bluuebunny/crossref_metadata_2025 huggingface dataset:
Studies on the Molecular Pathology and Pathogenesis of Bleeding in Severe Fibrinolytic States in Dogs
Authors: Kowalski E , Budzynski A. Z , Kopec Maria , Latallo Z. S , Lipinski B , Wegrzynowicz Z
Published: June 2018

1. In the course of fibrinogen digestion by plasmin in a plasma medium in vitro “early” and “late” fibrinogen degradation products (FDP) are formed.

2. The formation of the early FDP is correlated with the appearance of the “peak”, e.g. the highest plasma anticlotting activity. This activity after further FDP digestion with plasmin and formation of late FDP attains lower “plateau” values.

3. A similar effect is observed after SKP1 infusion into dogs.

4. The close similarity between the course of in vitro and in vivo digestion of fibrinogen allows to conclude that, as has been shown in purified systems, early FDP act predominantly as inhibitors of thrombin-fibrinogen reaction, whereas late FDP are responsible for the inhibition of fibrin monomer polymerization.

5. Methods for identification and differentation of circulating FDP are described.

6. The appearance of early FDP circulating in blood is correlated with the most pronounced prolongation of the bleeding time and with prof used bleeding.

7. It has been shown that circulating FDP interference with platelet adhesiveness, aggregation and viscous metamorphosis, the effect of early FDP being more pronounced than that of late FDP.

8. A concept is put forward according to which bleeding in plasma proteolytic states is due to the impairment of hemostatic function of platelets by FDP.
The Effect of Calcium and Magnesium on Rabbit Blood Platelet Aggregation in Vitro
Authors: Hovig Torstein
Published: June 2018

The effect of calcium and magnesium on the aggregation of rabbit blood platelets in vitro was studied, with the following results:

1. Platelet aggregation induced by ADP or collagen could be prevented by EGTA or EDTA. The aggregating effect was restored by recalcification. The effect was also restored by addition of magnesium in EDTA-PRP, but not in EGTA-PRP unless a surplus of calcium was present.

2. Calcium remained in concentrations of the order of 0.15–0.25 mM after dialysis or cation exchange of plasma. Aggregation of washed platelets resuspended in such plasma could not be produced with ADP or collagen, unless the calcium concentration was increased or that magnesium was added.

3. The adhesiveness of blood platelets to collagen was reduced in EGTA-PRP and EDTA-PRP. Release of ADP from platelets influenced by collagen could not be demonstrated either in EGTA-PRP (presence of magnesium) or in EDTA-PRP.

4. It is concluded that calcium is a necessary factor both for the reaction leading to release of ADP and for the the aggregation produced by ADP.

5. Thrombin induced aggregation of washed platelets suspended in tris-buffered saline in the presence of calcium. No effect of magnesium could be observed unless small quantities of calcium were present.
Thrombotic Thrombocytopenic Purpura as a Model of Accelerated Protein Synthesis
Authors: Barnhart Marion I. , McCutcheon Sue A. , Riddle Jeanne M. , Ohorodnik Julius M.
Published: June 2018

Proteins concerned in blood coagulation and clot lysis were studied during a fulminating and fatal case of thrombotic thrombocytopenic purpura.

One outstanding feature was the enhanced synthesis of several different plasma proteins. Specific fluorescent antibodies were used to detect cellular synthesis and storage of fibrinogen, prothrombin, albumin, Profibrinolysin and gamma globulin. Most liver cells were actively producing fibrinogen, prothrombin and albumin. Bone marrow eosinophils were synthesizing Profibrinolysin. Peripheral blood eosinophils still contained their packages of Profibrinolysin as if they were transporting this to intravascular thrombi.

Another significant finding was that polymorphonuclear leucocytes in the blood were marked with fluorescent antifibrinogen. Breakdown products of fibrin contained in these leucocytes most likely accounted for the attraction of the fluorescent marker. Polymorphonuclear leucocytes may provide an important defense mechanism for individuals in a thrombotic state.
Kinetics of Human Blood Coagulation Induced by Trypsin
Authors: Yin E. T
Published: June 2018

1. Trypsin is a potent activator of purified human serum factor X. In the presence of calcium the activation was greatly enhanced.

2. Trypsin did not activate purified human serum factor VII or crude human plasma factor V, with or without calcium.

3. A new trypsin inhibitor, Benzamidine-HCl (shown to be superior to soybean trypsin inhibitor) was used. The Benzamidine-HCl - trypsin complex did not interfere in the clotting system, whereas the soybean trypsin inhibitor-trypsin complex did.

4. Benzamidine-HCl was used to inactivate the trypsin at any desired stage during the activation of factor X.

5. The trypsin activated factor X was found to be very stable.

6. In the presence of activated factor X, factor V, cephalin and calcium, a very potent prothrombin activator was formed.

7. An apparent time-consuming reaction was observed when activated factor X was incubated with factor V in the presence of calcium, which required the subsequent addition of cephalin to convert prothrombin to thrombin.

8. The trypsin clotting mechanism is analogous to the clotting of blood by Russell’s viper venom.
Activation of Factor X
Authors: Lechner K , Deutsch E
Published: June 2018

1. Methods have been developed for the preparation of factor VII free of prothrombin and factor X, and of factor X with only a very low contamination with factor VII.

2. Factors VII and X could be found with one stage methods in purified prothrombin prepared according to Seegers.

3. Purified prothrombin was chromatographed on DE AE-cellulose. Two active fractions could be eluted, the first with the characteristics of Seegers’ DE AE-Prothrombin, the second with the characteristics of factor X.

