bluuebunny/crossref_metadata_2025 huggingface dataset:
Intra-Platelet Platelet Factor 4 (IP.PF4) and the Heparin-Mobilisable Pool of PF4 in Health and Atherosclerosis
Authors: O’Brien J R , Etherington M D , Pashley M
Published: July 2018

Some patients with clinical evidence of atherosclerosis and others with diabetes were compared with appropriate controls. The intraplatelet level of platelet factor 4 (PF4) was significantly decreased in the arteriopaths and was lower in the diabetics when compared with controls. Patients with transient ischaemic attacks and stroke have even lower values.

Intravenous heparin liberates large amounts of PF4 from an unknown reservoir, perhaps the endothelium, into the plasma. Arteriopaths liberated significantly more PF4 than the controls and the diabetics most. If a second heparin injection is given 24 hr after the first, the resultant plasma PF4 level was on average half that achieved after the first injection and again the patients had higher levels than the controls. Thus the reservoir originally “emptied” of PF4 by the heparin had been partially refilled in 24 hr and the reservoir in the atherosclerotic patients then contained more than the controls. Patients with atherosclerosis and especially diabetics differ from controls in the PF4 content of their platelets and in their response to heparin and in the rate of refill of the “heparin-mobilisable pool of PF4”.
Modulation of Rapid Plasminogen Activator Inhibitor in Plasma by Stanozolol
Authors: Verheijen J H , Rijken D C , Chang G T G , Preston F E , Kluft C
Published: July 2018

Fibrinolytic activity in plasma euglobulin fractions can be increased by oral administration of stanozolol. This increase is not caused by increased synthesis or release of tissue-type plasminogen activator. A decreased level of fast acting t-PA inhibition is very probably the cause of the higher activity. These results suggest that this inhibition has a regulatory role on fibrinolysis in vivo.
Biological and Thrombolytic Properties of Proenzyme and Active Forms of Human Urokinase – I. Fibrinolytic and Fibrinogenolytic Properties in Human Plasma In Vitro of Urokinases Obtained from Human Urine or by Recombinant DNA Technology
Authors: Zamarron C , Lijnen H R , Van Hoef B , Collen D
Published: July 2018

The fibrinolytic and fibrinogenolytic properties of recombinant pro-urokinase (Rec-pro-UK) and recombinant urokinase (Rec- UK) obtained by expression of the human urokinase cDNA in E. coli, were compared with those of natural urokinase (Nat-UK) of urinary origin and of tissue-type plasminogen activator (t-PA) in a system, composed of a radioactive human plasma clot immersed in citrated human plasma.

The specific fibrinolytic effects of Nat-UK, Rec-pro-UK and Rec-UK were very similar, causing significant clot lysis at concentrations of 100 IU/ml plasma or more. t-PA caused equivalent degrees of clot lysis at 10-fold lower concentrations.

Activation of the fibrinolytic system in the plasma (fib- rinogenolysis), was not observed with t-PA in concentrations which induced complete clot lysis within 5 hr (20-30 IU/ml plasma). With Nat-UK and Rec-UK, all concentrations which caused significant clot lysis (100-200 IU/ml plasma) also caused extensive activation of the plasma fibrinolytic system. With Rec- pro-UK an intermediate response was obtained. The highest amounts required for complete clot lysis in 5 hr (200 IU/ml plasma) also caused significant fibrinogenolysis. At intermediate concentrations (50-100 IU/ml), however, significant clot lysis (40-80%) was observed without systemic fibrinolytic activation.
Biological and Thrombolytic Properties of Proenzyme and Active Forms of Human Urokinase – IV. Variability in Fibrinolytic Response of Plasma of Several Mammalian Species
Authors: Lijnen H R , De Wreede K , Demarsin E , Collen D
Published: July 2018

The fibrinolytic and fibrinogenolytic properties of recombinant pro-urokinase (Rec-pro-UK) and recombinant urokinase (Rec- UK) were compared with those of natural urokinase (Nat-UK) and of tissue-type plasminogen activator (t-PA) in an in vitro system consisting of 125I-labeled autologous plasma clots immersed in plasma of humans, five primate species, dogs, rabbits and pigs. With each of the four plasminogen activators, a dose-dependent clot lysis was observed, the degree of which differed, however, very markedly from one species to the other.

At a concentration of 100 IU/ml of urokinase extensive plasma clot lysis was obtained in plasma of man, Macaca mulatta, Macaca fascicularis and Macaca radiata, while the plasma clots of Papio cynocephalus, Papio anubis and rabbit, dog and pig were much more resistant to lysis. No significant differences in the extent of lysis were observed between Rec-pro-UK and Rec-UK nor between Rec-UK and Nat-UK. Comparable degrees of lysis were obtained with t-PA at 3- to 5-fold lower concentrations. Lysis with Rec-UK or Nat-UK was always associated with extensive activation of the fibrinolytic system in plasma, evidenced by fibrinogen breakdown and plasminogen activation and a2-antiplasmin consumption. With t-PA, extensive clot lysis was obtained in the absence of fibrinolytic activation in the plasma. With Rec-pro-UK the response was intermediate; at high concentrations (200 IU/ ml) extensive lysis in the reactive species was associated with fibrinogen consumption, while at intermediate concentrations (50-100 IU/ml) significant clot lysis was obtained in the reactive species in the absence of marked activation of the fibrinolytic system in the plasma.
Acquired von Willebrand’s Syndrome Associated with Hydatid Disease of the Spleen – Disappearance after Splenectomy
Authors: Richard C , Sedano M C , Cuadrado M A , Recio M , Hermosa V , Zubizarreta A
Published: July 2018

A new case of acquired von Willebrand’s syndrome (vWS) is described in a 31-year-old woman with a hydatid splenomegaly and with a history of repeated abortions at an advanced stage of pregnancy, a positive serology for syphilis and a mildly elevated titre of antinuclear antibodies, with no family history of bleeding.

