bluuebunny/crossref_metadata_2025 huggingface dataset:
Two-dimensional graphitic C3N5 materials: promising metal-free catalysts and CO2 adsorbents
Authors: Huang Ling , Liu Zhiqiang , Chen Wei , Cao Dapeng , Zheng Anmin
Published: March 2018

This work describes the design of a new graphite-like carbon nitride material, g-C3N5, and found that g-C3N5 exhibits promising applications in metal-free ORR electrocatalysis, photocatalysis and CO2 capture.
Structural construction and photoluminescence tuning via energy transfer in apatite-type solid-state phosphors
Authors: Zhou Jun , Liu Quanlin , Xia Zhiguo
Published: March 2018

This review summarizes the structural discovery of new apatite-type phosphors and the photoluminescence tuning strategy involved.
The Relationship Between Speech, Language, and Phonological Awareness in Preschool-Age Children With Developmental Disabilities
Authors: Barton-Hulsey Andrea , Sevcik Rose A. , Romski MaryAnn
Published: March 2018

Purpose

A number of intrinsic factors, including expressive speech skills, have been suggested to place children with developmental disabilities at risk for limited development of reading skills. This study examines the relationship between these factors, speech ability, and children's phonological awareness skills.

Method

A nonexperimental study design was used to examine the relationship between intrinsic skills of speech, language, print, and letter–sound knowledge to phonological awareness in 42 children with developmental disabilities between the ages of 48 and 69 months. Hierarchical multiple regression was done to determine if speech ability accounted for a unique amount of variance in phonological awareness skill beyond what would be expected by developmental skills inclusive of receptive language and print and letter–sound knowledge.

Results

A range of skill in all areas of direct assessment was found. Children with limited speech were found to have emerging skills in print knowledge, letter–sound knowledge, and phonological awareness. Speech ability did not predict a significant amount of variance in phonological awareness beyond what would be expected by developmental skills of receptive language and print and letter–sound knowledge.

Conclusion

Children with limited speech ability were found to have receptive language and letter–sound knowledge that supported the development of phonological awareness skills. This study provides implications for practitioners and researchers concerning the factors related to early reading development in children with limited speech ability and developmental disabilities.
Performance analysis of wireless ad‐hoc network based on bidirectional full‐duplex and saturated state
Authors: Li Suoping , Sun Hongchun , Dou Zufang , Zhou Yongqiang
Published: March 2018

The transmission capacity (TC) of the wireless ad‐hoc network is one of the key properties to ensure the quality of network service. The main goal of this study is to explore the mobility of the network to establish a node mobile model with a saturated state and determine the TC and delay for the network based on the bidirectional full‐duplex (BFD) system. Considering the outage probability, packet arrival rate, and failure probability of packet attempting transmission, the node mobility models are established based on the node mobility and network self‐organization. In analysis, this study determines the mobile state, static state, communication state, and outage stat by defining the mobile rule and range of nodes, then the steady‐state probability of each state is obtained by calculating the state transition matrix. After optimising the existing saturated Markov model, the authors determine the network delay and TC based on the mobile nodes, contention window size, maximum number of given packet attempting retransmission, back‐off time and signal‐interference ratio (SIR) etc. The theoretical analysis and numerical simulation show that the TC of the bidirectional ad‐hoc network can be significantly improved by using space resources in two directions, and the introduction of the BFD system is indeed to reduce the network delay.
Exact and asymptotic ergodic capacity analysis of the hybrid satellite–terrestrial cooperative system over generalised fading channels
Authors: Zhao Yue , Chen Huifang , Xie Lei , Wang Kuang
Published: March 2018

In this study, the authors analyse the ergodic capacity of the downlink channel in a hybrid satellite–terrestrial cooperative system. The satellite link experiences shadowed Rician fading and the terrestrial link follows Rayleigh fading. Using the moment generating function‐based approach, they derived the formulae for the ergodic capacity with the amplify‐and‐forward protocol or the decode‐and‐forward protocol. Moreover, the asymptotic expression for the ergodic capacity at a high signal‐to‐noise ratio is derived, and the system multiplexing gain is also obtained. Using the asymptotic results, they propose a simple relay selection strategy, which only requires the knowledge of channel statistics. Monte Carlo simulations are provided to confirm the analytical results, and to illustrate the effect of different factors, in terms of the number of relays, channel conditions, and the cooperative protocol, on the ergodic capacity. Numerical results show that the analytical results are highly accurate in the single relay scenario and have low computational complexity in the multi‐relay scenario. In addition, the proposed relay selection strategy achieves low overhead in the price of a little performance degradation.
Alternative direction for 3D orthogonal frequency division multiplexing massive MIMO FDD channel estimation and feedback
Authors: Nasser Ahmed , Elsabrouty Maha , Muta Osamu
Published: March 2018

