bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-Term Anticoagulant Therapy After Myocardial Infarction in the Elderly Patient
Authors: de Vries W.A. , Tijssen J.G.P. , de Jonge H. , Loeliger E.A. , Roos J.
Published: May 2019

The Netherlands Federation of Thrombosis Services launched in 1976 a 3-year multi-centre double blind trial of oral anticoagulants versus placebo in 1000 patients suffering from transmural infarction and older than 60 years. The aim of the trial was to determine whether the risk of treatment in the elderly outweighs its supposed beneficial effect. The rate as observed in the two groups, of death, reinfarction, bleeding and possible other complications were as given in the table (will be presented). The level of anticoagulation was as proposed by the Federation of Arterial Thromboembolism Disease was computed according to the logrank method which allows a correction for differences to exposure time. The results will be presented.
Involvement of Energy Metabolism in Platelet Responses
Authors: Holmsen H.
Published: May 2019

Shape change, aggregation, arachidonate liberation and secretion of the contents of dense granules or α-granules and of acid hydrolases are distinct in vitro responses by platelets to physiological stimuli. They may participate in in vivo platelet functions and are abolished at a certain reduction of ATP availability in vitro which is specific for each response. The ATP level in platelets respond normally. Hence, with normal ATP turnover the responses are not dependent on the ATP level at the moment of induction When ATP turnover is shut off by addition of 2-deoxyglucose and glucono-δ-lactone to antimycin A-treated platelets, the ATP level falls rapidly and the initial rate of
aggregation and the extent of dense granule secretion are proportional to the ATP level at the moment of induction. Thus, these responses do not depend on ATP generation during execution and available ATP appears to be preferentially utilized to drive the responses. Myosin light chain phosphorylation precedes secretion, indicating ATP usage in contractile processes. A large proportion of ATP may bEt used to maintain actin in a non-polymerized state in restiug platelets. Since actin filaments appear during platelet stimulation, ATP may also be used in the unstimulated platelet to Keep these cells responsive (prevent actin polymerization).
The Role of Lipids in the Mechanism of Thrombosis
Authors: Nordϕy A.
Published: May 2019

Recent discoveries have emphazised the close connection between factors involved both in thrombogenesis and in atherogenesis. Lipoproteins seem to have a direct effect both n platelets and endothelial cells. LDL increases the sensitivity of platelets to aggregating substances and reduce the spontaneous release of prostacyclin (PGI2)from endo thelial cells. HDL may partially counteract this effect of LDL on endothelial cells grown in culture. Albumin bound fatty acids have also profound effects on platelet and endothelial cell function. The dual effects of the prostaglandin precursor fatty acids from the linoleic and linolenic sequences make these fatty acids crucial with regard to the Production of thromboxane A2 platelets and prostacyclin in endothelial cells. It is suggested that manipulation with the dietary fatty acid composition and other situations which will induce significant changes in the quantity and quality of plasma FFA may favour thrombus formation by disturbing the homeostatic balance between the function of platelets and endothelial cells.
The Effect of A Fat Meal on Platelet Function in Man
Authors: Johnston R.V. , Giner J.V. , Forbes C.D. , Prentice C.R.M.
Published: May 2019

Platelet function was studied in 7 healthy volunteers over a six hour period alter ingestion of 150 mls of cream in the fasting state, with and without pre-treatment with 300 mg aspirin taken 12 hrs previously. We measured platelet count, aggregation response to ADP, platelet aggregate ratio (Wu and Hoak, 1974), serum cholesterol and triglyceride. 180 mins after fat ingestion there was a significant fall (p<0.01) in platelet count which was abolished by aspirin, a fall (p<0.05) in platelet aggregate ratio which was abolished by aspirin, a mean rise in triglyceride of 1.29 mmol/1 without aspirin and 1.085 with aspirin. There was no rise in cholesterol. 6 hrs after fat ingestion there was a fall (p(0.001) in aggregation response to ADP. After aspirin the impaired aggregation response to ADP was not further reduced.Thus the rise in triglycerides is associated with circulating platelet aggregates, lowered platelet count and impaired response to ADP. These changes are prevented by aspirin, suggesting that in vivo activation of platelets may be caused by fat ingestion.
Snake Venoms and Haemostasis: Suggested Mechanisms of Their Action In Vivo and In Vitro
Authors: Talalak Phumara , Marsh N.A. , Gaffney P.J.
Published: May 2019

Details of the in vitro mode of action of the thrombin-like enzymes from four species are described, with emphasis on their ability to release fibrinopeptides A and B from fibrinogen and their activation of Factor XIII, thus promoting fibrin crosslinking. It was found that Bitis gabonica venom removed both A and B peptides from fibrinogen and thus may be considered most similar to thrombin; this venom also causes the activation of Factor XIII, as does thrombin; Trimeresurus erythrusus and T.popeorum venoms released only fibrinopeptide A, as does Agkistrodon rhodostoma and Bothrops atrox. The partly purified procoagulant fractions used in these studies activated Factor XIII in the following ascending order: A.rhodostoma, B.atrox, T.erythrusus and T.popeorum.

