bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrolytic approach towards the controllable synthesis of NiO nanocrystalline and self-assembly mechanism of Ni(OH)2 precursor under electric, temperature and magnetic fields
Authors: Wang Jian , Zhou Yuli , He Mingyang , Wangyang Peihua , Lu Yangfan , Gu Lin
Published: March 2018

We report that two-dimensional (2D) hexagonal nickel oxide (NiO) nanosheets have been successfully synthesized using the electrolysis of nickel plate as the anode in deionized water.
Aggregation-induced emission and the working mechanism of 1-benzoyl and 1-benzyl pyrene derivatives
Authors: Zhang Yingying , He Bairong , Liu Junkai , Hu Shimin , Pan Lingxiang , Zhao Zujin , Tang Ben Zhong
Published: March 2018

An apparent AIE phenomenon was observed for 1-benzoyl and 1-benzyl pyrene derivatives, and their working mechanism was elucidated.
Chiral polymorphism in the self-assemblies of achiral molecules induced by multiple hydrogen bonds
Authors: Miao Kai , Hu Yi , Xu Li , Dong Meiqiu , Wu Juntian , Miao Xinrui , Deng Wenli
Published: March 2018

Driven by multiple hydrogen bonds, chiral and achiral polymorphs are successfully fabricated at a liquid–solid interface.
An in situ spectroelectrochemical study on the orientation changes of an [FeiiiLN2O3] metallosurfactant deposited as LB Films on gold electrode surfaces
Authors: Brand Izabella , Juhaniewicz-Debinska Joanna , Wickramasinghe Lanka , Verani Claudio N.
Published: March 2018

An iron metallosurfactant in Langmuir–Blodgett films undergoes reduction which is accompanied by pronounced structural rearrangements of the adsorbed molecule.
Photoinduced processes in nucleic acids and proteins: concluding remarks
Authors: van Grondelle Rienk
Published: March 2018

Light induced charge and energy transport in nucleic acids and proteins is the basis of fundamental biological processes such as photosynthesis, vision, DNA-photostability, DNA-photodamage and photosensing.
Three-dimensional iron sulfide-carbon interlocked graphene composites for high-performance sodium-ion storage
Authors: Huang Wei , Sun Hongyu , Shangguan Huihui , Cao Xianyi , Xiao Xinxin , Shen Fei , Mølhave Kristian , Ci Lijie , Si Pengchao , Zhang Jingdong
Published: March 2018

Three-dimensional (3D) carbon-wrapped iron sulfide interlocked graphene (Fe7S8@C-G) composites for high-performance sodium-ion storage are designed and produced through electrostatic interactions and subsequent sulfurization.
High-temperature solvent-free sulfidation of MoO3confined in a polypyrrole shell: MoS2nanosheets encapsulated in a nitrogen, sulfur dual-doped carbon nanoprism for efficient lithium storage
Authors: Liu Ying , Zhu Jixin , Xu Jingsan , Liu Siliang , Li Le , Zhang Chao , Liu Tianxi
Published: March 2018

Yolk-shelled MoS2@NSC nanoprisms synthesized by high-temperature solvent-free sulfidation using MoO3@polypyrrole as the precursor manifest enhanced lithium storage properties.
Ab initioquantum transport in polycrystalline graphene
Authors: Dechamps Samuel , Nguyen Viet-Hung , Charlier Jean-Christophe
Published: March 2018

First-principles charge transport is performed through various grain boundaries including realistic disorder in polycrystalline graphene.
Enhanced performance of a graphene/GaAs self-driven near-infrared photodetector with upconversion nanoparticles
Authors: Wu Jianghong , Yang Zhenwei , Qiu Caiyu , Zhang Yuejiao , Wu Zhiqian , Yang Jingliang , Lu Yanghua , Li Jianfeng , Yang Dongxiao , Hao Ran , Li Erping , Yu Geliang , Lin Shisheng
Published: March 2018

A high performance near-infrared photodetector is achieved by the graphene/GaAs Schottky junction which can be further improved by coating NaYF4:Yb3+/Er3+ nanoparticles.
Pd-catalyzed intramolecular C(sp2)–H amination of phenylalanine moieties in dipeptides: synthesis of indoline-2-carboxylate-containing dipeptides
Authors: Zheng Yong , Song Weibin , Zhu Yefu , Wei Bole , Xuan Lijiang
Published: March 2018

Indoline-2-carboxylate-containing dipeptides were synthesized from dipeptides via Pd-catalyzed intramolecular C–H amination.
α-Tocopherol-based cationic amphiphiles with a novel pH sensitive hybrid linker for gene delivery
Authors: Muripiti Venkanna , Rachamalla Hari Krishnareddy , Banerjee Rajkumar , Patri Srilakshmi. V.
Published: March 2018

Endosomal escape is one of the barriers for the efficient liposomal gene delivery.
The carbon chain-selective adenylation enzyme TamA: the missing link between fatty acid and pyrrole natural product biosynthesis
Authors: Marchetti Piera M. , Kelly Van , Simpson Joanna P. , Ward Mairi , Campopiano Dominic J.
Published: March 2018

TamA is the adenylating enzyme that selects and activates fatty acids for tambjamine biosynthesis.
Recyclable cellulose-palladium nanoparticles for clean cross-coupling chemistry
Authors: Lu Zhichao , Jasinski Jacek B. , Handa Sachin , Hammond Gerald B.
Published: March 2018

Cheap, recyclable, and robust cellulose-palladium nanoparticles were developed and fully characterized by FTIR, TEM, XPS, TGA, and NMR.
A healing ionomer crosslinked by a bis-bidentate halogen bond linker: a route to hard and healable coatings
Authors: Dahlke J. , Tepper R. , Geitner R. , Zechel S. , Vitz J. , Kampes R. , Popp J. , Hager M. D. , Schubert U. S.
Published: March 2018