In this study, downlink channel estimation of three‐dimensional massive multiple‐input multiple‐output (3D‐MIMO) system operating in the frequency division duplexing (FDD) mode is considered. Inspired by the channel sparsity property, this study proposes a compressive sensing algorithm to exploit the channel sparsity structure in the angle–time domain. The proposed algorithm, named AMP‐ADM, combines the multiple approximate message passing (M‐AMP) algorithm with the alternative direction of multiplier (ADM) technique to efficiently exploit the sparsity structure of the 3D massive MIMO channel. First, the proposed AMP‐ADM is implemented in the case of the conventional estimation for the FDD protocol where the channel is estimated individually at each user equipment. Then, building on this algorithm, a low complexity feedback AMP‐ADM‐T scheme at the transmitting base station (BS) side is proposed. In the proposed feedback AMP‐ADM‐T technique the users' channels are jointly estimated at the BS to fully exploit the common sparsity basis. Complexity and convergence analyses are provided for both the AMP‐ADM and feedback AMP‐ADM‐T algorithms. Simulation results prove the improved performance of the proposed feedback AMP‐ADM‐T algorithm compared to different state‐of‐the‐art joint channel estimation techniques.
Mode division multiple access: a new scheme based on orbital angular momentum in millimetre wave communications for fifth generation
Authors: Wang Lei , Jiang Fa , Yuan Zhe , Yang Jie , Gui Guan , Sari Hikmet
Published: March 2018

Compared with the conventional degrees of freedom, the orbital angular momentum (OAM), which describes the helical phase structure of electromagnetic wave, provides a new degree of freedom. As a new multiple access scheme, mode division multiple access (MDMA) is constructed in millimetre wave frequency band utilising the orthogonality and high dimensionality in this study. Various traditional resources such as frequency, time and code pattern have been shared. Therefore, addresses of signals from different terminal users can be distinguished by OAM mode to realise multi‐address connection. In this study, the theoretical analysis of the number of terminals in MDMA scheme is carried out. According to the analysis results, infinite terminals can be connected together in the ideal case. Moreover, the simulation results show that compared with the conventional multi‐input multi‐output millimetre wave communication systems, the performance indicators of MDMA millimetre wave communication systems are improved remarkably.
Preference‐based unified criterion in virtual MIMO systems
Authors: Jia Boqi , Hu Honglin , Zeng Yu , Xu Tianheng , Yang Yang
Published: March 2018

Virtual multiple‐input multiple‐output (V‐MIMO) is an advanced technology in uplink systems, and a well‐designed user pairing and resource allocation scheme in V‐MIMO systems can effectively exploit multi‐user diversity to yield a significant performance gain. Recently, main attention has been devoted to the crucial user pairing issue with consideration of three key metrics, i.e. spectrum efficiency, energy efficiency and fairness. In this study, the authors investigate the unified tradeoff among all the three metrics for V‐MIMO systems with user pairing and resource allocation. They first formulate the three key metrics in a united form and derive a straightforward unified criterion based on the user‐specific preference to depict system performances. Through discussing several preference‐based cases, they observe that a portion of spectrum efficiency is considered redundantly. Thus, a modified unified criterion is proposed to remove the partial redundancy provided by spectrum efficiency contribution to the objective function. Based on the two unified criteria, they propose a user pairing scheme in flat fading channels and a joint user pairing and resource allocation scheme in frequency‐selective fading channels to balance the tradeoff flexibly. Simulation results show that, compared with existing schemes, the proposed scheme achieves a dynamical tradeoff among spectrum efficiency, energy efficiency and fairness.
Image seamless stitching and straightening based on the image block
Authors: Qu Zhong , Wang Tengfeng , An Shiquan , Liu Ling
Published: March 2018

Traditional image stitch methods based on feature point detection require long registration time for high resolution images. In the SIFT (scale invariant feature transform) algorithm, it builds difference‐of‐Gaussian by a linear Gauss expansion filter to obtain the feature. SIFT has poor real time. In this study, a novel image registration method based on image block is proposed to make a rough match for the blocked image and fine match in the most similar blocks by taking advantage of the FAST (features from accelerated segment test) algorithm which runs faster. This way can avoid spending a lot of time in the ineffective area, and enhance the precision and efficiency of the feature point. The accumulative error exists in the process of image stitching, so the image stitched by multiple images has wavelike effects, tilt, or distortion. The camera calibration method is utilised to eliminate the tilt and distortion of the image. The algorithm combining the optimal seam and multi‐resolution fusion is adopted to fuse the stitched image and realise seamless stitch of multiple images in order to achieve a seamless image of high resolution. Simulation experimental results show that the stitching method could realise seamless stitching and straightening of multiple images.
Synthesis of multi‐polarised upside conical frustum array antenna for 5G mm‐Wave base station at 28/38 GHz
Authors: Mahmoud Korany R. , Montaser Ahmed M.
Published: March 2018

In this study, a multi‐polarised millimetre‐wave (mm‐Wave) base station operating at 28/38 GHz is introduced for future fifth generation (5G) mobile communication networks. The proposed station employs 32‐element array antenna distributed in upside conical frustum configuration (UCFC) to synthesise multi‐beam patterns adopting directivity and polarisation control. First, the design of dual‐band circularly polarised antenna element at 28/38 GHz is discussed. The measured results show that the designed antenna element has a reflection coefficient less than −23 dB with a realised antenna gain of 8 dBi, on average, in the assigned frequency bands. Based on the designed antenna element, the antenna array performance is studied in terms of gain, radiation efficiency, reflection coefficient, and coverage efficiency. The results are compared with those obtained from 32‐element structured in an octagonal prism configuration (OPC). For antenna design parameters and multi‐beam pattern synthesis, a modified version of hybrid gravitational search algorithm and particle swarm optimisation is proposed. It is found that, the introduced UCFC outperformed the OPC by 19.8%. Moreover, distributing the antenna array in UCFC improved the convergence by 21.7% compared to OPC.
QCF for deep packet inspection
Authors: Al‐hisnawi Mohammad , Ahmadi Mahmood
Published: March 2018