Classification of fibrinogen and its fragments during controlled infusion of Ancrod indicated that the lysis of soluble, non-crosslinked fibrin polymers by plasmin was the mechanism of defibrination following the introduction of a DIC-like syndrome. Crotalus atrox venom dramatically defibrinated and affected a wide variety of clotting parameters during snake bite. A mechanism explaining the DIC-like defibrination syndrome associated with snake bite is presented.
Alterations of Haemostasis During Liver Failure by CCl4 in Pig
Authors: Morfini M. , Boncinelli S. , Biliotti G. , Bernabei P. , Marsili M. , Lorenzi P. , Seri A. , Turchi A. , Cordopatri F. , Rossi Ferrini P.
Published: May 2019

Ten pigs of 30-40 kg body weight,received a 0.05 ml/kg b.w. CCl4 injection in hepatic artery. Before and 30 min, 1, 3, 6, 9 and 24hr after injection a blood sample was drawn from femoral artery. White,red cells and platelet counts , APTT, Prothrombin, Fibrinogen, Factor VIII AHF(one-stage method), Platelet Aggregation(P.A.) according Born by ADP 2μM were performed. Very high levels of VIII AHF and fibrinogen and a reversible P.A. have been observed on basal sample. After CCl4 injection a progressive lowering of prothrombin, fibrinogen and platelets, and a prolonged APTT have been observed. P.A. was reduced to 20-3010%. VIII AHF showed variable levels during the first 3 hrs but a clear increase more than 150% of the initial value has been observed from the 6th to 9th hr. Unfortunatly many efforts to assay VIII AGN by an antiserum against human VIII AGN, have been failed. An activation of VIII AHF cannot be excluded but the late increase after liver necrosis seems to suggest a real VIII AHF increase. The high degree of variability of pigs survival, ranging from 9 to 24 hrs has prompted us to search for another experimental model of acute hepatic failure.
Changes in Fibrinmonomer and Fibrin Structure in Patients with Renal Failure
Authors: Klingemann H.-G , Egbring R. , Kaffarnik H.
Published: May 2019

Procedure: 54 patients subdivided in 3 groups were investigated: 1) 10 patients with acute renal failure. 2) 36 patients with chronic renal failure (serum Creatinin >5mg%). 3) 8 patients before and one hour after hemodialysis.

Fibrinmonomer and fibrin structure were studied by SDS-polyacrylamidgele-lectrophoresis according to Weber and Osborne. In addition factor XIII activity was determined immunologically according to the method of Bohn and Haupt.

Results: 1)Patients with acute renal failure showed a defective structure of fibrin with loss of polymerisation of the α-ehains but normal γ -dimers. In these patients factor XIII activity was lower than 60%. 2) In 21 out of 36 patients with chronic renal failure, fibrin polymerisation was incomplete though no factor XIII deficiency could be determined. 3) The changes in fibrin polymerisation could be demonstrated before as well as after hemodialysis.

Conclusions: 1)In acute renal failure, factor XIII deficiency induces an incomplete α-chain polymerisation of fibrin. 2) In chronic renal failure, the deficient α-chain polymerisation may be caused by an inhibitor which is not dialysable.
Comparison of One Stage and Two Stage Factor VIII Activity Assays in Healthy and Sick Subjects
Authors: Hathaway W.E. , Montgomery R.R.
Published: May 2019

For the past several years, factor VIII assays have been performed on the same sample of plasma by the partial thromboplastin time method (PTT-VIII) and the thromboplastin generation time method (TGT-VIII) in a variety of clinical conditions. Mean (range) values for representative subject groups are given.

The methods compare well in inflammatory and metabolic diseases like diabetes and nephrosis. However, higher PTT-VIII values are seen in vasculitis, sickle cell disease, the hemolytic-uremic syndrome, thrombosis, and DIC. Lower values for VIII activity were seen by VIII-TGT in a group of vWd variant patients. Obligate carriers of hemophilia were best detected by the VIII-PTT. Lower than expected values for factor VIII were demonstrated in Intensively transfused hemophiliacs by the VIII-PTT. These studies indicate that the level of factor VIII procoagulant activity is significantly different in many clinical situations depending upon the method of measurement.
Bleedings in Congenital Apibrinigenasmia
Authors: Hadnagy Cs. , Jaklovszlty A.
Published: May 2019

Authors presents 6 cases. The lack of the fibrinosen was confirmed immunologically, too (antiserum from Behringwerke). In four casas the umbilical bleeding was the first haemorrhage. whereas in two the teething. A patient presented haematuria and posttraumatic haemarthroma. The traumatic rupture of the spleen was chirurgically cured. Epistaxis, bleedings of the gums and posttraumatic bleedings ware also observed. Four of them deceased (at the age of 5 months, 10 months, 6 years and 6 years): one abdominal haemorrhage, two cerebral haemorrhage (autopsied cases) and one -in all probability- also a cerebral haemorrhage (after sunstroke; not autopsied). Authors observed a diminished and delayed platelet aggregation by ADP in the congenital afibrinoganaecnia cases.
The Procoagulant Properties of Amniotic Fluid
Authors: English Christine J. , Poller L.
Published: May 2019

The procoagulant properties of amniotic fluid have been studied in over one hundred and fifty serial specimens. The results suggest that amniotic fluid contains tissue procoagulant activity which is not related to gestational age. An activating effect in vitro, on tactor X, however, increases progressively throughout pregnancy. An additional action of amniotic fluid in potentiating clotting may be via a contact activation effect.
Inactivation of FVIII by Plasmin: Molecular Conformational Changes
Authors: Cockburn C.G.
Published: May 2019