4. It was confirmed that DE AE-Prothrombin does not activate to thrombin in 25% citrate, and does not generate autoprothrombin C.

5. The combination of both clotting active fractions coming from the DEAE-column restores the properties of non-chromatographed prothrombin.

6. DE AE-cellulose chromatography of prothrombin does not induce a molecular change of prothrombin, but separates factor X from prothrombin.

7. Factor X can be activated with tissue thromboplastin-factor VII or with high concentrated neutral salt solutions to a substance with the biological characteristics of autoprothrombin C.

8. TAMe activity is generated in factor X preparations after incubation with tissue thromboplastin and calcium.

9. Factor VII cannot be transformed into autoprothrombin C under the conditions tested.

10. Factor VII is necessary for the activation of factor X with tissue thromboplastin but not with RVV.

11. The amount of factor X available determines the amount of autoprothrombin C formed, whereas thromboplastin and factor VII influence the rate of the reaction.

12. The final conclusion is that activated factor X is similar to or identical with autoprothrombin C.
The Spectrophotometry Determination of Thrombin Activity in Plasma
Authors: Grannis G. F , Kazal L. A , Tocantins L. M
Published: June 2018

A method for the determination of thrombin activity, which is based on the spectrophotometry determination of the amount of fibrinogen clotted under standard conditions, was developed. The method was applied to the determination of the thrombin activity curve (TAC) of plasma and characteristic forms of the TAC were observed. The new method was applied to the preparation of a stable, platelet-poor defibrinogenated plasma, which was useful as a standard medium for making comparisons of normal and abnormal plasmas.
Inhibition of Prothrombin, Thrombin and Autoprothrombin C with Enzyme Inhibitors
Authors: June Caldwell M , Seegers Walter H.
Published: June 2018

Numerous chemical enzyme inhibitors were employed to determine the active polar groups in the prothrombin, thrombin and autoprothrombin C molecules. Prothrombin and autoprothrombin C activities were decreased by the reduction of disulfide bonds, but thrombin activity was affected only at higher concentrations of reducing agent. Amino groups were not essential for the activity of autoprothrombin C; however, the blocking of such groups decreased the activities of prothrombin and thrombin. The blocking of carbonyl groups decreased the activity of both prothrombin and autoprothrombin C, but thrombin was not inactivated by hydroxylamine. The activities of none of the three were decreased by sulfhydry] blocking agents. Nonspecific oxidizing agents reduced the activities of all three molecules ; however, oxidizing agents which specifically oxidize sulfhydryl groups, were incapable of decreasing the activities of prothrombin, thrombin or autoprothrombin C. The sulfhydryl groups are not essential for the activities of prothrombin, thrombin or autoprothrombin C.
Is There an Enhancing Effect of Neuroleptic Drugs on Blood Coagulation and Thrombosis
Authors: Astrup T , Rasmussen J
Published: June 2018

Sordinol (R), (clopenthixol, W.H. 0.), a potent sedative of the thiaxanthene group, in the concentrations used therapeutically, had no direct influence on blood coagulation as investigated by the thrombin generation test and the thromboplastin activation test. No significant direct effect on the fibrinolytic system was observed using urokinase, streptokinase activated human euglobulin, trypsin, porcine plasmin, or human plasmin. There was no effect on the urokinase-inhibiting effect of normal human plasma. The influence of the immobilization produced by heavy sedation on the development of thrombotic states is discussed. When the effects of drugs are evaluated it is necessary to distinguish between the direct effect of the drug and secondary effects caused by the treatment.
Platelet Changes after Adrenaline Infusions with and without Adrenaline Blockers
Authors: McClure P. D , Ingram G. I. C , Vaughan Jones R
Published: June 2018

Adrenaline infusions into young, healthy, male subjects produced a rise in both platelet counts and platelet adhesiveness. Pronethalol, a ß-blocker of adrenaline, blocked these changes. Phentolamine, an α-blocker, produced a fall in platelet count which interfered with the interpretation of its blocking effect. The results suggested however, that Phentolamine did not prevent the increase in platelet adhesiveness produced by adrenaline.
The in Vitro Anticoagulant Activity of Human Plasma Lipids
Authors: Cohen J , Reed C. F , Troup S. B
Published: June 2018

The present report describes the in vitro inhibition of prothrombin consumption by lipid extracted from normal human platelet-poor plasma. Pro-coagulant lipids and the test plasma lipids were dissolved in the same solvent and evaporated to dryness. The dried lipid mixture was emulsified in platelet-poor plasma, and the plasma clotted by recalcification. Inhibition of prothrombin consumption by plasma lipid was observed when the ratio of plasma lipid to procoagulant lipid equaled or exceeded 5:1. The inhibitory effect of plasma lipid on prothrombin consumption was not observed when procoagulant activity was provided by intact platelets or platelet granules.

