bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal wind turbine allocation and network reconfiguration for enhancing resiliency of system after major faults caused by natural disaster considering uncertainty
Authors: Nikkhah Saman , Jalilpoor Kamran , Kianmehr Ehsan , Gharehpetian Gevork B.
Published: July 2018

This study proposes a two‐stage stochastic optimisation model for jointly wind turbine (WT) allocation and network reconfiguration (NR) so as to increase the resiliency of distribution system in face of natural disasters. In this regard, in the first level, a possibilistic‐scenario method is proposed to select the line outage scenarios. The proposed model is capable with distribution systems and considers different failure probabilities for system components subject to the intensity of natural disaster in its associated zone. After selecting the line outage scenarios, in the second level, a multi‐stage optimisation framework is proposed for jointly NR and WT allocation in a multi‐zone and multi‐fault system, considering the uncertainty of system load and wind power generation. This strategy makes an interconnection between NR and islanded WTs to increase the resiliency of system and decreases the load shedding. Different economic objectives including, costs of load shedding and power generation are considered in the model. In addition, hardening budget is taken into consideration for the transmission lines, which is minimised during the optimisation process. The simulation results demonstrate the capability and necessity of proposed resiliency‐oriented method and prove the importance of hardening budgets.
Impacts of radiative accelerations on solar-like oscillating main-sequence stars
Authors: Deal M. , Alecian G. , Lebreton Y. , Goupil M. J. , Marques J. P. , LeBlanc F. , Morel P. , Pichon B.
Published: July 2018

Context. Chemical element transport processes are among the crucial physical processes needed for precise stellar modelling. Atomic diffusion by gravitational settling is usually taken into account, and is essential for helioseismic studies. On the other hand, radiative accelerations are rarely accounted for, act differently on the various chemical elements, and can strongly counteract gravity in some stellar mass domains. The resulting variations in the abundance profiles may significantly affect the structure of the star.

Aims. The aim of this study is to determine whether radiative accelerations impact the structure of solar-like oscillating main-sequence stars observed by asteroseismic space missions.

Methods. We implemented the calculation of radiative accelerations operating on C, N, O, Ne, Na, Mg, Al, Si, S, Ca, and Fe in the CESTAM code using the single-valued parameter method. We built and compared several grids of stellar models including gravitational settling, some with and others without radiative accelerations. We considered masses in the range [0.9, 1.5]M⊙and three values of the metallicity around the solar value. For each metallicity we determined the mass range where differences between models due to radiative accelerations exceed the uncertainties of global seismic parameters of theKeplerLegacy sample or expected for PLATO observations.

Results. We found that radiative accelerations may not be neglected for stellar masses higher than 1.1M⊙at solar metallicity. The difference in age due to their inclusion in models can reach 9% for the more massive stars of our grids. We estimated that the percentage of the PLATO core program stars whose modelling would require radiative accelerations ranges between 33% and 58% depending on the precision of the seismic data.

Conclusions. We conclude that in the context ofKepler, TESS, and PLATO missions which provide (or will provide) high-quality seismic data, radiative accelerations can have a significant effect when properly inferring the properties of solar-like oscillators. This is particularly important for age inferences. However, the net effect for each individual star results from the competition between atomic diffusion including radiative accelerations and other internal transport processes. Rotationally induced transport processes for instance are believed to reduce the effects of atomic diffusion. This will be investigated in a forthcoming companion paper.
Solar energetic particles and galactic cosmic rays over millions of years as inferred from data on cosmogenic26Al in lunar samples
Authors: Poluianov S. , Kovaltsov G. A. , Usoskin I. G.
Published: July 2018

Aims.Lunar soil and rocks are not protected by a magnetic field or an atmosphere and are continuously irradiated by energetic particles that can produce cosmogenic radioisotopes directly inside rocks at different depths depending on the particle’s energy. This allows the mean fluxes of solar and galactic cosmic rays to be assessed on the very long timescales of millions of years.

Methods.Here we show that lunar rocks can serve as a very good particle integral spectrometer in the energy range 20–80 MeV. We have developed a new method based on precise modeling, that is applied to measurements of26Al (half-life ≈0.7 megayears) in lunar samples from theApollomission, and present the first direct reconstruction (i.e., without any a priori assumptions) of the mean energy spectrum of solar and galactic energetic particles over a million of years.

Results.We show that the reconstructed spectrum of solar energetic particles is totally consistent with that over the last decades, despite the very different levels of solar modulation of galactic cosmic rays (ϕ= 496 ± 40 MV over a million years versus (ϕ= 660 ± 20 MV for the modern epoch). We also estimated the occurrence probability of extreme solar events and argue that no events with theF(>30 MeV) fluence exceeding 5×1010and 1011cm−2are expected on timescales of a thousand and million years, respectively.