Reduced SDS PAGE failed to detect proteolysis of the 200,000 subunit when purified FVIII was slowly inactivated by plasmin until less than 1% of the VIIIc was left. Graphs of VIIIc loss show highly repeatable discontinuities (8 expts.), suggesting a conformational change, as do transitorily increased then partially decreased VIII R:AG levels. The mobility of FVIII as judged by crossed-immunoelectrophoresis remained unchanged, but the area under the ‘arcs’ increased dramatically. Crossed-immunoelectrophoresis plates were washed, the ‘arcs’ cut out, melted and subjected to reduced SDS PAGE. Only the 200,000, IgG ‘H’ and ‘L’ bands were seen; the latter increased markedly in contrast to the 200,000 band. Also SDS denatured digestion aliquots were treated with a trace of mercaptoethanol and applied to running SDS PA gels. A rise, then fall in the 200,000 monomer:dimer ratio showed that during inactivation FVIII is more thoroughly ‘disorganised’ by SDS. 2.75 % PAGE (1) or SDS PAGE in similar gels (2) show that a linear relationship obtains between the log of the FVIII oligomer no. and their relative mobilities up to oligomers ‘8’ and ‘6’ respectively; above this new linear relationships obtain. When FVIII is briefly inactivated by a higher concentration of plasmin the ‘inflection point’ in (1) is lost and later reappears at ‘5’; in (2) it shifts to oligomer no. ‘3’ long after inactivation. These results show that during inactivation by plasmin FVIII undergoes a molecular ‘opening-out’ to reveal more antigenic sites before detectable breakdown of the 200,000 subunits and that changes occur in the native oligomeric series.
Streptokinase-Treatment Regimen in Childhood
Authors: Sutor A.H.
Published: May 2019

From our experience treating 35 children with streptokinase we drew the following conclusions: 1. For children with shock syndromes due to sepsis we recommend streptokinase (SK-) therapy with 4 000 U/kg (within 15 to 30 min.) as initial dose and 1 000 U/kg (over 12 to 24 hours) as maintenance. 2. Before treatment and as control of the SK-action the determination of the plasminogen-proactivator (pp-) content with a capillary blood test was found to be very useful. 3. Insufficient decrease of PP-values (>3%) under SK-therapy indicates the possibility of hyperplasminemia, which can be connecte, with bleeding complications and which leads to inefficient exogenous fibinolysis. In this case SK-dose has to be increased. The cause of the hyperplasminemia may be underdosage of SK or an abnormally high initial level of pp.
Coagulant Effects of Normal and Malignant Tissue
Authors: Tullis J.L. , Honegger H. , Hewitt L. , Flelschaker O.
Published: May 2019

A prospective study has been conducted on the procoagulant activity of tumor tissues and normal tissues removed during the course of surgery and therapeutic procedures. The presence of potent tissue thromboplastic action was demonstrated in cells removed from certain types of normal and malignant tissue. A less potent incomplete thromboplastin can be isolated from certain tumor tissues. The bulk of the activity is present in the cellular fraction although partial recovery can be achieved from the supernate after freezing and thawing. Assays for prothrombin, thrombin, fibrinogen and coagulant inhibitors revealed no activity by the standard assays which were employed.
Bleeding Complications in Acute Myeloblastic Leukaemia (AML)
Authors: Sutor A.H.
Published: May 2019

Bleeding is common in acute myeloblastic leukaemia (From our experience with 30 children suffering from AML we drew the following conclusions: At the time of diagnosis, the danger of bleeding cannot be predicted by laboratory means. However, the following factors represent increased risks: Promyeloblastic leukaemia, high blast count, low fibrinogen, low plasminogen. From coagulation studies performed at the time of bleeding complications, the pathomechanism leading to bleeding complications usually cannot be detected. The question, whether inpairment of production, consumption coagulopathy, or primary fibrinolysis causes the bleeding complications can only to answered by controlling frequently clinical and haemostatic criteria, which include the thrombocytic system as well as plasmatic coagulation and fibrinolysis. At the present time, the therapy of bleeding complications in AML is symptomatic. It consists of transfusion with thromlocytes or
fresh whole wood , respectively. Coagulation factor concentrates shouls only be given in combination with Heparin to prevent the deterioration of consumption coagulopathy.
Results in Preventing Thrombosis By Low-Dose Heparin in Consideration of Heparin Concentration and Antithrombin III in
Authors: Tilsner V. , Müller U.
Published: May 2019

The antithrombotic effect of low-dose heparin has been ascertained clinically. The postoperative activation of the coagulation factors must be decreased, without increasing any bleeding tendencies. In order to determine the optimal dosage in low-dose heparin prophylaxis we examined the RCT, PTT, TT, Factor Xa, AT III and heparin concentrations in 400 patients prior to and following emergency surgery. Any thrombotic or haemorrhagic complication was registered. All 100 cases
received one of the following treatment plans: 1) 5000 U heparin s.c. TID, 2) 7500 U heparin s.c. TID, 3) 100 U heparin/kg s.c. BID, 4) 150 U heparin/kg s.c. BID. Only plans 2 and 4 achieved a measureable heparin effect without increasing the risk of bleeding. The PTT did not shorten in either of these 2 groups and the thrombin time rose only occasionally to the upper normal limits. All other values remained within normal limits. The thrombo-embolic incidence amounted to 1% in groups 2 and 4, 2% in groups 3 and 5% in the first group.
Antithrombotic Activity of Polydeoxyribonucleotides of Maml1Alian Origin (Laboratory Code: Fraction P) in Experimental Animals
Authors: Niacia R. , Hantovani H. , Prino G. , Pescador R. , Nardi G.F.
Published: May 2019