Human plasma lipids have been fractionated on silicic acid columns to permit identification of the plasma lipid component responsible for the inhibition of prothrombin consumption. The inhibitory activity is present in a lipid fraction which is 95% lecithin. Other plasma lipid components exhibit little or no inhibitory activity.
Pharmakologie oraler Antikoagulanzien
Authors: Kemkes-Matthes Bettina , Matzdorff Axel
Published: June 2018

Alle oralen Antikoagulanzien vom Cumarin-Typ haben die gleiche Wirkung auf den Vitamin-K-Stoffwechsel, sie unterscheiden sich alleine in ihrer Pharmakokinetik. Von den gebräuchlichen Präparaten hat Acenocoumarol die kürzeste Halbwertszeit, Warfarin eine mittlere und Phenprocoumon eine lange Halbwertszeit. Acenocoumarol sollte deshalb zweimal täglich verabreicht werden. Phenprocoumon braucht bei einschleichender Dosierung ca. 2 Wochen, bis stabile Wirkspiegel erreicht werden. Nach dem Absetzen von Phenprocoumon vergeht eine vergleichbar lange Zeit, bis die Wirkung vollständig abgeklungen ist. Zum Beginn einer Therapie verursachen Präparate mit kurzer HWZ ein relativ größeres Ungleichgewicht zwischen Gerinnungsfaktoren mit pro- und antikoagulatorischer Wirkung (Prothrombin vs. Protein C) als Präparate mit langer HWZ. Dadurch kann es in dieser Phase zu einer Thrombose (Cumarin-Nekrose) kommen. Das Ungleichgewicht ist ganz besonders ausgeprägt, wenn die Therapie mit einer »Loading-Dose« begonnen wird. Wenn man die vier Faktoren (a) Zeit bis zum Erreichen therapeutischer Spiegel, (b) Zeit bis zum Abklingen der Wirkung nach Therapie-Ende, (c) tägl. Schwankungen der Plasmaspiegel und (d) Ungleichgewicht zwischen pro- und antikoagulatorischen Faktoren kombiniert, dann ergibt sich, daß ein Präparat mit einer HWZ von 20-30 Std. für den klinischen Einsatz am besten geeignet wäre.
Thrombophihe bei myeloproliferativen Syndromen
Authors: Schneider W. , Wehmeier A.
Published: June 2018

Erworbene hämatopoetische Stammzelldefekte sind ein eindrucksvolles Beispiel für Vielfalt und Komplexität des Zustandekommens von Hämo-stasestörungen. Blutungsneigungen erklären sich durch kompliziertes Zusammenspiel von zellulären, thrombozytopenischen Zuständen mit proteolytischen Vorgängen der Hyperkoagula-bilität und Hyperfibrinolyse. Throm-boembolischen Komplikationen aber scheinen noch komplexere Mechanismen zugrunde zu liegen. Neben gesteigerter Megakaryozytenproliferation bei reaktiver Thrombozytose und entarteter Megakaryozytenproliferation bei MPD scheinen auch die anderen Blutzellen erhebliche Einflüsse auf Schweregrad und Lokalisation einer entstehenden Thrombose ausüben zu können. Das sind die Erythrozyten durch den Hämatokritwert, möglicherweise auch durch die größeren Retikulozyten, wie die Komplikationen bei Aderlaßbehandlung der PCV andeuten, und eventuell noch durch Plättchenaktivierung bei Hämolyse. Das sind aber auch die leukämischen Promyelozyten durch größenbedingte Leukostasephänomene bei ATRA-Behandlung der PML. Und da ist schließlich auch das Monozyten-Makrophagen-System, dessen Aktivierung einerseits die intestinale Lokalisation der Thrombosen bei PNH erklären könnte. Andererseits aber macht es durch Expression von Adhäsionsmolekülen und deren besonderer Rea-gibilität mit Endothel der zerebralen Strombahn die bevorzugte zentralnervöse Lokalisation der Thromboseneigung bei PNH verständlich.
Heparinbehandlung des akuten ischämischen zerebralen Insultes
Authors: Busse O. , Glahn J.
Published: June 2018

Die Antikoagulation mit Heparin in der Akutphase des ischämischen Hirninfarkts ist keine kurative Maßnahme, sondern dient der Prophylaxe von Rezidivinsulten oder anderen thrombembolischen Komplikationen. Die subkutane Heparinbehandlung zur Prävention venöser thrombembolischer Komplikationen gilt im allgemeinen als gesichertes Therapieprinzip. Im Gegensatz hierzu ist die Wirksamkeit der intravenösen Heparinbehandlung mit PTT-wirksamen Dosen zur Rezidivprophylaxe nicht gesichert, wenn auch bei kardiogenen Embolien und Hochrisikopatienten mit atherothrombotischen Insulten sehr wahrscheinlich. Unverzichtbar vor der intravenösen Behandlung mit Heparin ist ein Computertomogramm zum Ausschluß einer Hirnblutung. Unter Berücksichtigung und Kenntnis potentieller Risikopatienten und Nebenwirkungen ist die Antikoagulation mit Heparin eine risikoarme Behandlung.
Myokardinfarkt und Thrombolyse
Authors: Priglinger Ute , Nikfardjam Mariani , Maurer G. , Huber K.
Published: June 2018

Die Thrombolysetherapie stellt wegen ihrer ubiquitären Zugänglichkeit und einfachen Applikationsweise einen Meilenstein in der Behandlung des akuten Myokardinfarktes dar. Mit dem natürlichen Gewebeplasminogenaktivator (t-PA) und seinen biochemisch modifizierten Varianten, die zumindest theoretisch bessere Eigenschaften aufweisen als die Muttersubstanz, stehen uns heute äußerst potente Fibrinolytika zur Verfügung. Andere neue Präparate wie z.B. Staphylokinase, Pro-Urokinase, oder der Vampir-Fledermaus-Plasminogen-Aktivator DSPA-alpha-1 stehen an der Schwelle zur kommerziellen klinischen Nutzung. Im vorliegenden Artikel wird besonders auf weitere Verbesserungsmöglichkeiten der Thrombolysetherapie, wie z. B. die Verkürzung der Zeitdauer Infarktbeginn - Lysebeginn, die Verbesserung der TIMI-Grad-3-Flußrate und die Optimierung der antithrombotischen Begleittherapie, eingegangen.
Cases of pN1b and pM1 Papillary Microcarcinoma of the Thyroid
Authors: Takebayashi Shinji , Shinohara Shogo , Mizuno Keisuke , Saida Koji , Hayashi Kazuki , Yamamoto Ryosuke , Michida Tetsuhiko , Kikuchi Masahiro , Fujiwara Keizo , Naito Yasushi
Published: June 2018