There is an inhibitory effect on factor VIII: C (antihaemophilic factor) as well as on factor VIIIR: Ag (related antigen) and on factor VIIIR:RCo (ristocetin cofactor), and it is precipitated by rabbit anti-IgG antiserum. This inhibitory effect was demonstrated using the patient’s plasma heated to 56° C for one hour so as to dissociate circulating immunocomplexes.

All the abnormalities of haemostasis, as well as the positive serology for syphilis, disappeared after splenectomy, and the ANA titre reverted to normal.

The clinical and biological peculiarities of the case are discussed, and are interpreted in the light of the findings recorded in patients showing “lupus” anticoagulant.
Role of Endogenous Proteinase Inhibitors in the Regulation of the Blood Clotting System of the Horseshoe Crab, Limulus Polyphemus
Authors: Armstrong Peter B , Levin Jack , Quigley James P
Published: July 2018

Blood clotting in Limulus is dependent on the activity of a proteinase which converts the zymogen, coagulogen, into a form that undergoes polymerization to form the clot. The abilities of a series of recently discovered endogenous proteinase inhibitors to inhibit this enzyme and thereby serve as potential regulators of its activity were explored. The blood plasma of Limulus contains a single inhibitor that is functionally and structurally homologous to vertebrate α2 macroglobulin. During exocytosis, the blood cells (amebocytes) release a series of inhibitors, including small quantities of the α2 macroglobulin homologue; a low molecular weight, acid-and heat-stable inhibitor; and an acid-labile activity. Of the three inhibitory activities, only the cell-released, acidlabile inhibitor is capable of inhibiting the clotting enzyme.
The Fast Inhibitor of Tissue Plasminogen Activator in Plasma During Pregnancy
Authors: Wiman B , Csemiczky G , Marsk L , Robbe H
Published: July 2018

The novel fast inhibitor to tissue plasminogen activator in plasma has been determined in 20 healthy non-pregnant women, 48 apparently healthy pregnant women and 136 women with risk pregnancies (preeclampsia, suspected fetal growth retardation, thrombosis or previous history of thrombosis, diabetes and others). In healthy fertile non-pregnant women, the inhibitor concentration was found to be 0.4 ± 0.7 U/ml. In pregnant women the concentration stayed at this level until week 10, but then an almost linear increase was found, reaching about 6.5 U/ml at week 40. In plasma samples from the patients with risk pregnancies many with deviating concentrations were found. Thus, in the last trimester a range of 0-24.0 U/ml was found in these patients, as compared to 4.0-6.4 U/ml in healthy pregnant women. The pathophysiological impact of this finding is at present unclear.
A Collaborative Study Designed to Establish the 4th International Standard for Heparin
Authors: Thomas D P , Curtis A D , Barrowcliffe T W
Published: July 2018

An international collaborative study, in which 22 laboratories participated, was carried out to establish a replacement for the International Standard for Heparin. A total of 248 assays were analyzed, including APTT, thrombin inhibition and anti-Xa assays, as well as pharmacopoeial assays. Overall, there was less than 5% difference in the mean potency estimates of the candidate preparations, by all assay methods. The freeze-dried preparation 82/502 demonstrated the closest parallelism by bioassay to the existing standard and was established by WHO as the 4th International Standard for Heparin, with an assigned unitage of 1780 i.u. per ampoule.
Masking of Fibrinolytic Response to Stimulation by an Inhibitor of Tissue-Type Plasminogen Activator in Plasma
Authors: Brommer E J P , Verheijen J H , Chang G T G , Rijken D C
Published: July 2018

Patients with hyperlipoproteinaemia or spontaneous thromboembolism, known to be poor responders to DDAVP or to venous occlusion with regard to the rise in fibrinolytic activity of the blood, appeared to show a normal increase in t-PA-antigen after the same procedure. In their plasma a higher than normal level of free, fast-acting t-PA-inhibitor was found as measured by titration with purified t-PA. This free t-PA-inhibitor level only decreased after the test, in contrast to its complete disappearance in normal responders. The same happened in a healthy volunteer who failed to exhibit a rise in fibrinolytic activity after exhaustive exercise.

We suppose that the lack of response of the fibrinolytic activity in these cases is due to a high inhibitor level and not to impaired release of t-PA into the blood.

In contrast, patients with terminal renal insufficiency showed only a slight increase in t-PA-antigen after DDAVP. The level of free fast-acting inhibitor was normal in most cases and did not change appreciably during DDAVP-infusion. In these patients, a true impairment of the release of t-PA appears to exist.
Pharmacokinetics and Anticoagulant Effect of Hirudin in Man
Authors: Markwardt F , Nowak G , Stürzebecher J , Grießbach Uta , Walsmann P , Vogel G
Published: July 2018

The pharmacokinetics and the effects on the haemostatic system of hirudin were assessed in six healthy subjects after single intravenous or subcutaneous dose (1000 AT-U/kg). When hirudin was given intravenously first-order elimination kinetics followed the initial distribution phase. The decline in plasma hirudin concentration was most adequately expressed by a biexponential equation describing a two compartment model. A mean elimination half-life of 0.84 hr and a mean volume of distribution of 12.9 1 were calculated. After subcutaneous injection a low hirudin level (∼0.5 AT-U/ml) was maintained for a prolonged period of time.