Conclusions.We conclude that the mean flux of solar energetic particles hardly depends on the level of solar activity, in contrast to the solar modulation of galactic cosmic rays. This puts new observational constraints on solar physics and becomes important for assessing radiation hazards for the planned space missions.
Impact Anlysis of Bow Flap on LHA-1 Ship Airwake
Authors: Wang Jinling , Jiang Guangwen , Shen Jun , Hu Chujun
Published: July 2018

The sharp 90°corner of bow found on American Tarawa class general amphibious assault ship LHA-1 will produce large separated region in the airwake over the ship, and the turbulence in the separation region seriously affects the operation safety of the helicopter. In order to reduce the separation in bow region of the LHA-1, and optimize the helicopter operating environment, the numerical simulation method is used to study the influence of the bow flap on the airwake of LHA-1. The study results show that: the ANSYS k-ε two equation model based on the hybrid grid can be used to predict the steady-state characteristics of the ship airwake; the bow flap can improve the flow field downwind of the flap installation position, and the impact range can cover two spots; in headwind, the optimal installation angle of the bow flap is 15°~25°. The research results of this paper can provide modification and improvement reference for the amphibious assault ship in-service and under construction, so as to achieve the purpose of optimizing the ship airwake, thereby improving the safety of helicopter landing process and extending the service life.
Research of Spacecraft Assembly Simulation with Ground Mechanical Equipments
Authors: Wen-xing HE , Chang-yu CHEN
Published: July 2018

In order to overcome the shortcomings of the physical test conditions, research and development of the spacecraft container simulation verification platform to enhance the level of digital development of the spacecraft container. Based on the theory of rigid-flexible coupling dynamics, the dynamic model of the box system is established. The dynamic external excitation is determined by obtaining the track spectrum and identifying the condition of the line. Based on the computational fluid dynamics, the thermal model of the spacecraft container is established, and the container is realized by simulating the natural convection and air conditioning control spacecraft container thermal simulation. Using modular design, C/S architecture and navigation process to achieve the simulation platform architecture versatility, ease of maintenance and scalability and other needs. Finally, the mechanics and thermal performance verification of the spacecraft container and physical test are carried out. The results show that the simulation results of the box dynamic system and the thermal system are in good agreement with the experimental results.
Evaluation Abilities and Requirements of the Wind Tunnel Hardware-in-the-loop Simulation for Evaluation of Missiles’ Flight Control Systems
Authors: Yang Xing-bao , Huang Min
Published: July 2018

In order to determine the flight control system (FCS) performances that wind tunnel hardware-in-the-loop simulation (WT-HILS) can evaluate, and lay foundations for designing the WT-HILS evaluation methods, the evaluation abilities and requirements of WT-HILS for FCS evaluation were analyzed. Firstly, the features of WT-HILS were pointed out. Then, according to the features of WT-HILS, what FCS performances WT-HILS can evaluate were analyzed, and the differences of evaluation abilities among the WT-HILS, the traditional hardware-in-the-loop simulation (HILS), and flight tests were compared. Lastly, from the aspects of testing, data processing, and FCS performance determination, the specific requirements of WT-HILS for evaluating FCS were analyzed.
Robust Optimization in Airlines' Hybrid Channels Coordination with Service-Level Constraints
Authors: ZHANG Feifei , HU Rong , ZHANG Junfeng
Published: July 2018

This essay considers the influence of the service level in the research of the robust optimization of airlines' hybrid channels coordination with uncertain demands. In the essay, the service level is taken as a constraint in the model that is established based on the characteristics of channels coordination and scenario analysis. In this way, it can make the airlines' hybrid channels coordination more effectively. Then three-dimensional numerical experiments of the robust optimization model are performed and the results show that the model proposed is robust to uncertain demands and fit for airlines' hybrid channels coordination; Airlines should focus on promoting the direct channel and passengers' stickiness; agents should focus on reducing the cost of the channels, and they should carry out improve-service-level cooperation to attract passengers; airlines and agents also should cooperate with each other to obtain win-win strategies.
Research on Applicability of Hot-Bulb Anemometer under Low Pressure
Authors: Xiyuan Li , Xiaofang Yin , Yaqin Hou , Qinghua Gao , jing Wang
Published: July 2018

In Mars and other deep space exploration missions, the planetary atmosphere makes the difference in heat transfer characteristics on the planetary surface and on-orbit environment. In order to achieve the purposes of thermal model correction and spacecraft verification in extreme environment, Mars rover needs to be tested in a simulated Mars environment including low pressure, solar heat flux, wind speed and background temperature. Thus, wind speed should be measured at multiple points in the Mars rover thermal test. In a general Mars rover thermal balance test, the requirement for wind speed control and measurement is 0-15m/s under 700Pa pressure. The current anemometer for industrial use is mainly based on the dynamic pressure, heat or ultrasound. They have a small signal and need to be recalibrated at low pressures. In this paper, a constant heat flux hot-bulb anemometer model has been built using dimensionless number analysis method, with which the anemometer response under low pressure has been calculated. A series of calibration test has been employed to verify the model in space environment chamber. The two methods above reached a similar result, which demonstrates the effectiveness of the analysis.
Risk and Relevance of Insulin Pump Therapy in the Aetiology of Ketoacidosis in People with Type 1 Diabetes
Authors: Giessmann Lena Christina , Kann Peter Herbert
Published: July 2018

Objective The aim of this systematic data analysis was to determine the prevalence of diabetic ketoacidosis (DKA) as well as hypoglycemic and hyperglycemic disorders during insulin pump therapy (CSII) in patients with type 1 diabetes. The main focus was to investigate whether CSII patients have more DKA than the general type 1 diabetes population.

Subjects and Methods This retrospective study with patients who were treated in our treatment center from 2003 to 2016 includes data from 229 patients (52.4% male, 47.6% female, 37.2±16.3 years; DKA: 93, hypoglycemia: 66, hyperglycemia: 70).

