with the available published data. The Direct Numerical Simulation (DNS) seems most reasonably satisfactory for VOF studies relating air-core compared to other different turbulence modeling approaches.
A Multi-objective Optimization Algorithm for Multiple Home Users Intelligent Power Management and Control Based on Pareto and Nash Equilibrium Game
Authors: Yu Zhou , Weifeng Hu , Dezhi Wang , Zheng Xu , Tao Yu
Published: May 2019

A multi-objective optimization model for multiple home users intelligent power management and control is proposed. A photovoltaic power model, an electric vehicle battery model and a load model are developed first, and then a strategy of home intelligent power management is presented based on battery operation and PV spontaneous self-use. Secondly, a multi-objective optimization model of multiple home users intelligent power management, including the user comfort, economy and optimization of load curve, is provided under the constraints. Then using a multi-objective optimization algorithm and Nash equilibrium game theory to solve the multi-objective problem. Finally, the 100-home power management and control simulation case show that the presented algorithm can improve the comfort and the economy of users effectively, but also help the power grid to peak load shifting.
Control of mechatronic drives considering the type and number of the nonlinearities of a mechanical converter
Authors: Tellez Ricardo , Morozov Valentin , Zhdanov Alexey , Novikova Elena , Gavrilov Dmitryi
Published: May 2019

In this article the particularities of the dynamics study of mechatronic drives that operate at low velocities are discussed; the origins of frictional self-exited oscillations to develop an algorithm for non-linearity correction are analyzed; a drive mathematical model and the qualitative picture of the self-exited oscillations regimes were presented for the three cases: a "system with clearance and friction-free"; a system without clearance with "dry friction" and a system with clearance and "dry friction". Therefore, an algorithm to compensate the frictional self-excited oscillations based on the feedback introduction for the sliding velocity of the linear motion output link was proposed.
An Improved Genetic Algorithms for Multi-objective Hybrid Flow-shop Scheduling Problem
Authors: Zijin Zhao , aimin Wang , Yan Ge , Lin Lin
Published: May 2019

To deal with the multi-objective hybrid flow Shop Scheduling Problem (HFSP), an improved genetic algorithms based on parallel sequential moving and variable mutation rate is proposed. Compared with the traditional GA, the algorithm proposed in this paper uses the two-point mutation rule based on VMR to find the global optimum which can make the algorithm jump out of the local optimum as far as possible, once it falls into the local optimum quickly. Decoding rules based on parallel sequential movement ensures that the artifact can start processing in time, so that the buffer between stages in the flow-shop is as little as possible, and the production cycle is shortened. Finally, a program was developed with the actual data of a workshop to verify the feasibility and effectiveness of the algorithm. The result shows that the algorithm achieves satisfactory results in all indexes mentioned above.
BP Neural Network Algorithms for Fault Diagnosis of Microwave Components
Authors: Kun Gao , Aimin Wang , Yan Ge
Published: May 2019

Intelligent diagnosis is the main trend of modern fault diagnosis technology. The emergence of artificial neural network technology provides a new way for this kind of intellectualization. Aiming at the problem of microwave module fault diagnosis, an intelligent fault diagnosis method based on BP(Back Propagation) neural network is proposed in this paper. In this paper, the process of determining the neural network model and the operation flow of BP algorithm are introduced, and the network is trained with training samples. By applying the neural network model to an AQ module for testing, the feasibility, accuracy and efficiency of the fault diagnosis of the microwave module are verified, which provides a new method for intelligent fault diagnosis of this kind of microwave module.
Towards a reconstruction of Supernova Neutrino Spectra in JUNO
Authors: Martellini Cristina , Maria Mari Stefano , Montini Paolo , Settanta Giulio
Published: May 2019

Observation of supernovae (SN) through their neutrino emission is a fundamental point to understand both SN dynamics and neutrino physical properties. JUNO is a 20kton liquid scintillator detector, under construction in Jiangmen, China. The main aim of the experiment is to determine neutrino mass hierarchy by precisely measuring the energy spectrum of reactor electron antineutrinos. However due to its properties, JUNO has the capability of detecting a high statistics of SN events too. Existing data from SN neutrino consists only of 24 events coming from the SN 1987A,the detection of a SN burst in JUNO at ~ 10kpc will yield ~ 5x103 inverse beta decay (IBD) events from electron antineutrinos, about 1500 from proton elastic scattering (pES) above the threshold of 0.2 MeV, about 400 from electron elastic scattering (eES), plus several hundreds on other CC and NC interaction channels from all neutrino species.
The Science Case for a Southern Wide Field of View Detector
Authors: Giuseppe Di Sciascio
Published: May 2019

EAS arrays are survey instruments able to monitor continuously all the overhead sky. Their sensitivity in the sub-TeV/TeV energy domain cannot compete with that of Cherenkov telescopes, but the wide field of view (about 2 sr) is ideal to complement directional detectors by performing unbiased sky surveys, by monitoring variable or flaring sources such as Active Galactic Nuclei (AGN) and to discover transients or explosive events (GRBs). Arrays are well suited to study extended sources, such as the Galactic diffuse emission, and to measure the spectra of Galactic sources at the highest energies (near or beyond 100 TeV). An EAS array is able to detect at the same time events induced by photons and charged cosmic rays, thus studying the connection between these two messengers of the non-thermal Universe. Therefore, these detectors are, by definition, multi-messenger instruments. All EAS arrays presently in operation or under installation are located in the Northern hemisphere. The scientific potential of a next-generation survey instrument in the Southern Hemisphere will be presented and briefly discussed.
Helium flux and elemental composition of galactic Cosmic Rays with the DAMPE space mission
Authors: Di Santo Margherita
Published: May 2019