In the 24 hour-urine up to 50 per cent of the administered amount of hirudin was excreted in active form.

Thrombin time, partial thromboplastin time and prothrombin time measured in plasma samples ex vivo were prolonged dependent on the hirudin plasma level. Platelet counts, fibrinogen level and the fibrinolytic system were unchanged. Bleeding time was prolonged twice at maximum.

Subcutaneous or intravenous administration of pure hirudin was tolerated without side-effects.
Platelet Survival in Patients with Angiographically Diseased and Normal Coronary Arteries
Authors: Verhaeghe R , Piessens J , Suy R , Verstraete M
Published: July 2018

Platelets may contribute to the pathogenesis of atherosclerosis and to the complications of coronary artery disease. Therefore, platelet kinetics were studied in 69 patients with angiographically documented coronary artery disease and in 16 patients with a normal coronary angiogram. Platelet survival time was calculated from the decay of radioactivity after injection of 51Cr-labeled autologous platelets. None of the mathematical models used was able to discriminate between the two patients groups. No correlation existed between survival time and extent of the arterial disease. Patients with a high serum cholesterol did not exhibit an enhanced platelet consumption. Thus, these studies do not support the idea that platelet turnover is enhanced in patients with coronary artery disease as compared to those with normal coronary arteries.
Detection of Enhanced In Vivo Platelet α-Granule Release in Different Patient Groups - Comparison of β-Thromboglobulin, Platelet Factor 4 and Thrombospondin Assays
Authors: Lane D A , Ireland H , Wolff S , Ranasinghe E , Dawes J
Published: July 2018

During the platelet release reaction β-thromboglobulin (βTG), platelet factor 4 (PF4) and thrombospondin (TSP) are released from the platelet into plasma and assays of these proteins can be used to monitor in vivo platelet activation. We have assessed their relative merits as markers of the in vivo platelet α-granule release reaction in a number of patient groups which have previously been shown to have elevated plasma βTG and/or PF4 levels. It is concluded that in diseases or conditions not complicated by its reduced clearance, βTG is the most sensitive marker of in vivo platelet α-granule release. However, the TSP assay may be the least ambiguous when monitoring the platelet α-granule release reaction in patients with renal failure who are undergoing haemodialysis with heparin anticoagulation. Under these circumstances plasma βTG, but not PF4 or TSP, levels are elevated because of impaired renal catabolism, and the presence of a heparin-releasable reservoir of PF4 on the endothelium complicates the use of the PF4 assay. In liver failure none of these assays may accurately reflect platelet α-granule release because of impaired hepatic or renal elimination of the proteins.
Shape and Spreading of Platelets from the Blood of Patients with Acute Myocardial Infarction
Authors: Vasilieva E J , Orlov V N , Barkagan Z S
Published: July 2018

The shape of platelets in circulating blood and alterations of this shape after the contact of platelets with glass surfaces, as well as spontaneous platelet aggregation, were examined in patients with acute myocardial infarction (AMI) and in controls.

The shape of circulating platelets were studied by scanning electron microscopy and the spreading - by differential interference contrast microscopy.

Most platelets circulating in the blood of the patients with AMI had non-activated discoid shape; the percentage of these nonactivated platelets was similar to that in the control group. However, these platelets of many AMI patients acquired an increased ability to undergo morphological changes after contact with glass. The percentage of spread platelets in controls was never higher than 50%. In contrast, this percent was higher than 50% in 73% of patients with AMI. Increased spontaneous platelet aggregation was determined only in 30% of AMI patients.
A Glanzmann’s Thrombasthenia Cluster Among Iraqi Jews in Israel
Authors: Seligsohn U , Rososhansky S
Published: July 2018

A country-wide survey of Glanzmann’s thrombasthenia in Israel identified 44 patients. The patients belong to 23 unrelated families, 17 of whom are of Iraqi Jewish origin. The frequency of thrombasthenia among Iraqi Jews in Israel (total population 270,000) is 1:7714 and thus the calculated frequency of the carrier state is 2.3%.
Platelet Aggregation, β-Thromboglobulin and Platelet Factor 4 in Diabetes Mellitus and in Patients with Vasculopathy
Authors: Fritschi J , Christe M , Lämmle B , Marbet G A , Berger W , Duckert F
Published: July 2018

We have studied 155 subjects, 48 normals, 36 diabetics without complications, 44 with complications and 27 patients with macroangiopathy. β-Thromboglobulin (β-TG) and platelet factor 4 (PF4) are elevated in the patients groups. There is no correlation between the plasma levels of β-TG and the stages of either retinopathy or macroangiopathy or nephropathy. The difference is more marked between normals and diabetics with neuropathy (p = 0.026). The aggregation response to ADP and platelet activating factor (PAF) is enhanced at lower stimulator concentration. Using the β-TG, PF4 and aggregation values the discriminant analysis allows a distinction of several subgroups especially with nephropathy and neuropathy (Table 6).
Abnormalities of Epinephrine-Induced Platelet Aggregation and Adenine Nucleotides in Myeloproliferative Disorders
Authors: Yamamoto Koichiro , Sekiguchi Eisuke , Takatani Osamu
Published: July 2018