Results Intensified insulin therapy was the most common treatment regimen in the study cohort (73.4%), followed by CSII (24%). However, 32.3% of the patients with DKA were on CSII. This number of DKA cases among the insulin pump users in our study cohort was higher than the prevalence reported in a previously published study by Reichel et al. (2013; p<0.05) and in a customer database (p<0.005). Most common causes of DKA in our study cohort were patient errors (43.3%) or insulin resistance induced by an underlying infection (29.8%). Device malfunction caused 13.5% of all DKA cases with an overwhelming majority on insulin pump treatment (93%). Overall, patient errors caused more DKA cases than device malfunctions.

Conclusions Our findings suggest that despite development of more sophisticated insulin pump devices, DKA is still more frequent with CSII than with other kinds of insulin treatment.
Efficient Synthesis of Indole Derivatives Containing the Tetrazole Moeity Utilizing an Ugi-Azide Post-Transformation Strategy
Authors: Balalaie Saeed , Nikbakht Ali , Baghestani Fatemeh , Rominger Frank
Published: July 2018

An efficient strategy has been developed for the synthesis of indole derivatives containing the tetrazole moiety using a AuCl3-catalyzed cyclization reaction. The precursors of the cycloadduct were easily prepared by an Ugi-azide 4-CR in methanol at room temperature. The merit of this protocol lies in its operational simplicity, readily available starting materials, high yields of product, and good functional group tolerance.
Regio- and Stereoselective Palladium-Catalyzed Intermolecular Three-Component Aryletherification of Terminal Allenes
Authors: Chen Shufeng , Wu Xin-Xing , Wang Chenjun , Zhao Wanrong , Zhao Haiying
Published: July 2018

A palladium-catalyzed three-component intermolecular aryl­etherification reaction of ferrocene-substituted allenes, aryl iodides and phenols or alcohols is reported. In this three-component reaction, two new C–C and C–O bonds are formed in one step with high regio- and stereoselectivity. The high selectivity obtained in this reaction can be attributed to the steric effect of the bulky ferrocene group.
Epitope Mapping of Inhibitory Monoclonal Antibodies to Human von Willebrand Factor by Using Recombinant cDNA Libraries
Authors: Piétu Geneviéve , Ribba Anne-Sophie , Chérel Ghislaine , Siguret Virginie , Obert Bernadette , Rouault Christine , Ginsburg David , Meyer Dominique
Published: July 2018

Two recombinant expression libraries containing small (300-600 base pairs) cDNA fragments of von Willebrand Factor (vWF) were screened in order to map the epitope of monoclonal antibodies (MAbs) to vWF. Among eleven MAbs tested, seven were effectively mapped. The epitopes of MAbs 418 and 522, which inhibit the binding of vWF to Factor VIII (FVIII), were localized between Leu 2 and Arg 53 and between Glu 35 and He 81 of the vWF subunit respectively, within the N-terminal trypsin fragment called SpIII-T4 [amino acids (aa) 1-272] which contains a binding domain for FVIII. The epitope of MAb 710, which inhibits the binding of vWF to glycoprotein lb (GPIb), was identified between Ser 593 and Ser 678 on the tryptic 52/48 kDa fragment (aa 449-728) which contains binding domains for GPIb, collagen, heparin, sulfatides and subendothclium extracellular matrices. The epitope of MAb 723, which does not interfere with any known function of vWF, was localized between Ser 523 and Gly 588. The epitopes of MAb 505 and MAb 400, which inhibit the binding of v WF to collagen, were identified between Leu 927 and Arg 1114 within the SPI fragment (aa 911-1365) corresponding to the central part of the vWF subunit. The epitope of MAb 9, which inhibits the binding of vWF to GPIIb/IIIa, was identified in the C-terminal part of the vWF subunit between Gin 1704 and Asp 1746, the latter being the third aa of the RGD sequence common to adhesive proteins and serving as a recognition site for integrin receptors.
Pharmacokinetic Properties of Recombinant Factor VIII Compared with a Monoclonally Purified Concentrate (Hemofil® M)
Authors: Morfini M , Longo G , Messori A , Lee M , White G , Mannucci P ,   The Recombinate Study Group
Published: July 2018

A recombinant FVIII preparation, Recombinate™, was compared with a high-purity plasma-derived concentrate, Hemofil® M, in 47 hemophilia A patients in a cross-over evaluation of pharmacokinetic properties. The recombinant material showed a significantly lower clearance, volume of distribution, and higher in vivo recovery, but a similar half-life to the plasma-based product.

In a comparison with reported data from other standard concentrates, the recombinant preparation exhibited potentially better pharmacokinetic properties in that its clearance was slower and its half-life was longer.

We conclude that the recombinant DNA method of preparation does not adversely affect the biological and pharmacological characteristics of the factor VIII molecule.
Immunochemical Detection of the Thomsen-Friedenreich Antigen (T-Antigen) on Platelet Plasma Membranes
Authors: Glöckner Wolfgang M , Kaulen Hermann D , Uhlenbruck Gerhard
Published: July 2018

Platelet plasma membranes were found to possess the disaccharide β--galactosyl(1−3)-N-acetyl-D-galactosamine which was measured by gas chromatography after release by alkaline borohydride treatment and desialylation. Immunological evidence using the specific lectins from Arachis hypogoea and Agaricus bisporus and an anti-T serum confirmed the presence of this disaccharide, the immunodominant group of the Thomsen-Friedenreich antigen (T-antigen). This receptor was only found after prior neuraminidase treatment indicating that it is normally a cryptic antigen, i.e. masked by sialic acid in the native membrane. Evidence for a second receptor with terminal N-acetylgalactosamine was obtained using the lectin from Helix pomatia. The binding of myxovirus and the lectins from Phaseolus vulgaris (PHA) and Canavalia ensiformis (Con A) to platelet membrane was also demonstrated.