Introduction Papillary thyroid carcinoma has a relatively good prognosis among malignant tumors of the thyroid. Therefore, a “wait and see” strategy is often adopted for patients with micropapillary thyroid carcinoma. On the other hand, patients with papillary thyroid carcinoma with N1b or M1 disease are known to show a poor prognosis. Here, we investigated the differences in the characteristics between patients with papillary thyroid microcarcinoma with and without N1b metastatic nodes/distant metastases to identify the risk factors for metastasis.

Methods The retrospective study was performed in patients with thyroid microcarcinoma who were treated at the Kobe City Medical Center General Hospital from 2007 to 2017. The characteristics of the patients with thyroid microcarcinoma who were classified as having N1b or M1 disease (N1b/M1 group) were compared with those of patients with the same cancer classified as having N0, N1a, or M0 disease (N0/N1a group).

Results A total of 65 patients were enrolled in this study; 12 were classified into the N1b/M1 group and 53 were classified into the N0/N1a group. The proportion of males was significantly higher in the N1b/M1 group than in the N0/N1a group. There were no statistically significant differences in the distribution of the tumor sites, the ultrasonographic findings, or the frequency of the presence of multiple carcinomas. Although three patients died due to other causes, there were no patients who died due to papillary thyroid carcinoma.

Conclusion No significant predictors were identified for classifying patients with papillary thyroid microcarcinoma into the N1b/M1 group in this study. However, our findings suggested that male patients with papillary thyroid microcarcinoma require more careful follow-up in comparison to female patients with this cancer.
Interfacial strength cross-over across silica- and graphite-cis-1,4-polyisoprene interfaces
Authors: Jose Jeeno , Swaminathan Narasimhan
Published: June 2018

A cross-over in the interfacial strength, with increase in the separation rate, is observed between graphite-cis-1,4-polyisoprene and amorphous silica-cis-1,4-polyisoprene interfaces. Molecular dynamics simulations are used to compare the traction-separation characteristics of the two interfaces in the opening mode of separation at various separation rates and temperatures above the glass transition temperature of cis-1,4-polyisoprene. It was observed that various parameters governing the interface strength, such as strength modulus (ratio of peak traction to the separation at peak traction), peak traction, and the work of adhesion are higher for the silica substrated interface at very low separation rates. However, at higher rates, the graphite substrated interface showed higher values for the strength parameters. The reasons for this interface strength cross-over are explained using the potential energy, mobility, entanglement strength, tensile stiffness, and densities of the polymer over both substrates and the interface cohesive binding energy. Based on these observations, it is concluded that silica filled rubber nanocomposites are suitable for normal automobile tire applications; however, graphite fillers may be more suitable for resisting very large impact loads.
Transition from nonlocal electron transport to radiative regime in an expanding blast wave
Authors: Marocchino A. , Ravasio A. , Levy A. , Lancia L. , Fukuda Y. , Jinno S. , Atzeni S. , Doria D. , Prigent C. , Lamour E. , Vernhet D. , Borghesi M. , Romagnani L.
Published: June 2018

We have investigated the formation, evolution, and late-time propagation of a laser-generated cylindrical blast wave (BW). The whole blast wave evolution over timescales of several nanoseconds was reconstructed experimentally (via temporally resolved interferometric measurements) and via hydrodynamic simulations that included modeling of nonlocal electron transport and radiation diffusion. Comparison between the experimental results and the simulations indicates that the early expansion phase is characterised by nonlocal electron heat transport causing energy spread on times shorter than the typical timescales for hydrodynamic expansion. Nonlocal electron transport ionizes the gas ahead of the plasma front and gives rise to a smooth radial density gradient. At later times, once the shock is launched and the BW is formed, radiation results in reduced shock velocity compared to the adiabatic case. These investigations provide a suitable and effective platform to benchmark the inclusion of kinetic and radiative effects in fluid modeling of the plasma dynamics over timescales that may be inaccessible to fully kinetic simulations.
Predicting molecular properties with covariant compositional networks
Authors: Hy Truong Son , Trivedi Shubhendu , Pan Horace , Anderson Brandon M. , Kondor Risi
Published: June 2018

Density functional theory (DFT) is the most successful and widely used approach for computing the electronic structure of matter. However, for tasks involving large sets of candidate molecules, running DFT separately for every possible compound of interest is forbiddingly expensive. In this paper, we propose a neural network based machine learning algorithm which, assuming a sufficiently large training sample of actual DFT results, can instead learn to predict certain properties of molecules purely from their molecular graphs. Our algorithm is based on the recently proposed covariant compositional networks framework and involves tensor reduction operations that are covariant with respect to permutations of the atoms. This new approach avoids some of the representational limitations of other neural networks that are popular in learning from molecular graphs and yields promising results in numerical experiments on the Harvard Clean Energy Project and QM9 molecular datasets.
New nickel-based hybrid organic/inorganic metal halide for photovoltaic applications
Authors: Ramirez Daniel , Jaramillo Franklin , Pérez-Walton Santiago , Osorio-Guillén Jorge M.
Published: June 2018

