bluuebunny/crossref_metadata_2025 huggingface dataset:
Complex Faulting and Triggered Rupture During the 2018 MW7.9 Offshore Kodiak, Alaska, Earthquake
Authors: Ruppert N. A. , Rollins C. , Zhang A. , Meng L. , Holtkamp S. G. , West M. E. , Freymueller J. T.
Published: July 2018

We combine aftershock relocations, source mechanisms, teleseismicPwave backprojection, and Global Positioning System data inversion to constrain complex faulting geometry of the 2018 MW7.9 offshore Kodiak earthquake. Relocated aftershocks delineate several N‐S trends including a prominent 110‐km‐long segment, as well as broad NE‐SW trends. Global Positioning System modeling and backprojection indicate that the NE‐SW trending left‐lateral strike‐slip segments released most energy dominating far‐field crustal deformation and radiated wavefield. Backprojection infers fast E‐to‐W rupture propagations superimposed on a slower S‐to‐N migration. We propose a five‐segment model of the rupture that was partially driven by dynamic triggering.
The Gauging and Modeling of Rivers in the Sky
Authors: Lavers David A. , Rodwell Mark J. , Richardson David S. , Ralph F. Martin , Doyle James D. , Reynolds Carolyn A. , Tallapragada Vijay , Pappenberger Florian
Published: July 2018

Atmospheric rivers (ARs) are responsible for most of the horizontal water vapor flux outside of the tropics and can cause extreme precipitation and affect the atmospheric dynamics and predictability. For their impacts to be skillfully predicted, it is essential for weather forecasting systems to accurately represent AR characteristics. Using the European Centre for Medium‐Range Weather Forecasts Integrated Forecasting System and dropsonde observations from the 2018 AR Reconnaissance field campaign over the Northeast Pacific Ocean, it is shown that the AR structure is modeled well but that short‐range water vapor flux forecasts have a root‐mean‐square error of 60.0 kgm−1 s−1 (21.9% of mean observed flux). These errors are most related to uncertainties in the winds near the top of the planetary boundary layer. The findings identify a potential barrier in the prediction of high‐impact weather and suggest an area where research should be focused to improve atmospheric forecast systems.
Transcutaneous vagus nerve stimulation and extinction of prepared fear: A conceptual non-replication
Authors: Burger Andreas M. , Van Diest Ilse , van der Does Willem , Hysaj Marsida , Thayer Julian F. , Brosschot Jos F. , Verkuil Bart
Published: July 2018

Transcutaneous stimulation of the auricular branch of the vagus nerve (tVNS) may accelerate fear extinction in healthy humans. Here, we aimed to investigate this hypothesis in healthy young participants in a prepared learning paradigm, using spider pictures as conditioned stimuli. After a fear conditioning phase, participants were randomly allocated to receive tVNS (final N = 42) or sham stimulation (final N = 43) during an extinction phase. Conditioned fear was assessed using US expectancy ratings, skin conductance and fear potentiated startle responses. After successful fear acquisition, participants in both groups showed a reduction of fear over the course of the extinction phase. There were no between-group differences in extinction rates for physiological indices of fear. Contrary to previous findings, participants in the tVNS condition also did not show accelerated declarative extinction learning. Participants in the tVNS condition did have lower initial US expectancy ratings for the CS− trials than those who received sham stimulation, which may indicate an enhanced processing of safety cues due to tVNS. In conclusion, the expected accelerated extinction due to tVNS was not observed. The results from this study call for more research on the optimal tVNS stimulation intensity settings.
Wave propagation in tunable lightweight tensegrity metastructure
Authors: Wang Y. T. , Liu X. N. , Zhu R. , Hu G. K.
Published: July 2018

Lightweight metastructures are designed consisting of prismatic tensegrity building blocks which have excellent strength-to-weight ratio and also enable unique compression-torsion coupling. A theoretical model with a coupled axial-torsional stiffness is first developed to study the band structures of the proposed lightweight metastructures. Then, various unit cell designs are investigated for bandgap generations at desired frequency ranges. Broadband full-wave attenuation is found in the tensegrity metastructure with special opposite-chirality. Furthermore, tunable stiffness in the prismatic tensegrity structure is investigated and ‘small-on-large’ tunability is achieved in the metastructure by harnessing the geometrically nonlinear deformation through an external control torque. Prestress adjustment is also investigated for fine tuning of the band structure. Finally, frequency response tests on the finite metastructures are preformed to validate their wave attenuation ability as well as their wave propagation tunability. The proposed tensegrity metastructures could be very useful in various engineering applications where lightweight and tunable structures with broadband vibration suspension and wave attenuation ability are in high demand.
Identification of a 57S translation complex containing closed-loop factors and the 60S ribosome subunit
Authors: Denis Clyde L. , Laue Thomas M. , Wang Xin
Published: July 2018

In eukaryotic translation the 60S ribosome subunit has not been proposed to interact with mRNA or closed-loop factors eIF4E, eIF4G, and PAB1. Using analytical ultracentrifugation with fluorescent detection system, we have identified a 57S translation complex that contains the 60S ribosome, mRNA, and the closed-loop factors. Previously published data by others also indicate the presence of a 50S-60S translation complex containing these same components. We have found that the abundance of this complex increased upon translational cessation, implying formation after ribosomal dissociation. Stoichiometric analyses of the abundances of the closed-loop components in the 57S complex indicate this complex is most similar to polysomal and monosomal translation complexes at the end of translation rather than at the beginning or middle of translation. In contrast, a 39S complex containing the 40S ribosome bound to mRNA and closed-loop factors was also identified with stoichiometries most similar to polysomal complexes engaged in translation, suggesting that the 39S complex is the previously studied 48S translation initiation complex. These results indicate that the 60S ribosome can associate with the closed-loop mRNA structure and plays a previously undetected role in the translation process.
Probing the speciation of quaternary ammonium polybromides by voltammetric tribromide titration
Authors: Kim Hyeonjeong , Jung Dayoung , Hwang Jiseon , Chae Junghyun , Chang Jinho
Published: July 2018

