bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of Platelet Function by Antiarrhythmic Drugs, Verapamil and Disopyramide
Authors: Han P , Boatwright C , Ardlie N G
Published: July 2018

Various cardiovascular drugs such as nitrates and propranolol, used in the treatment of coronary artery disease have been shown to have an antiplatelet effect. We have studied the in vitro effects of two antiarrhythmic drugs, verapamil and disopyramide, and have shown their inhibitory effect on platelet function. Verapamil, a calcium channel blocker, inhibited the second phase of platelet aggregation induced by adenosine diphosphate (ADP) and inhibited aggregation induced by collagen. Disopyramide similarly inhibited the second phase of platelet aggregation caused by ADP and aggregation induced by collagen. Either drug in synergism with propranolol inhibited ADP or collagen-induced platelet aggregation. Disopyramide at high concentrations inhibited arachidonic add whereas verapamil was without effect. Verapamil, but not disopyramide, inhibited aggregation induced by the ionophore A23187.
Non-Decalcified Barium Sulfate-Adsorbed Plasma A Potentially Useful Reagent for Studying Blood Clotting, Platelets or Complement
Authors: Zucker Marjorie B , Owen John
Published: July 2018

Plasma was prepared by rapid centrifugation of native blood followed by adsorption of vitamin K-dependent clotting factors with BaSO4. Compared to fresh citrated plasma, BaSO4-treated plasma contained about 80% of factor V and factor VIII and the same concentration of fibrinopeptide A. Assays were also carried out after overnight incubation of citrated plasma and BaSO4-adsorbed plasma with and without added citrate and compared to assays of fresh citrated plasma. Factor V decreased to about 25% in both citrated samples, factor VIII decreased to 45% in both samples of BaSO4-treated plasma, and fibrinopeptide A did not change. Thus loss of factor V activity depended on reduction in divalent cation concentration whereas loss of factor VIII activity may have resulted from effects of early traces of thrombin.
Subcellular Localization of Adenosine Diphosphatase in Cultured Pig Arterial Endothelial Cells
Authors: Lieberman Elisabeth G , Leake David S , Peters Timothy J
Published: July 2018

A role for vessel wall adenosine diphosphatase (ADPase) in limiting platelet aggregation has been suggested by a number of studies. The purpose of this study was to determine the properties and subcellular localization of ADPase in endothelial cells.

Homogenates were prepared from subcultured pig aortic endothelial cells and used to determine the kinetics of ADPase activity with a recently described rapid assay employing [²-32P]ADP. The activity was linear with incubation time and homogenate concentration. The pH optimum was 7.4 and the apparent Km was 43 ¼M. The enzyme displayed an absolute divalent cation requirement and its activity was unaffected by levamisole, a specific alkaline phosphatase inhibitor, or by 2-glycerophosphate, a substrate for non-specific phosphatases.

Post-nuclear supernatants were prepared from cell homogenates and were fractionated by sucrose density centrifugation. The distribution of ADPase activity in the gradient corresponded to 5'nucleotidase, a plasma membrane marker enzyme, and was clearly distinct from the other organelle marker enzymes. When the cells were treated with the cholesterol-binding agent, digitonin, before being homogenized, the activities of both 5'nucleotidase and ADPase shifted to a denser zone in the gradient, confirming their coincident localization to the plasma membrane.

Intact and sonicated cells were incubated with the poorly permeant enzyme inhibitor, diazotized sulphanilic add. With intact cells, ADPase and 5'nucleotidase were inhibited whereas lactate dehydrogenase, an intracellular enzyme, was unaffected; with sonicated cells all three enzymes were inactivated. ADPase is thus an ecto-enzyme on the plasma membrane of cultured pig aortic endothelial cells and is therefore ideally located for a role in limiting platelet aggregation.
Changes in Platelet Function, Blood Coagulation and Fibrinolysis During Insulin-Induced Hypoglycaemia in Juvenile Diabetics and Normal Subjects
Authors: Dalsgaard-Nielsen J , Madsbad S , Hilsted J
Published: July 2018

Haemostatic parameters were assessed before insulin induced hypoglycaemia and 0, 1 and 2 fu after discontinuation of insulin infusion in 7 non-diabetics, aged 28 (22-31) years (mean and range), and 8 juvenile diabetics, aged 3L (27-35) years, with a mean duration of diabetes of 4 years. The patients were normoglycaemic for at least L0 hr before the study.

Platelet aggregation in vitro was induced by lower adenosine diphosphate (ADP) concentrations in the diabetics than in the controls before hypoglycaemia and 0 and 60 min after insulin infusion. Platelet counts decreased significantly in the diabetics after hypoglycaemia, whereas no changes were seen in the control group. The activated partial thromboplastin time (APTT) was reduced in both groups and significantly lower in the diabetics than in the controls 120 min after insulin infusion.

Fibrinogen and factor VIII R: Ag increased after insulin infusion; highest values were seen in the diabetics. The euglobulin clot lysis time (ELT) was reduced in both groups during insulin infusion; L20 min after end of insulin infusion ELT was significantly longer in the diabetics than in the control group.
Patterns of Adsorption of Proteins From Human Plasma Onto Foreign Surfaces
Authors: Uniyal S , Brash J L
Published: July 2018

The deposition of proteins on blood-contacting surfaces is known to be a determining factor in subsequent thromboembolic events. The composition of the protein layers and how they change with time are unknown. To generate information relevant to these questions, the quantities of albumin, fibrinogen and IgG adsorbed on seven surfaces from human plasma as a function of time were measured using a tracelabeling method. Materials studied include several segmented polyether-urethanes, glass, siliconized glass (SG), polystyrene (PS) and polyethylene (PE).