In this work, we have synthesized and fabricated solar cells with the hybrid metal halide compounds with the general formula ABX3, where the A cation is methylammonium, the B cation is nickel, and the X anion is chlorine or a mixture of chlorine and iodine. We obtained experimental evidence that this material is a semiconductor with an orthorhombic crystalline structure which pertains to the space group Cmcm. The bandgap can be modulated from 1.4 eV to 1.0 eV by changing the chlorine anion to iodine. Therefore, we were able to obtain solar cells with efficiencies up to 0.16% with the CH3NH3NiCl2I composition. We have also studied by means of first-principles calculations, taking into account van der Waals dispersive forces, the ground state properties of these materials such as their crystal structure and formation and decomposition energies. We have found that these energies are lowered by the lighter mass anion, and the calculated decomposition energies show that only CH3NH3NiCl3 is stable with respect to the most probable decomposition pathway. The electronic band structure and band edge alignments have been calculated using quasiparticle effects through the GW0 approximation; these materials show an indirect bandgap with the valence band maxima at −6.93 and −5.49 eV with respect to vacuum and the conduction band minima at −5.62 and −4.60 eV with respect to vacuum for CH3NH3NiCl3 and CH3NH3NiI3, respectively. This work provides a pathway to explore new hybrid A+B2+X3−-type semiconductor materials.
Note: Temperature-frequency calibration method based on spectral analysis for QCR dew point sensor
Authors: Liu Jia , Nie Jing , Meng Xiaofeng
Published: June 2018

Each quartz crystal resonator (QCR) shows different frequency behavior as a function of temperature. To get the curve of the temperature effect compensation during the dew-deposition process, we use the active controlled temperature type of the QCR dew point sensor. In this note, a QCR temperature-frequency calibration method based on spectral analysis is described. It combines FFT and spectral refinement and the parameter table method to achieve high precision frequency extraction. Frequency identification accuracy is 10−6. The results showed that the method has a good performance in frequency extraction of the QCR sensors.
Experimental demonstration of hydraulic jump control in liquid metal channel flow using Lorentz force
Authors: Fisher A. E. , Kolemen E. , Hvasta M. G.
Published: June 2018

In this paper, hydraulic jump control using electromagnetic force in a liquid metal flow is presented. The control methods used give insight into the hydraulic jump behavior in the presence of magnetic fields and electrical currents. Flowing liquid metals is a proposed solution to heat flux challenges posed in fusion reactors, specifically the tokamak. Unfortunately, thin, fast-flowing liquid metal divertor concepts for fusion reactors are susceptible to hydraulic jumps that drastically reduce the liquid metal flow speed, leading to potential problems such as excessive evaporation, unsteady power removal, and possible plasma disruption. Highly electrically conductive flows within the magnetic fields do not exhibit traditional hydraulic jump behavior. There is very little research investigating the use of externally injected electrical currents and magnetic fields to control liquid metal hydraulic jumps. By using externally injected electrical currents and a magnetic field, a Lorentz force (also referred to as j × B force) may be generated to control the liquid metal jump behavior. In this work, a free-surface liquid metal—GaInSn eutectic or “galinstan”—flow through an electrically insulating rectangular duct was investigated. It was shown that applying a Lorentz force has a repeatable and predictable impact on the hydraulic jump, which can be used for liquid metal control within next-generation fusion reactors.
Coupled-perturbed DFTB-QM/MM metadynamics: Application to proton-coupled electron transfer
Authors: Gillet Natacha , Elstner Marcus , Kubař Tomáš
Published: June 2018

We present a new concept of free energy calculations of chemical reactions by means of extended sampling molecular dynamics simulations. Biasing potentials are applied on partial atomic charges, which may be combined with atomic coordinates either in a single collective variable or in multi-dimensional biasing simulations. The necessary additional gradients are obtained by solving coupled-perturbed equations within the approximative density-functional tight-binding method. The new computational scheme was implemented in a combination of Gromacs and Plumed. As a prospective application, proton-coupled electron transfer in a model molecular system is studied. Two collective variables are introduced naturally, one for the proton transfer and the other for the electron transfer. The results are in qualitative agreement with the extended free simulations performed for reference. Free energy minima as well as the mechanism of the process are identified correctly, while the topology of the transition region and the height of the energy barrier are only reproduced qualitatively. The application also illustrates possible difficulties with the new methodology. These may be inefficient sampling of spatial coordinates when atomic charges are biased exclusively and a decreased stability of the simulations. Still, the new approach represents a viable alternative for free energy calculations of a certain class of chemical reactions, for instance a proton-coupled electron transfer in proteins.
Temperature rise from fracture in a Zr-based metallic glass
Authors: Das A. , Kagebein P. , Küchemann S. , Maaß R.
Published: June 2018

Inhomogeneous serrated plastic flow and the subsequent fracture of a Zr-based metallic glass are probed by high-speed in-situ pyrometry and in-situ acoustic emission. Whilst the temperature rise during serrated flow remains below the detection threshold of 300 °C, fracture is accompanied by ΔT of up to approximately 600 °C within less than 100 μs. Heating rates during fracture are up to 107 K/s, for which a dynamic glass transition temperature can be determined. A continuous wavelet analysis of the acoustic-emission pulse from fracture reveals an intermittent crack propagation with phases of intense activity of ca. 5–15 μs. These findings quantify the final stage of a shear-band-to-crack transition in terms of time scales and temperature excursions, the latter of which remains well below the melting temperature of the material in this study.
Ferroelastic relaxation at 20 GHz evidenced by large frequency range picosecond acoustics
Authors: Devos A. , Casset F. , Le Rhun G. , Emery P. , Fanget S. , Defay E.
Published: June 2018