The implication of the T-antigen in elimination of the platelets and its role in the haemolytic-uraemic syndrome is discussed.
Antibody-Induced Acute Factor X Deficiency: Clinical Manifestations and Properties of the Antibody
Authors: Vijaya Mohan Rao L , Zivelin Ariella , Iturbe Ignacio , Rapaport Samuel I
Published: July 2018

A patient is described with serious bleeding due to a transient selective deficiency of factor X. Crossed immunoelectrophoresis of patient’s plasma with anti-factor X antibody revealed an abnormal factor X arc suggestive of the presence of plasma factor X/anti-factor X immune complexes. A similar abnormal arc was obtained on adding the patient’s IgG to normal plasma. Immunoblotting of factor X after reduced SDS-PAGE revealed that the patient’s IgG bound to the light chain of intact factor X but not Gla-domainless factor X. The patient’s IgG inhibited activation of factor X by Vila/tissue factor (TF), by IXa/VIIIa/phospholipid complex, and by Russell’s viper venom. The IgG failed to inhibit the proteolytic activity of factor Xa towards a chromogenic substrate. However, under reaction conditions of limited factor Xa availability, the IgG could be shown to impair hemostatic functions of factor Xa that require the participation of its light chain: activation of prothrombin by prothrombinase; activation of factor VII bound to TF; and inhibition of VIIa/TF activity by factor Xa/tissue factor pathway inhibitor complexes. A few earlier patients have been described with transient, selective factor X deficiency and serious bleeding, but in only one was evidence obtained of an antibody against factor X. It will be of interest to learn whether use of the techniques described in this report will permit the identification of immunoglobulin with similar binding and functional properties in future patients with this rare syndrome.
Inhibition of Platelet Recruitment to Arterial Lesions by Predeposition of Platelets Containing Encapsulated lloprost
Authors: Pfliegler George , El-Gamal Basiouny , José Badimon Juan , Badimon Lina , Crawford Neville
Published: July 2018

Drugs can be encapsulated within blood platelets by reversible electroporation and can be haemostatically targeted to vessel wall injury sites. Initial studies with iloprost-loaded pig platelets and pig aorta tunica media in perfusion circuits are presented. After autologous reconstitution into blood, no significant difference was observed in the deposition of 111Indium labelled sham-loaded and untreated platelets onto the tunica media during perfusion under low and high shear conditions. In paired experiments (n = 10 pairs), the deposition of iloprost-loaded platelets was significantly lower (mean 61%) after 5 min perfusion than the deposition from blood containing sham-loaded (control) platelets. A similar significant reduction (mean 54%) was seen after 10 min perfusion. Pre-perfusion of iloprost-loaded platelets for 10 min under low shear conditions (212/s), followed by 5 min perfusion of 111Indium labelled normal platelets, significantly reduced the secondary platelet deposition (p <0.01) when compared with the deposition seen when control untreated platelets were preperfused. Significant differences (p <0.001) in secondary deposition were also observed when primary and secondary platelet perfusions were made under high shear (1690/s).

Histology of the tunica media segments post perfusion, supported the inhibitory effect of predeposited iloprost-loaded platelets on secondary platelet recruitment. By exploiting their natural haemostatic propensity, drug-loaded platelets can be targeted to vessel wall injury sites. Appropriate drugs could be packaged that may passivate the carrier platelets at the lesion inhibiting thrombus formation or they may act as a depot for sustained drug release. This platelet drug delivery strategy may have application in the prevention of the thrombotic and reste-notic events that can occur post angioplasty, or following therapy with thrombolytics, or after more invasive surgical procedures involving vascular reconstruction or prosthetic implantation.
Evaluation of a Soluble Fibrin Assay in Patients with Suspected Deep Vein Thrombosis
Authors: Ginsberg Jeffrey S , Siragusa Sergio , Douketis James , Johnston Marilyn , Moffat Karen , Stevens Pamela , Brill-Edwards Patrick , Panju Akbar , Patel Ameen
Published: July 2018

Background. The objective of this study was to determine the clinical utility of an enzyme immunoassay (HIA) for soluble fibrin in patients with clinically suspected deep vein thrombosis (DVT).

Methods and Results. 101 unselected patients with clinically suspected DVT underwent blood sampling for measurement of plasma levels of soluble fibrin, and objective testing for DVT. According to results of the objective tests, patients were classified as DVT-positive (n = 34) or DVT-negative (n = 67). Using different cut-points of soluble fibrin results, the sensitivities, specificities, positive and negative predictive values of the soluble fibrin assay were calculated. A soluble fibrin result of ≤0.75 mg/ml showed a sensitivity and negative predictive value of 100%, and a specificity of 17.9% for DVT, a soluble fibrin result of ≤ 1.40 mg/ml showed a sensitivity of 91.2% and a negative predictive value of 93.6%, and a specificity of 65.7% for DVT, whereas a soluble fibrin result of ≤ 8.0 mg/ml showed a specificity and positive predicive value of 100% for DVT.