Fibrinogen, surprisingly, was not adsorbed from plasma to any of the hydrophilic surfaces. On PE and SG adsorption passed through an early maximum (before 2 min) then declined to near zero. Only on PS was adsorption substantial and constant with time. Albumin was also not detected on the hydrophilic materials, but was adsorbed substantially on the hydrophobic surfaces. IgG was detected on all surfaces, although in relatively low surface concentrations.

These results suggest: 1. that the plasma itself interacts with initially adsorbed proteins, 2. that the role of fibrinogen adsorption in foreign-surface initiated thrombosis may need to be reevaluated and 3. that since the major plasma proteins are only minimally adsorbed, trace proteins may be important in blood-material interactions.
A Clinical and Phlebographie Study of Postoperative Deep Vein Thrombosis Following Knee Meniscus Extirpation
Authors: Nilsen D W T , Westre B , Jaer Ø , Støren G , Jakobsen J Å
Published: July 2018

To evaluate the risk of deep vein thrombosis, a clinical and phlebographic examination was performed 7 to 16 days after a bloodless knee meniscus operation in 37 male patients aged 20 to 35 years. Anticoagulant prophylaxis was not administered. Phlebography revealed asymptomatic calf vein thrombosis in three patients and these were not treated. In two of these phlebography was repeated after six weeks, and complete regression of the thrombi was noted.

The present study may underestimate the frequency of postoperative venous thrombosis, as some thrombi may already have lysed at the time of phlebography. However, our results indicate a low incidence of thrombosis after knee meniscus extirpation.
Factor XII and Other Hemostatic Protein Abnormalities in Nephrotic Syndrome Patients
Authors: Thompson Arthur R
Published: July 2018

Factor XII clotting activities and antigen levels were assayed in 14 plasma samples from 10 patients with nephrotic syndrome; the group was heterogeneous clinically and histologically. Factor XII was low at initial sampling in 7 of the 10 patients; in 7 of the 14 samples, factor XII antigen was in excess over clotting activity. Inhibition of factor XII could not be demonstrated; excess plasma antigen and urinary antigen (when present) had normal patterns on crossed-immunoelectrophoresis, indicating no major changes in charge or size. In 3 patients tested more than once, plasma levels of factor XII were increased up to 6fold in steroid-induced remission.

Of other hemostatic factors assessed for comparison, factor VIII was elevated in 11 of the 14 samples; eight of these had elevated factor VII levels as well. Eight samples from six patients showed low antithrombin III levels; one of these patients had recurrent thromboses. Antithrombin III levels correlated with the serum albumin concentration.

Only two of the eight urines tested had detectable factor XII antigen; a third had factor IX and prothrombin and no factor XII. Plasminogen and antithrombin III were readily demonstrated in all urine samples with higher concentrations in those patients with less selective proteinuria. Urinary and plasma levels were not correlated, suggesting that increased consumption or turnover was not simply related to increased filtration.
Reactivity of Fibrinogen Derivatives with Antisera to Human Fibrin D-Dimer and Its γ-γ Chain Remnant
Authors: Cierniewski C S , Janiak A , Nowak P , Augustyniak W
Published: July 2018

Highly purified D-dimer was obtained from plasmin digest of human cross-linked fibrin. After reduction of its disulfide bonds, the γ-γ chain remnant, containing cross-linking site, was then isolated by ion-exchange chromatography on CM-cellulose. Antisera obtained by immunizing rabbits with D-dimer and its γ-γ chain remnant contained a small population of antibodies which specifically reacted with D-dimer. Thus, a specific radioimmunoassay system allowing detection and quantitation of D-dimer in the presence of fibrinogen and monomeric fragment D was made possible.
Opposite Effect of Lysine on Platelet Aggregation Induced by Arachidonate and by Other Aggregants
Authors: Ts'ao C , Hart S J , Krajewski D V , Sorensen P G
Published: July 2018

Earlier, we found that ε-aminocaproic acid (EACA) inhibited human platelet aggregation induced by adenosine diphosphate (ADP) and collagen, but not aggregation by arachidonic acid (AA). Since EACA is structurally similar to lysine, yet these two agents exhibit vast difference in their antifibrinolytic activities, we chose to study the effect of lysine on platelet aggregation. We used L-lysine-HCl in these studies because of its high solubility in aqueous solutions while causing no change in pH when added to human plasma. With lysine, we repeatedly found inhibition of ADP-, collagen- and ristocetin-induced aggregation, but potentiation of AA-induced aggregation. Both the inhibitory and potentiation effects were dose-dependent. Low doses of lysine inhibited the secondary phase of aggregation; high doses of it also inhibited the primary phase of aggregation. Potentiation of AA-induced aggregation was accompanied by increased release of serotonin and formation of malondialdehyde. These effects were not confined to human platelets; rat platelets were similarly affected. Platelets, exposed to lysine and then washed and resuspended in an artificial medium not containing lysine, remained hypersensitive to AA, but no longer showed decreased aggregation by collagen. Comparing the effects of lysine with equimolar concentrations of sucrose, EACA, and α-amino-n-butyric acid, we attribute the potent inhibitory effect of lysine to either the excess positive charge or H+ and C1− ions. The -NH2 group on the α-carbon on lysine appears to be the determining factor for the potentiation effect; the effect seems to be exerted on the cyclooxygenase level of AA metabolism. Lysine and other chemicals with platelet-affecting properties similar to lysine may be used as a tool for the study of the many aspects of a platelet aggregation reaction.
Thrombin Inhibition and Thrombin Generation by Cultured Aortic Endothelial and Smooth Muscle Cells from Minipig
Authors: Kirchhof B , Grünwald J
Published: July 2018

Endothelial and smooth muscle cells cultured from minipig aorta were examined for their inhibitory activity on thrombin and for their thrombin generating capacity.