We present a method to perform elastic measurements on a thin-film as a function of frequency between a few GHz and a few hundred GHz. The technique is mainly based on Picosecond Acoustics (PA), which is an ultrafast optical technique that realizes pulse-echo measurements in the hypersonic range. Here, we combine gold layers serving as transducers and several opto-acoustic detection mechanisms to extend the PA technique to the lowest accessible frequencies (a few GHz) up to hundreds of GHz. We can therefore use the same technique on the same material to explore its elastic properties at a certain frequency over a very large frequency range. We have then applied this technique to explore the elastic properties of a lead zirconate titanate thin film from 3 to 80 GHz. We report a 9% increase in the longitudinal sound velocity above 20 GHz, which corresponds to a 19% increase in the C33 elastic modulus. We interpret such an observation as a direct evidence of ferroelastic domain wall relaxation.
Analytic gradient and derivative couplings for the spin-flip extended configuration interaction singles method: Theory, implementation, and application to proton transfer
Authors: Liu Jie , Koslowski Axel , Thiel Walter
Published: June 2018

We present the formalism of analytic gradients and derivative couplings for the spin-flip extended configuration interaction with single excitations (SF-XCIS) method. We report an efficient implementation of the SF-XCIS method in the framework of semiempirical quantum chemistry that allows fast excited-state calculations for large systems. The performance of the SF-XCIS method in combination with semiempirical orthogonalization-corrected models (OMx) is statistically evaluated for vertical singlet excitation energies. The SF-XCIS method treats the ground state and excited states in a fully balanced manner and properly describes conical intersections involving the ground state. It can thus be used in fewest switches surface hopping (FSSH) simulations of nonadiabatic dynamics processes. This is demonstrated in an OM2/SF-XCIS FSSH pilot study of excited-state proton transfer in 7-(2-pyridyl)indole.
Local view of superconducting fluctuations
Authors: Wissberg Shai , Frydman Aviad , Kalisky Beena
Published: June 2018

Superconducting transitions are driven by thermal fluctuations close to the transition temperature, Tc. These fluctuations are averaged out in global measurements, leaving imprints on susceptibility and resistance measurements. Here, we use a scanning superconducting quantum interference device to image thermal superconducting fluctuations in Nb, a conventional BCS superconductor. We observe fluctuations in both space and time which manifest themselves as grains of weaker and stronger diamagnetic response, exhibiting telegraph-like noise as a function of time. Local fluctuations are also found in the imaginary component of the susceptibility demonstrating that the local vortex dissipation can also be used as a probe of the fluctuations. An important outcome of our measurements is the observation and realization that the susceptibility decrease to zero as the temperature is raised towards Tc always occurs in quantized steps irrespective of the sample geometry. The technique described here is expected to be a useful tool for studying the nature of fluctuations in more complex superconductors, providing important information on critical properties such as fluctuation length, time scales, and local viscosity.
Hydrogen-terminated polycrystalline diamond MOSFETs with Al2O3 passivation layers grown by atomic layer deposition at different temperatures
Authors: Ren Zeyang , Yuan Guansheng , Zhang Jinfeng , Xu Lei , Zhang Jincheng , Chen Wanjiao , Hao Yue
Published: June 2018

Metal oxide semiconductor field effect transistors (MOSFETs) with Al2O3 passivation layer grown by atomic layer deposition (ALD) at 200 oC and 300 oC were fabricated on hydrogen-terminated polycrystalline diamond by using gold mask technology. The device with 200 oC grown Al2O3 dielectric shows high output current, low on-resistance, large threshold voltage and high transconductance compared to that with 300 oC grown Al2O3. A maximum drain current of 339 mA/mm has been achieved by the 2-μm device of the former kind, which, as we know, is the best result reported for the diamond MOSFETs with the same gate length except the NO2-adsorbed case. The current-voltage (I-V) of gate diodes of both kinds of devices show the gate forward leakage is dominated by the Frenkel-Poole (FP) emission mechanism at a high electric field, and the gate of the latter device can sustain higher forward bias. The stability of successive I-V measurements of both kinds of devices was proved. We expect that a high performance H-diamond MOSFET with high stability can be achieved by a double-layer dielectric structure with 200 oC grown Al2O3 stacked by another high-quality high κ dielectric.
Guest Editorial: Special Topic on Data-Enabled Theoretical Chemistry
Authors: Rupp Matthias , von Lilienfeld O. Anatole , Burke Kieron
Published: June 2018

A survey of the contributions to the Special Topic on Data-enabled Theoretical Chemistry is given, including a glossary of relevant machine learning terms.
Disrupting LXRα phosphorylation promotes FoxM1 expression and modulates atherosclerosis by inducing macrophage proliferation
Authors: Gage M. C. , Bécares N. , Louie R. , Waddington K. E. , Zhang Y. , Tittanegro T. H. , Rodríguez-Lorenzo S. , Jathanna A. , Pourcet B. , Pello O. M. , De la Rosa J. V. , Castrillo A. , Pineda-Torra I.
Published: June 2018