Platelet aggregation was studied in 18 patients with myeloproliferative disorders, including 14 patients with chronic myelogenous leukemia, 2 with polycythemia vera, 1 with myelofibrosis and 1 with thrombocythemia. Fourteen patients (78%) were abnormal in epinephrine-induced platelet aggregation, while 3 (17%) and 4 (22%) cases showed impaired ADP or collagen induced platelet aggregation, respectively. A significant decrease of total ADP content in resting unstimulated platelets and of the amount released to the medium after aggregation was found in all six patients who were evaluated. ATP and AMP in resting platelets tended to be slightly higher in patients compared with the control group. Released ATP was also significantly less, and the percentage release of ADP and ATP was significantly decreased in patients. A storage pool deficiency of adenine nucleotides was considered to be responsible for abnormal platelet function in patients with myeloproliferative disorders.
Plasma Fibronectin Levels in Clinical Disease States and After Cryoprecipitate Infusion
Authors: Ragni Margaret V , Lewis Jessica H , Spero Joel A , Bontempo Franklin A
Published: July 2018

Fibronectin levels were measured in 151 hospitalized patients with liver disease, sepsis, malignancy, leukemia, and following trauma or surgery, using heterologous precipitating antibody in an immunoassay. The mean ( ± S.E.M.) in 25 controls was 0.95 ±0.06 U/ml, with females, 0.83 ± 0.07 U/ml, lower than males, 1.09 ± 0.09 U/ml. Mean fibronectin levels were decreased in all disease groups except in obstructive liver disease. The reduced levels in hepatocellular disease and the restoration of levels to normal after orthotopic liver transplantation in patients with hepatocellular disease supports the theory that hepatic synthesis contributes significantly to plasma fibronectin levels. Following cryoprecipitate infusion in four hemophiliac patients, plasma fibronectin levels rose to 32% to 45% of the levels predicted. In patients with reduced fibronectin and poor clinical response to standard treatment (antibiotics, chemotherapy), cryoprecipitate infusions may raise the levels of fibronectin and, perhaps, contribute to clinical improvement.
Gabexate Mesilate (Foy®) as an Anticoagulant in Extracorporeal Circulation in Dogs and Sheep
Authors: Oedekoven B , Bey R , Mottaghy K , Schmid-Schönbein H
Published: July 2018

Gabexate mesilate (GM), a synthetic serine protease inhibitor with a short half-life time of approx. 80 sec, was applied as the exclusive anticoagulant in small scale extracorporeal circulation in narcotized dogs and sheep. The animals underwent a veno-venous bypass. As the blood was drawn out of the femoral vein, GM was infused immediately into the extracorporeal system. GM was greatly reduced because of its short half-life time before the blood reentered the animal via a brachial vein. In order to control the coagulatory state of the blood, the Activated Clotting Time (ACT), Partial Thromboplastine Time (PTT) and Recalcification Time (RT) were measured in regular intervals. In addition, a screen pressure test device was used to monitor on line during ECC the tendency of blood clotting. It was shown that the blood of the extracorporeal system was sufficiently anticoagulated by an infusion of 0.03 mg/ml/min GM. During two hours ECC, simultaneously measured ACT - values of the animals only differed up to 10 percent from the native values. Pilot studies have shown that the results of these model investigations could be successfully transferred to extracorporeal circulation with membrane oxygenators and pumps as they are clinically used.
Effects of Arginine Vasopressin (AVP) Infusions on Circulating Concentrations of Platelet AVP, Factor VIII: C and von Willebrand Factor
Authors: Nussey S S , Bevan D H , Ang V T Y , Jenkins J S
Published: July 2018

To study the possible role of arginine vasopressin (AVP) in the control of haemostasis AVP infusions at 3 doses (0.1, 0.2 and 0.3 mU/kg/min) were performed in 6 male volunteers. Both plasma and platelet AVP concentrations rose in a dose-related manner. At doses of 0.2 and 0.3 mU/kg/min there was an increase in the plasma concentrations of both plasma Factor VIII and von Willebrand factor. The data support the hypothesis that AVP, by interacting with platelets and stimulating factor VIII and von Willebrand factor release, plays a role in the control of haemostasis.
Tissue Thromboplastin Induced Reversible DIC and Heparin-Enhanced Inhibitors in Dogs
Authors: Marbet German A , Griffith Michael J
Published: July 2018

Reversible acute disseminated intravascular coagulation (DIC) has been induced in dogs by intravenous injection of homologous tissue thromboplastin. There was no measurable consumption of antithrombin III and heparin cofactor II even if fibrinogen was reduced during DIC by more than 80% of its baseline. The prothrombin level remained practically constant. These data correspond to the generation of a few nanomoles of thrombin in vivo with subsequent pseudo-first order inactivation by the major thrombin inhibitors. An ex vivo measure of the pseudo-first order rate constant (dynamic thrombin inhibitory capacity, DTIC) was a sensitive probe of circulating heparin. There was no change of DTIC during DIC in the absence of exogenous heparin suggesting that heparin-like endogenous glycosaminoglycans were not released in substantial amounts. Pretreatment with heparin efficiently inhibited the development of tissue thromboplastin induced DIC. This animal model may serve as a tool for the study of glycosaminoglycan anticoagulants in vivo.
Tolerance and Biological Activity of Pentosan Polysulfate After Intramuscular or Subcutaneous Administration for Ten Days in Human Volunteers
Authors: Sié P , Albarede J L , Robert M , Bouloux C , Lansen J , Chigot C , Correll S , Thouvenot J P , Boneu B
Published: July 2018