The speciation of quaternary ammonium polybromides (QBr2n+1) was quantitatively determined by voltammetric tribromide titration on a Pt ultramicroelectrode (UME).
Chalcogen atom modulated persistent room-temperature phosphorescence through intramolecular electronic coupling
Authors: Xu Letian , Li Guoping , Xu Tao , Zhang Weidong , Zhang Sikun , Yin Shiwei , An Zhongfu , He Gang
Published: July 2018

A series of novel persistent room-temperature phosphorescence (pRTP) materials (PEPCz) obtainedviaa combination of chalcogen atoms (O, S, Se, and Te) and a carbazolyl moiety is reported.
On the exfoliation and anisotropic thermal expansion of black phosphorus
Authors: Sansone Giuseppe , Karttunen Antti J. , Usvyat Denis , Schütz Martin , Brandenburg Jan Gerit , Maschio Lorenzo
Published: July 2018

Strong anisotropic thermal expansion of solid black phosphorus is predicted by means of accurate dispersion-corrected density functional theory calculations.
A triple-amplification strategy for sensitive detection of telomerase at the single-cell level
Authors: Li Chen-chen , Zhang Yan , Liu Wen-jing , Zhang Chun-yang
Published: July 2018

We develop a triple-amplification strategy for sensitive detection of telomerase from cancer cells at the single-cell level.
Spontaneous curling of freestanding Janus monolayer transition-metal dichalcogenides
Authors: Xiong Qi-lin , Zhou Jianli , Zhang Jin , Kitamura Takayuki , Li Zhen-huan
Published: July 2018

In this paper, using molecular dynamics simulations we report spontaneous curling behaviors of freestanding Janus monolayer S–Mo–Se (MoSeS) structures.
Molecular clustering and percolation characteristics near the glass transition in aqueous trehalose and choline dihydrogen phosphate solutions
Authors: Nikulsin Nikita , Azhagiya Singam E. R. , Elliott Gloria , Jacobs Donald
Published: July 2018

Spatial and temporal characteristics of molecular structure in ternary solutions of trehalose and choline dihydrogen phosphate (CDHP) are studied using molecular dynamics simulations at 300 K for a range of solute concentrations with a 2 : 1 stoichiometric ratio of trehalose to CDHP.
Iron/NPK agrochemical formulation from superabsorbent nanocomposite based on maize bran and montmorillonite with functions of water uptake and slow-release fertilizer
Authors: Gharekhani Hamed , Olad Ali , Hosseinzadeh Farshad
Published: July 2018

Slow-release character of hydrogel nanocomposite makes it efficient in amending Fe nutritional disorder, fertilizer loss, and crops growth and yield.
Two novel pyrazole-based chemosensors: “naked-eye” colorimetric recognition of Ni2+ and Al3+ in alcohol and aqueous DMF media
Authors: Yang Geng , Meng Xia , Fang Shimin , Wang Lizhen , Wang Zhenzheng , Wang Fanwei , Duan Hongdong , Hao Aiyou
Published: July 2018

Sensors Pry-Flu and Pry-R6G were found to have a wide pH range (4–12), good anti-jamming ability and can be reused. And the sensors Pry-Rhy and Pyr-R6G could be quite useful for the fabrication of sensing devices with fast and convenient detection of Ni2+ and Al3+.
Evaluation of an Explicit Intervention to Teach Novel Grammatical Forms to Children With Developmental Language Disorder
Authors: Finestack Lizbeth H.
Published: July 2018

Purpose

Unlike traditional implicit approaches used to improve grammatical forms used by children with developmental language disorder, explicit instruction aims to make the learner consciously aware of the underlying language pattern. In this study, we compared the efficacy of an explicit approach to an implicit approach when teaching 3 novel grammatical forms varying in linguistic complexity.

Method

The study included twenty-five 5- to 8-year-old children with developmental language disorder, 13 of whom were randomized to receive an implicit-only (I-O) intervention whereas the remaining 12 participants were randomized to receive a combined explicit–implicit (E-I) intervention to learn 3 novel grammatical forms. On average, participants completed 4.5 teaching sessions for each form across 9 days. Acquisition was assessed during each teaching session. Approximately 9 days posttreatment for each form, participants completed probes to assess maintenance and generalization.

Results

Analyses revealed a meaningful and statistically significant learning advantage for the E-I group on acquisition, maintenance, and generalization measures when performance was collapsed across the 3 novel targets (
p
< .02, Φs > 0.60). Significant differences between the groups, with the E-I group outperforming the I-O group, only emerged for 1 of the 3 target forms. However, all effect sizes ranged from medium to large (Φs = 0.25–0.76), and relative risk calculations all exceeded 0, indicating a greater likelihood of learning the target form with E-I instruction than I-O instruction.

