bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Chimeric Streptokinase with Unexpected Fibrinolytic Selectivity
Authors: Goldstein Joel , Matsueda Gary R , Shaw Shyh-Yu 
Published: July 2018

SummaryChimeric 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.
The Inhibition Of Tissue Activator And Urokinase By Human Plasma
Authors: Walker J E , Ogston D 
Published: July 2018

The activity of urokinase (UK) on fibrin plates was inhibited by dilutions of normal plasma which failed to inhibit porcine heart activator (TA). Following passage of plasma through lysine-Sepharose inhibition was readily detected.Normal plasma separated on DEAE-Sepharose or, after passage through lysine-Sepharose, on Sephadex G-100 provided fractions in three regions capable of inhibiting the activity of TA.The high molecular weight fractions inhibited both TA and UK. When plasma was fractionated on Sepharose 4B the inhibitory activities against UK and TA eluted separately. UK inhibition appeared in the fractions containing α2 macroglobulin; the inhibitor of TA was present in fractions of higher molecular weight.Activator inhibition was found in two lower molecular weight regions of plasminogen-free plasma separated on Sephadex G-100: one region inhibited TA and coincided with the peak antiplasmin activity assessed by a chromogenic substrate. The other region comprised fractions which inhibited both TA and UK. Alpha1- antitrypsin and antithrombin III eluted after both inhibitory regions.It is concluded that normal plasma contains at least three proteins with inhibitory activity against TA and two which inhibit UK; one of these is capable of inhibiting both activators.
Substrate Specificity Of The Coagulant Enzymes From The Venom Of Vipera Russellii Russellii And Vipera Russellii Siamensis
Authors: Lavine Kathrine Kovach , Jackson Craig M 
Published: July 2018

Two enzymes that increase the rate of coagulation, are present in the venom of Vipera russellii and have been widely used as tools in investigating coagulation. Venoms from two subspecies of Vipera russellii are available, but the differences between these subspecies has not previously been investigated. The substrate specificities of these two enzymes and possible differences between the same enzyme from the two subspecies of Russell’s viper have not been extensively characterized. The “Factor X activator” activates not only Factor X, but Factor IX and Protein C. The relative rates of activation of these zymogens have been investigated by both their chromogenic substrate hydrolase activity and sodium dodecyl sulfate gel electrophoresis and have been observed to be markedly different. Factor X is activated far more rapidly than either Protein C or Factor IX. The “Factor X activator” from V. r. russellii and V. r. siamensis differ in their activities on these zymogens as well. Elimination of the region of the light chain of Factor X that contains the gamma carboxyglutamic acid residues also markedly reduces the rate at which it can be activated.The “Factor V activator”, which mimics thrombin in activating Factor V, appears to be much more specific. Little or no difference in the rate of Factor V activation by the enzymes from the two subspecies has been observed. Most importantly, the “Factor V activator” does not activate Protein C, making it a particularly useful tool for investigation of Factor V when the effects of Factor V degradation by activated Protein C are to be avoided.
Detection Of Antiplatelet Antibodies In Bstients With Idiopathic Thrombocytopenia Purpura (ITP) And In Patients With Rubella And Herpes Group Viral Infections
Authors: Kahane S , Dvilansky A , Estock L , Nathan I , Zolotov Z , Sorov I 
Published: July 2018