Significance

To date, the importance of liver X receptors (LXRs) in atherosclerosis development has been gleaned from their pharmacological or genetic manipulation. Here, we show that altering LXRα phosphorylation can shape proatherogenic responses to fat-rich diets, uncovering previously unrecognized mechanisms. Disrupting LXRα phosphorylation in myeloid cells triggers global changes in gene expression in macrophages, including the up-regulation of proliferation-promoting factors, consistent with increased proliferation of lesion-resident cells. This leads to an enhanced atherosclerotic plaque burden and plaques with altered phenotypic features. Notably, novel LXRα-regulated targets revealed by impaired LXRα phosphorylation are markedly distinct from those promoted by LXR ligand activation. Overall, this work reveals LXRα phosphorylation as an important determinant of atherosclerosis development. This could be exploited for the design of novel antiatherosclerotic strategies.
Hepatitis C Cascade of Care among People who Inject Drugs in Vancouver, Canada
Authors: Young Samantha , Wood Evan , Milloy M.-J. , DeBeck Kora , Dobrer Sabina , Nosova Ekaterina , Kerr Thomas , Hayashi Kanna
Published: June 2018

Background: People who inject drugs (PWID) have high rates of hepatitis C virus (HCV) infection. Little is known about the rates of diagnosis and treatment for HCV among PWID. Therefore, this study aims to characterize the cascade of care in Vancouver, Canada, to improve HCV treatment access and delivery for PWID. Methods: Data were derived from 3 prospective cohort studies of PWID in Vancouver, Canada, between December 2005 and May 2015. The progression of participants was identified through 5 steps in the cascade of care: (1) chronic HCV; (2) linkage to HCV care; (3) liver disease assessment; (4) initiation of treatment; and (5) completion of treatment. Predictors of undergoing liver disease assessment for HCV treatment were identified using a multivariable extended Cox regression model. Results: Among 1571 participants with chronic HCV, 1359 (86.5%) had ever been linked to care, 1257 (80.0%) had undergone liver disease assessment, 163 (10.4%) had ever started HCV treatment, and 71 (4.5%) had ever completed treatment. In multivariable analyses, human immunodeficiency virus (HIV) seropositivity, use of methadone maintenance therapy, and hospitalization in the past 6 months were independently and positively associated with undergoing liver disease assessment (all P < .001), whereas daily heroin injection was independently and negatively associated with undergoing liver disease assessment ( P < .001). Conclusions: Among this cohort of PWID, few had been started on or completed treatment for HCV. These findings highlight the need to improve the prescribing of HCV treatment among PWID with active substance use.
A two-step docking site model predicting different short-term synaptic plasticity patterns
Authors: Pulido Camila , Marty Alain
Published: June 2018

The strength of synaptic transmission varies during trains of presynaptic action potentials, notably because of the depletion of synaptic vesicles available for release. It has remained unclear why some synapses display depression over time, whereas others facilitate or show a facilitation and depression sequence. Here we compare the predictions of various synaptic models assuming that several docking/release sites are acting in parallel. These models show variation of docking site occupancy during trains of action potentials due to vesicular release and site replenishment, which give rise to changes in synaptic strength. To conform with recent studies, we assume an initial docking site occupancy of <1, thus permitting site occupancy to increase during action potential trains and facilitation to occur. We consider both a standard one-step model and a more elaborate model that assumes a predocked state (two-step model). Whereas the one-step model predicts monotonic changes of synaptic strength during a train, the two-step model allows nonmonotonic changes, including the often-observed facilitation/depression sequence. Both models predict a partitioning of parameter space between initially depressing and facilitating synapses. Using data obtained from interneuron synapses in the cerebellum, we demonstrate an unusual form of depression/facilitation sequence for very high release probability after prolonged depolarization-induced transmitter release. These results indicate a depletion of predocked vesicles in the two-step model. By permitting docking site occupancy to be <1 at rest, and by incorporating a separate predocked state, we reveal that docking site models can be expanded to mimic the large variety of time-dependent changes of synaptic strength that have been observed during action potential trains. Furthermore, the two-step model provides an effective framework to identify the specific mechanisms responsible for short-term changes in synaptic strength.
A lower bound of the hyperbolic dimension for meromorphic functions having a logarithmic Hölder tract
Authors: Mayer Volker
Published: June 2018

We improve existing lower bounds of the hyperbolic dimension for meromorphic functions that have a logarithmic tract

Ω
\Omega

which is a Hölder domain. These bounds are given in terms of the fractal behavior, measured with integral means, of the boundary of

Ω
\Omega

at infinity.
Hilbert space Lyapunov exponent stability
Authors: Froyland Gary , González-Tokman Cecilia , Quas Anthony
Published: June 2018

We study cocycles of compact operators acting on a separable Hilbert space and investigate the stability of the Lyapunov exponents and Oseledets spaces when the operators are subjected to additive Gaussian noise. We show that as the noise is shrunk to 0, the Lyapunov exponents of the perturbed cocycle converge to those of the unperturbed cocycle, and the Oseledets spaces converge in probability to those of the unperturbed cocycle. This is, to our knowledge, the first result of this type with cocycles taking values in operators on infinite-dimensional spaces. The infinite dimensionality gives rise to a number of substantial difficulties that are not present in the finite-dimensional case.
Children as visionary change agents in Danish school health promotion
Authors: Clausen Laura Tolnov , Schmidt Carina , Aagaard-Hansen Jens , Reinbach Helene Christine , Toft Ulla , Bloch Paul
Published: June 2018