Conclusions

Study findings indicate that, as compared to implicit instruction, children are more likely to acquire, maintain, and generalize novel grammatical forms when taught with explicit instruction. Further research is needed to evaluate the use of explicit instruction when teaching true grammatical forms to children with language impairment.
Tri‐band dual‐polarised omnidirectional antenna with high isolation for unmanned aerial vehicle applications
Authors: Gong Qing , Li Rong Lin , Cui Yuehui
Published: July 2018

A new tri‐band dual‐polarised omnidirectional antenna is proposed. The dual‐polarised antenna consists of a metal cuboid body with a vertical slot for horizontal polarisation (HP) and a rectangular back metal cavity with two folded horizontal slots for vertical polarisation (VP). A metal HP feedline is employed to coupling feed the vertical slot while a metal VP feedline is used to excite the two horizontal slots. Due to the coupling feed and the orthogonality between the vertical and horizontal slots, the dual‐polarised antenna features three bands and a high isolation. Experimental results show that the tri‐band dual‐polarised antenna covers the Chinese Unmanned Aircraft System bands (840.5–845, 1430–1444 and 2408–2440 MHz) with reflection coefficients <−10 dB and isolation >32 dB. Good omnidirectional radiation patterns are observed for both HP and VP.
Design and implementation of a new architecture of a real‐time reconfigurable digital modulator on FPGA
Authors: Andre W. , Couillard O.
Published: July 2018

One of the prerequisites of electronic warfare (EW) is to have the means to provide secure point‐to‐point wireless data and voice communications with other ground stations. New technologies are giving rise to bigger information security threats. This situation illustrates the best the urgency of reducing the development time of EW systems. Previous works suggest that digital systems are the best candidates for this purpose and therefore form the backbone of modern EW. As a result, digital modulation techniques are widely used in modern wireless communication systems. This is largely due to their high resistance to noise and their high transmission capacity that can be achieved through data multiplexing. In this Letter, a new reconfigurable architecture of a phase shift keying (PSK) modulator is described and implemented on FPGA. The latter can be configured in real time to produce the following modulation schemes: QPSK, 8‐PSK, and 16‐PSK without having to regenerate the FPGA configuration bits. This action can be done by software via programming or manually using a DIP switch. The proposed design is implemented on the Xilinx xc7k325tfbg900 FPGA using the Genesis 2 development board. The experimental results are in agreement with the simulations.
Light variations due to the line-driven wind instability and wind blanketing in O stars
Authors: Krtička J. , Feldmeier A.
Published: July 2018

A small fraction of the radiative flux emitted by hot stars is absorbed by their winds and redistributed towards longer wavelengths. This effect, which leads also to the heating of the stellar photosphere, is termed wind blanketing. For stars with variable winds, the effect of wind blanketing may lead to the photometric variability. We have studied the consequences of line driven wind instability and wind blanketing for the light variability of O stars. We combined the results of wind hydrodynamic simulations and of global wind models to predict the light variability of hot stars due to the wind blanketing and instability. The wind instability causes stochastic light variability with amplitude of the order of tens of millimagnitudes and a typical timescale of the order of hours for spatially coherent wind structure. The amplitude is of the order of millimagnitudes when assuming that the wind consists of large number of independent concentric cones. The variability with such amplitude is observable using present space borne photometers. We show that the simulated light curve is similar to the light curves of O stars obtained using BRITE and CoRoT satellites.
SPOTS: The Search for Planets Orbiting Two Stars
Authors: Asensio-Torres R. , Janson M. , Bonavita M. , Desidera S. , Thalmann C. , Kuzuhara M. , Henning Th. , Marzari F. , Meyer M. R. , Calissendorff P. , Uyama T.
Published: July 2018

Binary stars constitute a large percentage of the stellar population, yet relatively little is known about the planetary systems orbiting them. Most constraints on circumbinary planets (CBPs) so far come from transit observations with the Kepler telescope, which is sensitive to close-in exoplanets but does not constrain planets on wider orbits. However, with continuous developments in high-contrast imaging techniques, this population can now be addressed through direct imaging. We present the full survey results of the Search for Planets Orbiting Two Stars (SPOTS) survey, which is the first direct imaging survey targeting CBPs. The SPOTS observational program comprises 62 tight binaries that are young and nearby, and thus suitable for direct imaging studies, with VLT/NaCo and VLT/SPHERE. Results from SPOTS include the resolved circumbinary disk around AK Sco, the discovery of a low-mass stellar companion in a triple packed system, the relative astrometry of up to 9 resolved binaries, and possible indications of non-background planetary-mass candidates around HIP 77911. We did not find any CBP within 300 AU, which implies a frequency upper limit on CBPs (1–15 MJup) of 6–10% between 30–300 AU. Coupling these observations with an archival dataset for a total of 163 stellar pairs, we find a best-fit CBP frequency of 1.9% (2–15 MJup) between 1 and 300 AU with a 10.5% upper limit at a 95% confidence level. This result is consistent with the distribution of companions around single stars.
Percutaneous Treatment Options of Lower Urinary Tract Fistulas and Leakages
Authors: Kuetting Daniel , Pieper Claus
Published: July 2018

Background Lower urinary tract fistulas are currently a rather rare, but severe condition associated with considerable morbidity. Treatment is challenging, especially in fistulas caused by pelvic malignancy or radiation therapy. Surgical treatment attempts fail in a considerable number of patients, especially in those with pelvic malignancies/prior radiation therapy or are precluded altogether due to severe comorbidity. For such patients percutaneous approaches can provide alternative treatment.

Method This review is based on case studies and case reports dealing with percutaneous treatment options of lower urinary tract fistulas and leakages from the past four decades (1979 – 2017). The included techniques were ureteral fulguration, tissue adhesive-based embolization, non-detachable and detachable balloon occlusion, ureteral coiling, ureteral clipping, silicone or nylon plug as well as modified vascular plug embolization.

Results and Conclusion Percutaneous treatment options of lower urinary tract fistulas and leakages allow for either permanent or temporary, instant ureteral occlusion. In general, transrenal ureteral occlusion is a safe and reliable alternative to surgical treatment of ureteral fistulas and leakages. So far, no technique has been proven to be superior to the others. Depending on the underlying disease, the optimal percutaneous technique may vary and should be chosen according to the individual needs of the patients.