Endothelial cells showed both a thrombin inhibition and an activation of prothrombin in the presence of Ca++, which was enhanced in the presence of phospholipids. Smooth muscle cells showed an activation of prothrombin but at a lower rate. Both coagulation and amidolytic micro-assays were suitable for studying the thrombin-vessel wall interaction.
Activation of Factor IX by Factor XIa - A Spectrophotometric Assay for Factor IX in Human Plasma
Authors: Tans G , Janssen-Claessen T , van Dieijen G , Hemker H C , Rosing J
Published: July 2018

The activation of Factor IX by partially purified Factor XIa was followed by active site titration, gelelectrophoresis and by a spectrophotometric assay. The assay is based on the finding that the rate of Factor X activation in the presence of phospholipid and Ca2+ is linear in time and proportional to the amount of Factor IXa present and can be determined with the chromogenic substrate S2222. Conditions were found that allowed complete activation of Factor IX in human plasma by Factor XIa. The amount of Factor IXa present in the plasma sample can be determined with the spectrophotometric assay and is proportional with the amount of plasma present. In plasma from patients receiving vitamin-K antagonists reduced Factor IX activity is found with the spectrophotometric assay, and the new assay method may be useful in monitoring oral anticoagulant therapy.
Effect of Pyridoxal 5'-Phosphate (PALP) on Human Platelet Aggregation, Dense Granule Release and Thromboxane B2 Generation - Role of Schiff Base Formation
Authors: Krishnamurthi S , Westwick J , Kakkar V V
Published: July 2018

Pyridoxal 5’-phosphate (PALP) inhibited ADP, thrombin, adrenaline, PAF and AA induced aggregation and 14C-5HT release. Thromboxane B2 (TxB2) generation induced by all the above agents except AA was also inhibited indicating that PALP may be inhibiting AA release via phospholipase A2 activation rather than AA metabolism. PALP inhibited ristocetin induced aggegation in PRP and agglutination in formaldehyde-treated washed platelets (FWP). Inhibition of ADP, adrenaline, PAF and AA-induced aggregation and 14C-5HT release by PALP was found in resuspended platelets pretreated with PALP and sodium borohydride suggesting that inhibition was mediated by Schiff base formation with platelet surface amino groups.

Irreversible fixation of PALP to the platelet membrane by borohydride reduction also inhibited thrombin induced 14C-5HT release and TxB2 generation but not thrombin induced primary aggregation or ristocetin induced agglutination in FWP. This suggests that PALP may interact with specific glycoproteins on the platelet membrane involved in ADP, adrenaline and PAF induced primary aggregation and that PALP could be inhibiting ristocetin induced agglutination by direct interaction with ristocetin or FVIII RCoF.
The Incidence of Deep Venous Thrombosis in Patients with an Acute Myocardial Infarction Treated with Acenocoumarol or Indobufen
Authors: Peters S H A , Jonker J J C , de Boer A C , den Ottolander G J H
Published: July 2018

In a randomized double blind clinical trial, we compared indobufen, an antiplatelet drug, with acenocoumarol for the prevention of deep venous thrombosis (D. V. T.) in patients with acute myocardial infarction. Therapy was started on admission and continued for 10 days. All patients were screened daily with impedance plethysmography (I.P.G.) and 125I-fibrinogen leg scanning. Diagnosis of D.V.T. was made when either one or both tests became positive. 74 patients were randomized to treatment with indobufen (200 mg b.i.d.) and 76 patients to acenocoumarol (controlled by thrombotest). The incidence of venous thrombosis in patients with indobufen was 11% and in those treated with acenocoumarol 9%. Major bleeding was observed in 2 patients treated with acenocoumarol. In the indobufen group, no bleeding complications or other serious side-effects were observed. The majority of patients developed thrombosis after the first week of admission. For patients with and without thrombosis, there was no significant difference between the two treatment groups concerning the age, the coronary prognostic index, the maximum C.P.K. value, mobility, incidence of congestive heart failure and the site or extent of the infarct. In this study no clinical or laboratory (fibrinogen, platelet count and anti-thrombin III) parameter, either alone or in combination, was of predictive value for the development of D.V.T. It can be concluded that indobufen appears to be as good as acenocoumarol for the prevention of D.V.T. in patients with acute myocardial infarction. Because it is safe and easy to administer, indobufen seems to be preferable. Prophylaxis is required for at least 10 days.
Kinetics of the Inhibition of Plasmin in Acidified Human Plasma
Authors: Lijnen H R , Maes M , Castel M , Samama M , Collen D
Published: July 2018