This paper describes children’s perceptions and visions for a healthier social and physical environment in the setting of a primary school on the Danish island of Bornholm. Guided by an everyday-life perspective and applying participatory action research methods including social imagination and visual techniques within the framework of future creating workshops, the study engaged 50 children aged 6–9 years in creative processes of identifying health-related problem areas and solutions in their school setting. The study observed that the children were very capable of articulating their thoughts, ideas and visions for a better and healthier school environment. Identified problem areas and solutions differed widely and represented a broad perspective of health including social, physical, environmental and emotional aspects. The paper discusses advantages and challenges of involving children in decision-making processes and concludes that children are visionary and creative agents of change in health promotion projects provided that applied participatory methods are appealing to the children.
Testing tidal theory for evolved stars by using red giant binaries observed by Kepler
Authors: Beck P G , Mathis S , Gallet F , Charbonnel C , Benbakoura M , García R A , do Nascimento J-D
Published: June 2018

Tidal interaction governs the redistribution of angular momentum in close binary stars and planetary systems and determines the systems evolution towards the possible equilibrium state. Turbulent friction acting on the equilibrium tide in the convective envelope of low-mass stars is known to have a strong impact on this exchange of angular momentum in binaries. Moreover, theoretical modelling in recent literature as well as presented in this paper suggests that the dissipation of the dynamical tide, constituted of tidal inertial waves propagating in the convective envelope, is weak compared to the dissipation of the equilibrium tide during the red giant phase. This prediction is confirmed when we apply the equilibrium-tide formalism developed by Zahn, Verbunt & Phinney, and Remus, Mathis & Zahn on to the sample of all known red giant binaries observed by the NASA Kepler mission. Moreover, the observations are adequately explained by only invoking the equilibrium tide dissipation. Such ensemble analysis also benefits from the seismic characterization of the oscillating components and surface rotation rates. Through asteroseismology, previous claims of the eccentricity as an evolutionary state diagnostic are discarded. This result is important for our understanding of the evolution of multiple star and planetary systems during advanced stages of stellar evolution.
Measuring masses in low mass X-ray binaries via X-ray spectroscopy: the case of MXB 1659-298
Authors: Ponti Gabriele , Bianchi Stefano , Muñoz-Darias Teo , Nandra Kirpal
Published: June 2018

The determination of fundamental parameters in low-mass X-ray binaries (LMXBs) typically relies on measuring the radial velocity curve of the companion star through optical or near-infrared spectroscopy. It was recently suggested that high resolution X-ray spectroscopy might enable a measurement of the radial velocity curve of the compact object by monitoring the Doppler shifts induced by the orbital motion of the disc wind or the disc atmosphere. We analysed a Chandra-HETG+NuSTAR soft state observation of MXB 1659-298, an eclipsing neutron star LMXB. We measured a radial velocity curve whose phase offset and semi-amplitude are consistent with the primary star. We derived the value for the semi-amplitude of the radial velocity for the compact object K1 = 89 ± 19 km s−1, constrained the mass of the secondary (0.3 M⊙ ≤ M2 ≤ 0.8 M⊙) and the orbital inclination of the binary system (73°≤ i≤77°). These values are consistent with previous estimates from independent methods. Via the same technique, the next generation of X-ray observatories equipped with high spectral resolution instruments (e.g. Athena) will have the potential to measure the radial velocity curve of the primary in high inclination X-ray binaries to an accuracy of a few per cent.
Pliny the Younger
Authors: Coleman Kathleen M.
Published: June 2018

Pliny the Younger—to be distinguished from Pliny the Elder, his maternal uncle and the author of the encyclopedic Natural History—was born in Comum (modern Como) in Transpadane Italy c. 62 ce. His uncle adopted him, probably in his will. Pliny and his mother were living with him at Misenum when Vesuvius erupted in 79 ce. When his uncle went to investigate, Pliny stayed behind reading Livy, but his two eyewitness accounts of the event several decades later are among the most celebrated writings to have survived from Antiquity. As an adult, he led the busy life of a senator, landowner, and married man, dividing his time between the courts and Senate House in Rome and his estates in the country, which included villas at Comum, on the upper Tiber in Umbria, and on the coast of Latium south of Rome. He was highly educated and a dedicated member of intellectual circles in the city, attending recitations and writing risqué verse in his spare time. He advanced through the cursus honorum (series of public offices) to the consulship of 100. His effusive gratiarum actio (speech of thanks) to Trajan on his assumption of this office, which he polished up afterward in repeated drafts, has survived at the head of a collection of twelve Latin panegyrics and is known as the Panegyricus. Apart from the Apologia of Apuleius, which was probably delivered in 158/9 ce, it is the only Latin speech surviving intact between the last invective against Antony by Cicero—Pliny’s hero and model—in 43 bce and a panegyric celebrating the emperor Maximian’s birthday in 289 ce, and is therefore precious testimony to the development of Latin oratory under the empire. Yet it may not be representative of the many other speeches that Pliny composed and circulated, none of which has survived, and it may therefore skew our perceptions of his rhetorical skills. In the second decade of the 2nd century, Pliny’s career culminated in an appointment to govern the eastern province of Pontus-Bithynia as a special emissary of Trajan. A total of 107 letters exchanged between them while he was abroad constitute the tenth book of his Epistulae, prefaced by fourteen more addressed to Trajan earlier in Pliny’s career. Many of his vast circle of associates are visible elsewhere among the rich literary and epigraphic sources surviving for the Flavian and Trajanic periods, and in the nine books of private letters that he selected for publication, his skill as a raconteur and consummate stylist bring the kaleidoscope of contemporary society to life with unparalleled vividness of detail and elegance of expression. As a letter-writer and an orator, he has earned the posterity that—he frankly admits—he so ardently desired.