Deep packet inspection (DPI) acts as a tool to control and classify incoming network traffic depending on users,content, applications and becomes a very important aspect of every network today. Instead of utilising only incoming packet header information, Internet service providers utilise DPI for security purposes, flow management, and routing. The high‐performance challenges that face DPI techniques to manage line‐speed packet processing with restricted available memory are the increasing traffic volumes and link rates. Bloom (BF) and quotient (QF) filters are effective randomised data structures for performing approximate membership queries. They have been employed in many networking applications including DPI. Nevertheless, they consume more calculations which degrade the system performance. Consequently, in this paper, the authors propose a new variant of membership query data structure, called quotient‐based Cuckoo filter (QCF), that reflects a merging process between QF and CF to minimise the calculation overhead and employing it in a DPI system. QCF employs only two hash functions and consumes less calculation overhead than BF, QF, and CF. The implementation results show that using QCF as an identification tool in a DPI system result in a time improvement up to 77% over CF and up to 98% over BF and QF.
Non‐linear behavioural modelling of device‐level transients for complex power electronic converter circuit hardware realisation on FPGA
Authors: Lin Ning , Shi Bo , Dinavahi Venkata
Published: March 2018

Detailed device‐level models of the insulated‐gate‐bipolar‐transistor (IGBT) and diode are essential for power converter design evaluation for providing insight into circuit and device behaviours, as well as to shorten the design cycle and reduce costs. In this study, the non‐linear behavioural models of IGBT and power diode are utilised for emulating the modular multilevel converter (MMC) on the field programmable gate array. For digital hardware‐in‐the‐loop (HIL) emulation, these time‐domain continuous models are discretised and linearised prior to being designed into the corresponding hardware modules using the hardware description language VHDL that features a fully paralleled and pipelined implementation. A circuit partitioning approach is adopted according to the MMC structure to enhance computation efficiency and then, detailed information from the system‐level performance to the specific features of individual switches is available. HIL emulation and the subsequent comparison with results from the commercial off‐line simulation tools prove that the complex IGBT and diode models can be involved in the efficient simulation of large‐scale power converters.
High-energy environment of super-Earth 55 Cancri e
Authors: Bourrier V. , Ehrenreich D. , Lecavelier des Etangs A. , Louden T. , Wheatley P. J. , Wyttenbach A. , Vidal-Madjar A. , Lavie B. , Pepe F. , Udry S.
Published: March 2018

The high-energy X-ray to ultraviolet (XUV) irradiation of close-in planets by their host star influences their evolution and might be responsible for the existence of a population of ultra-short period planets eroded to their bare core. In orbit around a bright, nearby G-type star, the super-Earth 55 Cnc e offers the possibility to address these issues through transit observations at UV wavelengths. We used the Hubble Space Telescope to observe the transit in the far-ultraviolet (FUV) over three epochs in April 2016, January 2017, and February 2017. Together, these observations cover nearly half of the orbital trajectory in between the two quadratures, and reveal significant short- and long-term variability in 55 Cnc chromospheric emission lines. In the last two epochs, we detected a larger flux in the C III, Si III, and Si IV lines after the planet passed the approaching quadrature, followed by a flux decrease in the Si IV doublet. In the second epoch these variations are contemporaneous with flux decreases in the Si II and C II doublets. All epochs show flux decreases in the N V doublet as well, albeit at different orbital phases. These flux decreases are consistent with absorption from optically thin clouds of gas, are mostly localized at low and redshifted radial velocities in the star rest frame, and occur preferentially before and during the planet transit. These three points make it unlikely that the variations are purely stellar in origin, yet we show that the occulting material is also unlikely to originate from the planet. We thus tentatively propose that the motion of 55 Cnc e at the fringes of the stellar corona leads to the formation of a cool coronal rain. The inhomogeneity and temporal evolution of the stellar corona would be responsible for the differences between the three visits. Additional variations are detected in the C II doublet in the first epoch and in the O I triplet in all epochs with a different behavior that points toward intrinsic stellar variability. Further observations at FUV wavelengths are required to disentangle definitively between star-planet interactions in the 55 Cnc system and the activity of the star.
The Impact of the Rock Mass Deformation on Geometric Changes of a Historical Chimney in the Salt Mine of Bochnia
Authors: Szafarczyk Anna , Gawałkiewicz Rafał
Published: March 2018

There are many ways of the geometry measurement of slim objects, with the application of geodetic and photogrammetric methods. A modern solution in the diagnostics of slim objects is the application of laser scanning, with the use of a scanner of a scanning total station. The point cloud, obtained from the surface of the scanned object gives the possibility of generating not only information on structural surface deformations, but also facilitates obtaining the data on the geometry of the axis of the building, as a basic indicator of the characteristics of its deformation. The cause of the change in the geometry of slim objects is the impact of many external and internal factors. These objects are located in the areas of working or closed underground mines. They can be impacted by the ground and they can face the results of the convergence of cavities. A specific structure of the salt rock mass causes subsequent convergence of the post-exploitation cavities, which has the influence on the behaviour of the terrain surface and the related objects. The authors analysed the impact of the changes in the rock mass and the surface on the changes of the industrial chimney in the Bochnia Salt Mine.
Classical Measurement Methods and Laser Scanning Usage in Shaft Hoist Assembly Inventory
Authors: Jaśkowski Wojciech , Lipecki Tomasz , Matwij Wojciech , Jabłoński Mateusz
Published: March 2018