Acid-treated human plasma is a competitive inhibitor of the hydrolysis of D-Val-Leu-Lys-Nan (S-2251) by plasmin. The rate of hydrolysis is decreased to 50% by 750 fold diluted acidified normal plasma and by 60 fold diluted acidified α2-antiplasmin depleted plasma (α2-antiplasmin concentration less than 2%). These findings suggest that α2-antiplasmin is a contributary but not the main competitive inhibitor of acidified plasma. This interpretation is supported by the finding that α2-antiplasmin depleted plasma reconstituted with purified α2-antiplasmin inhibits the hydrolysis of S-2251 by plasmin at a 125 fold dilution following acidification and by the finding that in a purified system acid inactivated α2-antiplasmin inhibits the hydrolysis of S-2251 by plasmin with a Ki of 25 nM. Thus, besides α2-antiplasmin, other plasma proteins which are at least in part eliminated by the removal of α2-antiplasmin from plasma by immunoadsorption appear to be competitive inhibitors for plasmin in acidified plasma. It is suggested that several competitive inhibitors for plasmin are present and/or generated in acidified plasma and that these inhibitors may at least in part be responsible for the variability in the results of measurements of plasminogen and/or plasmin in plasma following acidification.
Purification of Human Tissue-Type Plasminogen Activator in Centigram Quantities from Human Melanoma Cell Culture Fluid and Its Conditioning for Use In Vivo
Authors: Collen D , Rijken D C , Van Damme J , Billiau A
Published: July 2018

Human tissue-type plasminogen activator was produced in centigram quantities from 50–60 1 batches of conditioned medium of a human melanoma cell culture. The yields of the procedure remained essentially unchanged during 50 subsequent preparations. The final products were of high purity as assessed by SDS gel electrophoresis.

These materials, after filtration on 0.22 μM Milliporefilters were sterile and free of viruses and pyrogens. Their stability was very good in the fluid form at temperatures up to 56° C. Material obtained by the present procedure has been used to investigate the biological and thrombolytic properties of tissue-type plasminogen activator.
Platelet Inhibitory Drugs: An In Vivo Method of Evaluation in Patients
Authors: Norcott H C , Goldman M , Hawker R J , Rafiqi E I , Drolc Z , McCollum C N
Published: July 2018

The measurement of platelet deposition in human thrombi is essential for the evaluation of platelet-inhibitory drugs and prosthetic materials for use in patients. The rate of 111Indiumlabelled platelet accumulation on Dacron arterial grafts was measured in 27 patients randomised to take either aspirin and dipyridamole (ASA + DPM) or placebo. Autologous platelets were labelled and re-injected seven days following surgery and the graft thrombogenidty index calculated as the daily rise in the ratio of emissions from the graft over a reference site.

The mean (± SD) thrombogenidty index in 12 patients undergoing femoro-popliteal bypass was 0.25 ± 0.09 on placebo and 0.16 ± 0.07 on ASA + DPM started pre-operatively (p Ã0.05). Post-operative ASA + DPM therapy started two days following platelet labelling in 15 patients with aorto-femoral grafts also significantly reduce thrombogenidty to 0.12 ± 0.05 compared with 0.25 ± 0.08 on placebo (p Ã0.01). In the latter patients the ratio of emissions from the graft over reference fell significantly on starting ASA + DPM, suggesting a net loss of platelets from the graft. These results indicate that the rate of in vivo platelet accumulation on Dacron grafts can be quantitated and that ASA + DPM reduced this rate in man.
The Suitability of Various Plasmin Preparations for the Functional Assay of α2-Antiplasmin in Plasma
Authors: Kluft C , Traas D W , Jie A F H , Nobel E Hoegee-de
Published: July 2018

Various plasmin preparations were tested for their suitability for use in the assay of α2-antiplasmin in blood plasma by the immediate plasmin inhibition test.

Activation of plasminogen, viz., 1-Glu-plasminogen and/or 77-Lys-plasminogen, by immobilized urokinase results in plasmin preparations suitable for this α2-antiplasmin test. Plasmins obtained by »spontaneous« activation procedures in glycerol containing solutions, however, appeared not to be suitable. In this second group, the behaviour of the plasmins resembles that of 442-Val-plasmin (miniplasmin), which is known to show a low inactivation rate with α2-antiplasmin due to the absence of lysine-binding sites in the plasmin molecule.

Evidence is presented that, in the nonsuitable plasmins, the lysine-binding sites, although not completely absent, have at least partly lost their functional integrity.
Platelet Aggregation in Whole Blood Determined Using the Ultra-Flo 100 Platelet Counter
Authors: Fox S C , Burgess-Wilson M , Heptinstall S , Mitchell J R A
Published: July 2018

The Ultra-Flo 100 Whole Blood Platelet Counter has proved a useful tool for measuring platelet aggregation in whole blood, the extent of aggregation being deduced from the number of single platelets that remain. The technique has allowed us to show that platelets aggregate spontaneously in citrated blood and in heparinized blood but not in whole blood collected into EDTA. The aggregation occurs during storage but its rate is enhanced by stirring and it occurs more readily when the whole blood has been exposed to plastic rather than glass. It occurs much more readily in whole blood from some individuals than from others and the process may involve adenosine diphosphate (ADP). The rate of aggregation in whole blood is enhanced by several aggregating agents including collagen, ADP and sodium arachidonate which are more usually studied in platelet-rich plasma.
Platelet Microtubules in Clot Structure Formation and Contractile Force Generation: Investigation of a Controversy
Authors: Jen C J , McIntire L V
Published: July 2018