Key Points 

Citation Format
The “Sparti” splint for rehabilitation of extensor tendon injuries in zones V-VII
Authors: Mouzopoulos George , Vlachos Christos , Ampadiotaki Margarita , Tsembeli Anastasia
Published: July 2018

Dynamic splinting is a well-known method for maintaining finger movement after ruptures of the extensor tendons. We describe a simple, inexpensive and
easy-to-construct modification of a dynamic splint, called the “Sparti” splint, suitable for a six-week period of rehabilitation of injured extensor tendons in
zones V-VII.
Interrater-Reliabilität bei der Beurteilung von Skaphoidfrakturen in CT-Aufnahmen des Skaphoids in der Ebene des Handgelenkes vs. in der
Ebene der langen Achse des Skaphoids
Authors: Wieschollek Stefanie , Kalb Karl-Heinz , Christopoulos Georgios , Geue Roland , Schmitt Rainer , Prommersberger Karl-Josef
Published: July 2018

Hintergrund Das Skaphoid gilt aufgrund seiner besonderen Form, Größe und Lage im Karpus als der Grundpfeiler der Handwurzel mit einer außerordentlich
wichtigen Funktion für die Biomechanik. Bei Frakturen kommt daher der genauen Evaluation der Frakturmorphologie eine hohe Bedeutung zu. Diesbezüglich gelten
Computertomografie -(CT)-Aufnahmen in der langen Achse des Skaphoids bereits seit längerem als Standard unter Experten, jedoch hat sich die Methode noch nicht
als flächendeckender Standard durchgesetzt, und eine ausreichende Studienlage bezüglich der Überlegenheit dieser Aufnahmetechnik fehlt.

Ziel Ziel dieser retrospektiven Studie war es zu prüfen, ob die Übereinstimmungsrate bei der Beurteilung von Skaphoidfrakturen bezüglich der Morphologie
zwischen den Beurteilern bei CT-Aufnahmen in der langen Achse des Skaphoids höher ist als bei CT-Aufnahmen in der Ebene des Handgelenkes und somit als
aussagekräftiger gewertet warden kann.

Methode Zwischen 01/2014 und 04/2016 wurde bei 42 Patienten mit frischer Kahnbeinfraktur ein CT in der langen Achse des Skaphoids durchgeführt. Aus diesen
CT-Aufnahmen wurden Rekonstruktionen in der Handgelenksebene angefertigt. Die Bilder dieser 84 Fälle wurden anonymisiert und randomisiert. Sie wurden 4
Beurteilern vorgelegt (2 Handchirurgen, 2 Radiologen). Diese wurden gebeten die Bilder zu beurteilen bezüglich: Lokalisation der Fraktur, Humpback, seitlichem
Versatz und Herbert-Klassifikation. Die Chirurgen sollten zusätzlich entscheiden, ob sie einen palmaren oder dorsalen Zugang sowie eine offene oder perkutane
Technik wählen würden. Die statistische Auswertung erfolgte durch eine unabhängige Statistikerin zwischen 2 und 4 Beurteilern.

Ergebnisse In allen evaluierten Parametern fand sich eine höhere Übereinstimmungsrate der Beurteiler im CT entlang der langen Achse des Skaphoids, wobei
sich jedoch nur für die Humpback-Deformität eine Signifikanz nachweisen ließ.

Schlussfolgerung Zur Evaluation und Beurteilung von Skaphoidfrakturen sind CT-Aufnahmen entlang der langen Skaphoidachse reliabler als CT-Aufnahmen in der
Handgelenksebene und daher zu bevorzugen.
The Erythrina Protease Inhibitor: Interactions with Tissue Plasminogen Activator
Authors: Heussen-Schemmer Christa , Merrifield Edwin H , Dowdle Eugene B D
Published: July 2018

The Kunitz-type trypsin and tissue plasminogen activator (t-PA)-inhibitor from Erythrina caffra seeds was cleaved by trypsin at low pH to yield a disulphide linked two-chain molecule with reduced hydrophobicity. This change was used to separate cleaved from native inhibitor by phenyl-Sepharose chromatography. The inhibitor was not cleaved by t-PA. Trypsin, but not t-PA, catalysed resynthesis of the cleaved bond.

Although the cleaved protein retained inhibitory activity for both trypsin and t-PA, 6-10 times higher concentrations were required for equivalent inhibition.

Removal of the active site arginine (Arg63) from the cleaved inhibitor by digestion with carboxypeptidase B resulted in a further loss of inhibitory activity towards both proteases. The activity of the inhibitor could also be decreased by modification of one susceptible arginine residue with peptidyl arginine deiminase. These results suggest that the trypsin-reactive site of the Erythrina inhibitor is also involved in the interaction between the inhibitor and t-PA.
Extrinsic Activation of Human Coagulation Factors IX and X on the Endothelial Surface
Authors: Bom Victor J J , van Hinsbergh Victor W M , Reinalda-Poot Hanneke H , Mohanlal Ramon W , Bertina Rogier M
Published: July 2018

In previous kinetic studies, the catalytic efficiency of the activation of human coagulation factors IX and X by factor VIIa in the presence of purified tissue factor apoprotein was found to be essentially equal. These activation reactions were now studied on the surface of human umbilical vein endothelial cells. The cells were stimulated with endotoxin to express tissue factor. This tissue factor activity was saturable with factor VIIa and could be inhibited by rabbit antibodies against human tissue factor apoprotein. Only stimulated cells supported factor VIIa activity. No difference in the reactivity of factor VII and VIIa was observed in the presence of factor X, due to rapid feedback activation of factor VII by factor Xa. However, the activation of factor IX by factor VII shows a 10 min lag-phase, which reflects that the activation of factor VII by factor IXa is a less efficient process. The kinetic parameters for the factor VIIa dependent activation of factor IX and factor X on the endothelial surface were: Km 0.09 εM, Vmax 0.13 pmol/min, and Km 0.071 εM, Vmax 0.41 pmol/min, respectively. The same ratio between the Vmax for factor X and factor IX activation was observed as in a cell free system. However, the Km of factor IX was 4-fold higher on the endothelial surface than in the cell free system. Together, these kinetic parameters will favour factor X activation 5-fold over factor IX activation at physiological concentrations of these proteins.