The shaft hoist assembly is the base of underground mining plant. Its efficiency and correct operation is subject to restrictive legal regulations and is controlled on a daily visual assessment by shaft crew and energomechanics. In addition, in the regular interval, the shaft hoist assembly is subject to a thorough inventory, which includes the determination of the geometrical relationships between the hoisting machine, the headframe and the shaft with its housing. Inventory measurements for shaft and headframe are used for years of conventional geodetic methods including mechanical or laser plumbing and tachymetric surveys. Additional precision levelling is also used for measuring shafts of hoisting machines and rope pulleys. Continuous modernization of measuring technology makes it possible to implement the further methods to the above mentioned purposes. The comparison of the accuracy and the economics of performing measurements based on many years of experience with comprehensive inventory of shaft hoist assembly using various research techniques was made and detailed in the article.
Constructing Indicators for Measuring Provincial Sustainable Development Index in Vietnam
Authors: Truong Van Canh , Lisowski Andrzej
Published: March 2018

Sustainable development is zeitgeist of our age. It is one kind of development that in this trajectory humanity can create a stable and developed socio-economic foundations, conserve environment and therefore able to continue for a long time. Using indicators is one of the best ways to monitor and measure the progress toward sustainable development. In this paper we have proposed the way to create indicators for measuring provincial sustainable development index in Vietnam. We firstly made a framework of elements for economic, social and environmental component and compiled a list of indicators of 20 national and international agencies in the world. We then applied the SMART framework (Specific, Measurable, Achievable, Relevant, and Time-related) to choose indicators which will be relevant for Vietnam and put them back to the elements. We then have 39 relevant indicators with 12 indicators for economy, 17 indicators for social and 10 indicators for environmental component. Finally, we have established the way to determine the worst and best value for each indicator from available data for countries in the world.
Versorgungsplanung in der Rheumatologie: Eckpunkte aus dem 2016 aktualisierten Memorandum der Deutschen Gesellschaft für Rheumatologie zur Versorgungsqualität
Authors: Zink Angela , Schneider Matthias
Published: March 2018

Es wird eine Übersicht über die wichtigsten Ergebnisse und Forderungen des 2016 aktualisierten Memorandums der Deutschen Gesellschaft für Rheumatologie (DGRh) zur Versorgungsqualität in der Rheumatologie gegeben. Eine interdisziplinär zusammengesetzte Kommission hat angesichts der veränderten Therapiestrategien und -ziele sowie aktueller Versorgungsstrukturen und politischer Rahmenbedingungen eine Neubearbeitung vorgenommen. Wesentliches Ziel war die Ermittlung des Bedarfs an internistischen Rheumatologen in der ambulanten, akutstationären und rehabilitativen Versorgung. Das Memorandum geht davon aus, dass der internistische Rheumatologe der primär zuständige Facharzt ist für die Versorgung von Personen mit entzündlich-rheumatischen Systemerkrankungen ist. Je 100000 erwachsene Einwohner werden mindestens 2, unter Einrechnung von Teilzeitbeschäftigung und nicht versorgungsbezogenen Aufgaben eher drei, internistische Rheumatologen in der ambulanten Versorgung gebraucht, dies sind 1350 bis 2000 Rheumatologen. Ende 2015 standen 776 Rheumatologen für die ambulante Versorgung zur Verfügung. Die DGRh fordert daher eine eigene ambulante Bedarfsplanung für internistische Rheumatologen, um das Versorgungsdefizit abzubauen. Nach Ansicht der DGRh sollte die akutstationäre Versorgung in spezialisierten Akutkliniken und -abteilungen erfolgen, die eine hohe Behandlungsqualität sicherstellen. Dies erfordert bis zu 50 Betten je 1 Mio. Einwohner, wobei Fehlbelegungen in nicht rheumatologisch spezialisierten Kliniken abgebaut werden sollten. Je 30 Betten werden mindestens 2 hauptamtlich stationär tätige Rheumatologen und drei weitere ärztliche Mitarbeiter (einschließlich Weiterbildungsassistenten) benötigt. Im Bereich der Rehabilitation sind je 1 Mio. Einwohner 40 Betten oder ambulante Plätze mit jeweils 1 hauptamtlich tätigen Rheumatologen und 1 weiteren ärztlichen Mitarbeiter erforderlich. Das Memorandum führt aus, dass im Sinne partizipativer Entscheidungsfindung in allen Versorgungssegmenten die internistischen Rheumatologen mit den Betroffenen die Behandlungsziele gemeinsam festlegen. Eine Versorgung in einem interdisziplinären Netzwerk unter Einbindung anderer ärztlicher Fachrichtungen, nichtärztlicher Heilberufe sowie Patientenorganisationen wird angestrebt.
Rare Recurrence of Traumatic Carotid Cavernous Fistula after Parent Artery Occlusion—Report of Two Cases and Review of Literature
Authors: Kumar Savith , Malik Virender , Rajan Jayadevan , Kannath Santhosh
Published: March 2018