Conclusions. This study demonstrates that the soluble fibrin assay used in the study has potential clinical utility as a diagnostic test in patients with clinically suspected DVT and supports further evaluation of this assay.
Effect of Fibrinogen Substitution in Afibrinogenemia on Hemorheology and Platelet Function
Authors: Reininger Armin J , Reininger Cornelia B , Spannagl Michael , Mellinghoff Achim , Porr Astrid , Heinzmann Ulrich , Wurzinger Laurenz J
Published: July 2018

Fibrinogen substitution can correct bleeding in afibrinogenemia. We assessed the effect of fibrinogen substitution in a patient lacking immunoreactive fibrinogen. Fibrinogen and thrombin time were not measurable before, but became detectable within 30 min after substitution, parallelled by an increase in ADP-induced platelet aggregation from <10% to 32%. Platelet adhesion, measured by Stagnation Point Flow Adhesio- Aggregometry, was notdetectable prior to substitution but attained normal values thereafter. Scanning electron microscopy of adhering platelets revealed pseudopodia protrusion and spreading. Morphometry revealed two populations of spread platelets one of which demonstrated inhibited spreading as compared to healthy controls. Immunoelectron microscopy revealed normal GPIIb/IIIa receptor expression, both before and after substitution. Dynamic and kinematic viscosity of plasma and whole blood remained below the 99.9% confidence border of a healthy control group. In afibrinogenemia fibrinogen levels as low as 10% of normal concentration sufficed to normalize coagulation, platelet adhesion, and, partially, spreading.
Effects of 6-[p-(4-Phenylacetylpiperazin-l-yl)-phenyl]-4,5-Dihydro-3(2H)-Pyridazinone (CCI 17810) and Aspirin on Experimental Arterial Thrombosis in Rats
Authors: Lecker Dorothy , Kumar Abhilash
Published: July 2018

An experimental model for arterial thrombosis has been investigated in rats. A loop of polythene tubing inserted in the left carotid artery induced thrombus formation on the arterial wall at the points of contact with the tips of the cannula. Sprague Dawley (CFY) rats were more susceptible to the thrombotic stimulus than were Wistar (WAG) rats. Whole blood platelet adhesiveness measured by a glass bead column method was higher in CFY rats than in WAG rats.

6 - [p - (4-Phenylacetylpiperazin-1 - yl) - phenyl] - 4,5 - dihydro-3(2H)-pyridazinone (CCI 17810) inhibited thrombus formation in CFY rats. Both the incidence of occlusion of the cannulated artery and the mean thrombus weight were reduced by CCI 17810 in doses of 25, 50 or 100 mg/kg administered orally twice daily; the effects were dose-related.

The effects of aspirin depended on the dose administered. A high dose (200 mg/kg) did not inhibit thrombus formation whereas a low dose (20 mg/kg) reduced the incidence of occlusion and the mean thrombus weight. These results are in accord with the differential effects of aspirin on platelet and blood vessel wall cyclooxygenase.
Disseminated Intravascular Coagulation Is a Frequent Complication of Systemic Inflammatory Response Syndrome
Authors: Gando Satoshi , Kameue Takashi , Nanzaki Satoshi , Nakanishi Yoshimi
Published: July 2018

To evaluate the role of disseminated intravascular coagulation (DIC) and to determine the influence of antithrombin, protein C, and plasminogen activator inhibitor 1 on multiple organ dysfunction syndrome (MODS) and outcome in patients with systemic inflammatory response syndrome (SIRS), we made a prospective cohort study. The study subjects consisted of thirty-five patients who exhibited two or more of the conditions of SIRS for more than three consecutive days. They were classified into subgroups of survivors (n = 13) and nonsurvivors (n = 22). The global coagulation and fibrinolytic markers, antithrombin, protein C, and plasminogen activator inhibitor 1 were measured on the day of the diagnosis of SIRS, and also on the 1st, 3rd, and 5th days. The results of these measurements, demographic data, criteria of severity, incidence of MODS were compared between the subgroups. For prediction of patient’s death, a receiver operating characteristic (ROC) curve analysis was made. DIC was frequently associated with SIRS patients (29/35, 82.9%). A significant decrease in the DIC score was found in the survivors (p = 0.0001). None of them suffered from DIC on the 5th day. In the nonsurvivors, low levels of protein C and antithrombin and markedly high values of plasminogen activator inhibitor 1 continued up to the 5th day, no improvement of the DIC was observed during the study period and the number of the dysfunctioning organs were significantly higher than in the survivors. Plasminogen activator inhibitor 1 on the 5th day had prognostic value for the prediction of death on the SIRS patients. In conclusion, DIC occurs commonly in patients with SIRS and may be the main determinant for the outcome of these patients. Changes in antithrombin, protein C, and plasminogen activator inhibitor 1 are one of the aggravating factors of MODS. Furthermore, plasminogen activator inhibitor 1 is a good predictor of death in these patients.
Distribution and Occlusiveness of Thrombi in Patients with Surveillance Detected Deep Vein Thrombosis after Hip Surgery
Authors: Ascani Alessandra , Radicchia Stefano , Parise Pasquale , Nencl Giuseppe G , Angelli Giancarlo
Published: July 2018

Venous thromboembolism is a leading cause of in-hospital postoperative morbidity and mortality. Postoperative deep vein thrombosis (DVT) is usually asymptomatic. A number of studies have consistently shown that the non invasive diagnostic methods are inaccurate in the screening of asymptomatic DVT. Failure of non invasive diagnostic methods to detect thrombi in asymptomatic patients has been suggested to be due to the features of thrombi in these patients. The aim of this study was to assess the distribution and the occlusiveness of thrombi in a series of 321 asymptomatic hip surgery patients with adequate bilateral venography of the lower limbs.