A bis-bidentate halogen bond linker was introduced into a fully organic, phosphate based ionomer, yielding a crosslinked network with healing abilities and improved mechanical properties.
Melatonin-directed micellization: a case for tryptophan metabolites and their classical bioisosteres as templates for the self-assembly of bipyridinium-based supramolecular amphiphiles in water
Authors: Wang Zhenzhen , Cui Hui , Sun Zhimin , Roch Loïc M. , Goldner Amanda N. , Nour Hany F. , Sue Andrew C.-H. , Baldridge Kim K. , Olson Mark A.
Published: March 2018

A structure–property analysis of two tryptamine-derivatives augers well for templation of soft matter assemblies by l-tryptophan-based metabolites.
Pronounced effects of the densities of threaded rings on the strain-dependent Poisson's ratio of polyrotaxane gels with movable cross-links
Authors: Tanaka Akira , Kato Kazuaki , Ito Kohzo , Urayama Kenji
Published: March 2018

The density of threaded ring molecules in polyrotaxane (PR) chains influences pronouncedly the equilibrium Poisson's ratio of PR gels where the cross-linked ring molecules are slidable along the network strands.
Pilot power allocation for maximising the sum rate in massive MIMO systems
Authors: Dao Hieu Trong , Kim Sunghwan
Published: March 2018

In this study, the authors investigate the issue of pilot power allocation in multi‐cell multi‐user massive multiple‐inputmultiple‐output (MIMO) systems to maximize the sum rate. In contrast to conventional scheme that assigns equal pilot power for all users in the system, they assume that different users can be assigned different pilot powers while the total pilot power per cell is fixed. They show that when the number of BS antennas goes to infinity, the signal‐to‐interference‐and‐noise ratio of a user only depends on the large‐scale fading and pilot power of users who have the same pilot sequence. From that they derive an optimization problem to maximize the total uplink achievable rate of a target cell and prove that this problem is convex, which can be solved by the well‐known Lagrange multiplier method. They also propose an extended optimization problem that solves the issue of zero‐pilot power in the original problem. Eventually, two algorithms corresponding to the original and extended optimization problems are proposed to obtain the optimized pilot power set for all users in the systems. Numerical results show that the proposed algorithms outperform the existing methods relating to pilot power allocation problem as well as conventional scheme.
Automatic underwater moving object detection using multi‐feature integration framework in complex backgrounds
Authors: Vasamsetti Srikanth , Setia Supriya , Mittal Neerja , Sardana Harish K. , Babbar Geetanjali
Published: March 2018

Moving object detection in a video sequence is one of the leading tasks of marine scientists to explore and monitor applications. The videos acquired in the underwater environment are usually degraded due to the physical properties of water medium as compared with images acquired in the air and that affects the performance of feature descriptors. In this study, a new feature descriptor, multi‐frame triplet pattern (MFTP) is proposed for underwater moving object detection. The MFTP encodes the structure of local region based on three sets of frames, which are calculated by considering local differences in intensities between the centre pixel and its nine neighbours. Furthermore, the robustness of the proposed method is increased by integrating it with colour and motion features. The performance of the proposed framework is tested by conducting seven experiments on Fish4Knowledge database for underwater moving object detection applications. The results of the proposed method show a significant improvement as compared with state‐of‐the‐art techniques in terms of their evaluation measures.
Chemical modeling of internal photon-dominated regions surrounding deeply embedded HC/UCHII regions
Authors: Stéphan G. , Schilke P. , Le Bourlot J. , Schmiedeke A. , Choudhury R. , Godard B. , Sánchez-Monge Á.
Published: March 2018

Aims. We aim to investigate the chemistry of internal photon-dominated regions (PDRs) surrounding deeply embedded hypercompact (HC) and ultracompact (UC) HII regions. We search for specific tracers of this evolutionary stage of massive star formation that can be detected with current astronomical facilities.

Methods. We modeled hot cores with embedded HC/UCHII regions (called HII region models in the article despite the fact that we do not model the HII region itself), by coupling the astrochemical code Saptarsy to a radiative transfer framework obtaining the spatio-temporal evolution of abundances as well as time-dependent synthetic spectra. In these models where we focused on the internal PDR surrounding the HII region, the gas temperature is set to the dust temperature and we do not include dynamics thus the density structure is fixed. We compared this to hot molecular core (HMC) models and studied the effect on the chemistry of the radiation field which is included in the HII region models only during the computation of abundances. In addition, we investigated the chemical evolution of the gas surrounding HII regions with models of different densities at the ionization front, different sizes of the ionized cavity and different initial abundances.

Results. We obtain the time evolution of synthetic spectra for a dozen of selected species as well as ratios of their integrated intensities. We find that some molecules such as C, N2H+, CN, and HCO do not trace the inner core and so are not good tracers to distinguish the HII/PDR regions to the HMCs phase. On the contrary, C+ and O trace the internal PDRs, in the two models starting with different initial abundances, but are unfortunately currently unobservable with the current achievable spatial resolution because of the very thin internal PDR (Δ rPDR < 100 AU). The emission of these two tracers is very dependent on the size of the HII region and on the density in the PDR. In addition, we find that the abundance profiles are highly affected by the choice of the initial abundances, hence the importance to properly define them.
The host galaxy of the short GRB 111117A at z = 2.211
Authors: Selsing J. , Krühler T. , Malesani D. , D’Avanzo P. , Schulze S. , Vergani S. D. , Palmerio J. , Japelj J. , Milvang-Jensen B. , Watson D. , Jakobsson P. , Bolmer J. , Cano Z. , Covino S. , D’Elia V. , de Ugarte Postigo A. , Fynbo J. P. U. , Gomboc A. , Heintz K. E. , Kaper L. , Levan A. J. , Piranomonte S. , Pugliese G. , Sánchez-Ramírez R. , Sparre M. , Tanvir N. R. , Thöne C. C. , Wiersema K.
Published: March 2018