The authors present two cases of recurrence of traumatic carotid cavernous fistula (CCF) following complete exclusion by parent artery occlusion (PAO). In both cases, the fistula recurred through the development of indirect CCF and reconstitution of the occluded artery through the development of vasa vasorum or simple recanalization of the parent artery. The cavernous venous sac was patent in both cases. The patent cavernous sac along with the inflammatory or angiogenetic factors might have induced dural neovascularization leading to the development of indirect CCF. These factors along with ischemia of the arterial wall secondary to the steal phenomenon due to persistent shunt flow would have triggered the development of vasa vasorum. Thus the cavernous sac embolization may have to be considered in addition to PAO when PAO is planned as a therapeutic option for direct CCF.
Model of a Ternary Complex between Activated Factor VII, Tissue Factor and Factor IX
Authors: Chen Shu-wen , Schved Jean-François , Pellequer Jean-Luc , Giansily-Blaizot Muriel
Published: March 2018

Upon binding to tissue factor, FVIIa triggers coagulation by activating vitamin K-dependent zymogens, factor IX (FIX) and factor X (FX). To understand recognition mechanisms in the initiation step of the coagulation cascade, we present a three-dimensional model of the ternary complex between FVIIa:TF:FIX. This model was built using a full-space search algorithm in combination with computational graphics. With the known crystallographic complex FVIIa:TF kept fixed, the FIX docking was performed first with FIX Gla-EGF1 domains, followed by the FIX protease/EGF2 domains. Because the FIXa crystal structure lacks electron density for the Gla domain, we constructed a chimeric FIX molecule that contains the Gla-EGF1 domains of FVIIa and the EGF2-protease domains of FIXa. The FVIIa:TF:FIX complex has been extensively challenged against experimental data including site-directed mutagenesis, inhibitory peptide data, haemophilia B database mutations, inhibitor antibodies and a novel exosite binding inhibitor peptide. This FVIIa:TF:FIX complex provides a powerful tool to study the regulation of FVIIa production and presents new avenues for developing therapeutic inhibitory compounds of FVIIa:TF:substrate complex.
Two Different β3 Cysteine Substitutions Alter αIIbβ3 Maturation and Result in Glanzmann Thrombasthenia
Authors: Milet-Marsal S. , Breillat C. , Peyruchaud O. , Nurden P. , Combrié R. , Bourre F. , Nurden A.
Published: March 2018

We report the defects responsible for Glanzmann thrombasthenia in two patients showing traces of abnormally migrating platelet β3 in immunoblotting. Using PCR-SSCP and direct sequencing, we identified a novel homozygous mutation in exon 10 of the β3 gene of patient 1 which gave a C457 to Y amino acid substitution. A C542 to R substitution in β3 of patient 2 was previously reported by us. These cysteines are present in EGF-domains 1 and 3 respectively of β3. We therefore constructed mutants carrying substitutions on cysteine residues in each of the first three EGF domains of β3, C457, C495 and C542 respectively. Transient expression of these mutants in COS-7 cells, including the C542 and C547 double mutant, proved that disulfide disruption directly affects cell surface expression of the integrin. We then showed by metabolic (35S) labeling and Endo-H glycosidase treatment that these substitutions strongly affected complex maturation within the cell.
Studies on Reference Intervals for Platelet Counts in Three Cities in China and one in Japan
Authors: Ruan Changgeng , Wu Yun , Okada Tokuhiro , Motoi Shigemi , Kondo Tamiaki , Jiang Meiyi , Xin Xiaomin , Peng Liming , Ichihara Kiyoshi , Ikeda Yasuo
Published: March 2018

Hematological parameters including platelet counts, etc. were determined in 1,140 healthy subjects living in four cities: Suzhou (Jiangsu Province), Chengdu (Sichuan Province) and Harbin (Heilongjang Province) in China, and Kobe in Japan. Then, the reference intervals for platelet counts were calculated and compared. The reference interval for platelet count of subjects aged between 18 and 60 years was 60-259 × 109/L in Suzhou and 52–202 × 109/L in Chengdu, and subjects with platelet counts of 100 × 109/L or less accounted for about 30% of the subjects examined in these cities. The reference intervals in Harbin and Kobe were within the range of 150–350 × 109/L, and no subject having a platelets count of 100 × 109/L or less was detected. Mean platelet volume (MPV) determined concurrently was negatively correlated with platelet count, and the reference intervals for MPV in Chengdu and Suzhou were higher than those in Harbin and Kobe.
Antithrombin I. Inhibition of thrombin generation in plasma by fibrin formation
Authors: Mosesson Michael
Published: March 2018

Thrombin substrate binding is mediated through fibrinogen recognition “exosite 1” in thrombin, resulting in fibrinopeptide cleavage to form fibrin. In addition, thrombin exhibits “non-substrate” binding to fibrin, an activity termed “Antithrombin I”. Antithrombin I (AT-I) is characterized by two classes of throm-bin binding sites, the first of “low affinity” in the fibrin E domain, and the other of high affinity, that is situated between C-terminal residues 414 and 427 of a variant γ chain termed γ’ 1-427L. Plasma fibrinogen molecules containing γ ’ chains (“fibrino-gen 2”) are virtually all heterodimers containing one γA chain (platelet-binding) and one γ’ chain. The remaining fibrinogen (~ 85%) is homodimeric, lacks high affinity thrombin-binding potential, and is termed “fibrinogen 1” (γA/γA). Thrombin generation in recalcified fibrinogen-depleted or congenital afibrinogenemic plasma is increased. Repletion with fibrino-gen 1 has a modest effect in normalizing thrombin generation, whereas repletion with fibrinogen 2 (γA/γ’) has a more marked effect. A post-translational γ’ chain derivative, γ’ 1-423P, accounts for 3%-34% of the γ’ chain population, lacks thrombin binding potential, and arises by proteolytic processing at the expense of γ’ 1-427L chains. Little is known about its effect on plasma AT-I activity under normal or pathological circumstances. In summary, fibrin formation (Antithrombin I) inhibits throm-bin generation in clotting blood by sequestering thrombin, and “high-affinity” thrombin-binding (i.e., via γ’ chains) plays a dominant role in this process. AT-1 should be considered when assessing the pathogenesis of thromboembolic disease.
Inherited Macrothrombocytopenia with Distinctive Platelet Ultrastructural and Functional Features
Authors: Ranelletti Franco , Maggiano Nicola , Ciabattoni Giovanni , De Cristofaro Raimondo , Landolfi Raffaele , Rocca Bianca
Published: March 2018