The activation of factor X by factor VIIa on the endothelial surface was characterized by a short lag-phase, which was absent in factor IX activation. Further, both the activation of factor X and factor IX were down regulated by factor Xa.
Coagulation and Fibrinolytic Activity in Behçet's Disease
Authors: Hampton K K , Chamberlain M A , Menon D K , Davies J A
Published: July 2018

Coagulation and fibrinolytic activities were studied in 18 subjects with Behçet's disease and compared with results from 14 matched control patients suffering from sero-negative arthritis. Significantly higher plasma concentrations (median and range) were found in Behçet's patients for the following variables: fibrinogen 3.7 (1.7-6.9) vs 3.0 (2.0-5.1) g/1, p <0.05; von Willebrand factor antigen, 115 (72-344) vs 74 (60-119)%, p <0.002; plasminogen activator activity (106/ECLT2) 219 (94-329) vs 137 (78-197) units, p <0.002; tissue plasminogen activator inhibitor (t-PA-I) activity, 9.1 (5.5-19.3) vs 5.1 (1.8-12.0) IU/ml, p <0.002; and PAI-1 antigen, 13.9 (4.5-20.9) vs 6.4 (2.4-11.1) ng/ml, p <0.002. Protein C antigen was significantly lower: 97 (70-183) vs 126 (96-220)%, p <0.02. No differences were observed in antithrombin III activity or antigen, factor VIII coagulant activity, fibrinopeptides A and Bβ15-42, plasminogen, α-2-antiplasmin, functional and immunological tissue-plasminogen activator, thrombin-antithrombin complexes and D-dimer. Levels of tissue plasminogen activator inhibitor (activity and antigen) correlated with disease activity while fibrinogen and von Willebrand factor concentrations did not. Seven of the 18 subjects with Behçet's disease had suffered thrombotic events but it was not possible to distinguish these from the 11 patients without thrombosis using the assays performed. The results suggest the abnormal fibrinolytic activity in Behçet's disease is due to increased inhibition of tissue plasminogen activator. No abnormality of coagulation or fibrinolytic activity specific to Behçet's disease was detected.
Limited Proteolysis of Vitronectin by Plasmin Destroys Heparin Binding Activity
Authors: Sane David C , Moser Tammy L , Greenberg Charles S
Published: July 2018

Vitronectin (VN) stabilizes plasminogen activator inhibitor type 1 (PAI-1) activity and prevents the fibrin(ogen)-induced acceleration of plasminogen activation by t-PA. These antifibrinolytic activities as well as other functions are mediated by the glycosaminoglycan (GAG) binding domain of VN. Since the GAG binding region is rich in arginyl and lysyl residues, it is a potential target for enzymes such as plasmin. In this paper, the dose and time-dependent proteolysis of VN by plasmin is demonstrated. The addition of urokinase or streptokinase (200 units/ml) to plasma also produced proteolysis of VN. With minimal proteolysis, the 75 kDa band was degraded to a 62-65 kDa form of VN. This minimal proteolysis destroyed the binding of [3H]-heparin to VN and reversed the neutralization of heparin by VN.

Thus, the plasmin-mediated proteolysis of the GAG binding activity of VN could destroy the antifibrinolytic activity of VN during physiologic conditions and during thrombolytic therapy. Furthermore, other functions of VN in complement and coagulation systems that are mediated by the GAG binding domain may be destroyed by plasmin proteolysis.
Loss of Thrombin-Induced Ca2+ Mobilization in a Subpopulation of Platelets during Storage
Authors: Fijnheer Rob , Homburg Christa H E , Hooibrink Berend , Boomgaard Martine N , de Korte Dirk , Roos Dirk
Published: July 2018

Thrombin-induced changes in cytosolic free Ca2+ ([Ca2+]i) were studied in human platelets that had been stored for up to 6 days. Changes in [Ca2+]i were measured with Indo-1-loaded platelets and quantitated with two different methods: (i) measurement of the changes in total fluorescence; (ii) measurement of the [Ca2+]i changes in individual platelets in a flow cytometer, allowing the detection of non-responding platelets. The maximal concentration of [Ca2+]i after stimulation with 0.5 U of thrombin/ml decreased from 544 ± 58 nM (mean ± SEM, n = 6) on day 0, to 276 ± 9 nM on day 3 and to 203 ± 23 nM on day 6. The percentage of platelets responding to 0.5 U of thrombin/ml declined from 90 ± 2% on day 0 to 72 ± 4% on day 3, and to 47 ± 8% on day 6. Nevertheless, also the responding platelets showed a decreased rise in [Ca2+]i.