DAMPE (DArk Matter Particle Explorer) is a space mission project promoted by the Chinese Academy of Sciences (CAS), in collaboration with Universities and Institutes from China, Italy and Switzerland. The detector is collecting data in a stable sun-synchronous orbit lasting 95 minutes at an altitude of about 500 km. It has been launched in December 17th, 2015, from the Jiuquan Satellite Launch Center, in the Gobi Desert. The main goals of the mission are: indirect search for Dark Matter, looking for signatures in the electron and photon spectra with energies up to 10 TeV; analysis of the flux and composition of primary Cosmic Rays with energies up to hundreds of TeV; high energy gamma-ray astronomy. Preliminary results about the Helium flux and Cosmic Ray composition will be presented and discussed.
Montecarlo simulation of the High Energy Particle Detector on board the satellite CSES
Authors: Carfora Luca
Published: May 2019

The High-Energy Particle Detector (HEPD) is an instrument devoted to the measurement of cosmic particles from few MeV up to hundreds of MeV. The HEPD will contribute to the China Seismo-Electromagnetic Satellite mission by measuring the precipitation of trapped particles and by studying the solar-terrestrial environment especially during impulsive events like coronal mass ejections and solar energetic particle emissions.

A Monte Carlo software was realized to study the performance of HEPD, such as its particle discrimination capability, the energy threshold for trigger and the maximum energy detectable in full containment.

This contribution reports the main features of the HEPD Monte Carlo simulation and some results of the detector performance based on it. A comparison with beam tests was carried out, showing a good agreement with the simulation.
The “As Low As Reasonably Achievable” (ALARA) principle: a brief historical overview and a bibliometric analysis of the most cited publications
Authors: Yeung A.W.K.
Published: May 2019

The “As Low As Reasonably Achievable” (ALARA) principle is largely followed in the radiology field. The current article provided a historical overview on the evolution and development of the ALARA principle and its related concepts. Meanwhile, the scientific impact of papers dealing with the ALARA principle was largely unknown. The current study aimed to identify the body of literature dealing with the ALARA principle, which of them were cited the most, and which of their references were cited the most. The Web of Science database hosted by Clarivate Analytics was accessed. Relevant papers were identified and analyzed. The search identified 979 relevant publications. Six journals (Health Physics, Pediatric Radiology, Radiation Protection Dosimetry, Transactions of the American Nuclear Society, Fusion Engineering and Design, and American Journal of Roentgenology) have accounted for nearly one-fifth of these publications. The most cited publications and references mainly related to two patient groups, children and pregnant women. It is important to adhere to the ALARA principle whenever a decision is made to irradiate a patient, because the exact effect of radiation on the patient health is not yet totally understood and predictable.
Akuter Bauchschmerz: einweisen oder nicht? Und was dann?
Authors: Garbe Jakob , Michl Patrick , Klement Andreas
Published: May 2019

Acute abdominal pain (AAP) is a common symptom and reason for encounter in family practices and emergency rooms. About every tenth hospital emergency room consultation is dealing with AAP, the most important reason is the “suspected acute abdomen”. Important diagnostic considerations and clarification steps in family practice and emergency room are presented with the question: in which cases further treatment must be inpatient – or can be done on an outpatient basis. Acute abdominal pain has a complex differential diagnostic spectrum. Early detection of urgent cases is crucial to the outcome. The most important diagnostic means are history (“inductive foraging”), physical examination and sonography. “Yellow flags” provide valuable information for risk groups. Interdisciplinary cooperation is crucial, in doubt: “four eyes principle”. If the cause is unclear, follow-up should be planned.
Foudroyante nekrotisierende Fasziitis bei einem 47-jährigen Mann
Authors: Gamon Eike , Rahe Katharina , Beckschulze Henrik
Published: May 2019

Die nekrotisierende Fasziitis ist eine potenziell letale Entzündung des Weichteilgewebes, die sich durch rasant fortschreitende Gewebsnekrosen auszeichnet 1, 2. Im Folgenden wird ein fulminanter Fall einer nekrotisierenden Fasziitis präsentiert. Nach einem Bagatelltrauma nahm die Infektion einen hochgradigen septischen Verlauf, der trotz maximaler Intensivtherapie und chirurgischer Intervention nicht zu beherrschen war.
Antithrombotische Therapie der peripheren arteriellen Verschlusskrankheit – ein Überblick über aktuelle Evidenz, Praxis und Ausblick
Authors: Bauersachs Rupert , Espinola-Klein Christine , Lawall Holger , Storck Martin , Zeller Thomas , Debus Sebastian
Published: May 2019

Die periphere arterielle Verschlusskrankheit ist eine häufige, chronische Störung der arteriellen Durchblutung v. a. der unteren Extremitäten, wobei fibröse Plaques der Gefäßwand zu Stenosen und Thrombenbildung führen. Bei betroffenen Patienten besteht ein hohes Risiko für kardiovaskuläre Komplikationen im gesamten arteriellen Gefäßsystem, auch nach dortigen Eingriffen. Daher besteht Optimierungsbedarf bei der antithrombotischen Therapie. Zur Mehrfach-Thrombozytenaggregationshemmung durch neue Arzneimittelklassen werden in den nächsten Jahren Studiendaten erwartet. Aktuelle Studien zeigten bei Hemmung der Gerinnungskaskade durch direkte orale Antikoagulanzien klinische Vorteile bei vertretbarem Sicherheitsprofil. Grundlage medikamentöser Therapie bleibt das Management von Risikofaktoren wie Übergewicht und Nikotin sowie die Korrektur metabolischer Störungen. Diese Aspekte sollten den behandelnden Ärzten bekannt sein, um eine optimale Versorgung und Motivation der Patienten zu erreichen.
Patients with gastric MALT lymphoma revealing persisting endoscopic abnormalities after successful eradication of Helicobacter pylori can be safely managed by a watch-and-wait strategy
Authors: Fischbach Wolfgang , Dorlöchter Christian
Published: May 2019