Fraction P(FP)is a polydeoxyribonucleotidic substance of mammalian 9rigin which was found able to ac tivat e the fibrinolytic system of some experimental animals.We have investigat ed the possible antithrombotic activity of FP in three different experimental models. In the col lagen-induced thrombosis of the rabbit femoral vein,pretreatment with FP i.v.(50, 100 or 200 mg/kg) reduced the thrombus dry weight by 427, (P < 0.005). 50% (P < 0.001) and 72% (P < 0.001), respectively; pretreatment with FP peros02.5, 25 or 50 mg/kg) decreased the thrombus dry weight by 22% (n.s.), 46% (P < 0.001) and 69% (P < 0.001), respectively. In the electrical l y induced thrombosis of rat carotid artery, pretreatment with FP i.v. (37.5, 75 or 150 mg/kg)reduced the fall in arterial surface temperature by 20%(P < 0.005), 62% (P < 0.025) and 86% (P < 0.001), respectively. In the hamster cheek pouch model, venular thrombosis induced by iontophoresis of ADP was inhibited by 85 %(P < 0.025) when the animals were pretreated with FP i.v. (2 mg/kg) or by 957, (P < 0.025) when FP was given per os (1 mg/kg). These antithrombotic effects lasted longer than the activation of fibrinolysis measured in ex vivo studies in the same animal species. This would suggest that a more complex mechanism(possibly including vascul ar factors at local level)could be responsible for the in vivo effect of FP as an inhibitor of thrombus formation.
Nicergoline, an Anti-Aggregating Agent which Inhibits Release of Arachidonic Acid from Human Platelet Phospholipids
Authors: Lagarde M. , Guichardant M. , Dechavanne M.
Published: May 2019

Nicergoline is a vasoactive compound with an α-blocking adrenolytic activity which blocks human platelet aggregation induced by the most agents in vitro. The drug strongly decreases malondialdehyde formation stimulated by thrombin or collagen but not exogenous arachidonic acid. In the same way, the drug inhibits production of thromboxane B2, 12-hydroxyheptadecatrienoic acid (HHT) and 12-hydroxyeicosatetraenoic acid (HETE) induced by thrombin, but not decreases exogenous arachidonic acid utilization by platelet prostaglandin synthetase and lipoxygenase.
Determination of Malonalvehyve in Viabetic Patients
Authors: Voisin Ph. , Pointel J.P. , Vrouin P. , Stoltz J.F.
Published: May 2019

Halushka, Colwell et al. Showed the increase of Endoperoxydes in patients with disbetes mellitus. In this case Malomaldekyde level could be considered as an indication of pro-aggregationg prostaglandins synthesis. It was interesting to determine the Malomaldehype level in disbttices and to examine its possible correlation with complications.
Intravascular Platelet Formation
Authors: Popescu E. , Fitzgerald M.
Published: May 2019

Some platelets in patients with extensive myelofibrosis after splenectomy contain a small nucleus similar to a Howell-Jolly body. This Involutive nuclear structure Is the last step oE a process initiated in a circulating lymphoid cell recognizable as platelet precursor on electron microscopy. The nucleus of this maturing cell decreases in size and chromatin density and eventually disappears, while its cytoplasm becomes a large, dysplastic platelet. These latter show signs of immaturity such as: large amounts ot endoplasmic reticulum, huge Golgi apparatus, presence ofnuclear remnants and a minimal or no microtubular system. Since the marrow scans and the histological studies in such cases disclosed no hematopoiesis in the bone marrow, spleen and liver it was concluded that these abnormal platelets result from the activation of the circulating stem cells which is taking place when other sources are unavailable.
Effects of Hormonal Contraception on Hemostatic and Lipidic Profiles
Authors: Masure R. , Hurlet A. , Haes E. , Gillard F. , Col-DeBeys C. , Moriau M. , Meyer C. , DuboisPèlerin F. , Vekemans M.
Published: May 2019

Haemostatic and lipid parameters were determined for groups of women treated for at least 3 years with different types of hormonal contraception (HO, and compared to data of matched control groups without contraception and with IUD. A group of women starting HC were examined before HC, and after I cycle, 3 cycles and 1 year of HC.

Slight increases of factor VII and thrombotest were observed immediately with all HC. Cold activation of thrombotest was observed with much higher frequency and at higher levels in HC groups than in controls. Decrease of antithrombin III was most markedly observed with the immunological assay, and occurred progressively throughout the first year of treatment. Fibrinolytic activity was affected differently by progestagen which fnc eased euglobulin lysis time, and by combined HC which shortened it. Plasminogen activator values confirmed these results. Response to local anoxia was not significantly modified. Significant increases of total lipids and phospholipidsand a slight increase of chblesterol occurred progressively during the first year of HC.

As these modifications are possibly involved in thrombotic accidents in predisposed or high-risk women, and are more likely to occur during the initial period of He, closer supervision remains advisable during this period.
Factors Increasing red Blood Cell Aggregation in Men with Coronary Artery Disease
Authors: Boss N. , Bruder W. , Bierner M. , Koenig - Erich S. , Fleck E. , Ruhenstroth-Bauer G.
Published: May 2019

Red blood cell aggregation value (AW) was found to be of good diagnostic value ror coronary artery disease. Causes of increased aggregation value were investigated by means of protein analytical methods and standard laboratory techniques in 41 men with angiographically documented coronary artery disease. Best correlation coefficients were found between the red blood cell aggregation value and IgG, precipitable by 25g/1 polyethyleneglycol 6000 (r = 0.536; 2P ≤ 0.001). In coronary artery disease patients with no previous myocardial infarction (N=15) polyethyleneglycol precipitable IgM was found to correlate best with red blood cell aggregation (r = 0.707; 2P ≤ ! 0.01 ). In contrast to these results, patients without coronary stenosis demonstrated no significant correlation between the red blood cell aggregation value and the latter factors