A highly sensitive enzyme linked immunosorbent assay (ELISA) technique was developed for serological detection of antibodies against platelets. Protein A covalently bound to Sepharose CL-4B was used to enrich sera in the IgG3 subclass. The assay uti lized antigen-coated polystyrene microplates; antigen consisted of sonicated platelets obtained from 0, Rh negative donors. Goat anti-human IgG peroxidase conjugate was used to detect antigen bound antiplatelet antibodies. The ELISA procedure was applied to detect antiplatelet antibodies in patients with herpes or rubella viral infections and in patients with idiopathic thrombocytopenic purpura (ITP). Twenty-eight sera from 13 thrombocytopenic patients showed high levels of antiplatelet antibodies. Two splenectomized patients in remission became negative for antiplatelet antibodies.Seventy-four sera from patients with serological diagnosis of herpes group viral infections comprising 10 cases of cytomegalovirus, 9 cases of varicella, 6 cases of herpes simplex and 4 cases of Epste in-Barr virus were examined for the presence of antiplatelet antibodies. All ten patients with acute CMV infection presented high titers against platelets. In four of them the highest titer of antiplatelet antibodies was observed even when the specific anti-CMV titer was still very low. All six patients with herpes simplex and all four cases with EBV as well as seven out of nine patients with varicella showed positive titers of antiplatelet antibodies. Out of eight cases of rubella which were also examined seven displayed antibodies against platelets. Sera from a group of 51 healthy controls were evaluated for antiplatelet antibodies. Forty-nine (96%) were negative ( 40), whereas the other two were only slightly positive.
Normalization By Suloctidil Of Decreased Platelet Survival In Patients With Heart Prosthetic Valves In Randomized Controlled Double Blind Trial
Authors: Ciavarella N , Antoneecchit S , D’Elia N , Ranieri P , Manzini A 
Published: July 2018

Platelets play an important role in thromboembo lie episodes in the life of patients with heart prosthetic valves. Decreased platelet survival and increased B-Tromboglobulin and Platelet F4 in the blood are constant features of such condition.45 patients on long term anticoagulant treatment (thrombotest 5-10%),26 males(mean age 46) and 19 females(mean age 44), were studied. 22 normal sub jects served as controls.Platelets survival was studied with MDA production after 5oo mg Aspirin intake and was found signifi canly reduced in patients in comparison to contro Is(p.8.00±1.4 days;c.10.00±1.67 days; P<0.01).BTG and PF4 as measured by RIA were increased (BTG:p.97.8±59 NG/ML;c.29.18±22.40 NG/ML; P<0.01) (PF4:p.36.6±26.5 NG/ML;c.6.29±4.78 NG/ML; P<0.01) The patients were randomly allocated to one of the following groups( 15 subjects each): placebo, Suloctidil 600 mg:die, Suloctidil 1200 mg:die. Duration treatment was 30 days.The effect of Suloctidil was significantly different from that of placebo( P<0.005),as regards Platelet survival without difference between dosa ges of the drug;as concerns BTG and PF4 the chang es under placebo and drug were not different.
Preparation Of Factor IX-Deficient Human Plasma Using RFF-IX/1 Monoclonal Antibody
Authors: Rotblat F , Goodall A H , Janossy G , Kemble G , O’Brien D P , Rawlings E , Russell G , Tuddenham E G D 
Published: July 2018

A cell line that secretes a monoclonal antibody to factor IX has been produced by fusing spleen cells from a mouse that had been hyper immunised to purified factor IX with mouse myeloma cells (line P3-NSI/I-Ag4-1). Hybrid cells were selected and a monoclonal cell line has been established in culture. This cell line secretes an IgGl(k) antibody (RFF-IX/1) with high affinity for a site related to the coagulant function of factor IX.Monoclonal antibody was partially purified from ascitic fluid from mice implanted with the RFF-IX/1 secreting cells by precipitation at 50% saturation with ammonium sulphate. This fraction has typically 630 NIH units/ml anti IX activity and 13.5 mg/ml protein. It was coupled to cyanogen bromide activated Sepharose 2B in the ratio of 9 mg. protein/1 ml gel. A column containing 10 ml of this gel removed all the assayable factor IX from the first 280 ml of normal ci.trated plasma that was passed over it. After that volume small amounts of factor IX could be detected in the effluent. Subsequently 10-20% of the factor IX activity adsorbed could be recovered by eluting the column with 3 M potassium iodide.Immuno-affinity depleted plasma could be used as substrate in a one-stage factor IX assay under routine laboratory conditions and was undistinguishable for that purpose from severe Christmas disease plasma.
Influence Of Fibrin Clots On The Development Of Granulation Tissue In Preformed Cavities
Authors: Hedelin H , Johansson S , Peterson H I , Teger-Nilsson A C , Pettersson S 
Published: July 2018