It is notoriously difficult to localize short γ-ray bursts (sGRBs) and their hosts to measure their redshifts. These measurements, however, are critical for constraining the nature of sGRB progenitors, their redshift distribution, and the r-process element enrichment history of the universe. Here we present spectroscopy of the host galaxy of GRB 111117A and measure its redshift to be z = 2.211. This makes GRB 111117A the most distant high-confidence short duration GRB detected to date. Our spectroscopic redshift supersedes a lower, previously estimated photometric redshift value for this burst. We use the spectroscopic redshift, as well as new imaging data to constrain the nature of the host galaxy and the physical parameters of the GRB. The rest-frame X-ray derived hydrogen column density, for example, is the highest compared to a complete sample of sGRBs and seems to follow the evolution with redshift as traced by the hosts of long GRBs. From the detection of Lyα emission in the spectrum, we are able to constrain the escape fraction of Lyα in the host. The host lies in the brighter end of the expected sGRB host brightness distribution at z = 2.211, and is actively forming stars. Using the observed sGRB host luminosity distribution, we find that between 43% and 71% of all Swift-detected sGRBs have hosts that are too faint at z ~ 2 to allow for a secure redshift determination. This implies that the measured sGRB redshift distribution could be incomplete at high redshift. The high z of GRB 111117A is evidence against a lognormal delay-time model for sGRBs through the predicted redshift distribution of sGRBs, which is very sensitive to high-z sGRBs. From the age of the universe at the time of GRB explosion, an initial neutron star (NS) separation of a0 < 3.1 R⊙ is required in the case where the progenitor system is a circular pair of inspiralling NSs. This constraint excludes some of the longest sGRB formation channels for this burst.
Spectroscopic Parameters and atmosphEric ChemIstriEs of Stars (SPECIES)
Authors: Soto M. G. , Jenkins J. S.
Published: March 2018

Context.The detection and subsequent characterisation of exoplanets are intimately linked to the characteristics of their host star. Therefore, it is necessary to study the star in detail in order to understand the formation history and characteristics of their companion(s).

Aims.Our aims are to develop a community tool that allows the automated calculation of stellar parameters for a large number of stars, using high resolution echelle spectra and minimal photometric magnitudes, and introduce the first catalogue of these measurements in this work.

Methods.We measured the equivalent widths of several iron lines and used them to solve the radiative transfer equation assuming local thermodynamic equilibrium in order to obtain the atmospheric parameters (Teff, [Fe/H], logg, andξt). We then used these values to derive the abundance of 11 chemical elements in the stellar photosphere (Na, Mg, Al, Si, Ca, Ti, Cr, Mn, Ni, Cu, and Zn). Rotation and macroturbulent velocity were obtained using temperature calibrators and synthetic line profiles to match the observed spectra of five absorption lines. Finally, by interpolating in a grid of MIST isochrones, we were able to derive the mass, radius, and age for each star using a Bayesian approach.

Results.SPECIES obtains bulk parameters that are in good agreement with measured values from different existing catalogues, including when different methods are used to derive them. We find discrepancies in the chemical abundances for some elements with respect to other works, which could be produced by differences inTeff, or in the line list or the atomic line data used to derive them. We also obtained analytic relations to describe the correlations between different parameters, and we implemented new methods to better handle these correlations, which provides a better description of the uncertainties associated with the measurements.
Complex cyanides as chemical clocks in hot cores
Authors: Allen V. , van der Tak F. F. S. , Walsh C.
Published: March 2018

Context. In the high-mass star-forming region G35.20−0.74N, small scale (~800 AU) chemical segregation has been observed in which complex organic molecules containing the CN group are located in a small location (toward continuum peak B3) within an apparently coherently rotating structure.

Aims. We aim to determine the physical origin of the large abundance difference (~4 orders of magnitude) in complex cyanides within G35.20−0.74 B, and we explore variations in age, gas/dust temperature, and gas density.

Methods. We performed gas-grain astrochemical modeling experiments with exponentially increasing (coupled) gas and dust temperature rising from 10 to 500 K at constant H2 densities of 107 cm−3, 108 cm−3, and 109 cm−3. We tested the effect of varying the initial ice composition, cosmic-ray ionization rate (1.3 × 10−17 s−1, 1 × 10−16 s−1, and 6 × 10−16 s−1), warm-up time (over 50, 200, and 1000 kyr), and initial (10, 15, and 25 K) and final temperatures (300 and 500 K).

Results. Varying the initial ice compositions within the observed and expected ranges does not noticeably affect the modeled abundances indicating that the chemical make-up of hot cores is determined in the warm-up stage. Complex cyanides vinyl and ethyl cyanide (CH2CHCN and C2H5CN, respectively) cannot be produced in abundances (vs. H2) greater than 5 ×10−10 for CH2CHCN and 2 ×10−10 for C2H5CN with a fast warm-up time (52 kyr), while the lower limit for the observed abundance of C2H5CN toward source B3 is 3.4 ×10−10. Complex cyanide abundances are reduced at higher initial temperatures and increased at higher cosmic-ray ionization rates. Reaction-diffusion competition is necessary to reproduce observed abundances of oxygen-bearing species in our model.