This study reports on the tolerance and the pharmacological activity of pentosan polysulfate (PPS) administered to healthy volunteers for 10 days. Three groups of 10 subjects received either one daily injections of 100 mg of PPS by I. M. route (group I), or two daily injection of 50 mg of PPS by I. M. or S. C. route (groups II and III, respectively). In each group two random subjects received a placebo for the 10 days; on day 0, each subject was injected by a placebo. Clinical tolerance was checked by a daily physical examination; biological tolerance was assessed comparing the results of the main biochemical and haematological constants measured before starting the treatment (day 0) and 12 or 24 h after the end of the treatment (day 11). The pharmacological activity was measured on serial samples taken before treatment and between 1 and 6 h after the drug injection on days 1, 3 and 10; the results were compared to those obtained on day 0. Clinical tolerance was good. The biological side effects concern the transaminase levels and the platelet counts. An increase above the upper normal limit was observed in 18/i4 and 3/24 for alanine and aspartic transaminase respectively. The mean platelet reduction ranged between 24 and 34% according to the groups. The drug injection induced a slight Quick time (PT) prolongation, no significant alteration of factors II, VII-X, V levels and of thrombin clotting time. The activated partial thromboplastin time (APTT) was significantly prolonged and there was a weak but significant circulating anti-Xa activity. The fibrinolytic activity was enhanced without increase in the tissue plasminogen activator antigen level. These pharmacological effects were at their maximum between 2 and 4 h after the drug injection and returned to the pre-injection equilibrium between 4 and 6 h except for circulating anti-Xa activity; these effects remained unchanged all over the 10-day therapeutic period. The comparison between group I and II indicates that the PT and APTT effects are dose-dependent while the anti-Xa and the profibrinolytic effects are not; the comparison between group II and III indicates that the S. C. and I. M. route are bioequivalent.
Heparin-Induced Thrombocytopenia Platelet Aggregation Studies in the Presence of Heparin Fractions or Semi-Synthetic Analogues of Various Molecular Weights and Anticoagulant Activities
Authors: Blockmans D , Bounameaux H , Vermylen J , Verstraete M
Published: July 2018

One case of heparin-induced thrombocytopenia is reported. Aggregation was observed in the platelet-rich plasma of this patient in the presence of two commercial standard heparin preparations (from a final concentration of 0.025 IU/ml upwards), of two semi-synthetic heparin analogues (0.1 APTT U/ml) and of three low-molecular weight heparin (LMWH) fractions (0.1 anti-Xa U/ml) but not in the presence of five other LMWH fractions.

The patient’s isolated platelets no longer aggregated in the presence of heparin but the phenomenon recurred after addition of the patient’s platelet poor plasma (PPP).

Furthermore, addition of patient’s PPP to control platelets led to heparin-induced aggregation.

The phenomenon was associated with thromboxane generation and could be blocked by in vitro addition of aspirin, PGI2, and PGD2 whereas the lag phase was dose-dependently prolonged by adenosine.

It is concluded that platelet aggregation may be induced in some patients by standard heparin and by certain LMWH fractions or semi-synthetic analogues, independently of their molecular weight and anticoagulant activity.
Rabbit Polyclonal Antibodies Against the Calcium-Dependent Conformation of Factor IX and Their Application in Solid Phase Immunoradiometric Assays
Authors: Poort S R , Linden I K van der , Es C Krommenhoek-van , Briët E , Bertina R M
Published: July 2018

Two subpopulations of antibodies were isolated from rabbit polyclonal antiserum directed against human factor IX: one against the Ca(II)-dependent conformation of factor IX and one against the Ca(II)-independent conformation of factor IX. The two subpopulations were used for the development of immunoradiometric assays (IRMA’s) for factor IX: Ca(II)Ag and factor IX: NonCa(II)Ag respectively. Ranges for the concentration of factor IX:Ca(II)Ag and factor IX: NonCa(II)Ag were established in plasmas of healthy volunteers, patients treated with oral anticoagulants and hemophilia B patients. In the group of patients using oral anticoagulant therapy a progressively reduced ratio of factor IX:Ca(II)Ag to factor IX: NonCa(II)Ag was observed with increasing intensity of oral anticoagulant treatment. Variant factor IX molecules from hemophilia B patients . (CRM-, CRMRed and CRM+) with a defective Ca(II) binding or defective conformational transition induced by Ca(II) binding, were identified. These defects are absent in variant factor IX molecules from one hemophilia Bm patient and from patients with hemophilia B Leyden.
Burnout in Ophthalmology Residency: A National Survey
Authors: Feng Shu , Taravati Parisa , Ding Leona , Menda Shivali
Published: July 2018

Purpose To determine prevalence of burnout in ophthalmology residents in the United States using the Maslach Burnout Inventory—Human Services Survey and to identify factors associated with burnout and wellness.

Methods Anonymous survey distributed to residents via residency program directors.

Results Ninety-one programs out of 113 (80.5%) confirmed survey distribution. Of 267 included respondents, 23 (8.6%) met criteria for high burnout, and 169 (63.3%) met criteria for at least one aspect of burnout. Longer work hours, longer hours spent on call, higher number of consults seen on call, fewer hours of sleep on call, and not meeting recommended physical activity minimums were associated with higher emotional exhaustion. Most common factors cited to improve wellness included physical activity, nurturing relationships, and co-resident support, whereas most commonly cited factors that contributed to burnout included sleep deprivation, call, and workload.