We have recently presented a new technique for occlusion of long standing fistulae by excochleation and plugging with a fibrin clot (Lancet, 1979). The intention with the technique was to keep the fistulous tract dry and occluded by a species-specific substance until healing had occurred. To study the importance of the fibrin clot in the present context an experimental study in rats has been performed. Perforated Teflon cylinders were implanted subcutaneously, removed after 1, 2 and 4 weeks and subjected to macro-and microscopic examination. Comparison was made between empty cylinders and cylinders filled with a fibrin clot.The examination after one week revealed the initially fibrin clot filled cylinders still to be filled by the clot. Ingrowth of granulation tissue through the cylinder perforations had started. The initially empty cylinders were still empty. At the 2-week examination the initially fibrin clot filled cylinders were at the peripheral half filled by ingrowing granulation tissue, the central half was filled by the implanted fibrin clot. The initially empty cylinders were filled to a lesser degree by ingrowing granulation tissue and a loose exdogenous clot centrally.The 4-week examination revealed both the initially empty and the initially fibrin clot filled cylinders to be completely filled up by granulation tissue of varying organisation.During the time it takes for the granulation tissue to grow into the cylinder the clot remains intact centrally and together they keep the cylinder filled up. It furthermore appears as if the fibrin clot induces a more rapid ingrowth into the cylinder. Both observations confirms the importance of the clot for the fistula occlusion.
Evidence For The Appearance Of Two Different Sets Of Polymerization Sites Upon The Sequential Release Of Fpa And Fpb
Authors: Brosstad F , Kierulf P 
Published: July 2018

Human des-AA (fmA) and des-AABB (fmAB) fibrin monomers were prepared from fibrinogen (F) exposed to insol. rep- tilase or thrombin in 2.5M urea, pH 7.4, for lh. FPA-RIA and N-term. amino acid anal, confirmed full conversion to fm species as above. Solubility of fmA and fmAB ( ) was determined by stepwise addition under whirlmixing to: I. Citrated plasma=10% (7.5%). II. BaSO4-adsorbed, recalcified plasma=3% (2.5%). III. F in 0.15 M Tris pH 7.4=17% (13%). Labeled fmA and fmAB incubated with FSF (preactivated with insol. thrombin) disclosed lower rates of gamma-gamma dimer formation and especially alphapolymer formation in fmA-clots than in fmAB clots. Affinity towards fibrinogen-Sepharose was definitely lower with fmA compared to fmAB when existing in soluble form in plasma. Increasing amounts of F progressively retarded and finally inhibited the polymerization of fmA and fmAB, and the retardation was linearly proportional to the F/fm ratio. The polymerization of fmA at a given F/fm ratio was more retarded than was that of fmAB. Ultracentrifugation (Airfug, Beckmann) of BaSO4-adsorbed, recalcified plasma containing I125f and T131 fmA or fmAB suggests complex formation between F and fm. Similar experiments with EDTA-plasma disclosed no fmA-F complex formation, whilst fmAB-F complexes still could be traced.From the above experiments it is concluded that two different sets of polymerization domains are exposed during the sequential release of FPA and FPB. Since fmAB solubility is far less than twice that of fmA, and the amount of F required to inhibit fmAB polymerization is far less than twice the amount of F necessary for inhibition of fmA polymerization, it is concluded that the polymerization domains exposed upon FPB release are less avid than the corresponding domains exposed upon FPA release.
Protein S mRNA in Patients with Protein S Deficiency
Authors: Sacchi E , Pinotti M , Marchetti G , Merati G , Tagliabue L , Mannucci P M , Bernardi F 
Published: July 2018

SummaryA protein S gene polymorphism, detectable by restriction analysis (BstXI) of amplified exonic sequences (exon 15), was studied in seven Italian families with protein S deficiency. In the 17 individuals heterozygous for the polymorphism the study was extended to platelet mRNA through reverse transcription, amplification and densitometric analysis. mRNA produced by the putative defective protein S genes was absent in three families and reduced to a different extent (as expressed by altered allelic ratios) in four families. The allelic ratios helped to distinguish total protein S deficiency (type I) from free protein S deficiency (type IIa) in families with equivocal phenotypes. This study indicates that the study of platelet mRNA, in association with phenotypic analysis based upon protein S assays in plasma, helps to classify patients with protein S deficiency.
Some Observations on the Coagulation Defect During Treatment with the Anticoagulant “Sintrom”
Authors: Vermeulen H. J , ten Bokkel Huinink S. A , Radhakishun K. S 
Published: July 2018