Conclusions. Within the context of this model, reproducing the observed abundances toward G35.20−0.74 Core B3 requires a fast warm-up at a high cosmic-ray ionization rate (~1 × 10−16 s−1) at a high gas density (>109 cm−3). The abundances observed at the other positions in G35.20-0.74N also require a fast warm-up but allow lower gas densities (~108 cm−3) and cosmic-ray ionization rates (~1 × 10−17 s−1). In general, we find that the abundance of ethyl cyanide in particular is maximized in models with a low initial temperature, a high cosmic-ray ionization rate, a long warm-up time (>200 kyr), and a lower gas density (tested down to 107 cm−3). G35.20−0.74 source B3 only needs to be ~2000 years older than B1/B2 for the observed chemical difference to be present, which maintains the possibility that G35.20−0.74 B contains a Keplerian disk.
The Lyman Alpha Reference Sample
Authors: Micheva Genoveva , Östlin Göran , Zackrisson Erik , Hayes Matthew , Melinder Jens , Guaita Lucia , Cannon John M. , Bridge Joanna S. , Kunth Daniel , Sandberg Andreas
Published: March 2018

Context. The Lyman α Reference Sample (LARS) of 14 star-forming galaxies offers a wealth of insight into the workings of these local analogs to high-redshift star-forming galaxies. The sample has been well-studied in terms of Lyα and other emission line properties, such as H I mass, gas kinematics, and morphology.

Aims. We analyze deep surface photometry of the LARS sample in UBIK broadband imaging obtained at the Nordic Optical Telescope and the Canada-France-Hawaii Telescope, and juxtaposition their derived properties with a sample of local high-redshift galaxy analogs, namely, with blue compact galaxies (BCGs).

Methods. We construct radial surface brightness and color profiles with both elliptical and isophotal integration, as well as RGB images, deep contours, color maps, a burst fraction estimate, and a radial mass-to-light ratio profile for each LARS galaxy. Standard morphological parameters like asymmetry, clumpiness, the Gini and M20 coefficients are also obtained and analyzed, as well as isophotal asymmetry profiles for each galaxy. In this context, we compare the LARS sample to the properties of the BCG sample and highlight the differences.

Results. Several of these diagnostics indicate that the LARS galaxies have highly disturbed morphologies even at the level of the faintest outer isophotes, with no hint at a regular underlying population, as found in many BCG sample galaxies. The ground-based photometry reaches isophotes down to ~28 mag arcsec−2, while the space-based data reach only ~26 mag arcsec−2. The ground-based observations therefore reveal previously unexplored isophotes of the LARS galaxies. The burst fraction estimate suggests a spatially more extended burst region in LARS than in the BCGs. Comparison to stellar evolutionary models in color–color diagrams reveals complex behavior of the radial color profiles, often inconsistent with a single stellar population of any age and metallicity, but instead suggesting a mixture of at least two stellar populations with a typical young mass fraction in the range 0.1–1%.

Conclusions. The galaxies in the LARS sample appear to be in earlier stages of a merger event compared to the BCGs. Standard morphological diagnostics like asymmetry, clumpiness, Gini and M20 coefficients cannot separate the two samples, although an isophotal asymmetry profile successfully captures the average difference in morphology. These morphological diagnostics do not show any correlation with the equivalent width or the escape fraction of Lyman Alpha.
Advances in the Synthesis of Isatins: A Survey of the Last Decade
Authors: Bogdanov Andrei , Mironov Vladimir
Published: March 2018

Isatin derivatives are widely used in organic synthesis, in medicinal chemistry and in the chemistry of materials. This report summarizes modern trends in the synthesis of substituted indolin-2,3-diones covering the literature from 2007 to 2017. Studies on the influence of the structure of substituents in the initial substrates on the formation of the heterocyclic isatin system and the yields of the target compounds are also discussed.

1 Introduction

2 Oxidation of Indole Derivatives

3 Cyclization of o-Aminoacetophenones

4 Cyclization of N-Acylanilines

5 Miscellaneous

6 Conclusion
Dihalogen and Solvent-Free Preparation of syn-Bimane
Authors: Grynszpan Flavio , Neogi Ishita , Das Partha
Published: March 2018

Fluorescent bimanes are low molecular weight and low toxicity molecules with applications ranging from biology to LASER dyes. The widespread use of these molecular probes has presumably been stalled by the hazards involved in their current synthetic preparation which involve handling of dangerous halogens like chlorine (gas) and bromine (liq.). The accessibility achieved by the simple and safe dihalogen and solvent-free methodologies described here open the floodgates to additional future practical applications of bimanes.
Synthesis of C-Nor-D-homo-steroidal Alkaloids and Their Derivatives
Authors: Giannis Athanassios , Mousavizadeh Farnoush , Meyer Daniel
Published: March 2018

The C-nor-D-homo-steroidal alkaloid cyclopamine was discovered in the 1969 and in 2000 it was shown to act as an inhibitor of the hedgehog signaling (Hh) pathway, which is aberrantly activated in some tumors. Subsequently it was revealed that this natural occurring alkaloid has also antidiabetic and antiviral properties. In this review we present syntheses of selected C-nor-D-homo-steroidal alkaloids and their analogues and also discuss a general access to C-nor-D-homo-steroids. Some historical as well as biomedical aspects are also presented.

1 Introduction

2 Total Synthesis of Cyclopamine

2.1 Synthesis of exo-Cyclopamine and Further Cyclopamine Analogues

2.2 Synthesis of a Carbacyclopamine Analogue

3 D-Homocyclopamine: Saridegib (IPI-926)

4 Synthesis of Nakiterpiosin

5 Lewis Acid Mediated Nazarov Cyclization as a Versatile Method for C-Nor-D-homo-steroid Synthesis

6 Conclusion
Systemische Behandlung des fortgeschrittenen differenzierten und medullären Schilddrüsenkarzinoms
Authors: Kreissl M.C. , Fassnacht M. , Mueller S.P.
Published: March 2018