Background In current guidelines, Helicobacter pylori eradication is recommended as first-line therapy in patients with gastric MALT lymphoma. This leads to complete lymphoma regression in the majority of patients. Those who show persisting histological residuals of lymphoma after eradication of the bacterium and normalization of endoscopic findings are managed by a watch-and-wait strategy. We aim to show that such an approach can be extended to patients with persisting endoscopic abnormalities.

Methods Thirteen patients (7 female and 6 male; 62 years, range: 43 – 80) with gastric MALT lymphoma of stages I and II1 had received exclusive H. pylori eradication. Control endoscopies performed every 3 – 4 months during the first 2 years and 6 and 12 times monthly 2 – 5 and > 5 years after diagnosis, respectively, revealed successful eradication of H. pylori but persisting endoscopic abnormalities. Histologically, complete regression of the lymphoma or minor residuals were observed.

Results Persisting endoscopic changes included thickened folds with or without superficial erosions, nodular mucosal surface with or without angiectasia, focal or diffuse atrophy, focal erythema, or a mixture of these findings. During a follow-up of 89.9 (12 – 329) months, the outcome of these patients was excellent with no single case of lymphoma progression.

Conclusion A watch-and-wait strategy can be recommended for patients with gastric MALT lymphoma showing persisting endoscopic abnormalities after eradication of H. pylori. There is no need for any oncological treatment provided that regular endoscopic-bioptic controls do not reveal any progressive changes. A standardized description of the endoscopic changes as well as a thorough bioptic technique should be included.
Intramolecular Aldol Ring Closures of Cysteine Derivatives Leading to Densely Functionalised Pyroglutamates
Authors: Almahli Hadia , Jimenez Niamh C. , Moloney Mark G.
Published: May 2019

The synthesis of densely functionalised pyroglutamates derived from cysteine by an aldol cyclisation strategy has been achieved.
Do Thromboxane-Sensitive Receptors Mediate Platelet Aggregation In The Rat?
Authors: Duncan G G , Smith G M
Published: May 2019

Evidence has been produced to suggest that platelets of rabbits and humans contain receptors sensitive to thromboxane A2 (TxA2) and that inhibition of platelet aggregation can be achieved by preventing the conversion of the cyclo endoperoxides to TxA2 or by competitive antagonism of TxA2 at these TxA2-sensitive receptors. Conflicting evidence has been published on the possible role of TxA2 in the rat and this communication will attempt to explain the effects of agonists and inhibitors in rats and rabbits.

Platelet aggregation was measured in vivo by continuously measuring the circulating platelet count using the Technicon Auto-counter. Collagen, PGH2 and the synthetic prostanoids U446l9 and U44069 were studied in rats and collagen and PGH2 were also studied in rabbits. The effects of cyclo-oxygenase inhibitors, thromboxane synthetase inhibitors and thromboxane receptor antagonists on aggregation produced by collagen and PGH2 were studied. Collagen, U44069 and PGH2 produced a dose-dependent fall in platelet count in rats. U46619 was inactive at nontoxic doses. Cyclo-oxygenase inhibitors partially inhibited collagen-induced aggregation in both rats and rabbits. 1-n-butylimidazole (25 mg/kg) and phthalazinol (1 mg/kg) (reported to be a thromboxane receptor antagonist) both inhibited aggregation produced by collagen and PGH2 in the rabbit but they did not affect aggregation produced by collagen in the rat.

The activity of the cyclo-oxygenase inhibitors suggests that collagen-induced aggregation is partially mediated by products of arachidonic acid in rats and rabbits but evidence that the conversion of PGH2 to TxA2 is necessary for aggregation to be produced in rats by this pathway could not be obtained.
A Family Of Hereditary Dysplasminogenemia
Authors: Kazama M , Abe T A , Tahara C , Kasai N , Suzuki Z
Published: May 2019

The proband was 41 year-old male without any history of thrombosis. Recurrent thrombosis were developed after he had received an accidental contusion on his chest, and coagulation analysis revealed no abnormality except for low plasminogen activity, about 20% of normal value.

No thrombotic trait was claimed by patient’s family but there wascorisanguineous marriage in his parents. Results of coagulation analysis of 15 members of this family were as follows; platelet count, platelet aggregation and clot retraction were normal. Activity of all coagulation factors and antigenicity as well as activity of α2-M, α2-PI, AT-III and α1,-antitrypsin were within normal ranges. Plasminogen activity, hoever, were 20-60% of normal value in 9 out of 15, it was 80-120% in 6.

Plasminogen of each member was isolated by affinity chr- omatorgraphy with lysine-Sepharose column and kinetic study was performed with these isolated plasminogen. Km’s of all members were ranged in 170-230μM/L as compared to 170μM/L in normal control. But Vmax’s were distributed from 0.19 to 3.28M/min.ml as compared to 3.1 in normal control. On the other hand, antigencicity of plasminogen of these members were ranged in 10-14.2 mg/lOOml except for a case with 17.6 mg/100ml.