Venography was performed 10 ± 1 days after hip surgery. DVT was found in 180 limbs (28.0%). The distribution of thrombi was as follows: 26 (14.4%) isolated proximal thrombi, 55 (30.6%) proximal and distal thrombi, 99 (55.0%) isolated calf thrombi. We found that 14 of the 81 proximal trombi (17.3%) involved the superficial femoral vein either as exclusive location or in association with calf veins. An involvement of common femoral, superficial femoral and popliteal vein was observed in 37 (45.7%), 39 (48.1%) and 44 (54.3%) cases of the 91 proximal DVT. These thrombi were non occlusive in 25 (67.6%), 22 (56.4%) and 26 (59.1%) limbs, respectively. An involvement of at least one peroneal, anterior tibial and posterior tibial veins was observed in 118,13 and 89 cases of the 220 distal thrombi. These thrombi were non occlusive in 61 (51.7%), 10 (76.9%) and 30 (33.7%) of the cases.

We conclude that the majority of thrombi found in asymptomatic hip surgery patients are non occlusive. In view of this, non invasive diagnostic methods based upon venous flow measurement will be unlikely to improve the diagnosis of asymptomatic DVT. The high incidence of isolated superficial femoral vein thrombosis necessitates that real-time B-mode ultrasonography should be performed examining the entire proximal venous system.
Platelet-Associated Anti-Glycoprotein (GP) IIb-IIIa Autoantibodies in Chronic Immune Thrombocytopenic Purpura Mainly Recognize Cation-Dependent Conformations: Comparison with the Epitopes of Serum Autoantibodies
Authors: Kosugi Satoru , Tomiyama Yoshiaki , Shiraga Masamichi , Kashiwagi Hirokazu , Mizutani Hajime , Kanakura Yuzuru , Kurata Yoshlyuki , Matsuzawa Yuji
Published: July 2018

Platelet-associated and serum anti-glycoprotein (GP) IIb-IIIa autoantibodies were investigated in 57 patients with chronic immune thrombocytopenic purpura (ITP). In modified antigen capture ELISA (MACE) using GPIIb-IIIa-specific-, GPIIb-specific-, and GPIIIa-speci-fic-monoclonal antibody (mAb) for antigen capture, platelet-associated anti-GPIIb-IIIa antibodies were detected in 14 out of 37 patients (38%), and these antibodies could be detected with all 3 mAbs used for antigen capture. In the MACE using EDTA-treated platelets at 37° C, the reactivity of platelet-associated anti-GPIIb-IIIa antibodies in 9 out of 10 patients was markedly reduced in both cases of GPIIb-specific- and GPIIIa-specific-mAb used. Immunoprecipitation experiments further confirmed that the EDTA-treatment abrogated the antigenicity of GPIIb-IIIa for platelet-associated antibodies in 2 patients. Serum anti-GPIIb-IIIa autoantibodies were detected in 23 out of 57 patients (40%). However, only 7 out of 23 serum anti-GPIIb-IIIa antibodies could be detected with all 3 mAbs. The MACE using EDTA-treated platelets further showed that the features of serum anti-GPIIb-IIIa antibodies were different from those of platelet-associated antibodies even in the same patient. Our data demonstrate that the platelet-associated anti-GPIIb-IIIa antibodies mainly recognize the cation-dependent antigenic determinants on GPIIb-IIIa and that serum anti-GPIIb-IIIa antibodies may contain some components which differ in specificity from platelet-associated antibodies.
UHG-based Mutation Screening in Type 2B von Willebrand’s Disease: Detection of a Candidate Mutation Ser547Phe
Authors: Wood Nigel , Standen Graham R , Bowen Derrick J , Cumming Anthony , Lush Christopher , Lee Richard , Bidwell Jeffery
Published: July 2018

We have recently described a novel mutation screening technique for the diagnosis of type 2B von Willebrand’s disease (vWD). Analysis involves the use of a synthetic universal heteroduplex generator (UHG). To test the validity of the technique, we have applied UHG screening to seven type 2B vWD patients of previously unknown genotype. Characteristic heteroduplex patterns for Arg543Trp and Val553Met mutations were found in three patients and one patient, respectively. A fifth patient gave a novel pattern and direct sequencing revealed a hitherto unreported candidate mutation (Ser547Phe) 8 bases downstream of an “identifier” deletion in the UHG molecule. The two remaining patients gave normal heteroduplex patterns; an Arg578Gln mutation was identified by PstI digestion in one individual and no mutation could be identified in the sequence covered by the UHG in the final patient. Using a combination of UHG technology and restriction analysis, over 85% of type 2B vWD patients can be rapidly diagnosed by genotype.
Effects on Haemostasis of Hormone Replacement Therapy with Transdermal Estradiol and Oral Sequential Medroxyprogesterone Acetate: A 1 -year, Double-blind, Placebo-controlled Study
Authors:   The Writing Group for the Estradiol Clotting Factors Study
Published: July 2018

After menopause the haemostatic balance shifts towards a latent hypercoagulable state. To evaluate the effects of two regimens of transdermal estradiol (E2) combined with progestin on the balance between procoagulant factors and inhibitors, 255 women in physiological menopause for 1-5 years were randomly allocated to 1 year of treatment with cyclic transdermal E2 (50 Μg/day for 21 days) plus medroxyprogesterone acetate (MPA) (10 mg/day from days 10 to 21), continuous transdermal E2 (50 Μg/day for 28 days) plus MPA (10 mg/day from days 14 to 25), or placebo. Fibrinogen, factor VII (FVII), factor VIII:C (FVIII:C), antithrombin III (ATIII), protein C, protein S, heparin cofactor II (HCII) and plasminogen activator inhibitor (PAI-1) levels were measured at baseline and after 6 and 12 cycles. 167 women who took the treatment for at least 6 cycles were evaluable. The continuous treatment group had significantly lower final values of fibrinogen, FVII, ATIII, protein S and HCII than the placebo group; the cyclic treatment reduced fibrinogen in comparison with placebo but the difference was not significant.