Conclusions1. The decrease of activity of prothrombin, occuring during administration of “Sintrom”, becomes only manifest when the activity of “factor VII” has fallen to less than half its normal value.2. The behaviour of the thrombin time is the manifestation of an important difference between the coagulation defect in hepatitis and that on administration of Sintrom.
Regulation, Location and Activity of Plasminogen Activator Inhibitor 2 (PAI-2) in Peripheral Blood Monocytes, Macrophages and Foam Cells
Authors: Ritchie Helen , Jamieson Alec , Booth Nuala A 
Published: July 2018

SummaryMonocytes, macrophages and foam cells are central to atherogenesis. We have examined the potential ability of monocytes, macrophages and foam cells to affect the stability of deposited fibrin, characteristic of the atherosclerotic plaque, by their production of plasminogen activators and their inhibitors. Monocytes respond to thrombin and LPS by up-regulation of PAI-2 synthesis, and PAI-2 is their major product among the plasminogen activators/inhibitors. In contrast, macrophages and foam cells, while they did produce PAI-2, did not respond to thrombin and LPS by an increase in its synthesis. All PAI-2 produced by macrophages and foam cells was accumulated intracellularly, whereas monocytes also secreted PAI-2. Secreted PAI-2 was active as an inhibitor of u-PA, whereas intracellular PAI-2 required detergent treatment to generate activity. Thus monocytes, but not macrophages or foam cells, produce and secrete active PAI-2, thus potentially affecting fibrin stability in the local environment.
Impact of Crystalloid or Albumin Priming of the Heart–Lung Machine on Inhospital Outcome after Coronary Artery Bypass Surgery
Authors: Weiler Pia , Hamiko Marwan , Mellert Fritz , Roell Wilhelm , Roell Martina , Welz Cecilia , Duerr Georg Daniel 
Published: July 2018

Abstract
Background Crystalloid priming is a cost-effective, free from immunological reactions, and independent from human plasma delivery. However, there is some debate on the negative impact of low plasma colloid pressure and higher incidence of systemic inflammatory response syndrome (SIRS). The aim of the study was to rule out any adverse effects of crystalloid priming on the postoperative outcome.
Methods We investigated 520 consecutive patients, including emergencies, who had isolated on-pump coronary artery bypass grafting in 2009 by retrospective analysis in our clinic. Crystalloid priming (n = 294) was introduced as an alternative to albumin (n = 226). Reviewing patient charts and IT-based data generated a dataset of perioperative parameters.
Results There were no differences with respect to demographical data and preexisting comorbidities between both groups. Despite equal perfusion times, more volume had to be substituted during extracorporeal circulation following crystalloid priming. However, this did not influence the inhospital outcomes. According to the definition of the “Sepsis-3 Guidelines,” the incidence of SIRS was similar. There was no difference in the need for a vasopressor treatment, and only transient higher serum lactate levels were found in the crystalloid group. The incidence of neurologic and organ-related adverse events, as well as 30-day mortality was comparable.
Conclusion The use of crystalloid priming is safe in coronary artery bypass grafting surgery in adults. However, there might be a greater need for crystalloid fluids during surgery.
Foam-driven fracture
Authors: Lai Ching-Yao , Rallabandi Bhargav , Perazzo Antonio , Zheng Zhong , Smiddy Samuel E. , Stone Howard A. 
Published: July 2018

Significance
Hydraulic fracturing plays an important role in meeting today’s energy demands. However, the substantial use of fresh water in fracturing and wastewater returning to the surface pose risks to the environment. Alternative technology has been developed that reduces the water-related risks by injecting aqueous foam instead of water to fracture shale formations, but the mechanism is poorly understood. Here, we show, using laboratory experiments, that the injection of foam instead of water dramatically changes the fracture dynamics when the foam compressibility is important. We develop a scaling argument for the fracture dynamics that exhibits excellent agreement with the experimental results. Our findings extend to other systems involving compressible foams, including fire-fighting, energy storage using compressed foams, and enhanced oil recovery.
Teachers’ curriculum agency in teaching a standards‐based curriculum
Authors: Alvunger Daniel 
Published: July 2018