In den vergangenen Jahren wurden drei neue Substanzen für die molekular gezielte Therapie des fortgeschrittenen und progredienten Schilddrüsenkarzinoms zugelassen: Vandetanib und Cabozantinib für das medulläre Schilddrüsenkarzinom sowie Sorafenib für das Radioiod-refraktäre differenzierte Schilddrüsenkarzinom. Die Selektion der Patienten durch ein interdisziplinäres Team sowie die Aufklärung der Patienten spielt eine wesentliche Rolle, wenn diese Behandlung in Betracht gezogen bzw. begonnen wird. Nur Patienten mit hoher Tumorlast und/oder symptomatischer bzw. progredienter Erkrankung, die lokalen Therapien nicht zugänglich ist, sollten behandelt werden. Um eine gute Lebensqualität zu erhalten, ist das Management der unerwünschten Arzneimittelwirkungen von größter Bedeutung. Aufgrund der Wirkweise der Tyrosinkinasehemmer ist der Verlauf der Tumormarker Calcitonin und Thyreoglobulin nur bedingt zur Beurteilung des Therapieansprechens und zum Follow-up geeignet, deshalb kommt der morphologischen und metabolischen Bildgebung besondere Bedeutung zu. Ein umschriebener oder geringer Progress sollte nicht unbedingt die Beendigung der Behandlung oder eine Therapieumstellung nach sich ziehen. In der nahen Zukunft werden weitere Substanzen verfügbar sein.

Nachdruck aus und zu zitieren als: Nuklearmedizin 2015; 54: 88–93
A Novel Diazomethane-Mediated Synthesis of Azetidine-Embedded Tetracyclic Ketal Systems
Authors: Rao G.
Published: March 2018

Herein, the first diazomethane-mediated synthesis of azetidine-embedded tetracyclic ketal systems is reported. Reactions of norbornyl hemiaminal acetals with diazomethane afford azetidine-embedded tetracyclic ketals in good to excellent yields. The bridgehead-bromo-substituted hemiaminal acetals give higher yields compared to the corresponding bridgehead-chloro-substituted hemiaminal acetals. The hemiaminal acetals are prepared stereoselectively via nucleophilic addition of various amines to norbornyl α-diketones from the exo face.
Factor VII Activity Is an Independent Predictor of Cardiovascular Mortality in Elderly Women of a Sicilian Population: Results of an 11-year Follow-up
Authors: Noto D. , Barbagallo C. , Cefalu A. , Cavera G. , Sapienza M. , Notarbartolo A. , Davi’ G. , Averna M.
Published: March 2018

The aim of the Epidemiological project “Ventimiglia di Sicilia” is to identify the cardiovascular risk factors in a Sicilian population with a low risk profile and healthy nutritional habits. The risk of cardiovascular mortality in older subjects (over 60 years of age) is presented for an 11 year follow-up. Females showed higher prevalence of diabetes mellitus, hypertension, obesity and higher levels of total, LDL and HDL cholesterol, factor VII activity and fibrinogen compared to males. Cardiovascular mortality was related to hypertension and obesity in males, to high factor VII activity, obesity and diabetes mellitus in females. In a Logistic Regression model the same variables were independently correlated to cardiovascular mortality with the exception of obesity. In conclusion, these findings suggest that in a population with a low risk profile, other factors, such as factor VII activity, may emerge as predictors of cardiovascular mortality.
Prospective Study on Soluble Thrombomodulin and von Willebrand Factor and the Risk of Ischemic and Hemorrhagic Stroke
Authors: Jansson Jan-Håkan , Boman Kurt , Nilsson Torbjörn , Stegmayr Birgitta , Hallmans Göran , Johansson Lars
Published: March 2018

The aim of the present study was to examine if soluble thrombomodulin (sTM) and von Willebrand factor (VWF) could predict a first-ever ischemic or hemorrhagic stroke.

This study was an incident case-referent study from within a population-based cohort in northern Sweden. Up to 1996 about 44,000 subjects had been screened and stroke cases were classified according to the WHO MONICA criteria. A first-ever stroke occurred in 108 cases. A total of 216 controls were selected from the same cohort.

This prospective study found no association with sTM or VWF and the development of a first-ever ischemic stroke (n = 87) in the logistic regression model. For the hemorrhagic stroke cases (n = 18), the multivariate logistic regression model revealed a significant negative association with sTM. When dichotomized, the upper level (>17.3 µg/L) of sTM, as compared with the lower level (<17.3 µg/L), showed one fifth of the risk for hemorrhagic stroke (OR, 0.18; CI, 0.05 to 0.69). No significant association was found for VWF. We suggest that the novel finding of an inverse relation between sTM and hemorrhagic stroke should be investigated in a larger study.
Paradoxical Platelet Activation Was not Observed on Dissociation of Abciximab from GPIIb-IIIa Complexes
Authors: Ndoko Serge , Poujol Christel , Combrié Robert , Nurden Alan , Nurden Paquita
Published: March 2018

The ability of abciximab to bind and dissociate from platelets raises the question of the conformational state of GPIIb-IIIa complexes losing abciximab and the risk of paradoxical drug-induced platelet activation. Platelets incubated with abciximab and mixed in vitro with c7E3 Fab-free platelets lost the drug to the new platelets giving a single platelet population with a unimodal abciximab distribution within 17 h. Prelabeling the receiving platelets with phycoerythrin-labeled anti-GPIb monoclonal antibody (MoAb), permitted their identification by flow cytometry. Binding of PAC-1 and AP6, two MoAbs specific for activated GPIIb-IIIa, was then assessed to both losing and receiving platelet populations during transfer of abciximab. The subpopulation losing c7E3 Fab failed to show increased binding of these MoAbs. However, PAC-1 binding increased in both subpopulations after addition of ADP. Thus GPIIb-IIIa complexes are not in an activated state after dissociation of abciximab unless there is an additional source of activation.
Anticoagulant Effect at the Time of Epidural Catheter Removal in Patients Receiving Twice-daily or Once-daily Low-molecular-weight Heparin and Continuous Epidural Analgesia after Orthopedic Surgery
Authors: Kinnon Krystyna , Crowther Mark , Douketis James
Published: March 2018