These results indicate a possible link between coronary artery disease, immune complexes and red blood cell aggregation. Platelet aggregation, as well as the coagulation system may also be influenced by these possibly specific immune complexes.
Changes in the Plasma Level of Heparin and Coagulation Factors During the Postoperative Prophylaxis with Heparin and Heparin-Dihydroergotamin.
Authors: Popov-Cenic S. , Schander K. , Etzel F.
Published: May 2019

In a randomised prospective study a homogenous total of 70 women undergoing abdominal hysterectomy and bilateral adnexectomy is subdivided in 7 different groups with the following treatment schadules: A. no postoperative prophylaxis of thromboembolism, B. every 12 hrs 0.5 mg dihydroergotamin (DHE), C. every 12 hrs 2500 I.U . Na-heparin +DHE, D. every 12 hrs 5000 I.U. heparin, E. every 12 hrs 5000 I.U. heparin + DHE, F. every 8 hrs 5000 I.U: heparin, G. every 8 hours 5000 I.U. heparin + DHE.

The following parameters are examined pre- and postoperatively as well as on the first, second and seventh postoperative day prior to and 3 hrs after the respective treatments: plasma-levels of heparin, anti Xa and antithrombin III with chromogenous substrate 2160 and 2222, PTT and plasma thrombin time as well as the factors of the coagulation and fibrinolytic system.

The preliminary data indicate that under the combined administration of heparin plus dihydroergotamin heparin levels rise further and PTT is more prolonged as compared to heparin prophylaxis alone.
Präoperative Hypertonie – Muss der Elektiveingriff verschoben werden?
Authors: Unterberg Matthias , Nowak Hartmuth
Published: May 2019

Leitlinien zur Klassifikation und Therapie der Volkskrankheit „essenzielle Hypertonie“ sind über nationale 1 und internationale Fachgesellschaften verfügbar und unterliegen einem regelmäßigen Review- und Novellierungsprozess. Eine spezifische Leitlinie zum Management von hypertensiven Patienten in der perioperativen Sondersituation stellt ein Novum dar und richtet sich an alle im perioperativen Setting beteiligten Fachdisziplinen 3.
Correlation of dielectric dispersion with distributed Curie temperature in relaxor ferroelectrics
Authors: Chen Yong , Liu Kang Hui , Luo Qian , Mei Ming , Chen Gan Lin , Pan Rui Kun , Qi Ya Jun , Cao Wan Qiang
Published: May 2019

The fascinating dielectric property of relaxor ferroelectrics is investigated on the basis of phase-transition dynamics within the mean-field theory. With a power-law distribution of the Curie temperature for the second order phase transition ferroelectrics, the complex dielectric permittivity is derived. The result shows that the modified Curie–Weiss relation in the paraelectric phase follows the power-law distribution directly. The significant conclusion is that the “rediscovered” distributed Curie temperature can describe the universal dielectric dispersion for both real part and imaginary part of dielectric permittivity with temperature and frequency in relaxor ferroelectrics, and it conforms well to experimental results.
Practical rare event sampling for extreme mesoscale weather
Authors: Webber Robert J. , Plotkin David A. , O’Neill Morgan E , Abbot Dorian S. , Weare Jonathan
Published: May 2019

Extreme mesoscale weather, including tropical cyclones, squall lines, and floods, can be enormously damaging and yet challenging to simulate; hence, there is a pressing need for more efficient simulation strategies. Here, we present a new rare event sampling algorithm called quantile diffusion Monte Carlo (quantile DMC). Quantile DMC is a simple-to-use algorithm that can sample extreme tail behavior for a wide class of processes. We demonstrate the advantages of quantile DMC compared to other sampling methods and discuss practical aspects of implementing quantile DMC. To test the feasibility of quantile DMC for extreme mesoscale weather, we sample extremely intense realizations of two historical tropical cyclones, 2010 Hurricane Earl and 2015 Hurricane Joaquin. Our results demonstrate quantile DMC’s potential to provide low-variance extreme weather statistics while highlighting the work that is necessary for quantile DMC to attain greater efficiency in future applications.
Molecular dynamics simulation of shish-kebab crystallization of polyethylene: Unraveling the effects of molecular weight distribution
Authors: Zhao Li , Hu Yanling , Shao Yunqi , Liu Zhen , Liu Boping , He Xuelian
Published: May 2019

By means of molecular dynamics simulations, extensional flow was performed on five polyethylene models with different molecular weight distributions (MWDs) precisely designed in view of Grubbs, metallocene, Ziegler-Natta, and chromium-based catalysts, while ignoring the sequence distributions of short branches to shed light on the molecular mechanism of MWD on shish-kebab formation. The formation of shish-kebab crystallites can be divided into three stages: the emergence of precursors, evolution from precursors to shish nuclei, and the formation of lamellar crystallites. The results demonstrated that the precursors initiated from trans-rich segments with local order and minor crystallinity grew into large shish nuclei and eventually evolved into lamellae. There were more inconsecutively trans-state bonds occurring in long chains rather than in short chains, which promoted an easier transformation from precursors to shish nuclei. Therefore, broader MWDs make positive contributions to the formation of shish nuclei, increase the crystallization speed, and the generation of a more regular, compact, and thicker lamella with less tie molecule fractions, while the final crystallinity is independent of MWD.
Large tetragonality and room temperature ferroelectricity in compressively strained CaTiO3 thin films
Authors: Haislmaier Ryan C. , Lu Yanfu , Lapano Jason , Zhou Hua , Alem Nasim , Sinnott Susan B. , Engel-Herbert Roman , Gopalan Venkatraman
Published: May 2019