The study shows that during platelet storage a decrease in the rise in [Ca2+]i upon thrombin stimulation occurs. This decrease is partly due to the formation of a subpopulation of platelets that is completely unresponsive and partly due to a decreased responsiveness in the remainder of the platelets; it is not due to a gradual decline in [Ca2+]i rise in all platelets. This phenomenon provides new insight in the functional defect of stored platelets.
Plasminogen Activators t-PA, u-PA and Its Inhibitor (PAI) in Normal Males and Females
Authors: Koh Stephen C L , Yuen R , Viegas O A C , Chua S E , Ng B L , Sen D K , Ratnam S S
Published: July 2018

We determined the plasma levels of tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI) activity and their antigen levels including urokinase plasminogen activator (u-PA) in 33 male and 27 female normal subjects. Males had mean t-PA activity of 0.50 iu/ml which was significantly lower (p <0.01) than the females 0.64 iu/ml. Males had higher (p <0.001) mean PAI activity (15.5 AU/ml) as compared to females 10.3 AU/ml. The respective mean levels of t-PA and PAI antigen were significantly higher (p <0.01) in males (8.1 ng/ml and 17.6 ng/ml) than in females (6.2 ng/ml and 12.1 ng/ml). The mean u-PA level in males was 1.54 ng/ml which was significantly higher (p <0.01) than in females with 1.02 ng/ml. In post-venous occlusion studies, females had a greater mean response of 8.6 fold in t-PA activity as compared to males with a mean of 4.5 fold increase. The mean t-PA antigen response in males was 2.0 fold increase as compared to 2.6 fold increase in the females. No significant responses were seen in both sexes in either PAI activity or antigen levels when compared with the resting state. In zymography studies, free t-PA, its inhibitor complexes and u-PA were demonstrated in the euglobulin fractions of stored plasma. This study demonstrates that significant differences in t-PA, u-PA and PAI exist between male and female subjects which should be taken into account when determining their levels in clinical conditions.
The Measurement of Haemostatic Factors in 16 European Laboratories: Quality Assessment for the Multicentre ECAT Angina Pectoris Study
Authors: Thompson S G , Duckert F , Haverkate F , Thomson J M
Published: July 2018

As part of a European multicentre prospective study involving the measurement of a number of haemostatic factors, a quality assessment (QA) scheme was organized. This paper describes the preparation, design and results of the first Qa exercise, involving 16 European laboratories and 10 haemostatic assays. The design allowed the investigation, for each assay, of the variability between duplicates and the variability between days within each centre, and of the agreement between centres. A graphical presentation of each centre’s performance in comparison to that of others was adopted, which preserved the confidentiality of each centre’s results. The factor VIII clotting activity assay (VIII: C) and the rocket immuno-electrophoresis assays of von Willebrand factor related antigen (vWF R:Ag), antithrombin III, protein C and histidine-rich glycoprotein showed the highest betweenduplicate and between-day coefficients of variation (CVs), whereas the clotting assays of activated partial thromboplastin time and fibrinogen had the lowest CVs. CVs for the enzymatic assays using synthetic substrates of antithrombin III, plasminogen and alpha-2-antiplasmin were between these extremes. The between-centre CVs were high for both the VIII:C and vWFR:Ag assays. The QA exercise showed that, in multicentre studies involving the measurement of haemostatic factors, it is feasible to undertake analysis locally at each centre.
High Risk of Acquired Immune Deficiency Syndrome (AIDS) and of AIDS Related Complex (ARC) in Hemophiliacs Seropositive for more than 5 Years
Authors: Stain C , Pabinger-Fasching I , Guggenberger K , Köller U , Stain M , Hartl H , Heinz F , Mayerhofer S , Kyrle P A , Lechner K , Korninger C
Published: July 2018

A group of 90 hemophiliacs who had been regularly treated with non virus-inactivated factor VIII or IX concentrates were studied in 1983. At that time 50 patients were HIV-1-antibody positive, 6 additional seroconversions occurred until 1985. 26 of the 50 patients seropositive in 1983 are currently asymptomatic. 4 patients have developed the lymphadenopathy syndroffie, 9 patients AIDS and 11 patients ARC (CDC IV C 2). 6/9 cases of AIDS and 10/11 cases of ARC have occurred only after 1985. Patients, who subsequently became symptomatic, had significantly higher IgG levels in 1983, otherwise no predictive laboratory tests were identified. Patients with T4 counts above 500/μl became symptomatic later, but after 5 years the indicence of AIDS was comparable in patients with original T4 counts of more than or below 500/μl.
Platelet Distribution in Rabbits Following lnfusion of Liposomes
Authors: Doerschuk Claire M , Gie Robert P , Bally Marcel B , Cullis Pieter R , Reinish Lawrence W
Published: July 2018

This investigation determined the organ distribution of liposomes containing egg phosphatidylcholine and cholesterol with egg phosphatidylglycerol (PG liposomes) or without (PC liposomes) and the effect of each liposome on platelet distribution in rabbits. Eight minutes after51 chromium-labelled platelets were given intravenously, either saline (n = 7), iodinated PG liposomes (n = 5) or iodinated PC liposomes (n = 5) were infused. T\ro minutes later the organ distribution of 51Cr-platelets and 125I-liposomes were compared. The PG liposomes produced a 41λ5% reduction in circulating platelet counts while PC liposomes did not. The PG liposomes decreased circulating 51Cr-platelets by a factor of 2 and increased platelet recoveries in the liver and lungs. The increased platelet recovery in the liver was associated with a greater PG liposome recovery. When animals receiving PG liposomes were studied over 60 minutes, both the labelled and unlabelled platelet counts returned to control values by 30 minutes and the 51Cr-platelet distribution between organs was similar to control values. These data indicate that platelets and PG liposomes initially sequester together and that this plateletliposome interaction is specific for PG liposomes. However, the platelet sequestration is transient and by 60 minutes the platelets were released and circulating.
The Effect of Vascular Cell Seeding on Platelet Deposition in an In Vitro Capillary Perfusion Model
Authors: Dekker A , Poot A , Beugeling T , Bantjes A , van Aken W G
Published: July 2018

In view of the reported beneficial effects of cell seeding on the performance of synthetic vascular grafts, we determined the deposition of 111Indium-labelled human platelets in polyethylene capillary tubes covered with human endothelial cells (HEC) or smooth muscle cells (SMC) using an in vitro perfusion model. Platelet deposition decreased with increasing vascular cell coverage and was virtually absent when the number of adherent vascular cells of both types exceeded 50,0001cm2. Platelet deposition increased with increasing she ar rate (300-900 s-1) only when surface coverage was less than 50,000 vascular cells/cm2.