SDS-gel electrophoresis revealed that activation of this plasminogen with SK yielded two subunits, H and L, and plasmin formed a complex with α2, similar as normal plasmin did.

It was concluded that this family had dysplasminogenemia inherited by a dominant mode, and plasminogen of these patients were a heterologous mixture composed of normal and abnormal plasminogen.
Antithrombotic And Opposite Effects Of Drugs Influencing The Prostaglandin System
Authors: Zimmermann R , Peter J , Jung G , Horsch A , Mörl H , Harenberg J
Published: May 2019

The prostaglandin metabolites prostacyclin (PGI2) and thromboxane affect the aggregation of platelets and their interaction with the vessel wall. An increase of the PGI2 availability or inhibition of the thromboxane synthesis may induce antithrombotic activity.

The antithrombotic effects of some drugs influencing the prostaglandin metabolism were investigated therefore in 220 rabbits. Arterial and venous thrombus formation was produced in a standardized experimental model of silver nitrate induced thrombosis. The following substances were examined:
1.PGI2 20 ng/kg/min,2.PGI2 10 ng/kg/min,3.a substance which increases the PGI2 availability (BAY g 6575) 10 mg/kg,4.the thromboxane synthetase inhibitor UK-37,248-01 ,5.BAY g 6575 in combination with aspirin 10 mg/kg and 6.BAY g 6575 and aspirin 50 mg/kg. A reduction of the arterial and venous thrombus growth could be observed after treatment with 1.PGI2 20 ng/kg/min (arterial system:-74%, significant [s],venous system:-64%,s), 2.PGI2 10ng /kg/min (-34%,s,-34%,s), 3.BAY g 6575 (-50%,s,-75 %,s), 4.UK-37,248-01 (-41 % , s ,-36% , s) , 5.BAYg 6575 in association with aspirin 10 mg/kg (-41%,not s, -50%,ns) and 6.BAY g 6575 and aspirin 50 mg/kg (-22%,ns,-21%,ns).

Our data suggest that PGI2 and drugs increasing the availability of PGI2 induce a pronounced and significant antithrombotic activity. A less efficient reduction of thrombus formation can be expected after inhibition of thromboxane synthesis. The decrease of the antithrombotic property of BAY g 6575 when combinated with aspirin suggests an instability of the antithrombotic activity of substances acting by influencing the prostaglandin metabolism.
Coagulation Changes Under An Effective Urokinase Dosage Regimen
Authors: Schöffel G , Zimmermann R , Harenberg J
Published: May 2019

In preliminary studies we demonstrated an increased thrombolytic activity with higher dosages of urokinase in the therapy of deep vein thrombosis. From that time this higher urokinase dosage schedule (loading dose 250,000 IU, initial maintenance dosage 2000 IU/kg/h in combination with 1520 U heparin/kg/h) was used and suggested as ideal.

In 10 patients with deep vein thrombosis treated according to this dosage schedule following coagulation parameters were determined before the beginning of the therapy, after 1,4,12 h and then at least once per day up to 7-14 days:aPTT, thrombin clotting time, fibrinogen (according to Clauss, Ratnoff and Menzie and radial immunodiffusion), TEG, euglobulin clot lysis time, inhibitors of fibrinolysis, plasminogen, antithrombin III, fpA, clotting factors V and VIII. The coagulation analysis showed a progressive decrease of fibrinogen to 50100 mg% and of plasminogen to about 40 % within 12-36 h. At this time a reduction of the urokinase dose by 30-40 % and further only slight corrections became necessary. Additional investigations demonstrated a more pronounced fibrinogenolytic effect when dissolving and applying urokinase in plastic material and avoiding contact with glass surfaces. These findings suggested a 30% saving of urokinase.

The highly effective urokinase dosage schedule here described has been proved practicable and rendered too frequent coagulation controls superfluous. The saving of urokinase by using plastic material introduced a modification of our urokinase regimen:Loading dose 250,000 IU, followed by 2000 IU/kg/h for only 8 h, then 1000 IU/kg/h with further slight individual dose corrections.
Effect Of Heparin And Other Polyanions On Collagen Induced Platelet Aggregation
Authors: Tiffany M Lois , Penner John A
Published: May 2019

Despite the fact that relatively high concentrations of polyanions are capable of inducing spontaneous platelet aggregation following a brief incubation period, collagen induced platelet aggregation was actually decreased when a low concentration (1 ug/ml) of.the polyanions, Heparin (gut or lung fractionated), Dextran, Sulfate (mol. wt. 500,000) and polyvinyl Sulfate (mol. wt. 100,000) were incubated for 5 minutes with human platelet rich plasma.

An explanation for this apparent anomalous effect of low polyanion concentrations may rest with compliment activation. We have proposed that collagen interacts with platelet-bound Cls inducing Cls esterase activity, and have suggested that this interaction results in platelet aggregation and release. Therefore, an explanation of the effect of these polyanions on collagen induced platelet aggregation is found in their known potentiation of the inhibitor, Cl-lNA, on the induction of esterase activity in Cls.