Ferroelectricity and piezoelectricity are desirable for a variety of high-temperature applications such as actuators and sensors in heat engines, high-temperature manufacturing, and space technologies; however, the material candidates are currently limited. Here, we demonstrate that CaTiO3, the prototype perovskite mineral, abundantly found in the Earth, which as a nonpolar material in bulk form, becomes a high-temperature ferroelectric oxide under compressive strain when grown as a thin film. A strain-phase-temperature diagram of CaTiO3 films is created by growing films on various substrates with different in plane strains in order to map out the polar behavior for compressive and tensile strain. Using temperature dependent optical second harmonic generation analysis, we show that tensile strained films exhibit predominantly in-plane polarization with orthorhombiclike point group symmetry with a phase transition below room temperature. On the other hand, compressively strained CaTiO3 films exhibit a near-tetragonal unit cell with a c/a ratio of 1.03, larger than that of classic ferroelectric, e.g., BaTiO3 (c/a ∼ 1.01). These films exhibit a robust and switchable out-of-plane polarization at room temperature, with a ferroelectric transition temperature up to ∼800 K. Density functional theory calculations reveal that compressive strain gives rise to a large out-of-plane displacement of Ti-cations inside the TiO6 octahedral cages and is the major contributor to the calculated polarization of ∼9 µC/cm2. Given that nearly half of the perovskites exhibit the bulk symmetry of CaTiO3, compressive strain tuning of this perovskite family may prove to be a fertile ground for the discovery of strain-induced piezoelectrics and ferroelectrics at high-temperatures.
Challenges and advances of positronium Bose-Einstein condensation
Authors: Mondal Nagendra Nath
Published: May 2019

While scientists in the USA have accomplished Bose-Einstein Condensation (BEC) of inert gas and alkaline atoms successfully, a challenging question comes into the other’s mind why not BEC of Positronium (Ps), even though, its lowest lifetime (142 ns)? A few auspicious methods of having BEC were invented and successfully applied in the atoms of infinite lifetime. But in case of Ps-BEC laser cooling is considered to be the best method provided we can meet the requisite parameters. Using the medium range e+ beam intensity we explored some solid surfaces for the laser cooling of Ps but Ps-BEC could not be achieved. Because the intensity of pulsed beam was not enough to have the phase space density, outgoing Ps from the surface with thermal motion could not be controlled inside the scattering chamber and laser-Ps interaction was without synchronization. Hence, scientists of different laboratories have been searching materials of high density Ps production, intense pulsed e+ beam, advanced detector and image reconstruction techniques. Recently we have developed calumnious silicon nano-wires of various diameters and found the signature of a long-life component of Ps and estimated the Ps production density about 1015 Ps/cm3. It is an ideal case for the achievement of the Ps-BEC. The details of these systems are explained in the following sections.
Pressure-induced phase transition in 1,3,5-triamino-2,4,6-trinitrobenzene (TATB)
Authors: Steele Brad A. , Clarke Samantha M. , Kroonblawd Matthew P. , Kuo I-Feng W. , Pagoria Philip. F. , Tkachev Sergey N. , Smith Jesse S. , Bastea Sorin , Fried Laurence E. , Zaug Joseph M. , Stavrou Elissaios , Tschauner Oliver
Published: May 2019

Determining the unreacted equation of state of 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) is challenging because it exhibits low crystal symmetry and low X-ray scattering strength. Here, we present the first high-pressure single-crystal X-ray diffraction (SXD) study of this material. Our SXD results reveal a previously unknown transition to a monoclinic phase above 4 GPa. No abrupt change of the volume occurs but the compressibility changes. Concomitant first principles evolutionary crystal structure prediction USPEX calculations confirm this transition and show that it involves a pressure-induced in-plane shift of the layers of TATB molecules with respect to the ambient-pressure phase.
Signature identification by Minkowski dimension
Authors: Rudyi Semyon S. , Vovk Tatiana A. , Rozhdestvensky Yuri V.
Published: May 2019

In this article, we propose and investigate the possibility of signature identification based on its fractal Minkowski dimension. We consider a signature as a trajectory of a pen tip that obeys the Langevin equations, for which we calculate the fractal Minkowski dimension. This parameter is different for original and intentionally falsified signatures, thus allowing one to reliably distinguish between the signatures left by different persons. The proposed approach together with machine learning techniques is a potentially powerful tool for identification and verification of signatures and any other kind of notations.
Suspended particle motion close to the surface of rotating cylindrical filtering membrane
Authors: Zheng Jiajia , Cai Jiancheng , Wang Dongyun , E Shiju , Mochalin Ievgen
Published: May 2019

The rotational filtration principle is known as an effective approach to slow the plugging of pores in a cylindrical filtering membrane. The existing applications are based on the study of the Taylor-Couette cell with a weak imposed radial inflow through a rotating inner cylinder. They are mostly related to thin filtration with a high transmembrane pressure. We consider a possible flow mode characterized by a high through-flow rate providing the subcritical liquid rotation within the inner cylinder boundary layer. An interphase interaction model is substantiated for the typical conditions considered and equations of a suspended solid particle motion are obtained in a dimensionless form giving similarity criteria of the problem. A number of benefits can be achieved with using this proposed flow mode when the particle size is one order of magnitude less than the boundary layer thickness. The influence of centrifugal force on the phase slip is the most notable when the particles are of the above size. It is possible, in particular, to exclude the contact of such particles with the membrane surface. The results obtained allow extending the application area of the high performance rotational filtration.
Light-induced processes in nature: Coherences in the establishment of the nonequilibrium steady state in model retinal isomerization
Authors: Dodin Amro , Brumer Paul
Published: May 2019