Whether platelet microtubules are involved in clot retraction/ contraction has been controversial. To address this question we have simultaneously measured two clotting parameters, clot structural rigidity and isometric contractile force, using a rheological technique. For recalcified PRP clots these two parameters began rising together at about 15 min after CaCl2 addition. In the concentration range affecting microtubule organization in platelets, colchicine, vinca alkaloids and taxol demonstrated insignificant effects on both clotting parameters of a recalcified PRP clot. For PRP clots induced by adding small amounts of exogenous thrombin, the kinetic curves of clot rigidity were biphasic and without a lag time. The first phase corresponded to a platelet-independent network forming process, while the second phase corresponded to a platelet-dependent process. These PRP clots began generating contractile force at the onset of the second phase. For both rigidity and force parameters, only the second phase of clotting kinetics was retarded by microtubule affecting reagents. When PRP samples were clotted by adding a mixture of CaCl2 and thrombin, the second phase clotting was accelerated and became superimposed on the first phase. The inhibitory effects of micro tubule affecting reagents became less pronounced. Thrombin clotting of a two-component system (washed platelets/ purified fibrinogen) was also biphasic, with the second phase being microtubule-dependent. In conclusion, platelet microtubules are important in PRP clotted with low concentrations of thrombin, during which fibrin network formation precedes platelet-fibrin interactions. On the other hand they are unimportant if a PRP clot is induced by recalcification, during which the fibrin network is constructed in the presence of platelet-fibrin interactions. The latter is likely to be more analogous to physiological processes in vivo.
Prophylaxis of Thromboembolic Disease and Platelet-Related Changes Following Total Hip Replacement: A Comparative Study of Aspirin and Heparin-Dihydroergotamine
Authors: Alfaro M J , Páramo J A , Rocha E
Published: July 2018

A prospective study involving 120 consecutive patients undergoing total hip replacement was performed to compare the effectiveness of aspirin (high and low dose) or a combination of heparin plus dihydroergotamine (heparin-DHE) in preventing isotopic and phlebographic deep vein thrombosis (DVT), and to evaluate their effect on postoperative platelet changes. Phlebographic DVT was demonstrated in 9 cases (30%) in control group, in 1 (3.3%) in aspirin (high-dose) group (p <0.01), in 1 (3.3%) in aspirin (low-dose) group (p <0.01) and in 5 (16.6%) in heparin-DHE group (p = NS). Aspirin was able to reduce the postoperative increase in circulating platelet aggregates, platelet factor 4 and p-thromboglobulin observed in control group. This study shows that aspirin is effective in the prevention of DVT for patients undergoing total hip replacement. Small aspirin dose (250 mg/day) represents an effective form of prophylaxis in these patients.
Megakaryocytes from the Marrow of a Patient with Glanzmann’s Thrombasthenia Lacked GPII b-III a Complexes
Authors: Hourdillé P , Fialon P , Belloc F , Namur M , Boisseau M R , Nurden A T
Published: July 2018

Although it is recognized that glycoprotein (GP) IIb-IIIa complexes are deficient in platelets in Glanzmann’s thrombasthenia, little is known of the origin of the defect. We have examined the megakaryocytes in a bone marrow aspirate obtained from a thrombasthenia patient during surgery. Analysis of platelet proteins by SDS-polyacrylamide gel electrophoresis confirmed the patient to be of the type I subgroup. The megakaryocytes were examined by immunofluorescence or by immunocytochemical procedures combined with electron microscopy. Antibodies used included the murine monoclonal antibody, AP-2 and the human allo-antibody, IgG L, both of which recognize determinants on GP IIb-IIIa complexes. Bound antibody was detected by anti-IgG antibodies coupled to fluorescein isothiocyanate or adsorbed on gold particles. In the immunofluorescence studies, permeabilized megakaryocytes were identified by double staining using an antibody to von Willebrand factor (vWF). Whereas mature megakaryocytes and their small precursor cells from normal individuals were strongly fluorescent with AP-2 and IgG L, most vWF positive cells from the Glanzmann’s thrombasthenia patient were negative and the remainder gave but a weak background fluorescence. Immunogold staining on the surface of marrow cells was severely reduced. Our results confirm a deficiency of GP IIb-IIIa complexes in megakaryocytes in thrombasthenia.
Immunopurification of Human Coagulation Factor IX Using Monoclonal Antibodies
Authors: Bessos Hagop , Prowse Christopher V
Published: July 2018

This study examines the suitability of four recently characterised monoclonal antibodies (MAbs) for the immunoaffinity purification of human coagulation factor IX (FIX) from plasma concentrates. Initial studies using 125I-FIX indicated that appreciable amounts of bound FIX could be eluted from immobilised MAbs with 0.2 M glycine, 50% ethanediol pH 10 (buffer N). Further studies with FIX concentrates showed that buffer N eluted FIX without compromising the activity of the zymogen. Although FIX was eluted from all four MAbs with this buffer, the best yield (82%) was obtained with MAb ESN-3. ESN-3 bound 40 to 60 iu FIX per mg MAb when immobilised on Sepharose 4B. After washing, column elution with buffer N yielded FIX at 100-200 iu/mg. The purity of the product was confirmed by sodium-dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and by Western blotting. The product contained no detectable mouse IgG (<3%) and <1% FII, X, or protein C.
Gibt es Unterschiede von Lebensqualität und funktioneller Gesundheit zwischen der Kombination eines Leistungslasers mit Manueller Therapie im Vergleich zu Ultraschall mit Manueller Therapie?
Authors: Best Norman , Loppar Ariane , Derlien Steffen , Bocker Barbara , Aurich Matthias
Published: July 2018

Ziel der Studie Nachweis von Wirkunterschieden von Ultraschall bzw. Leistungslaser in Kombination mit Manueller Therapie auf die Lebensqualität bei LWS- und Schulterpatienten.