In support of this concept is our findings that, the polyanion, polyanethanol sulfonate, which inhibits the activity of Cl-lNA, enhances collagen induced platelet aggregation when used at the same low concentration and under the same experimental conditions as used with the other polyanions discussed.
ANTIBODIES AGAINST MEMBRANE GLYCOPROTEINS: AGGREGATION, CROSS IMMUNOELECTROPHORESIS STUDIES, AND RELEVANCE TO GLANZMANN’S THROMBASTHENIA
Authors: Jenkins C S P , Ali-Briggs E F , Clemetson K J
Published: May 2019

In Glanzmann’s thrombasthenia, glycoproteins (GPs) IIb and IIIa are missing or strongly reduced in concentration and aggregation to ADP, collagen and thrombin is impaired. Antibodies against GPs IIb and IIIa did not entirely induce a thrombasthenia-like state in normal platelets; however they did strongly inhibit collagen-induced aggregation, inhibited the second wave of aggregation induced by ADP, inhibited to some extent thrombin-induced aggregation and clot retraction, and were totally without effect on ristocetin-human VIIIR:WF.

Crossed immunoelectrophoresis studies using Triton X-100 extracts of whole platelets and platelet membranes with these antibodies gave a single immunoprecipitate. This immunoprecipitate was absent when similar studies were carried out with thrombasthenie platelets. Anti-whole platelets antibodies gave a number of immunoprecipitates with normal platelets and differences were observed with thrombasthenie platelets, the most notable of which was a marked reduction in one of the major immunoprecipitates.

These results provide further evidence that GPs IIb and IIIa are involved in the later stages of platelet aggregation.
Enhanced Platelet Aggregation And Arachidonic Acid Metabolism Associated To Reduced Sensitivity To Exogenous Prostacyclin In Hypercholesterolemic Subjects
Authors: Tremoli E , Maderna P , Colli S , Sirtori M , Sirtori C R
Published: May 2019

The platelet sensitivity to aggregating agents and the production of arachidonic acid (AA) metabolites were studied in 97 hypercholesterolemic patients (WHO types IIA and IIB;serum cholesterol levels >250 mg/dl, LDL>170 mg/dl,triglycerides >180 mg/dl). The findings were compared with those of 55 age and sex matched normocholesterolemic subjects.

Platelet aggregation was studied in platelet rich plasma (PRP) with ADP, collagen, epinephrine and thrombofax* as aggregating agents. Malondialdehyde (MDA) production was determined according to Smith et al.. Thromboxane B2 (TXB2) was measured in washed platelets stimulated with AA by a specific RIA. The platelet sensitivity to the inhibitory effect of synthetic prostacyclin (PGI2) was also assessed in 40 of the patients and in 20 age and sex matched control subjects, using fixed concentrations of aggregating agents.

Platelets from patients required to aggregate significantly lower concentrations of collagen, epinephrine and thrombofax* (p< 0.001) and of ADP ( p<O.05); MDA production by thrombin and collagen and TXB formation were significantly raised (p<0.001) in the patient group. Higher concentrations of PGI2 were required to inhibit the aggregation of platelets in the type II patients.

The reported findings confirm in a large clinical series the potential role of platelet hyperreactivity in the thrombotic risk of type II hypercholesterolemia.
Systemic Effects Of Thromboxanes Released By Positive Endexpiratory Pressure
Authors: Hechtman H B , Utsunomiya T , Krausz M M , Dunham B , Feuerstein G , Shepro D
Published: May 2019

Positive end-expiratory pressure (PEEP) stimulates prostaglandin production at the same time that cardiovascular functions are altered. This study explores a possible regulatory role for prostaglandins to mediate cardiovascular functions and other effects of PEEP. Eight healthy volunteers breathed against 10 cm H2O PEEP for 15 min. There was a mean increase in functional residual capacity of 838 ml (p < 0.001); the stable metabolite of the vasoconstricting and pro-aggregating agent thromboxane A2, thromboxane B2, rose from 0.03 to 0.09 ng/ml (p < 0.03). ADP induced platelet aggregation increased from 35 to 48% (p < 0.03); plasma 5-hydroxytryptamine increased from 45 to 57 ng/ml (p < 0.005); and diastolic pressure rose from 73 to 93 mm Hg (p < 0.005). A circulating agent which depressed myocardial function was detected by in-vitro assays. PEEPplasma decreased: (1) developed tension of a rat papillary muscle (p < 0.005); (2) Ca++-ATPase activity of two rat myocardial subfractions, myofibrils (p < 0.005) and sarcoplasmic reticulum (p < 0.03); (3) succinate dehydrogenase activity (p < 0.05) of mitochondria isolated from rat heart. There was no change in concentration of the stable metabolite of prostacyclin, 6-keto-PGF1α. Treatment of volunteers with 650 mg aspirin 12 h prior to PEEP reduced baseline thromboxane B2 concentration from 0.03 to 0.002 ng/ml (p < 0.005). During PEEP these lowered thromboxane B2 levels were unchanged as was cardiovascular function and platelet sensitivity to ADP induced aggregation. This study shows that a short period of PEEP produces sufficient thromboxanes to effect significantly cardiovascular and platelet functions, which are preventable with aspirin.
Platelet associated IgG in chronic hepatitis
Authors: Landolfi R , Fedeli G , Storti S , Laghi F , Leone G
Published: May 2019