Conclusion Burnout in ophthalmology residents is common, occurring at similar rates as reported in residencies of other specialties.
Coarse-grained entanglement classification through orthogonal arrays
Authors: Seveso Luigi , Goyeneche Dardo , Życzkowski Karol
Published: July 2018

Classification of entanglement in multipartite quantum systems is an open problem solved so far only for bipartite systems and for systems composed of three and four qubits. We propose here a coarse-grained classification of entanglement in systems consisting of N subsystems with an arbitrary number of internal levels each, based on the properties of orthogonal arrays with N columns. In particular, we investigate in detail a subset of highly entangled pure states which contains all states defining maximum distance separable codes. To illustrate the methods presented, we analyze systems of four and five qubits, as well as heterogeneous tripartite systems consisting of two qubits and one qutrit or one qubit and two qutrits.
Modular suspension system with low acoustic coupling to the suspended test mass in a prototype gravitational wave detector
Authors: Fang Qi , Zhao Chunnong , Blair Carl , Ju Li , Blair David G.
Published: July 2018

Low acoustic loss suspension systems are essential components in low thermal noise instruments including gravitational wave detectors. Monolithic fused silica suspensions have been used successfully with fused silica test masses but may not be suitable in next generation detectors that may use sapphire or silicon test masses. Here we report a study of a modular suspension system with high replaceability. The system is based on high pressure gravitationally attached mechanical contacts which have been previously shown to contribute low acoustic losses to sapphire resonators. Here we combine high pressure contacts with cantilevers and fibres to create sets of four suspension modules which are shown to have low loss contributions to fused silica test masses in a 74-m high-finesse optical cavity. Results are combined with finite element simulations to estimate the strain energy distributions of the eigenmodes. By combining the simulations and measurement results, the test mass loss angle due to the coupling to the suspension system was estimated. The modular suspension system is shown to contribute <10% to the total test mass acoustic loss. Such suspension systems could have applications for test masses or subsystems in next generation gravitational wave detectors.
Effect of thermal annealing on crystal structures and electrical properties in BaTiO3 ceramics
Authors: Khanal Gopal Prasad , Kim Sangwook , Fujii Ichiro , Ueno Shintaro , Moriyoshi Chikako , Kuroiwa Yoshihiro , Wada Satoshi
Published: July 2018

Mechanical damage and stress caused by polishing and cutting of ferroelectric materials could deteriorate their dielectric, ferroelectric, and piezoelectric properties. BaTiO3 piezoelectric ceramics were polished and cut, and thermally annealed at 600, 800, 1000, and 1200 °C for recovery. The electrical measurements revealed a reduction in the coercive field, elimination of imprint behavior, and an increase in saturation polarization in the thermally annealed ceramics. Furthermore, the electromechanical properties measured by the resonance method, prior to thermal annealing were d33 = 184 pC/N, k33 = 0.36, and s33E = 10.9 × 10−12 m2/N, while the values after 1200 °C-4 h thermal annealing were d33 = 287 pC/N, k33 = 0.54, and s33E = 12.1 × 10−12 m2/N. The in situ crystal structure evaluation and Williamson-Hall analysis suggested the decrement of microstrain from 6.38 × 10−4 to 5.20 × 10−4, indicating the retrieval of the residual stress imposed. The enhancement of piezoelectricity by 56% was ascribed to the effective annealing out of the surface mechanical damaged layers.
Optical band gap analysis and modeling for ultra-thin high-k dielectrics in high-k/metal gate transistors
Authors: Dai Min , Zhao Qiang , Hu Dawei , Schepis Dominic , Di Ming
Published: July 2018

A highly precise band gap measurement based on deep UV spectroscopic ellipsometry along with Bruggeman effective model approximation was developed for high-k/metal gate CMOS with ultrathin EOT (<1.5 nm). By applying and comparing the measurement for HfO2 on SiO2 and SiON interfacial layers with different thicknesses, N%, and annealing conditions, two new sub band gap states corresponding to nitrogen in the film are observed. Together with X-ray photoelectron spectroscopy and electrical measurements, it is found that the band gap energies can be correlated to N% and the leakage current of the high-k films by linear regression (R2 = 0.95). This indicates that the method is capable of quantifying physical and electrical properties of high-k dielectrics, and therefore a time consuming physical analysis or expensive electrical test on fully built devices for gate dielectrics can be avoided.
Accurate spin-densities based on the domain-based local pair-natural orbital coupled-cluster theory
Authors: Saitow Masaaki , Neese Frank
Published: July 2018

Exploiting locality in the electron correlation reduces the computational cost for solving the Coupled-Cluster (CC) equations. This is important for making CC theory applicable to routine computational chemistry applications where it promises to deliver results of “gold-standard” quality. Recently, we have proposed a series of CC formulations in the domain-based local pair-natural orbital framework [DLPNO-coupled-cluster with singles and doubles (CCSD) and DLPNO-coupled-cluster singles and doubles with perturbative triples] which are designed to reproduce approximately 99.9% of the canonical correlation energy. In our previous work, the DLPNO-CCSD method has been extended to the high-spin open-shell reference and shown to possess comparable accuracy to the closed-shell counterpart [M. Saitow et al., J. Chem. Phys. 146, 164105 (2017)]. The so-called Λ-equations have been formulated in the DLPNO framework for the closed-shell species as an exact derivative of the DLPNO-CCSD Lagrangian with respect to the PNO-based cluster amplitudes [D. Datta et al., J. Chem. Phys. 145, 114101 (2016)]. In this paper, we extend the DLPNO-based Lagrangian scheme to the high-spin open-shell reference cases, thus enabling the accurate computation of the electron- and spin-densities for large open-shell species. We apply this newly developed approach to various first-order electronic and magnetic properties such as isotropic and anisotropic components in the hyperfine coupling interactions and the electric field gradient. We demonstrate that the DLPNO-CCSD results converge toward the respective canonical CC density and also that the DLPNO-CCSD-based properties are more accurate than the conventional density functional theory (DFT) results in real-life applications. The additional computational cost is not more than one energy evaluation in the DLPNO-CCSD framework.
Stability of electron beam generation by forevacuum-pressure plasma-cathode electron beam source based on a cathodic arc
Authors: Burdovitsin Victor A. , Kazakov Andrey V. , Medovnik Alexander V. , Oks Efim M.
Published: July 2018