AbstractIn 2011, Sweden introduced explicit standards for the curriculum used in compulsory schooling through the implementation of ‘knowledge requirements’ that align content, abilities and assessment criteria. This article explores and analyses social science teachers’ curriculum agency through a theoretical framework comprised of ‘teacher agency’ and Bernstein's concepts of ‘pedagogic device’, ‘hierarchical knowledge structure’ and ‘horizontal knowledge structure’. Teachers’ curriculum agency, in recontextualisation of the curriculum, is described and understood through three different ‘spaces’: a collective space, an individual space and an interactive space in the classroom. The curriculum and time are important for the possibilities of agency – the teachers state that the new knowledge requirements compel them to include and assess a lot of content in each ‘curriculum task’. It is possible to identify a recontextualisation process of ‘borrowing’ and combining content from curriculum tasks across the different subjects. This process is explained by the horizontal knowledge structure and ‘weak grammar’ of the social sciences. Abilities, on the other hand, stand out as elements of a hierarchical knowledge structure in which a discursive space is opened for knowledge to transcend contexts and provides opportunities for meaning‐making. The space gives teachers room for action and for integrating disciplinary content.
Ethics
Authors: Inwood Brad 
Published: July 2018

Abstract
Ethics is the part of the Stoics’ legacy that is most prominent and influential today. Their theory of the good life for human beings falls into the family of theories associated with Socrates and his followers. This tradition includes Plato and most Platonists, Xenophon, the Cynics, Aristotle, and later Aristotelians, all of whom share the view that virtue, the excellence of a human being, is the highest value and is its own reward. ‘Ethics’ discusses the Stoics’ views on human nature and rationality; the four basic virtues: justice, courage, wisdom, and moderation or self-control; and the doctrine that the fully rational and wise person will be free of passions.
Is What You Put in What You Get Out? —Textbook-derived Lexical Bundle Processing in Beginner English Learners
Authors: Northbrook Julian , Conklin Kathy 
Published: July 2018

AbstractUsage-based approaches to second language acquisition put a premium on the linguistic input that learners receive and predict that any sequences of words that learners encounter frequently will experience a processing advantage. The current study explores the processing of high-frequency sequences of words known as ‘lexical bundles' in beginner learners of English in Japanese secondary school. To do this we use a phrasal judgment task, testing students on items taken directly from their teaching materials. Students responded to lexical bundles that occurred in their textbooks significantly faster and more accurately compared with non-lexical bundles, and were sensitive to the frequency of occurrence in their textbooks. This study shows, perhaps for the first time, that even very low-level, beginner secondary students are sensitive to the frequency of lexical bundles which appear in the input they receive from teaching materials, a finding that has important implications for teaching and material design.
DiscoverSL: an R package for multi-omic data driven prediction of synthetic lethality in cancers
Authors: Das Shaoli , Deng Xiang , Camphausen Kevin , Shankavaram Uma 
Published: July 2018

Abstract

Summary
Synthetic lethality is a state when simultaneous loss of two genes is lethal to a cancer cell, while the loss of the individual genes is not. We developed an R package DiscoverSL to predict and visualize synthetic lethality in cancers using multi-omic cancer data. Mutation, copy number alteration and gene expression data from The Cancer Genome Atlas project were combined to develop a multi-parametric Random Forest classifier. The effects of selectively targeting the predicted synthetic lethal genes is tested in silico using shRNA and drug screening data from cancer cell line databases. The clinical outcome in patients with mutation in primary gene and over/under-expression in the synthetic lethal gene is evaluated using Kaplan–Meier analysis. The method helps to identify new therapeutic approaches by exploiting the concept of synthetic lethality.

Availability and implementation
DiscoverSL package with user manual and sample workflow is available for download from github url: https://github.com/shaoli86/DiscoverSL/releases/tag/V1.0 under GNU GPL-3.

Supplementary information
Supplementary data are available at Bioinformatics online.