Raised levels of platelet-associated IgG have been described in many pathological conditions such as ITP, LES, rheumatoid arthritis, lymphoma, drug thrombocytopenia. We measured surface-bound platelet IgG in 60 patients suffering from chronic hepatitis. In all cases diagnosis was confirmed by needle biopsy of the liver and by pertinent laboratory data; the technique used was that described by Dixon et al.(1975).In chronic active hepatitis (40 cases) we found increased amounts of platelet-associated IgG with values ranging from 110 to 480 ng/107platelets (mean 195ng; p :0.001). In persistent hepatitis (20 cases) surface-bound platelet IgG were always less than 70 ng/107platelets. A significant inverse correlation between increased amount of platelet IgG and the platelet count was not found. This test can be of considerable help in the differential diagnosis of chronic hepatitis as well in the follow up of these patients for prognostic and therapeutic decisions.
The Determination of Factor X Using an Automated Amidolytic Technique
Authors: van Wijk E , Kahlé L , ten Cate J
Published: May 2019

An automated method for the determination of factor X has been developed using a procoagulant fraction from Russell’s Viper Venom (RVV), which activates FX within 4 minutes at pH 8.6, resulting in a Xa activity that is assayed using the chromogenic substrate S 2222. The amidolytic activity generated by sufficient RVV is proportional to the FX level of the plasma and is not influenced by antithrombin III within the time studied. By using polybrene, the influence of heparin (up to 10 U/ml) can be eliminated. The method has been adapted for performance automatically on an Automated Kinetic Enzyme and Substrate analyzer (Vitatron). Comparison of FX activities of 30 normals and 41 patients with bleeding disorders revealed a close correlation of this method with the one stage clotting assay using thromboplastin (r=0.93). Values obtained in a group of 83 patients on oral anticoagulant therapy showed good correlation (r=0.87) but tended to be about 8% higher compared to the one stage method. No significant differences were found when RW was used in the clotting assay (r=0.91). The values obtained by the amidolytic assay correlated well with thrombotest (r=0.87).
Bovine Factors X1And X2: Activation Peptide Based Chromatographic Differences
Authors: Morita Takashi , Jackson Craig
Published: May 2019

Bovine Factor X is eluted in two forms (X1and X2) from anion exchange chromatographic columns. These two forms have indistinguishable amino acid compositions, molecular weights and specific activities. The amino acid sequences containing the γ-carboxyglutamic acid residues have been shown to be identical in X1 and X2(H. Morris, personal communication). An activation peptide is released from the N-terminal region of the heavy chain of Factor X by an activator from Russell’s viper venom. This peptide can be isolated after activation by gel filtration on Sephadex G-100 under nondenaturing conditions. The activation peptides from a mixture of Factors X1 and X2 were separated into two forms by anion-exchange chromatography. The activation peptide (AP1) which eluted first was shown to be derived from Factor X1. while the activation peptiae (AP2) which eluted second was shown to be derived from X2 on the basis of chromatographic separations carried out on Factors X1 and X2 separately. Factor Xa was eluted as a symmetrical single peak. On the basis of these and other data characterizing these products, we conclude that the difference between X1 and X2 are properties of the structures of the activation peptides. (Supported by a grant HL 12820 from the National Heart, Lung and Blood Institute. C.M.J. is an Established Investigator of the American Heart Association).
Factor X Activation by washed human platelets
Authors: van Wijk E , Kahlé L , ten Cate J
Published: May 2019

In a system of washed human platelets, Ca2+and purified human factors X anc II, a sufficient amount of thrombin is generated in about 10 minutes to aggregate the platelets. This thrombin is formed through the activation of FX by the platelets. In a system with either FX or FII present, no aggregation occurs. In addition no aggregation is observed when hirudin, a specific thrombin inhibitor, or when soybean trypsin inhibitor, which inhibits factor Xa, are added to the mixture. The formation of factor Xa can be monitored indirectly through the generation of thrombin, in the presence of an excess of prothrombin, using a thrombin sensitive chromogenic substrate. When washed platelets are incubated with FX alone for 10 minutes, no aggregation occurs and after the addition of prothrombin aggregation starts within 6 minutes. These findings confirm that washed platelets possess a factor X activating property. The generation of FXa proceeds in the absence of added Ca2+, whereas in the presence of Ca2+factor Xa activity reaches a maximum in 3 minutes, whereafter the activity progressively decreases. This may be due to the binding of Xa to the platelets in the presence of calcium ions.
Factor X Vorarlberg, A New Variant of Hereditary Factor X Deficiency
Authors: Lechner K , Mähr G , Margariteller P , Deutsch E
Published: May 2019

The proposita, a 56 years old woman, has a mild bleeding tendency. Prothrombin time was 112 sec (control 17.0 sec), stypven time 13.7 sec (control 11.5 sec) and APTT 54 sec (control 40 sec). Factor I, II (funct.and imm.), V, VII, VIII, IX, XI, XII, AT III were normal. - Factor X activity was < 1% by extrinsic system assay (tissue thromboplastin), 12% by RVV assay and 32% by intrinsic system (APTT) assay. Similar results were obtained when factor X activity was determined using the synthetic substrate S 2222. Immunoassay (antibody neutralisation, heterologous antibody to factor X) demonstrated a decreased level (20%) of immunoreactive factor X. The patient plasma had no inhibitory activity. Factor X activity could be completely absorbed on barium sulfate and eluted with 5% sodium citrate. It was eluted at the same position from a Sephadex G-200 column as normal factor X, but had a slower electrophoretic mobility when subjected to disc electrophoresis. Family studies (22 members studied) suggest an autosomal recessive inheritance. A second unrelated family with the same defect was subsequently detected in the same valley of Vorarlberg (Austria). - It is concluded that this hereditary coagulation disorder is due to a grossly abnormal factor X-molecule.