We describe our experimental research on the stable generation of large-radius pulsed high-current electron beams using a forevacuum-pressure plasma-cathode electron beam source with cathodic arc plasma generation. We find that increased gas pressure and the use of gas with a higher ionization cross-section considerably decrease the stable emission current due to loss of electric strength of the acceleration gap (breakdown). Increased pulse duration results in a decrease in the emission current, but the influence of the gas species and its pressure remains for all pulse durations. There is an extremum in the dependence of emission current on the acceleration gap length and the optimum gap length depends on the gas pressure and the kind of gas. The experiment results can be explained by the effect of back-streaming ion flow, which charges dielectric inclusions on the emission electrode (anode grid) and thereby amplifies the electric field.
Quantum key distribution using in-line highly birefringent interferometers
Authors: Martinez Amos , Fröhlich Bernd , Dynes James F. , Sharpe Andrew W. , Tam Winci , Plews Alan , Lucamarini Marco , Yuan Zhiliang , Shields Andrew J.
Published: July 2018

Secure communication networks enabled by commercial quantum key distribution (QKD) are already available. However, their widespread deployment will require great efforts towards reducing the currently prohibitive cost of QKD systems. Here, we propose a compact and cost-effective alternative to the asymmetric Mach-Zehnder interferometer commonly used to implement phase encoding in the Bennett-Brassard 1984 (BB84) QKD protocol. Our solution consists of an all-fiber, in-line, highly birefringent interferometer (HBI). The HBI shows improved tolerance to length mismatches and a simpler assembly, making it particularly desirable for the fabrication of multi-user systems where several interferometers must have matched delays and where cost and space considerations can be most critical, such as quantum access networks. As a proof-of-principle, we demonstrate point-to-point QKD operation with HBIs over 15.5 km drop fiber and an 8-port passive optical network splitter. We achieve a secure key generation rate of 299.4 ± 16.4 kbit/s with a quantum bit error rate of 2.89 ± 0.31% for a continuous 25 h operation period.
Magnetic configuration effects on the Reynolds stress in the plasma edge
Authors: Manz P. , Stegmeir A. , Schmid B. , Ribeiro T. T. , Birkenmeier G. , Fedorczak N. , Garland S. , Hallatschek K. , Ramisch M. , Scott B. D.
Published: July 2018

Breaking the poloidal symmetry of the magnetic shear induced tilt of turbulent structures, by either divertor X-point resistivity or limiter positions, can lead to a finite (residual) contribution to the flux-surface averaged radial-binormal Reynolds stress. This residual stress supports or works against the radial electric field at the plasma edge of a tokamak. The impact of divertor geometry on the poloidal pattern of the Reynolds stress is studied by flux-coordinate-independent fluid simulations. Clear modifications of the Reynolds stress are found due to the magnetic shear in the confined region. The impact of different poloidal limiter positions on the radial electric field and the Reynolds stress is studied by means of magnetic field aligned gyrofluid simulations. Only if the limiter is close to the outer midplane can its position have a substantial effect on the radial electric field.
Lithium-ion conducting glass ceramics for electrostatic gating
Authors: Philippi Marc , Gutiérrez-Lezama Ignacio , Ubrig Nicolas , Morpurgo Alberto F.
Published: July 2018

We explore solid electrolytes for electrostatic gating using field-effect transistors (FETs) in which thin WSe2 crystals are exfoliated and transferred onto a lithium-ion conducting glass ceramic substrate. For negative gate voltages (VG < 0), the devices work equally well as ionic liquid gated FETs while offering specific advantages, whereas no transistor action is seen for VG > 0. For VG < 0, the devices can nevertheless be driven into the ambipolar injection regime by applying a large source-drain bias and strong electroluminescence is observed when direct band-gap WSe2 monolayers are used. Detecting and imaging the emitted light is much simpler in these FETs as compared to ionic liquid gated transistors, because the semiconductor surface is exposed (i.e., not covered by another material). Our results show that solid electrolytes are complementary to the existing liquid gates, as they enable experiments that are not possible when the semiconductor is buried under the liquid itself.
Locally coupled open subsystems: A formalism for affordable electronic structure calculations featuring fractional charges and size consistency
Authors: Mosquera Martín A. , Ratner Mark A. , Schatz George C.
Published: July 2018

This manuscript introduces a methodology (within the Born-Oppenheimer picture) to compute electronic ground-state properties of molecules and solids/surfaces with fractionally occupied components. Given a user-defined division of the molecule into subsystems, our theory uses an auxiliary global Hamiltonian that is defined as the sum of subsystem Hamiltonians, plus the spatial integral of a second-quantized local operator that allows the electrons to be transferred between subsystems. This electron transfer operator depends on a local potential that can be determined using density functional approximations and/or other techniques such as machine learning. The present framework employs superpositions of tensor-product wave functions, which can satisfy size consistency and avoid spurious fractional charges at large bond distances. The electronic population of each subsystem is in general a positive real number and is obtained from wave-function amplitudes, which are calculated by means of ground-state matrix diagonalization (or matrix propagation in the time-dependent case). Our method can provide pathways to explore charge-transfer effects in environments where dividing the molecule into subsystems is convenient and to develop computationally affordable electronic structure algorithms.
Numerical and experimental investigation of 4 mm wavelength microwave oscillator based on high-current compact accelerator
Authors: Rostov V. V. , Romanchenko I. V. , Tsygankov R. V. , Yushchenko A. Y. , Emelyanov E. V. , Sadykova A. G. , Sharypov K. A. , Shunailov S. A. , Ul'masculov M. R. , Yalandin M. I.
Published: July 2018