We report a family with inherited macrothrombocytopenia and characteristic large membrane complexes in the platelets. Two affected subjects had platelet counts of 40 and 65X109/L respectively as assessed by contrast phase microscopy. Ultrastructural studies revealed giant spheroid platelets with characteristic large membrane complexes and/or giant vacuoles containing platelet organelles. Immunohistochemical studies of actin and tubulin showed a disorganization of the microtubule and actin systems. These abnormalities were absent in leukocytes, indicating a platelet-specific cytoskeleton disorder.

Platelet autoantibodies were repeatedly absent. Nevertheless, in the peripheral blood we observed several figures of platelet phagocytosis by macrophages and neutrophils. The in vitro aggregometric response of platelets to ADP, collagen, thrombin, ristocetin was present, but shape change was absent. The urinary excretion of thromboxane A2 metabolites of the affected subjects were approximately 2 standard deviations above control values, in spite of a reduced maximal biosynthetic capacity of thromboxane from giant platelets assessed in vitro during whole blood clotting.

This inherited platelet disorder shows structural and functional features which allow to distinguish it from other syndromes associated with giant platelets. We also propose to include ultrastructural and cytoskeletal studies in the diagnosis as well as in the classification of inherited giant platelet disorders.
A Comparison of INRs Determined with a Whole Blood Prothrombin Time Device and two International Reference Preparations for Thromboplastin
Authors: van den Besselar A. M. H. P.
Published: March 2018

Oral anticoagulant therapy is usually monitored with the prothrombin time (PT) on citrate plasma samples. In recent years instruments have been developed for measurement of the PT in non-citrated whole blood. In the present study, the manufacturer’s calibration of one type of device (CoaguChek®) in terms of the international normalized ratio (INR) was evaluated by one laboratory. Three subsequent lots of test strips for the CoaguChek were investigated using blood samples from 56 coumarin-treated patients. Citrated plasma samples from the same patients were analysed with two international reference preparations for thromboplastin (IRP), i. e., rTF/95 (recombinant human) and RBT/90 (rabbit brain). There were statistically significant INR differences between CoaguChek and the international reference preparations (p <0.001), but the mean relative deviation of the INR was not greater than 0.104. Clinically relevant criteria were used to assess the agreement between the CoaguChek and the IRP results. Standard agreement ranged from 82% to 95%. It is concluded that these test strips achieved a clinically acceptable level of accuracy. Further studies of patient management with these strips are justified.
Adenoviral Gene Transfer of a u-PA Receptor-binding Plasmin Inhibitor and Green Fluorescent Protein: Inhibition of Migration and Visualization of Expression
Authors: Lamfers M. L. M. , Wijnberg M. J. , Grimbergen J. M. , Huisman L. G. M. , Aalders M. C. , Cohen F. N. B. , Verheijen J. H. , van Hinsbergh V. W. M. , Quax P. H. A.
Published: March 2018

Smooth muscle cell migration plays a role in the development of intimal hyperplasia. Given the established role of the plasminogen activation system in cell migration, an approach to therapy is to overexpress an inhibitor of plasmin. Therefore, an adenoviral vector was constructed encoding the hybrid protein ATF.BPTI, which contains the active domain of bovine pancreas trypsin inhibitor (BPTI), fused to ATF, the amino terminal fragment or receptor-binding domain of u-PA. Adenoviral vectors expressing ATF and BPTI individually were also constructed, and a fourth vector was constructed encoding ATF.BPTI linked by an internal ribosomal entry site to Green Fluorescent Protein (ABIG). Both the expression and functionality of the recombinant proteins were established in human vascular smooth muscle cells. Adenoviral gene transfer of ATF.BPTI inhibited SMC migration more efficiently than the expression of ATF or BPTI individually. Expression of ABIG resulted in the co-expression of ATF.BPTI and Green Fluorescent Protein, thereby providing a tool to monitor transfection efficiency and the behavior of the transfected cells.
Desensitization of the Platelet Aggregation Response to ADP: Differential Down-regulation of the P2Y1 and P2cyc Receptors
Authors: Baurand Anthony , Eckly Anita , Bari Nadège , Léon Catherine , Hechler Béatrice , Cazenave Jean-Pierre , Gachet Christian
Published: March 2018