Supported by Ö.F.F.W.F. (grant No. M2-2090)
The Heterogeneity of Congenital factor X deficiency
Authors: Porter N , Malia R , Cooper P , Preston F
Published: May 2019

Two unrelated patients with congenital factor X deficiency are described. R.N. a four year old Pakistani child of consanguinous marriage presented with gastrointestinal haemorrhage. Routine tests of coagulation revealed a grossly prolonged prothrombin time and KCCT. All factor assays, other than factor X, were normal. Factor X, measured by three unrelated methods, was < 1%. Factor X related antigen (FXRAg) measured by antibody neutralisation was undetectable. In other, less affected members of the family FXC/FXRAg = 1 An infusion of factor X concentrate raised the factor X to 140%. The rate of decline was biphasic with an initial rapid component, T½ = 4 hours, and a slower second component T½ = 33 hours. The second patient, P.P. a Caucasian female presented with persistent post-dental extraction haemorrhage. Routine tests of coagulation revealed a prolonged prothrombin time and KCCT. All factor assays, other than factor X, were normal. Factor X, measured by two unrelated methods was 20 - 32% (normal 58 - 134%) FXRAg was 71% (normal 60 - 120%). FXC/FXRAg = 0.35. Similar ratios were obtained on three other affected members of the family. The ratio represents an important difference between the two families. Studies using the modified thrombotest strongly suggest an abnormal molecular complex in P.P. The results provide further evidence of the heterogenity of factor X deficiency states.
The Effects Of Three Potential Antithrombotic Agents On Platelet Activities Ex Vivo
Authors: Cockbill S , Taylor Patricia , Heptinstall S
Published: May 2019

The effects of ingested acetylsalicylic acid (ASA), flurbiprofen (FN) and indomethacin (IN) on the platelet release reaction (ADP-induced release of 3H-serotonin fran platelet) and on prostaglandin synthetase activity (PGSA; conversion of arachidcnic acid to malondialdehyde by platelets) were determined. The studies were carried out on platelets from volunteers who had ingested a single dose of ASA (300 mg), FN (50 mg) or IN (25 mg) or were taking ASA (1×300 mg), FN (4×50 mg) or IN (4×25 mg) daily. Two hours after a single dose of ASA both the release reaction and PGSA were completely inhibited. Both activities slowly returned in parallel over several days. During the continuous administration of ASA both activities were completely abolished until the ASA was discontinued. The effects of FN and IN on platelet activity were similar to each other but different from those of ASA. Two hours after a single dose the release reaction was abolished but. PGSA was only partially inhibited. An effect on the release reaction could still be observed after 24 hours whereas PGSA had returned to normal. During the continuous administration of FN and IN, PGSA remained steady at about 15% and 50% of normal respectively, returning to normal 24 hours after the drugs were discontinued. Since FN and IN inhibit release without a long-lasting effect on PGSA they should be investigated further as potential antithrombotic agents.
Immunochemical studies on fibrinogen
Authors: Gollwitzer R , Tanswell P , Lotter H , Henschen A , Timpl R
Published: May 2019

The immunochemistry of fibrinogen has been subject of concise studies during the last years. Fibrinogen is a strong immunogen, based on a large variety of antigenic determinants located at different sites in the molecule. By using purified antibodies several of the surface and masked antigenic determinants on the individual chains and the large disulfide bonded CNBr-peptides were identified. According to these investigations the γ-chain is partially buried in the native molecule, whereas the antigenic determinants of a CNBr-peptide covering the C-terminal half of the α-chain are located on the surface of the protein. The structure of the antigenic determinants of this peptide which exhibits an extreme species variability has been more precisely defined in both bovine and human fibrinogen. A distinct structural variability was also observed for different antigenic determinants located m fibrinopeptides A and B.

Supported by the Deutsche Forschungsgemeinschaft, SFB 51.
On The Release Function Of Adhering Platelets
Authors: Malmgren R , Larsson R , Olsson P , Tornling G , Unge G
Published: May 2019

A method for measuring the continuous uptake and release of serotonin during 60 minutes by platelets adhering to a polymer surface is presented.

Heparinized human blood with autologous 51Cr and 14C-serotonin labelled platelets is exposed to the polymer in Chandler loops rotated slowly for different periods. Initially the adhering platelets take up serotonin from non-adhering aggregating platelets by an active process and then slowly begin to release serotonin. Acetylsalicylic acid treated platelets adhere and take up serotonin to the same extent as untreated platelets, but do not undergo a release reaction.

Coating of the polymer surface with fibrinogen prior to blood exposure or with fibrin (achieved by thrombin treatment of the fibrinogen adsorbate) does not affect the degree of adhesion and serotonin uptake, but inhibits the release reaction. When only fibrino-peptide A is split off with Defibrase from the fibrinogen layer the release function of the adhering platelets reappears.