The concept of two-wave relativistic Cherenkov oscillator for the generation of nanosecond microwave pulses at ∼72 GHz central frequency has been applied. A moderately oversized sectioned slow wave structure (average diameter ≈2.5 wavelength) provides the interaction of electrons simultaneously with a slow (or surface) TM01 wave and a fast (or volume) TM02 wave, which govern the microwave energy output. The generation of 85 MW, 1.3-ns long microwave pulses has been demonstrated in a single pulse operation with a pulsed guiding magnetic field of 3.8 T on the base of the desktop high-current accelerator RADAN-303.
Probing the free-carrier absorption in multi-layer black phosphorus
Authors: Aytac Y. , Mittendorff M. , Murphy T. E.
Published: July 2018

We study the carrier relaxation dynamics in thin black phosphorus (bP) using time-resolved differential transmission measurements. The inter-band and intra-band transitions, relaxation, and carrier recombination lifetimes are revealed by tuning the mid-infrared probe wavelength above and below the bandgap of black phosphorus. When the probe energy exceeds the bandgap, Pauli blocked inter-band transitions are observed. The differential transmission signal changes sign from positive to negative when the probe energy is below the bandgap, due to the absence of inter-band transitions and enhancement in the free-carrier absorption. The minority carrier lifetime and radiative recombination coefficient are estimated to be 1.3 ns and 5.9 × 10−10 cm3/s, respectively. The overall recombination lifetime of bP is limited by radiative recombination for excess carrier densities larger than 5 × 1019 cm−3.
Linear integral equations, infinite matrices, and soliton hierarchies
Authors: Fu Wei , Nijhoff Frank W.
Published: July 2018

A systematic framework is presented for the construction of hierarchies of soliton equations. This is realised by considering scalar linear integral equations and their representations in terms of infinite matrices, which give rise to all (2 + 1)- and (1 + 1)-dimensional soliton hierarchies associated with scalar differential spectral problems. The integrability characteristics for the obtained soliton hierarchies, including Miura-type transforms, τ-functions, Lax pairs, and soliton solutions, are also derived within this framework.
Electrostatic lock in the transport cycle of the multidrug resistance transporter EmrE
Authors: Vermaas Josh V. , Rempe Susan B. , Tajkhorshid Emad
Published: July 2018

Significance

EmrE is a small membrane transporter found inEscherichia colithat exports drug-like molecules from the cell, contributing to antibiotic resistance. In EmrE, as well as in the wider small-multidrug resistance transporter family, a specific anionic amino acid (E14) has been implicated in governing the conformational changes that export drugs. However, due to sparse structural information, the exact interactions remain unidentified. Through interactive molecular dynamics to incorporate existing cryo-electron microscopy data, we create a fully refined atomic model of EmrE. We then embed this model in a lipid bilayer and evaluate the interactions within EmrE under different loading states. We find that E14 makes specific hydrogen bonds to neighboring residues, coupling observed experimental phenomena to interactions at the atomic scale.
“Shepherd’s crook” neurons drive and synchronize the enhancing and suppressive mechanisms of the midbrain stimulus selection network
Authors: Garrido-Charad Florencia , Vega-Zuniga Tomas , Gutiérrez-Ibáñez Cristián , Fernandez Pedro , López-Jury Luciana , González-Cabrera Cristian , Karten Harvey J. , Luksch Harald , Marín Gonzalo J.
Published: July 2018

Significance

In a crowded environment, animals must direct their behavior to the stimulus with the highest priority at each moment. Stimulus selection seems to develop from competitive interactions between concurrent neural inputs. In the avian midbrain, a neural network that reciprocally connects the optic tectum to the isthmi forms a simple neural mechanism for stimulus competition, where neurons mediating enhancement and suppression of tectal inputs are located in separate isthmic nuclei. Here, we show that collaterals of the same tectal neurons simultaneously drive these nuclei, synchronizing both antagonistic processes. These results contribute to our understanding of how distinctive neurons integrate inputs from different sources to drive in parallel several concurrent neural processes underlying a complex behavior.
Study: wear and superhydrophobic behaviour of PTFE-ceria composite
Authors: Singh Harprabhjot , Sodhi Gurvinder Pal Singh , Singh Malkeet , Chelliah Nagaraj M. , Singh Harpreet
Published: July 2018

The present work aims at developing a novel superhydrophobic polymer matrix composite with enhanced wear resistance. First, polytetrafluoroethylene (PTFE) matrices were reinforced with different weight percentages (ranging from 0 to 20%) of ceria particles using the powder metallurgy method. Subsequently, the microtexture of the fabricated composites was varied by sanding them with different grit sizes of emery sheets. The effect of reinforcement was analysed on tribological behaviour of fabricated composites via a pin-on-disk test. Hydrophobic behaviour of textured PTFE and PTFE-20% ceria composite has been discussed. Surface topography and wear morphology of the polymer matrix composites were examined with an aid of SEM. Tribological data revealed that lower friction coefficient and higher wear resistance can be achieved by increasing the weight percentage of ceria particles. A maximum contact angle of 158° with a minimum roll-off angle of less than 3° was found for the PTFE-20% ceria composite.