Methodik 2×20 Patienten mit LWS- bzw. Schulterbeschwerden wurden randomisiert in ein Parallel-Design eingeschlossen. Nach 2 Wochen Wash-Out-Phase erfolgte die Behandlung mit Ultraschall bzw. Laser und Manueller Therapie über 2 Wochen mit insgesamt 6 Behandlungsterminen. Ein Follow-up von 4 Wochen wurde ebenfalls in die Untersuchung einbezogen. An 4 Messzeitpunkten wurden SF-36, EQ-5D, DASH bzw. FFbH-R ausgewertet.

Ergebnisse Besserungen sämtlicher Assessmentscores im Studienzeitraum. Kein Unterschied zwischen Regionen und Anwendungen.

Schlussfolgerung Laser und Ultraschall in Kombination mit Manueller Therapie führten bei der Studienpopulation zur Besserung der Assessmentscores.
Immuncheckpoint-Inhibitoren: Aktuelle Indikationen und mögliche zukünftige Konzepte
Authors: Schlaak Max , Baues Christian , Trommer-Nestler Maike , Berking Carola , Belka Claus , Theurich Sebastian
Published: July 2018

Immuno-oncological therapy concepts have already achieved great success in the treatment of a number of advanced malignancies, thereby rapidly gaining access to clinical practice. Immuncheckpoint inhibitors are also being reviewed in the adjuvant setting. In malignant melanoma, they have already shown efficacy. Different combination strategies of Immuncheckpoint inhibitors are currently undergoing clinical evaluation to further improve treatment outcomes. However, this has so far also been associated with a significantly increased immune-mediated rate of side effects. Effective and safe immuno-oncology requires good clinical management of immune-mediated side effects. Radiological assessment is challenging under immunotherapy and requires new standards (iRECIST). Encouraging is the fact that immunotherapy also causes long-term remissions in some of the patients. This raises the hope for a fundamentally curative potential of immuno-oncological therapeutic approaches.
Policy change and the narratives of Russia’s think tanks
Authors: Bacon Edwin
Published: July 2018

Russia’s ruling regime, dominated by Vladimir Putin since he first became president in 2000, is often seen as presenting a consistent and coherent narrative and allowing little space for plurality of opinions. While it is the case that at the level of metanarrative, a consistent official story of a Russia resurgent both domestically and internationally has been told, analysis of the work of think tanks within the purview of Russia’s political leadership reveals that conflicting narratives remain at play within the regime’s political tent. Analysis of a decade of think tank activity shows that the Medvedev presidency (2008–2012) saw the rise and then decline of the liberal INSOR think tank, while the most prominent think tank in Putin’s third term as president (2012–2018) was the anti-liberal Izborskii Club, which followed a similar pattern of waxing and waning prominence. From the point of view of Russia’s leadership, the existence of these think tanks has a functionalist explanation, allowing what is essentially a non-ideological regime to engage with and adopt different positions according to its proximate requirements. Such a functionalist approach runs the risk of undermining the coherence and persuasiveness of the regime’s narrative(s). From the point of view of the political science classification of the extant Russian regime, Russia’s post-Soviet ‘transition’ remains to be resolved in terms of its chosen course even a quarter of a century on from the collapse of Communism.
Symmetries of the hydrogen atom and algebraic families
Authors: Subag Eyal M.
Published: July 2018

We show how the Schrödinger equation for the hydrogen atom in two dimensions gives rise to an algebraic family of Harish-Chandra pairs that codifies hidden symmetries. The hidden symmetries vary continuously between SO(3), SO(2, 1), and the Euclidean group O(2)⋉R2. We show that the solutions of the Schrödinger equation may be organized into an algebraic family of Harish-Chandra modules. Furthermore, we use Jantzen filtration techniques to algebraically recover the spectrum of the Schrödinger operator. This is a first application to physics of the algebraic families of Harish-Chandra pairs and modules developed in the work of Bernstein et al. [Int. Math. Res. Notices, rny147 (2018); rny146 (2018)].
Optical bistability in shape-memory nanowire metamaterial array
Authors: Nagasaki Yusuke , Gholipour Behrad , Ou Jun-Yu , Tsuruta Masanori , Plum Eric , MacDonald Kevin F. , Takahara Junichi , Zheludev Nikolay I.
Published: July 2018

Non-volatile temperature-induced structural phase transitions such as those found in chalcogenide glasses are known to lead to strong changes in optical properties and are widely used in rewritable optical disk technology. Herein, we demonstrate that thermally activated optical memory can be achieved via the nanostructural reconfiguration of a metallic nanowire metamaterial array made from a shape-memory alloy: A nickel-titanium film of nanoscale thickness structured on the subwavelength scale exhibits bistability of its optical properties upon temperature cycling between 30 °C and 210 °C. The structure, comprising an array of NiTi nanowires coated with a thin film of gold to enhance its plasmonic properties, can exist in two non-volatile states presenting an optical reflectivity differential of 12% via nanoscale mutual displacements of alternating nanowires in the structure. Such all-metal shape-memory photonic gratings and metamaterials may find applications in bistable optical devices.
A new preclinical ultrasound platform for widefield 3D imaging of rodents
Authors: Czernuszewicz Tomasz J. , Papadopoulou Virginie , Rojas Juan D. , Rajamahendiran Rajalekha M. , Perdomo Jonathan , Butler James , Harlacher Max , O’Connell Graeme , Zukić Dženan , Aylward Stephen R. , Dayton Paul A. , Gessner Ryan C.
Published: July 2018