Dynamics and coherences in retinal isomerization are investigated in a standard two-mode two-state model irradiated by natural incoherent light using the Markovian partial-secular Bloch-Redfield formalism. The two-mode two-state model is a minimal model of retinal that considers vibronic states on a ground and excited electronic manifold coupled to two continuous Ohmic harmonic baths. All light-induced coherent oscillations are shown to disappear as the turn-on time becomes realistically slow. Rather, an interplay between incoherent-light induced coherences and environmentally induced coherences is exposed as the system approaches a nonequilibrium steady state. The dynamics of the system reveal stable steady state coherences under realistic conditions, producing a small but robust transient enhancement of quantum yield.
Néel vector reorientation in ferromagnetic/antiferromagnetic complex oxide nanostructures
Authors: Bang A. D. , Hallsteinsen I. , Olsen F. K. , Slöetjes S. D. , Retterer S. T. , Scholl A. , Arenholz E. , Folven E. , Grepstad J. K.
Published: May 2019

In this study, we report on a temperature-driven antiferromagnetic (AF) spin reorientation transition in micro- and nanostructures of AF/ferromagnetic (FM) LaFeO3/La0.7Sr0.3MnO3 thin film bilayers. Using a combination of x-ray photoemission electron microscopy and x-ray absorption spectroscopy, the Néel vector is shown to reorient 90° as a result of the competition between a shape-imposed anisotropy in the AF layer and interface coupling to the adjacent FM layer. We demonstrate how a temperature dependence of the AF/FM spin configuration in line-shaped nanomagnets can be tuned by variation of their linewidth. This work provides insight into the AF/FM interface exchange coupling in complex oxide heterostructures and the possibilities of spin control by nanostructuring in thin film spintronics.
Hypersonic aerodynamic heating over a flared cone with wavy wall
Authors: Si Wufei , Huang Ganglei , Zhu Yiding , Chen Shiyi , Lee Cunbiao
Published: May 2019

The influence of a wavy wall on the hypersonic boundary layer transition and the related aerodynamic heating is investigated on a flared cone at a range of unit Reynolds numbers. Experiments are conducted in a Mach 6 wind tunnel using Rayleigh-scattering flow visualization, fast-response pressure sensors, and infrared thermography. The results show that compared to the smooth-wall cone, the wavy-wall one can suppress the second-mode instability to a certain degree and eliminate the local heating spot before transition is completed (denoted as HS). These verify our recent work on aerodynamic heating that HS is caused by the second-mode instability.
Optimisation of the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 : single-guide RNA (sgRNA) delivery system in a goat model
Authors: Huang Yu , Ding Yige , Liu Yao , Zhou Shiwei , Ding Qiang , Yan Hailong , Ma Baohua , Zhao Xiaoe , Wang Xiaolong , Chen Yulin
Published: May 2019

The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system is an efficient method for the production of gene-edited animals. We have successfully generated gene-modified goats and sheep via zygote injection of Cas9 mRNA and single-guide RNA (sgRNA) mixtures. However, the delivery system for microinjection largely refers to methods established for mice; optimised injection conditions are urgently required for the generation of large animals. Here, we designed a study to optimise the Cas9 mRNA and sgRNA delivery system for goats. By comparing four computational tools for sgRNA design and validating the targeting efficiency in goat fibroblasts, we suggest a protocol for the selection of desirable sgRNAs with higher targeting efficiency and negligible off-target mutations. We further evaluated the editing efficiency in goat zygotes injected with Cas9:sgRNA (sg8) and found that injection with 50ngμL−1 Cas9 mRNA and 25ngμL−1 sgRNA yielded an increased editing efficiency. Our results provide a reference protocol for the optimisation of the injection conditions for the efficient editing of large animal genomes via the zygote injection approach.
Multiple slopes in the negative differential resistance region of NbOx-based threshold switches
Authors: Herzig Melanie , Weiher Martin , Ascoli Alon , Tetzlaff Ronald , Mikolajick Thomas , Slesazeck Stefan
Published: May 2019

Niobium oxide devices exhibit threshold switching behavior which enables their use as selectors in memory arrays or as locally active devices for neuromorphic computing. Among the basic dynamical phenomena appearing in non-linear circuits, the oscillations generated in a relaxation oscillator, which is making use of the negative differential resistance (NDR) effect of a threshold switching device, are of special significance for the design of neuromorphic electronic systems. Here, the necessary requirements for the emergence of oscillations of this kind in a simple relaxation oscillator circuit and their influence on the shape of the measured quasi-static I–

characteristic of the threshold switch are examined. In the corresponding experiments multiple NDR regions were found to appear in the quasi-static I–

characteristic of the threshold switch concurrently with the occurrence of oscillations. The observed ‘multiple NDR phenomenon’ is therefore merely a measurement artefact due to the averaging effect associated to the operating principles of the source measure unit (SMU) utilized to measure the device current and voltage. In this work, we analyzed how the emergence of oscillatory behavior in the relaxation oscillator depends upon the device layer stack composition. The probability of the appearance of oscillations within a large current range can be increased by decreasing the oxygen content in the sub-stoichiometric bottom layer of a niobium oxide bi-layer stack. It is shown that this trend is caused by the resulting decrease in the value of the product between thermal capacitance and thermal resistance of the threshold switching device. Furthermore, the changed stack composition reduces the variability and changes the forming voltage, which goes hand in hand with a change of the threshold voltage.
Thermographic phosphor heat flux measurements of laminar methane/air flame impinging on a cylindrical surface
Authors: Oketch Peter Obara , Gonchikzhapov Munko , Bergmann Ulf , Atakan Burak
Published: May 2019