In patients who receive co-administered low-molecular-weight heparin (LMWH) and continuous epidural analgesia (CEA) after orthopedic surgery, there is concern about an increased risk of a spinal epidural hematoma. The practice of twice-daily LMWH dosing in North America might, in part, account for the greater number of epidural hematomas reports compared to Europe where once-daily LMWH is used. We performed a prospective cohort study in patients who had orthopedic surgery and received co-administered LMWH and CEA. We investigated the trough anticoagulant effect, as measured by an anti-Xa heparin level, at the time of epidural catheter removal in patients who received twice-daily or once-daily LMWH. Twenty-five patients who received enoxaparin, 30 mg twice-daily, and 25 patients who received dalteparin, 5,000 IU once-daily, had anti-Xa heparin levels measured on the second or third post-operative day at the time of epidural catheter removal. In patients who received twice-daily enoxaparin, or once-daily dalteparin, the anti-Xa heparin level was measured, on average, 10.4 h and 21.8 h, respectively, after the preceding LWMH dose. All 25 patients who received once-daily LMWH had an anti-Xa heparin level <0.10 U/ml at the time of catheter removal. Of 25 patients who received twice-daily LMWH, the anti-Xa heparin level at the time of catheter removal was >0.20 U/ml in 5 patients (P = 0.050), and >0.10 U/ml in 7 patients (P = 0.009). We conclude that in patients who are receiving co-administered LMWH and CEA after orthopedic surgery, twice-daily but not once-daily LMWH administration is more likely to be associated with a clinically important anticoagulant effect at the time of epidural catheter removal.
Low Dose Oral Vitamin K to Reverse Acenocoumarol-induced Coagulopathy: A Randomized Controlled Trial
Authors: Crowther M. , Steidl L. , Ultori C. , Mera V. , Dentali F. , Squizzato A. , Marchesi C. , Venco A. , Ageno W.
Published: March 2018

Low dose oral vitamin K rapidly reverses warfarin-associated coagulopathy. Its effect in patients receiving acenocoumarol is uncertain. We compared the effect of withholding acenocoumarol and administering 1 mg oral vitamin K with simply withholding acenocoumarol in asymptomatic patients presenting with INR values between 4.5 and 10.0. The primary end-point of the study was the INR value on the day following randomisation. We found that patients receiving oral vitamin K had more sub-therapeutic INR levels than controls (36.6% and 13.3%, respectively; RR 1.83, 95% confidence interval 1.16, 2.89) and a lower, but non-significant, proportion of INR values in range (50% and 66.6%, respectively) on the day following randomisation. After 5 ± 1 days, there were more patients with an INR value in range in the vitamin K group than in controls (74.1% and 44.8%, respectively). There were no clinical events during 1 month follow-up. We conclude that the omission of a single dose of acenocoumarol is associated with an effective reduction of the INR in asymptomatic patients presenting with an INR value of 4.5 to 10.0. Furthermore, the use of a 1 mg dose of oral vitamin K results in an excessive risk of overreversal of the INR.
Possible Synergy between Recombinant Factor VIIa and Prothrombin Complex Concentrate in Hemophilia Therapy
Authors: Christie Beverly , Henderson Nicole , Key Nigel , Nelsestuen Gary
Published: March 2018

Recombinant factor VIIa (rFVIIa; Novoseven™) is used for treatment of hemophilia patients with inhibitors. There are poorly defined differences in clinical responsiveness between individuals. Prior to licensure in the United States, rFVIIa was available through the compassionate use program, during which two patients described in this study demonstrated an excellent response. More recently, one of these individuals showed a sub-optimal response to rFVIIa. One possible explanation for different treatment outcomes was sequential therapy with prothrombin complex concentrates (PCC) followed by rFVIIa in the compassionate use program. In support of this, an in vitro test showed that this patient had an exceptionally strong response to rFVIIa when it was added to whole blood after the patient received PCC therapy. Results with other patients supported this hypothesis. With further evaluation, a therapeutic approach combining sequential PCC and rFVIIa may prove useful for treatment of bleeding refractory to either agent used alone.
Inter-laboratory Variability of Anti-β2-glycoprotein I Measurement
Authors: Schousboe Inger , Tincani Angela , Sanmarco Marielle , Kveder Tanja , de Moerloose Philippe , Boffa Marie-Claire , Arvieux Josiane , Reber Guido
Published: March 2018

Inter-laboratory variability of anti-β2-glycoprotein I antibody measurements (IgG and IgM) was investigated in the frame of the European Forum on Antiphospholipid Antibodies and its Standardization Group. Twenty-eight samples from patients with autoimmune diseases, two samples from blood donors and a set of six calibrators obtained by dilution with normal plasma of a pool of patient samples were sent to 21 European centers. Six of them used commercial kits and the others home-made assays. Marked differences in the steepness of the calibration curves obtained with the calibrator provided were observed. The standard deviations of sample measurement were high. Cut-off of positivity varied from 7 to 90 Forum Units (FU) for IgG and from 10 to 138 FU for IgM, whereas the rate of positivity varied from 50 to 93% for IgG and from 13 to 70% for IgM. No clear relationship between cut-off values and positivity rate could be established for either isotype. Adopting a common cut-off did not markedly improve the overall agreement between centers in positive/negative sample classification. Because of the majority of low positive samples, excellent concordance between centers (as defined by kappa values from 0.8 and 1) occurred only in 13% of cases for IgG and in 6% of cases for IgM, because many selected samples were low-positive. Despite the large variability of anti-β2-glycoprotein I measurements between centers, the agreement on results with highand medium-positive samples was good.
Von Willebrand Factor Modulates Factor VIII Immunogenicity: Comparative Study of Different Factor VIII Concentrates in a Haemophilia A Mouse Model
Authors: Behrmann Mathias , Pasi John , Saint-Remy Jean-Marie , Kotitschke Ronald , Kloft Michael
Published: March 2018