Noninvasive in vivo imaging technologies enable researchers and clinicians to detect the presence of disease and longitudinally study its progression. By revealing anatomical, functional, or molecular changes, imaging tools can provide a near real-time assessment of important biological events. At the preclinical research level, imaging plays an important role by allowing disease mechanisms and potential therapies to be evaluated noninvasively. Because functional and molecular changes often precede gross anatomical changes, there has been a significant amount of research exploring the ability of different imaging modalities to track these aspects of various diseases. Herein, we present a novel robotic preclinical contrast-enhanced ultrasound system and demonstrate its use in evaluating tumors in a rodent model. By leveraging recent advances in ultrasound, this system favorably compares with other modalities, as it can perform anatomical, functional, and molecular imaging and is cost-effective, portable, and high throughput, without using ionizing radiation. Furthermore, this system circumvents many of the limitations of conventional preclinical ultrasound systems, including a limited field-of-view, low throughput, and large user variability.
Evolutionary quantum minority game: A wireless network application
Authors: Zabaleta O. G. , Arizmendi C. M.
Published: July 2018

The users of wireless communication networks usually face a resources scarcity issue by competing for places in a limited frequency spectrum. This problem is modeled as a quantum minority game with both some dynamic features of the classic minority game and quantum properties. The game is played by agents with memory exploring a finite space of classic and quantum strategies in an evolutionary way. The player actions are based on the m previous outcomes, their insights about other future actions, and their own expectation thresholds.
Ultrafast scanning electron microscope applied for studying the interaction between free electrons and optical near-fields of periodic nanostructures
Authors: Kozák M. , McNeur J. , Schönenberger N. , Illmer J. , Li A. , Tafel A. , Yousefi P. , Eckstein T. , Hommelhoff P.
Published: July 2018

In this paper, we describe an ultrafast scanning electron microscope setup developed for the research of inelastic scattering of electrons at optical near-fields of periodic dielectric nanostructures. Electron emission from the Schottky cathode is controlled by ultraviolet femtosecond laser pulses. The electron pulse duration at the interaction site is characterized via cross-correlation of the electrons with an infrared laser pulse that excites a synchronous periodic near-field on the surface of a silicon nanostructure. The lower limit of 410 fs is found in the regime of a single electron per pulse. The role of pulse broadening due to Coulomb interaction in multielectron pulses is investigated. The setup is used to demonstrate an increase in the interaction distance between the electrons and the optical near-fields by introducing a pulse-front-tilt to the infrared laser beam. Furthermore, we show the dependence of the final electron spectra on the resonance condition between the phase velocity of the optical near-field and the electron propagation velocity. The resonance is controlled by adjusting the initial electron energy/velocity and by introducing a linear chirp to the structure period allowing the increase of the final electron energy gain up to a demonstrated value of 3.8 keV.
Creating monodispersed droplets with electrowetting-on-dielectric step emulsification
Authors: He Binbin , Huang Xing , Xu Haoyan , Xu Zhongbin , Wang Pengfei , Ruan Xiaodong
Published: July 2018

Monodisperse droplets are important in drug screening, and cell-based and biochemical research. However, conventional methods for creating droplets, such as co-flow, T-junction and flow-focusing, have poor monodispersity because of fluctuations in the flow rate. Because step emulsification is based on the principle of Laplace pressure, it is insensitive to the flow rate and yields a constant and high monodispersity. In the present study, we combine electrowetting and step emulsification to reduce the negative influence of flow-rate fluctuations and to prepare highly monodisperse droplets. We demonstrate that the flow rate and voltage applied to the droplets can independently influence the droplet size. This method has great potential in chip-based bioanalysis and cell-based studies where highly monodisperse droplets are needed.
Accurate rovibrational energies of ozone isotopologues up to J = 10 utilizing artificial neural networks
Authors: Petty Corey , Spada Rene F. K. , Machado Francisco B. C. , Poirier Bill
Published: July 2018

In recent years, ozone and its isotopologues have been a topic of interest in many fields of research, due to its importance in atmospheric chemistry and its anomalous isotopic enrichment—or the so-called “mass-independent fractionation.” In the field of potential energy surface (PES) creation, debate over the existence of a potential barrier just under the dissociation threshold (referred to as a “potential reef”) has plagued research for some years. Recently, Dawes and co-workers [Dawes, Lolur, Li, Jiang, and Guo (DLLJG) J. Chem. Phys. 139, 201103 (2013)] created a highly accurate global PES, for which the reef is found to be replaced with a (monotonic) “plateau.” Subsequent dynamical calculations on this “DLLJG” PES have shown improved agreement with experiment, particularly the vibrational spectrum. However, it is well known that reaction dynamics is also highly influenced by the rovibrational states, especially in cases like ozone that assume a Lindemann-type mechanism. Accordingly, we present the first significant step toward a complete characterization of the rovibrational spectrum for various isotopologues of ozone, computed using the DLLJG PES together with the ScalIT suite of parallel codes. Additionally, artificial neural networks are used in an innovative fashion—not to construct the PES function per se but rather to greatly speed up its evaluation.
Low-frequency magnetohydrodynamic spectra of plasmas with anisotropic pressure in axisymmetric toroidal systems
Authors: Lakhin V. P. , Sorokina E. A.
Published: July 2018