The stagnation point heat fluxes of methane/air flames impinging normal on a cylindrical surface were determined experimentally. Light induced phosphorescence from thermographic phosphors was used to investigate surface temperatures at the stagnation point from a nearly 1D laminar premixed flame burning against a water-cooled ceramic tube. The ceramic tube was coated with 1.1% chromium-doped alumina (ruby) at the impingement area and excited with a green light-emitting diode (LED) to measure the surface temperature. The flame temperature profiles were also measured with a thermocouple of type R (Pt/Pt  +  13% Rh). Effects on variations in cold gas velocity (0.1 m s−1–0.5 m s−1) relative to the flame speed, equivalence ratio (Ф  =  0.85–1.2), burner to impingement surface spacing (H/d  =  0.5–2) and surface curvature are reported. The stagnation point heat fluxes are strongly influenced by the flame stabilization mechanism, which changes from burner to wall stabilization, which also is seen from the measured flame temperature profiles. Increasing the cold gas velocity of the reactants leads to higher stagnation point heat fluxes. In addition, decreasing the distance between the burner and impingement surface increases the heat flux, with higher heat fluxes recorded for a tube compared to a flat plate.
Omadacycline for Acute Bacterial Skin and Skin Structure Infections
Authors: Abrahamian Fredrick M , Sakoulas George , Tzanis Evan , Manley Amy , Steenbergen Judith , Das Anita F , Eckburg Paul B , McGovern Paul C
Published: May 2019

Background

Within the last decade, methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a frequent cause of purulent skin and soft tissue infections. New therapeutic options are being investigated for these infections.

Methods

We report an integrated analysis of 2 randomized, controlled studies involving omadacycline, a novel aminomethylcycline, and linezolid for the treatment of acute bacterial skin and skin structure infections (ABSSSI). Omadacycline in Acute Skin and Skin Structure Infections Study 1 (OASIS-1) initiated patients on intravenous omadacycline or linezolid, with the option to transition to an oral formulation after day 3. OASIS-2 was an oral-only study of omadacycline versus linezolid.

Results

In total, 691 patients received omadacycline and 689 patients received linezolid. Infection types included wound infection in 46.8% of patients, cellulitis/erysipelas in 30.5%, and major abscess in 22.7%. Pathogens were identified in 73.2% of patients. S. aureus was detected in 74.7% and MRSA in 32.4% of patients in whom a pathogen was identified. Omadacycline was noninferior to linezolid using the Food and Drug Administration primary endpoint of early clinical response (86.2% vs 83.9%; difference 2.3, 95% confidence interval –1.5 to 6.2) and using the European Medicines Agency primary endpoint of investigator-assessed clinical response at the posttreatment evaluation. Clinical responses were similar across different infection types and infections caused by different pathogens. Treatment-emergent adverse events, mostly described as mild or moderate, were reported by 51.1% of patients receiving omadacycline and 41.2% of those receiving linezolid.

Conclusions

Omadacycline was effective and safe in ABSSSI.

Clinical Trials Registration

NCT02378480 and NCT02877927.
Early Clinical Response in Community-acquired Bacterial Pneumonia: From Clinical Endpoint to Clinical Practice
Authors: Ramirez Julio A , Tzanis Evan , Curran Marla , Noble Robert , Chitra Surya , Manley Amy , Kirsch Courtney , McGovern Paul C
Published: May 2019

Background

Early clinical response (ECR) is a new endpoint to determine whether a drug should be approved for community-acquired bacterial pneumonia in the United States. The Omadacycline for Pneumonia Treatment In the Community (OPTIC) phase III study demonstrated noninferiority of omadacycline to moxifloxacin using this endpoint. This study describes the performance of the ECR endpoint and clinical stability relative to a posttreatment evaluation (PTE) of clinical success.

Methods

ECR was defined as symptom improvement 72–120 hours after the first dose of study drug (ECR window), no use of rescue antibiotics, and patient survival. Clinical success at PTE was an investigator assessment of success. Clinical stability was defined based on vital sign stabilization, described in the American Thoracic Society and Infectious Diseases Society of America community-acquired pneumonia treatment guidelines.

Results

During the ECR window, ECR was achieved in 81.1% and 82.7% of omadacycline and moxifloxacin patients, respectively. Similar numbers of patients achieved clinical stability in each treatment group (omadacycline 74.6%, moxifloxacin 77.6%). The proportion of patients with improved symptoms who were considered clinically stable increased across the ECR window (69.2–77.6% for omadacycline; 68.0–79.7% for moxifloxacin). There was high concordance (>70%) and high positive predictive value (>90%) of ECR and clinical stability with overall clinical success at PTE.

Conclusions

Omadacycline was noninferior to moxifloxacin, based on a new ECR endpoint. Clinical stability was similarly high when measured in the same time frame as ECR. Both ECR and clinical stability showed high concordance and high positive predictive value with clinical success at PTE.

Clinical Trials Registration

NCT02531438.