The development of an immune response towards factor VIII (FVIII) remains the major complication of haemophilia A replacement therapy. Product-related risk factors have recently been identified on the basis of epidemiological studies, but the mechanism is not understood. To this end, various commercially available FVIII concentrates were administered by the IV route to FVIII-knockout mice and the resulting immune response was characterised. Significantly higher inhibitor titres (Bethesda assay) were observed for one recombinant FVIII and one plasma-derived FVIII product depleted in von Willebrand factor (VWF). Inhibitor titres were reduced upon pre-incubation of FVIII with purified VWF. Epitope specificity of anti-FVIII IgG was characterised using FVIII-fragments produced in E. coli. Concentrates with no or reduced VWF-level elicited antibodies recognising predominantly the acidic a1 and a3 regions. Addition of VWF prior to injection also modified the epitope specificity. FVIII concentrates, therefore, show qualitative and quantitative variations in immunogenicity, which are at least partly modulated by VWF.
Distribution of Endothelial Cell Protein C/Activated Protein C Receptor (EPCR) During Mouse Embryo Development
Authors: Crawley James , Gu Jian-Ming , Ferrell Gary , Esmon Charles
Published: March 2018

The endothelial cell protein C receptor (EPCR) augments protein C activation by the thrombomodulin•thrombin complex. Deletion of the EPCR gene in mice has been reported to lead to embryonic lethality before embryonic day 10 (E10.0). To identify potential mechanisms responsible for this lethality, we performed an immunohistological analysis of EPCR distribution during mouse embryogenesis. EPCR was detected in the trophoblast giant cells at the feto-maternal boundary from E7.5 and at later time points in the trophoblasts of the placenta, suggesting a role in the haemostatic regulation of the maternal blood that irrigates these surfaces. In the embryo, EPCR was weakly detected in aortic endothelial cells from E13.5. Thereafter, EPCR levels increased in certain large blood vessel endothelial cells suggesting that the specificity of EPCR to large vessels is conferred in utero. However, not until postnatal day 7 did the intensity and distribution of EPCR staining mimic that observed in adult mice.

Abbreviations: APC – activated protein C, AP – alkaline phosphatase, EC – endothelial cell, EPCR – endothelial cell protein C/activated protein C receptor, FITC – fluorescein isothiocyanate, HRP – horseradish peroxidase, PBS – phosphate-buffered saline, TM – thrombomodulin, WT – wild–type
Inhibition of Human Osteoblast Growth by Unfractionated Heparin and by Low Molecular Weight Heparins in vitro
Authors: Kock H. J. , Handschin A. E.
Published: March 2018

Abbreviations: LMWHs: Low molecular weight heparins, UFH: Unfractionated heparin
The Diagnostic Value of Compression Ultrasonography in Patients with Suspected Recurrent Deep Vein Thrombosis
Authors: Lensing Anthonie , Bernardi Enrico , Villalta Sabina , Bagatella Paola , Girolami Antonio , Prandoni Paolo ,   for the DERECUS Investigators Group
Published: March 2018

Diagnosis of recurrent deep-vein thrombosis (DVT) is difficult because of limitations in distinguishing acute from old thrombi. In the past, an ultrasound method for diagnosis of recurrent ipsilateral DVT was developed, which relies on repeated measurements of the diameters of the common femoral and popliteal veins. To assess the safety of withholding anticoagulation from patients with improved or stable compression vein diameters, 205 consecutive patients presenting with suspected recurrent ipsilateral DVT were evaluated. The vein diameter was measured under compression with the transducer and compared with earlier ultrasound results. Patients with stable or improved ultrasound findings had repeat ultrasound assessments after 2 (± 1) and 7 (± 1) days. Patients with repeatedly normal ultrasound results were followed-up for six months to determine the incidence of symptomatic recurrent venous thromboembolism.

Of the 205 patients, 153 had stable or improved ultrasound findings. Repeat ultrasound assessment became abnormal in 3, and recurrence was confirmed by venography in all. A six months follow-up was done in the remaining 150 patients with repeatedly normal ultrasound tests and showed 2 (1.3%; 95% CI, 0.02 to 4.7%) confirmed non-fatal venous thromboembolic complications. The positive predictive value of a stable or improved ultrasound was 90% (95% CI, 77 to 97%).

In conclusion, it is safe to withhold anticoagulant treatment from patients with suspected recurrent ipsilateral DVT in whom compression ultrasonography showed improved or stable vein diameters.
The Structure of Synthetic Oligosaccharides in Relation to Factor IXa Inhibition
Authors: Hérault J. P. , Gaich C. , Bono F. , Driguez P. A. , Duchaussoy P. , Petitou M. , Herbert J. M.
Published: March 2018

We investigated the effect of various oligosaccharides (OS) on the inhibition of factor IXa by antithrombin (AT) in a purified system. The OS comprised the AT-binding pentasaccharide sequence prolonged by saccharide chains with various lengths and charges. We show that factor IXa inhibition depended on the molecular weight of the OS. Factor IXa was not inhibited by the AT-binding pentasaccharide alone, but was inhibited if it was prolonged by a sulphated dodecasaccharide at the non-reducing end. The overall charge was also important since factor IXa inhibition was negligible if the pentasaccharide was prolonged by a non-sulphated dodecasaccharide. Using compounds containing a non-sulphated spacer, we showed that the central part of the OS was not critical. This study therefore demonstrates that the minimal OS structure necessary for catalysing factor IXa inhibition by AT is close to that required for catalysing thrombin inhibition.
Reduced Factor V Concentration and Altered FV1/FV2 Ratio do not fully Explain R2-associated APC-resistance
Authors: Castoldi Elisabetta , Nicolaes Gerry , Tans Guido , Rosing Jan , Govers-Riemslag José
Published: March 2018