The low-frequency ideal magnetohydrodynamic (MHD) spectra of anisotropic pressure plasmas in axisymmetric toroidal systems are analyzed. In the framework of the Chew-Goldberger-Low model, the continuum spectrum equations for the coupled localized Alfvén and slow magnetosonic modes are derived. The equations are applied to study the continuous spectra for low-pressure plasmas in large aspect ratio tokamaks. It is shown that for some classes of plasma equilibria the pressure anisotropy results in instability of continuous modes. Such an instability is due to anisotropic plasma stratification over poloidal angle on the magnetic surfaces. It takes place for both the zonal flow modes with (m, n) = 0 and the general electromagnetic modes with (m, n) ≠ 0. The latter are unstable only if they are localized near the rational magnetic surface. A stabilization of this instability due to the Alfvén effect is shown for the modes localized away from the rational magnetic surface.
On the method of photoconductive detection of defects in semiconductors by vibrational mode-related Fano resonances
Authors: Herklotz F. , Chaplygin I. , Lavrov E. V.
Published: July 2018

The method of photoconductive detection of defect-related vibrational modes in semiconductors by Fano resonances is validated by a combined photoconductivity and infrared absorption study of the interstitial hydrogen donor in ZnO. Depth-resolved isotopic substitution experiments with varying concentrations of H and D show that the effect of vibrational mode-related absorption has to be taken into account in order to allow for an unambiguous interpretation of the experimental data. A quantitative model is presented which describes the influence of sample thickness, defect concentration, and the presence of other donors on the sign, magnitude, and shape of the Fano resonances. Implications for the photoconductive detection of defect-related vibrational modes are discussed.
Polar projections for big data analysis in applied superconductivity
Authors: Talantsev E. F. , Mataira R. C.
Published: July 2018

There is a growing problem to represent and analyse large experimental datasets in many emerging fields of science aside of traditional big data-based disciplines, i.e., elementary particles, genetics/genomics and geoscience. One of these emerging fields is applied superconductivity where recently a large, regularly up-dated, public database of critical currents of commercial superconductors was established. The size, dimensionality and resolution of this data makes current methods of display and analysis inadequate. As is often the case in physics and materials science, when dealing with any anisotropic properties, one measures the effects of rotations around a low symmetry axis, this is also the case in critical current measurements as found in applied superconductivity. In this paper we propose the use of polar projected images to map these much larger data sets into useful visualizations for analysis. Where we suggest the radial coordinate and the colour represent amplitudes of two measured parameters, and sample rotation angle is naturally mapped to the polar coordinate. We demonstrate the advantage of this projection for analysing, otherwise unwieldy large, critical current datasets, and naturally recover previously used empirical relations.
Optical near-fields of nanostructures probed with electron interactions at femtosecond scales
Authors: Wolverton Mark
Published: July 2018

An ultrafast scanning electron microscope measurement reveals nanoscale interactions between electrons and optical near-fields.
Applying Cognitive Linguistics: Identifying some current research foci (figurative language in use, constructions and typology)
Authors: Piquer-Píriz Ana M. , Alejo-González Rafael
Published: July 2018

In recent years, Cognitive Linguistics (CL) has established itself not only as a
solid theoretical approach but also as an important source from which different
applications to other fields have emerged. In this introductory chapter, we
explore some of the current, most relevant topics in applied CL-oriented studies grouped into three main strands: Analyses of figurative language (both metaphor and metonymy) in use, constructions and typology. An outline of the contents of the eight chapters included in this volume is provided, explaining their contributions to these research areas and highlighting their methodological rigour.
Showing versus telling: Representing speech events in English and Spanish
Authors: Caballero Rosario
Published: July 2018

In this chapter, I provide a qualitative description of the verbs used to introduce Direct Speech (DS) in fictional narratives written in English and their Spanish translations in order to compare the way these two languages reconstruct speech events in texts by means of both speech verbs (e.g., say/decir, counter/argumentar, declare/manifestar) and non-speech verbs (e.g., grin/sonreír, scowl/fruncir el ceño). Using a corpus of popular fictional narrative genres and drawing upon typological research on motion after the work by Talmy (1985, 1988, 1991) and Slobin (1996a, 1996b, 2004, 2005, 2006), I look into the strategies used in English and Spanish for recreating speech events in order to explore whether the typological differences between these languages are replicated in the case of speech. The hypothesis is that, contrary to what happens with motion events, the differences between English and Spanish do not rest upon lexical availability but, rather, on the weight placed in different speech elements in agreement with two different agendas regarding speech events. While congruent with typological studies, this piece of research attempts to broaden their scope and explore a topic still underexplored.
The variable use of determiners in Old French and the argument DP hypothesis
Authors: Dufresne Monique , Tremblay Mireille , Déchaine Rose-Marie
Published: July 2018

Theargument DP hypothesis, adopted by many syntactic analyses, claims that nominal arguments are introduced by a determiner (D), which may be covert or overt. While overt D is obligatory in Modern French (consistent with the argument DP hypothesis), it was not obligatory in earlier stages of French. We explore the factors that contributed to this change – includingsemantic class, syntactic function, number, anddefiniteness – focusing on a shift that occurred in the D-paradigm in two Anglo-Norman texts of the 12th century. Quantitative analysis (Goldvarb) yields two major findings. First, the effect ofsyntactic functionremains constant: subject position favours overt D, but object position inhibits it. Second, there is a change in the effect ofsemantic class: count nouns increasingly favour overt D, but non-count (mass and abstract) nouns increasingly inhibit it. More generally, the gradual disappearance of bare Ns in French reflects the emergence of paradigmatically conditioned D.