Deposition of Ca2+-ionophore A 23187-activated platelets in capillary tubes completely covered with SMC was significantly higher compared to capillaries covered with a similar number of HEC.

When HEC-lined capillaries were treated with aspirin, only the deposition of activated platelets increased slightly, but significantly. This platelet reactivity was more evident when the endothelial lining was not confluent.

These results demonstrate that, although seeding of HEC and SMC may both prevent the deposition of non-activated platelets to surfaces, non-aspirin-treated confluent HEC linings offer the best protection against deposition of activated platelets.
Detection of Lupus-Like Anticoagulants by an Enzyme-Linked Immunosorbent Assay Using a Partial Thromboplastin as Antigen; A Comparative Study
Authors: Arnout J , Huybrechts E , Vanrusselt M , Falcon C , Vermylen J
Published: July 2018

Clotting assays allow qualitative rather than quantitative detection of the lupus anticoagulant. We have therefore studied the usefulness of an ELISA using a commercial partial thromboplastin, Thrombofax, oS antigen; the results obtained on 146 selected patient plasmas were compared to the results of coagulation tests (kaolin clotting time, tissue thromboplastin inhibition test, activated partial thromboplastin time) and of ELISAs using cardiolipin or phosphatidylserine as antigen. While satisfactory agreement was found within the group of coagulation tests or that of ELISAs, only a moderate agreement was obtained between clotting tests and ELISAs, the best being with the partial thromboplastin ELISA using low plasma dilutions. The study further indicates that ELISA techniques cannot entirely replace coagulation tests for the detection of a lupus anticoagulant, even when a partial thromboplastin is used as antigen. On the other hand, coagulation tests are less sensitive than ELISAs for the detection of antiphospholipid antibodies.
Physical Exercise Enhances Plasma Levels of Extrinsic Pathway Inhibitor (EPI)
Authors: Hansen John-Bjarne , Olsen Jan-Ole , Østerud Bjarne
Published: July 2018

The risk of cardiovascular complications is reported to be several times higher in severe exercise than in daily activity. EPI-mediated inhibition of factor VTIa/thromboplastin enzymatic activity is believed to be an important modulator of blood coagulation during hemostasis. The plasma concentration of EPI, corrected for changes in plasma volume, was determined in healthy male subjects prior to, immediately after and at various time intervals after strenuous exercise of different duration. A slight, but significant decrease in EPI (7.5 ± 2.8%, p <0.03) was found after a short term run (1.7 km), whereas no significant change was seen after a middle term run (4.8 km). In contrast, we observed a marked increase in EPI after a long term run (20.3 ± 6.9%, p <0.03) and in a second group of athletes participating in the Norwegian championship of 30 km cross country skiing (39.9 ± 10.3%, p <0.02). A peak value was reached 2 h after the run, and after that the curve started to approach baseline values. The rise in EPI might reflect a significant release of EPI from the endothelium that is greater than eventually any consumption. Another explanation for this enhancement in EPI might be that the increase in lipoprotein lipase activity after physical exercise causes a rise in the availability of EPI since EPI is known to be associated with lipoproteins in the circulation.

It is hypothesized that mobilization of EPI during extensive physical exercise may suppress activation of the clotting system.
Bleeding Times in Rats Treated with Heparin, Heparin Fragments of High and Low Anticoagulant Activity and chemically Modified Heparin Fragments of Low Anticoagulant Activity
Authors: Palm Maud , Mattsson Christer , Svahn Carl Magnus , Weber Michael
Published: July 2018

A template bleeding time study in the rat was undertaken to see if it is possible to correlate bleeding times with the molecular weight, anticoagulant activity or chemical composition of heparin or heparin-derived compounds. Heparin from porcine intestinal rnucosa (PM-heparin) and from bovine lung (BL-heparin) as well as heparin fragments from these sources were compared. Heparin fragments of low anticoagulant activity were prepared by affinity chromatography on immobilized antithrombin as well as by chemical modification. A heparin fragment of high affinity for antithrombin (HA-fragment) caused a marked and dose-dependent increase in bleeding time while the corresponding heparin fragment with low affinity for antithrombin (LA-frugment) had a marginal and non-dose dependent effect on the bleeding time. Similar results were also obtained with PM-heparin with high and low affinity for antithrombin. A high anti-FXa activity was not always correlated with a marked bleeding tendency. Provided that a fragment was devoid of activated partial thromboplastin time (APTT) activity, it was not possible to provoke a bleeding time of 20 min or longer, although the compound was administered at a dose of 1,088 U/kg (anti-FXa activity). On the other hand, & Nacetylated chemically oversulphated heparin fragment, with a very low anti-FXa activity (1 U/mg) and with an APTT activity of 34UlmtB, caused a bleeding time of 20 min or longer in 70% of the animals after injection of the same number of Aprr units, 1,088 U/kg. These data indicate that the APTT activity is a better and more sensitive indicator of the bleeding than is the anti-FXa activity.
Primary and Secondary Lysosomes in Megakaryocytes and Platelets from Cattle with the Chediak-Higashi Syndrome
Authors: Ménard Michèle , Meyers Kenneth M , Prieur David J
Published: July 2018