Carriership of the factor V (FV) R2 haplotype is associated with mild APC-resistance, moderately reduced FV levels and a relative increase of the more thrombogenic FV isoform, FV1. Since low FV levels and increased FV1 can theoretically cause APC-resistance, we investigated whether these alterations can quantitatively account for R2-associated APC-resistance. In order to determine the effect of FV concentration and FV isoform composition on the APC-response, we reconstituted FV-deficient plasma with purified FV1 and FV2 in different molar ratios and to varying FV concentrations. APC sensitivity ratios (APCsr) were determined with the Coatest® APCTM Resistance V, which probes the effect of APC on both FV-a and FVIIIa-inactivation, and with the Immunochrom® APC response test, which only quantifies the effect of APC on FVIII(a)-inactivation. In both assays, low FV concentrations and/or high relative amounts of FV1 rendered plasma samples more resistant to APC. APCsr were also determined in FVdeficient plasma reconstituted with purified FV at levels and isoform ratios observed in R2-homozygotes (98% FV, 42% FV1) and agematched controls (119% FV, 26% FV1). In both tests the APCsr of reconstituted control plasma was the same as that of plasma from controls, whereas reconstituted R2-plasma was less APC-resistant than plasma from homozygous carriers of the R2 haplotype. We conclude that the low FV levels and altered FV isoform ratio cannot fully explain R2-associated APC-resistance.
15-Deoxy-Δ12,14-Prostaglandin J2 Inhibits Tissue Factor Expression in Human Macrophages and Endothelial Cells: Evidence for ERK1/2 Signaling Pathway Blockade
Authors: Eligini S. , Banfi C. , Brambilla M. , Camera M. , Barbieri S. S. , Poma F. , Tremoli E. , Colli S.
Published: March 2018

Basic and clinical evidence has provided insight into the molecular events that link inflammation and coagulation. Increased expression of tissue factor (TF) by circulating and vascular cells has been indicated as responsible for the thrombotic complications associated with acute and chronic inflammation. TF is indeed inducible in circulating and vascular cells by cytokines and bacterial lipopolysaccharide (LPS) and its expression triggers the coagulation. The cyclopentenone prostaglandins are naturally occurring prostaglandin D2 (PGD2) derivatives that comprises prostaglandin J2 (PGJ2) and its metabolites Δ12-PGJ2 and 15-deoxyΔ12, 14-prostaglandin J2 (15d-PGJ2). These compounds, detected in vivo in a later phase of the inflammatory response, are characterized by anti-inflammatory activity and participate to the resolution of inflammation. We have here investigated the effect of 15d-PGJ2 on TF expression in human macrophages and endothelial cells (HUVEC). Our results indicate that 15d-PGJ2 down-regulates LPSand TNFα-induced TF activity, protein and mRNA through inhibition of TF gene transcription. The effect of 15d-PGJ2 is targeted to the NF-κB/I-κB pathway and to the mitogen activated protein kinase ERK1/2. A role of PPARγ activation in TF inhibition by 15d-PGJ2 was excluded. We conclude that 15d-PGJ2 negatively affects TF expression in macrophages and endothelial cells through a PPARγ-independent mechanism. This down-regulation may be crucial to limit excessive blood clotting activation in immuno-inflammatory diseases.
DX-9065a inhibition of factor Xa and the prothrombinase complex: mechanism of inhibition and comparison with therapeutic heparins
Authors: Rezaie Alireza
Published: March 2018

Factor Xa (fXa) is the key enzyme of the prothrombinase complex that generates thrombin hence it is a good target for antithrombotic therapy. Here, the anti-fXa and anti-prothrombinase activities of DX-9065a which is an active-site directed inhibitor of fXa, and therapeutic heparins which are dependent on antithrombin (AT) for their anticoagulant function, were studied in amidolytic and proteolytic activity assays. It was found that DX-9065a is a competitive inhibitor of the Spectrozyme FXa (SpFXa) cleavage by both fXa and prothrom-binase with similar Ki values of ~10-20 nM. However, DX-9065a acted as a non-competitive inhibitor of prothrombin activation by prothrombinase with a Ki of ~26 nM. On the other hand, therapeutic heparins were effective catalysts of both fXa and prothrombinase inhibition by AT in the presence of SpFXa, but were ineffective in the presence of prothrombin. Further studies revealed that Tyr99, a residue in the extended S2-S4 binding pocket of fXa, plays a key role in determination of specificity of the DX-9065a interaction.
Plasma membrane Ca2+-ATPase isoform 4b is phosphorylated on tyrosine 1176 in activated human platelets
Authors: Wan Tina , Zabe Martin , Dean William
Published: March 2018

Plasma membrane Ca2+-ATPase isoform 4b (PMCA4b) is phosphorylated on a tyrosine residue during platelet activation resulting in inhibition of its ATPase activity. We now report that tyrosine 1176 (Y1176) in the carboxyl (C-) terminal domain of PMCA4b is the phosphorylated residue. Two tyrosine residues located in the C-terminus of PMCA4b, Y1122 and Y1176 can be removed by calpain-dependent cleavage. This truncation removes all of the tyrosine phosphates added to PMCA during platelet activation. Sequence analysis indicates that Y1176 is a likely substrate for focal adhesion kinase (FAK), while Y1122 is not located in a tyrosine phosphorylation motif. This is the same residue we reported earlier to be phosphorylated by Src kinase in vitro. Thus we conclude that Y1176 is the only tyrosine phosphorylated during platelet activation. Results of co-immunoprecipitation, treatment with tyrosine kinase inhibitors and integrin inhibition experiments suggest that FAK is responsible for PMCA4b tyrosine phosphorylation during platelet activation.