Platelets activated by ADP become refractory to restimulation, but the mechanism of this process is not well understood. A normal platelet response to ADP requires coactivation of the P2Y1 receptor responsible for shape change and the P2cyc receptor, responsible for completion and amplification of the response. The aim of the present study was to characterize the desensitization of platelets to ADP and to determine whether or not these two receptors are desensitized simultaneously through identical pathways when platelets become refractory to ADP. It was found that full inhibition of platelet aggregation in response to restimulation by ADP required the presence of ADP in the medium or use of a high concentration (1 mM) of its non-hydrolysable analogue ADP β S. Platelets incubated for 1 h at 37° C with 1 mM ADP β S and resuspended in Tyrode’s buffer containing apyrase displayed a stable refractory state characterized by the inability to aggregate or change shape in response to ADP. ADP β S treated platelets loaded with fura2/AM showed complete blockade of the calcium signal in response to ADP, whereas the capacity of ADP to inhibit PGE1 stimulated cAMP accumulation in these platelets was only diminished. Consequently, serotonin was able to promote ADP induced aggregation through activation of the Gq coupled 5HT2A receptor while adrenaline had no such effect. These results suggested that the refractory state of ADP β S treated platelets was entirely due to desensitization of the P2Y1 receptor, the P2cyc receptor remaining functional. Binding studies were performed to determine whether the P2Y1 and/or P2cyc binding sites were modified in refractory platelets. Using selective P2Y1 and P2cyc antagonists (A3P5P and AR-C66096 respectively), we could demonstrate that the decrease in [33P]2MeSADP binding sites on refractory platelets corresponded to disappearance of the P2Y1 sites with no change in the number of P2cyc sites, suggesting internalization of the P2Y1 receptor. This was confirmed by flow cytometric analysis of Jurkat cells expressing an epitope-tagged P2Y1 receptor, where ADP β S treatment resulted in complete loss of the receptor from the cell surface. We conclude that the P2Y1 and P2cyc receptors are differently regulated during platelet activation.
Binding of von Willebrand Factor to Collagen Type III: Role of Specific Amino Acids in the Collagen Binding Domain of vWF and Effects of Neighboring Domains
Authors: van der Plas R. , Gomes Lucio , Marquart J. , Vink Tom , Meijers Joost C. , de Groot Philip , Sixma Jan , Huizinga Eric
Published: March 2018

Binding of von Willebrand Factor (vWF) to sites of vascular injury is the first step of hemostasis. Collagen types I and III are important binding sites for vWF. We have previously determined the threedimensional structure of the collagen binding A3 domain of vWF (Huizinga et al., Structure 1997; 5: 1147). We hypothesized that the top face of this domain might be the collagen-binding site. Based on this hypothesis, we made seven vWF mutants (D934A/S936A, V1040A/ V1042A, D1046A, D1066A, D1069A, D1069R, and R1074A). Collagen binding of these mutants was investigated in ELISA and with Surface Plasmon Resonance (BIAcore). In addition, we studied collagen binding of mutants lacking the A2 or D4 domains, which flank the A3 domain.

In ELISA, all point mutants and deletion mutants bound to collagen in amounts similar to wild type (WT)-vWF. In the BIAcore we found that WT-vWF has an apparent KD for collagen of 1-7 nM on a subunit base. The apparent kinetic parameters of the point mutants and deletion mutants were not significantly different from WT-vWF, except for DA2-vWF, which had a lower KD, indicating that the A2 domain somehow modulates binding of vWF to collagen type III.

Based on our results, we conclude that the amino acid residues mutated by us are not critically involved in the interaction between vWF and collagen type III, which suggests that the collagen binding site is not located on the top face of the A3 domain.
Early Embryonic Expression of Murine Coagulation System Components
Authors: Ong Kelly , Horsfall Wendy , Conway Edward , Schuh Andre
Published: March 2018

The development of the embryonic coagulation system, and its contribution to the maintenance of vascular integrity during the formation of embryonic blood vessels, remain poorly understood. We have characterized the temporal expression patterns of 27 hemostasis-related genes during murine development. We show that, although most coagulation and fibrinolysis-related factors are expressed coordinately b 7.5 dpc, several, including FIX, FXII and PAI2, are not detectable until later developmental timepoints. The expression of hemostasis-specific genes prior to the formation of a functional circulatory system supports the view that some coagulation factors have additional non-hemostatic functions during development. In addition, the discordant expression of some factors suggests that the embryonic hemostatic system may be distinct from that of the adult. These analyses will help to elucidate the regulation of hemostasis during embryonic/vascular development, and will provide a framework to facilitate the interpretation of gene inactivation studies.
Regulation of Murine Protein C Gene Expression In Vivo: Effects of Tumor Necrosis Factor-α, Interleukin-1, and Transforming Growth Factor-β
Authors: Shimokawa Takayoshi , Kojima Tetsuhito , Loskutoff David , Saito Hidehiko , Yamamoto Koji
Published: March 2018

Protein C is a precursor of the anticoagulant serine protease, activated protein C, which inhibits coagulation factors Va and VIIIa. Although the liver appears to be the primary site of protein C synthesis, we previously demonstrated that the kidney and male reproductive organs also expressed abundant protein C mRNA in the mouse. In the present study, we further investigated the effects of tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), and transforming growth factor-β (TGF-β) on the expression of protein C mRNA in the principal producing organs, i.e., the liver, kidney, and testis. Both quantitative reverse transcription-PCR assay and in situ hybridization analysis revealed that TNF-α decreased protein C mRNA expression in the liver, kidney, and testis. IL-1 also down-regulated protein C mRNA expression in the liver and testis, but not in the kidney. In contrast, TGF-β unchanged the expression level of protein C mRNA in these three organs. These observations suggest that TNF-α and IL-1 may contribute to an increase in the procoagulant potential by down-regulation of protein C synthesis in the tissues during inflammatory processes.
Rapid Release of Matrix Metalloproteinase (MMP)-2 by Thrombin in the Rat Aorta: Modulation by Protein Tyrosine Kinase/Phosphatase
Authors: Fernandez-Patron Carlos , Zhang Yunlong , Radomski Marek , Hollenberg Morley , Davidge Sandra
Published: March 2018