The ultrastructure of lysosomes from megakaryocytes (MK) and platelets of cattle with the Chediak-Higashi syndrome (CHS) was characterized using acid phosphatase histochemistry with beta-glycerophosphate as substrate and cerium as a capturing agent. Acid phosphatase was localized in the trans aspect of the Golgi complex and/or granules in MK at all stages of maturation. Morphometric analysis of the diameter of each lysosome was performed on MK from CHS cattle and compared to MK from normal cattle. Lysosomes in CHS MK were neither enlarged nor different with respect to classification as secondary lysosomes, which composed 35% of the lysosomes in CHS MK. Lysosomes were demonstrated in 22% of the CHS platelet sections and appeared similar to those from normal cattle, 56% of them being classified as secondary lysosomes. Why lysosomes are not enlarged in bovine CHS MK and platelets, whereas they are enlarged in most other cell types, remains unknown.
The Binding of Phosphatidylglycerol Liposomes to Rat Platelets Is Mediated by Complement
Authors: Loughrey H C , Bally M B , Reinish L W , Cullis P R
Published: July 2018

Previous work has shown that intravenous administration of phosphatidylglycercol (PG) containing liposomes to rats results in a rapid transient decline in platelet count (1). Here the interactions of PG liposomes with rat platelets in vitro have been examined with the aim of charactenzing factors associated with the decline. It is shown that PG liposomes induce formation of rat (but not human) platelet-liposome microaggregates in vitro. The PG liposome dependent thrombocytopenia observed in vivo can therefore be attributed to sequestration of PG liposome-platelet aggregates. Further, the aggregation of platelets with PG liposomes, which can be moni ored as a reduction in platelet count using a coulter counter, is shown to be mediated by a serum complement fgctor, likely C3b. This is indicated by a requirement of plasma for the in vitro reduction in platelet count induced by PG liposomes, and the inhibition of this effect by heat treatment of plasma, by incubation of plasma with purified cobra venom factor, or by removal of C3 from plasma.
Hereditary Protein S Deficiency in Young Adults with Arterial Occlusive Disease
Authors: Allaart C F , Aronson D C , Ruys Th , Rosendaal F R , van Bockel J H , Bertina R M , Briët E
Published: July 2018

Protein S is the vitamin K dependent cofactor of activated protein C. It has an important role in the regulation of blood coagulation and fibrinolysis. Hereditary protein S deficiency is associated with familial venous thrombophilia. Since a few patients with arterial occlusions have been reported to be protein S deficient, it is speculated that hereditary protein S deficiency may be also a risk factor for the development of arterial thrombosis. In a group of 37 consecutive patients with arterial occlusive disease presenting before the age of 45, three patients were found heterozygous for hereditary protein S deficiency. None of the patients had a protein C deficiency or an antithrombin III deficiency. Family investigations showed a clear association between the hereditary deficiency and venous thrombosis, but a relation between the deficiency and arterial thrombosis was less obvious. A review of previous literature on patients with arterial thrombosis and protein S deficiency revealed that more extensive studies are needed to demonstrate whether or not hereditary protein S deficiency is a risk factor for the development of arterial thrombosis.
Isolation and Characterization of a Coagulation Factor Xa Inhibitor from Black Fly Salivary Glands
Authors: Jacobs John W , Cupp Eddie W , Sardana Mohinder , Friedman Paul A
Published: July 2018

We have discovered and charact enzed a novel coagulation
factor Xa inhibitor from the salivary gland of the black fly, Simulium vittatum. Salivary glands were surgically dissected from the flies and a crude salivary gland extract was tested for inhibition of a number of coagulation assays. The gland extract inhibited both thrombin and factor Xa. Tic purify further the factor Xa inhibitor, a factor Xa affinity column was utilized. Final purification of the black fly factor Xa inhibitor was achieved by reverse-phase C8 microbore high pressure liquid chromatography. Inhibition of factor Xa was nearly stoichiometric by the purified inhibitor with no inhibitor of thrombin detected. SDSpolyacrylamide gel electrophoresis indicated the inhibitor had a molecular weight of 18,000 and sequence analysis of the inhibitor revealed a blocked amino terminus. These data indicate that the blood-sucking black fly has evolved a highly potent inhibitor of mammalian coagulation factor Xa to disrupt its host normal hemostatic clotting mechanisms.
Validation of a Procedure for Potency Assessing of a High Purity Factor VIII Concentrate -Comparison of Different Factor VIII Coagulant Assays and Effect of Prediluent
Authors: Mazurier Claudine , Parquet-Gernez Armelle , Goudemand Maurice
Published: July 2018

The assessment of factor VIII coagulant activity (FVTII: C) in recently available highly purified and concentrated FVTII therapeutic products calls for careful evaluation of assay methodologies. We assayed more than 130 batches of a concentrate with a specific activity of about 150 FVTII :C units/mg protein, using one-stage and two-stage clotting and chromogenic methods. There was good agreement between the potency estimates obtained with the different methods. We also compared the FVTII :C potencies obtained after predilution in buffer or FVIII-deficient plasma using either calibrated plasma or FVTII concentrate as references. With the one-stage assay we found a marked discrepancy between the potency values obtained with buffer and with FVTII-deficient plasma used as prediluents. In order to validate our “in vitro” data we performed 6 “in vivo” analyses in severe haemophilia A patients. On the basis of the overall data obtained we chose to label FVIII potency by using FVIII-deficient plasma as prediluent, reference plasma as standard and the chromogenic assay method.