In conclusion, both regimens produce a clinically relevant decrease of fibrinogen levels; the continuous regimen affects also the levels of FVII and inhibitors suggesting that the haemostatic balance is shifted to a more physiological state.
Role of the A+ Helix in Heparin Binding to Protein C Inhibitor
Authors: Elisen Marc G L M , Maseland Machiel H H , Church Frank C , Bouma Bonno N , Meijers Joost C M
Published: July 2018

Interactions between proteins and heparin(-like) structures involve electrostatic forces and structural features. Based on charge distributions in the linear sequence of protein C inhibitor (PCI), two positively charged regions of PCI were proposed as possible candidates for this interaction. The first region, the A+ helix, is located at the N-terminus (residues 1-11), whereas the second region, the H helix, is positioned between residues 264 and 280 of PCI. Competition experiments with synthetic peptides based on the sequence of these regions demonstrated that the H helix has the highest affinity for heparin. In contrast to previous observations we found that the A+ helix peptide competed for the interaction of PCI with heparin, but its affinity was much lower than that of the H helix peptide.

Recombinant PCI was also used to investigate the role of the A+ helix in heparin binding. Full-length (wild-type) rPCI as well as an A+ helix deletion mutant of PCI (rPCI-Δ2-l 1) were expressed in baby hamster kidney cells and both had normal inhibition activity with activated protein C and thrombin. The interaction of the recombinant PCIs with heparin was investigated and compared to plasma PCI. The A+ helix deletion mutant showed a decreased affinity for heparin in inhibition reactions with activated protein C and thrombin, but had similar association constants compared to wild-type rPCI. The synthetic A+ helix peptide competed with rPCI-Δ2-11 for binding to heparin. This indicated that the interaction between PCI and heparin is fairly non-specific and that the interaction is primarily based on electrostatic interactions.

In summary, our data suggest that the H helix of PCI is the main heparin binding region of PCI, but the A+ helix increases the overall affinity for the PCI-heparin interaction by contributing a second positively charged region to the surface of PCI.
Ablation Characteristics of Arterial Vessel Walls Irradiated with the Pulsed Dye Laser - An Analysis of Variance
Authors: Arndt Volker R , Duda Stephan H , Wehrmann Manfred , Huppert Peter E , Haase Konstantin K , Claussen Claus D
Published: July 2018

Background and Objective: Since most clinical laser angioplasties require the use of over-the-wire delivery systems, we studied the effects of pulsed dye laser energy (504 nm, 1.4 μs) on arterial vessel walls in combination with a multifiber catheter system.

Material and Methods: Postmortem arterial segments (n = 368) were exposed under blood or saline. Laser pulses (n = 100-800) were transmitted via 9F-multifiber-catheters, at energy densities of 3-16 J/cm2. Ablation characteristics revealed by histologic examination and morphometry were analyzed by multiple analysis of variance.

Results: Ablation occurred more frequently in saline compared to blood. Below an energy density of 10 J/cm2 ablation occurred in saline only. Specimens irradiated under blood showed only thermal changes at 10 J/cm2. In saline, 92% of normal, 88% of fibro-fatty and 60% of calcified tissue showed ablation at 13 J/cm2. The average ablation threshold in saline was about 3-4 J/cm2 per pulse for normal tissue, 5 J/cm2 for fatty plaques, and 8-9 J/cm2 for calcified plaques. In blood, the average ablation thresholds did not differ significantly between the different stages of arteriosclerosis (12 J/cm2 for normal tissue, 11 J/cm2 for fatty plaque, and 10 J/cm2 for calcified tissue). Carbonization and vacuolization were seen regularly at energy levels ≥13.4 J/cm2.

Conclusions: Selective ablation of arteriosclerotic tissue with the pulsed dye laser could not be found. Further investigation is needed before an effective ablation of arteriosclerotic arterial tissue can be expected.
Activation of Factor X by Factor VIIa Complexed with Human-mouse Tissue Factor Chimeras Requires Human Exon 3
Authors: Fang Carrie H , Lin T-C , Guha Arabinda , Nemerson Yale , Konigsberg William H
Published: July 2018

In an attempt to define sequence elements in human and mouse tissue factor (TF) that are responsible for the species specificity observed in their interaction with human factor VIIa (HVIIa), we constructed human-mouse chimeric TF cDNAs, inserted them into plasmid vectors, and induced their expression in E.coli. Assays for procoagulant activity were carried out with the resulting E. coli lysates using (HVIIa) human and mouse (MVIIa). The ratio of the procoagulant activities, HVIIa/MVIIa, revealed that human TF exon 3 was essential for activity when the TF:VIIa complex was formed with HVIIa. By ligating the maltose binding protein (MBP) gene to TF cDNAs it was possible to construct, express and purify MBP-TF chimeras as well as to estimate their specific activities. With selected MBP-TF chimeras and HVIIa we determined kinetic parameters for the activation of human factor X. Replacement of exon 3 in human TF cDNA with the corresponding exon from mouse TF cDNA resulted in both lower affinity for HVIIa and failure to convert bound HVIIa into a potent protease
A Chimeric Streptokinase with Unexpected Fibrinolytic Selectivity
Authors: Goldstein Joel , Matsueda Gary R , Shaw Shyh-Yu
Published: July 2018