Matrix metalloproteinase-2 (MMP-2, gelatinase A) and thrombin contribute to many long-term (patho)physiological processes requiring the proteolytic breakdown of the vascular extracellular matrix (e.g., normal tissue repair, remodeling, tumor invasion, atherosclerosis plaque rupture). Thrombin (10 to 1000 nM, 0.5 to 50 U/ml) induced a rapid secretion of MMP-2 from freshly isolated rat aortic tissue (detectable after 1 min of thrombin exposure). This secretion was mediated by an unidentified thrombin receptor, distinct from the proteinase activated receptors (PAR)-1 and -2. Protein tyrosine kinase/phosphatase activity differentially modulated the basal and the thrombin-induced release of MMP-2. The inhibitors of protein tyrosine kinase, herbymicin A, genistein, and tyrphostin 1288 (1 to 100 μM), enhanced the basal release of MMP-2 but did not affect the thrombin-induced secretion of MMP-2. The inhibitor of phosphotyrosine phosphatases, vanadate (100 μM), selectively inhibited the thrombin-induced, but not the basal, release of MMP-2. Rapid release of vascular MMP-2 by thrombin could contribute to short-term processes where thrombin is involved such as the regulation of platelet aggregation and vascular reactivity. Vascular tyrosine kinase/phosphatase likely modulates this action of thrombin to prevent exaggerated platelet aggregation, thrombosis, and vasospasm.
RPR120844, a Novel, Specific Inhibitor of Coagulation Factor Xa Inhibits Venous Thrombosis in the Rabbit
Authors: Bentley Ross , Morgan Suzanne , Brown Karen , Chu Valeria , Ewing Richard , Spada Alfred , Pauls Henry , Perrone Mark , Dunwiddie Christopher , Leadley Robert , Bostwick Jeffrey
Published: March 2018

The in vivo antithrombotic activity of RPR120844, a novel synthetic coagulation factor Xa (fXa) inhibitor (Ki = 7 nM), was assessed by its ability to inhibit thrombus formation in a damaged segment of the rabbit jugular vein. Intravenous dose-response studies were performed and thrombus mass (TM), activated partial thromboplastin time (APTT), prothrombin time (PT), inhibition of ex vivo fXa activity and plasma drug levels (PDL) were determined. TM, measured at the end of a 50 min infusion, was significantly reduced (p <0.05 vs saline-treated animals) by RPR120844 at 30 and 100 μg/kg/min. At doses of 10, 30 and 100 μg/kg/min, APTT was prolonged by 2.1, 4.2 and 6.1-fold, and PT was prolonged by 1.4, 2.2 and 3.5-fold, respectively. PDL were determined by measuring anti-fXa activity using an amidolytic assay. Peak PDL were 0.8 ± 0.3, 1.5 ± 0.9 and 2.4 ± 0.6 μM, respectively. The drug effect was reversible with APTT, PT and PDL returning toward pretreatment values 30 min after termination of treatment. The results suggest that RPR120844, or similar compounds, may provide an efficacious, yet easily reversible, means of inhibiting thrombus formation.
Antiplatelet Activity of Clopidogrel in Coronary Artery Bypass Graft Surgery Patients
Authors: Limet R. , David J. L.
Published: March 2018

Clopidogrel is a recently introduced platelet ADP receptor antagonist, belonging to the thienopyridine derivatives, like its analogue ticlopidine. Its potential advantage is to be safer than ticlopidine. At 75 mg/od clopidogrel significantly inhibits platelet aggregation in ambulatory patients with symptomatic atherosclerotic disease and it prevents the recurrence of ischemic events more efficiently than aspirin. Its adequate dose in more acute situations remained to be determined. Therefore, sixty two patients with coronary artery disease were randomly assigned in four groups treated, within 24 h after coronary artery bypass graft, by clopidogrel 50 mg/od, 75 mg/od or 100 mg/od or by ticlopidine 250 mg/bid which was considered as the reference. The tolerance of clopidogrel was fairly good during the whole period of the study. Bleeding time and ex-vivo platelet aggregation induced by ADP 2 μM and 5 μM were performed at day -1, +9 and +28 after surgery. Like ticlopidine, the three dose levels of clopidogrel significantly inhibited ex-vivo platelet activity and prolonged the bleeding time at day 28. However, unlike ticlopidine, the inhibitory effects of clopidogrel were not significant at day 9, especially with 75 mg/od, a dose which was found to significantly protect patients in a chronic situation. Hence, although the clinical outcome for patients included in this limited study was the same in the four groups, these results suggest that the dose regime of clopidogrel should be more extensively investigated during the early period following coronary artery bypass graft, facing an overproduction of young and hyperreactive platelets. By analogy, the dose regime should be also investigated in other situations with an acute risk of arterial thrombotic occlusion.