It is concluded that the release mechanism of adhering platelets is not only dependent of the functional state of the platelet itself, but also on the ultimate composition of the protein layer to which the platelets adhere.
Vitamin K-Dependent Carboxylase: Purification and Properties
Authors: suttie J
Published: May 2019

The vitamin K-dependent Plasma clotting factors are synthesized as inactive precursors and converted to active forms by the carboxylation of specific glutamyl residues to γ-carboxyglutamyl residues. A stable preparation (complex A) of the rat liver microsomal vitamin K-dependent carboxylase has been obtained by selective extraction of other proteins from the membrane. Treatment of crude microsomes with dilute nonionic detergent, chaotropic agents and sodium cholate yields a preparation that is 150-fold purified over the starting microsomes and is substantially increased in total activity. This lipoprotein complex has a high requirement for vitamin KH2 and is not active with [vitamin K + NADH]. Organic hydroperoxides will drive carboxylation in the absence of vitamin K in crude microsomes but not in complex A. In many other respects, complex A has properties similar to detergent-solubilized microsomes. The microsomal carboxylase converts Phe-Leu-Glu-Glu-Leu predominately to two forms of phe-Leu-Gla-Glu-Leu which can be separated by ion exchange chromatography. The more acidic of these two forms can be metabolized to the more basic form by crude microsomes, but complex A has lost the ability to carry out this conversion. About half of the carboxylase activity of complex A can be solubilized in a high concentnation of Triton x-100, and this material can be further purified by affinity chromatography.
Measurement of Des-Arginine-Fibrinopeptide B (DES-ARG-FPB) in Plasma by Radioimmunoassay
Authors: Eckhardt T , La Gamma K , Nossel H
Published: May 2019

During thrombin induced clotting of fibrinogen, fibrin I(des-fibrinopeptide A(FPA)-fibrin) and fibrin II (des-FPA-FPB-fibrin) are formed sequentially. As fibrin II forms thicker strands and is more rapidly crosslinked by factor XIIIa than fibrin I, measurement of FPB, reflecting fibrin II-formation, is of special interest. The radioimmunoassay for FPB cannot be applied to plasma, because 1. cross-reacting fragments cleaved from the N-terminal portion of the Bβ chain of fibrinogen by plasmin and fibrinogen are present and 2. cleavage of arginine 14 of FPB in blood by carboxypeptidase B results in a 20-fold reduction in immunoreactivity. These difficulties have been overcame as follows: fibrinogen is precipitated with ethanol; N-teiminal fragments such as Bβ 1-42 are selectively adsorbed to bentonite; FPB is converted by plasma carboxypeptidase B to des-arg-FPB which is measured using antiserum R29 (sensitive to des-arg-FPB), 125I-tyrosinated synthetic des-arg-FPB analogue as tracer and native des-arg-FPB standard. When added to blood, FPB is completely recovered as des-arg-FPB immunoreactivity. The lowest detectable level of des-arg-FPB in samples processed and assayed as described is 0.4pmol/ml. Preliminary data suggest that the des-arg-FPB level in normals is less than 0.7pmol/ml.
Effects of Aspirin and Sulfinpyrazone on Thromboxane and Prostacyclin Synthesis in Rabbits
Authors: McDonald J , Cerskus A , Ali M
Published: May 2019

Arachidonic acid (AA) or collagen were infused into rabbits causing intravascular platelet aggregation with thrombocytopenia, hypotension and death. Thromboxane and prostacyclin synthesis were measured by radioimmunoassay of plasma TXB2 and 6-keto-PGF1α. The effects of pretreatement with aspirin (ASA) or sulfinpyrazone(SPZ) were assessed.

Death in drug-treated rabbits was always associated with elevations of plasma TXB2(1-40 ng/ml) and of 6-keto-PGF1α(1-20 ng/ml). Collagen produced only small elevations of plasma TXB2 compared to AA but protection by ASA correlated better with inhibition of TXB2 and 6-keto-PGF1α synthesis than with inhibition of aggregation. Low dose ASA produced less inhibition of prostacyclin synthesis than high dose ASA but was less effective in preventing thromboxane synthesis and death.
Inhibition of Human Platelet Function Induced by Sulphinpyrazone
Authors: Maguire E , Pay G , Turney J , Wallis R , Weston M , White A , Williams L , Woods H
Published: May 2019

A single 400 mg dose of sulphinpyrazone (S) administered orally to 5 volunteers inhibited arachidonic acid (AA)-induced platelet aggregation and platelet MDA production ex vivo biphasically. The initial inhibitory phase coincided with the maximum plasma concentration of S but the second phase occurred 24 h after dosing when no plasma S was detectable. At 2 h the concentration of AA inducing half-maximal aggregation was increased 1.95 times and at 24 h by 1.61 times. Dosing 7 volunteers with 200 mg q.d.s. for 7 days and 5 volunteers with 400 mg b.d.s. for 5 days also led to inhibitory activity against AA-induced platelet aggregation and MDA production which declined to zero 48 h after the last dose. Platelet count, fibrinogen, F VIII, β-TG and AT III were not influenced by the longer term treatment but bleeding time was slightly extended in all but one subject.
Biphasic Prolonged Inhibition of Platelet Prostaglandin Biosynthesis Induced by Sulphinpyrazone
Authors: Butler K , Pay G , Wallis R , White A
Published: May 2019

In rabbits, high doses of sulphinpyrazone (S) result in prolonged inhibition of in vivo collagen-induced thrombocytopenia and platelet MDA production (Buchanan et al., Thromb. Res. 1978, 13., 883). After confirming these results we have shown in guinea pigs that 7 h after oral administration of S there was greater inhibition of AA-induced platelet aggregation than 1 h afterwards, i.e. at the peak plasma S concentration. Thus the concentration of AA needed to induce 50% maximal platelet aggregation at 7 h was raised 2.36 times and 4.73 times after 3 mg/kg and 10 mg/kg of S respectively. When in vivo thrombocytopenia was induced with the Arthus reaction the second phase of inhibition occurred down to a dose of 10 mg/kg p.o. with the first phase seen at higher doses. The inhibitory activity is associated with a high M.W. fraction of plasma proteins (50,000-100,000 Daltons). Phenylbutazone, aspirin andticlopidine did not induce the plasma-borne effect.