Chimeric 59D8-SK was designed to confer fibrin-selectivity to streptokinase by fusion of the Fab fragment of anti-fibrin antibody 59D8 to the N-terminus of streptokinase (SK: Ile1-Lys414). It was expressed in a mouse hybridoma cell line and purified by affinity chromatography on a 59D8-antigen column. Chimeric 59D8-SK is a disulfide-linked heterodimer composed of an antibody light chain (Mr 27,000) and a N-glycosylated chimeric heavy chain (Mr 90,000). The fibrin targeting by 59D8 increased plasma clot lysis by 2-fold, but connecting 59D8 to SK has provided 59D8-SK several unique properties: (i) 59D8-SK activated human Glu-plasminogen with a significant lag period that coincided with limited proteolysis of 59D8-SK similar to that observed for wild-type SK. In a kinetic study, both gave very similar kinetic parameters for the activation of Glu-plasminogen even though 59D8-SK was N-glycosylated in its SK portion; (ii) 59D8-SK was relatively inactive in human plasma, compared to SK, but it became activated in the presence of clots; (iii) 59D8-SK lysed clots slowly but completely whereas SK lysed clots rapidly but incompletely. Even though the mechanism behind these new properties is not fully understood, they are characteristics of a second-generation plasminogen activator.
Studies Related To Tobacco Glycoprotein: A Claimed Activator Of Coagulation, Fibrinolysis, Complement, Kinin, And A Claimed Allergen
Authors: Bick R L , Stedman R L , Kronick P L , Hillman E , Fareed J
Published: July 2018

Brown pigments from cured tobacco leaf, cigarette smoke condensates and saline extracts of smoke have been referred to as tobacco glycoprotein (TGP) and have been reported to produce allergic skin reactions, induce the formation of IgE antibodies, and to activate clotting factor XII and subsequently activate the fibrinolytic and complement system. These sequential pathological events have been claimed to represent the pathophysiological link between cigarette smoking and cardiopulmonary disease which is observed statisl- tically. To more carefully investigate these claims TGP was extracted by the previously published method of Becker et. al. (Proc. Natl. Acad. Sci. 73:1712-1716, 1976) and the resultant material subjected to in vitro assays related to the claimed biological activities of TGP. It was found that TGP cannot be isolated following the above procedure; the final product obtained by the isolation procedure contains a contaminant introduced by PAGE separation. The contaminant (CMT) appears to be a linear polyacrylate. When this isolated material was subjected to clotting system assays it was found to complex with factor XII, depleting about 15% of factor XII from plasma and,thus, giving the superficial appearance of activating factor XII however, no such activation occurred as noted by non-shortening of the non-activated PTT system, and coagulation factor assays. CMT was found to have no activity on the complement, fibrinolytic, or kinin system. Acrylates are known allergens and thrombus-inducing agents, and these studies suggest that CMT, instead of TGP, has been isolated from cigarette derivitives by the above reported method and CMT rather than TGP has many of the biological activities previously, and perhaps mistakenly, ascribed to TGP.
Quantitation Of Platelet Lysis, Platelet Consumption On Oxygenator And Stabilization Of Platelet Membrane With Prostacyclin And Ibuprofen During Cardiopulmonary Bypass Surgery In Dogs
Authors: Dewanjee M K , Vogel S R , Peterson K A , Kaye M P
Published: July 2018

Prostacyclin (PGI2) and Ibuprofen (IP) may preserve platelet integrity and function during cardiopulmonary bypass (CPB). Platelet consumption on bubble and membrane oxygenator, platelet lysis, and platelet microembolism were studied in 7 control, 6 PGI2-, and 5 IP-treated dogs undergoing CPB. At 18 hours after I.V. administration of autologous In-Ill-labeled platelets (300 μCi), 7 heparinized dogs (300 u/kg), and 6 dogs treated with I.V. infusion of PGI2 (25 ng/kg/min) and heparin (100 u/kg), and 5 dogs with I.V. IP (12.5 mg/kg) 15 min prior to bypass procedure underwent CPB for 1 hour. In-111 in plasma obtained from platelet lysis was determined by centrifugation at 200,000 G of serial blood samples at 5-min intervals during CPB. Hemodilution was measured with I-125-labeled serum albumin (10 μCi). Platelet deposition on oxygenator was imaged with a gamma camera and quantitated with an ionization chamber. An insignificant amount of platelet (<0.2%) was found in the heat exchanger. In-111-labeled platelet level in blood of control dogs 20 min after CPB initiation decreased to 23 ± 5% of prebypass level, 38 ± 5% in PGI2 group, and 25 ± 5% in the IP group. Plasma In-111 increased to 34±7% in control, 15±5% in PGI2 group, and 17±3% in IP group (p< 0.01). Platelet deposition on the oxygenator amounted to 20±5% of In-111 platelets in control, 11±3% of PGI2, and 13±4% in IP group (p< 0.01). These results indicate that both PGI2 and IP significantly reduce platelet consumption in oxygenator and platelet lysis during CPB. Thus PGI2 may reduce postoperative bleeding. Ibuprofen, although preserving platelet function, has a longer duration of action and, hence, systemic administration prior to CPB is not practical. Surface coating of extracorporeal surfaces with IP might be beneficial.