bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Red Blood Cells in the Early Stages of Platelet Activation by Collagen
Authors: Teresa Santos M , Vallés Juana , Aznar Justo , Luis Pérez-Requejo J
Published: July 2018

Red blood cells (RBC) increase the proaggregatory capacity of a cell-free supernatant obtained by stimulating platelet-rich plasma (PRP) samples with collagen (1 μg/ml) as measured by the BASIC wave; this effect increases with the number of RBC and is proportionally greater with a lower number of platelets or when lower collagen concentrations are used.

Aspirin (ASA) modifies the RBC behaviour in relation to their platelet-collagen interaction. This is demonstrated by the fact that when PRP and RBC obtained from the same subjects before and two hours after the ingestion of ASA (0.5 g) were mixed, it was found that non-AS A-RBC stimulate ASA-PRP, probably through a platelet cyclooxygenase independent pathway; ASA-RBC, however, stimulate non-ASA-PRP, but not ASA-PRP, which suggests that they may need an active platelet cyclooxygenase system for their action. This effect of ASA on RBC is not transient and was also observable 48 h after ASA ingestion. In addition, it was found that ASA-RBC greatly increase the activation of a mixture containing a small proportion of non-ASA-PRP in ASA-PRP, a situation that is expected to be encountered “in vivo” after ASA treatment. This effect of ASA-RBC on platelet activation may help to explain the sometimes contradictory clinical effect of aspirin as an antithrombotic drug.
Measurement of Urokinase-Type Plasminogen Activator (u-PA) with an Enzyme-Linked Immunosorbent Assay (ELISA) Based on Three Murine Monoclonal Antibodies
Authors: Darras V , Thienpont M , Stump D C , Collen D
Published: July 2018

An enzyme-linked immunosorbent assay (ELISA) for the measurement of urokinase-type plasminogen activator (u-PA) was developed. Three murine monoclonal antibodies to single chain urokinase-type plasminogen activator (scu-PA) were isolated and shown to react with non-overlapping epitopes in scu-PA. Two of the three antibodies were coated onto microtiter plates and bound u-PA was quantitated with the third antibody conjugated to horseradish peroxidase. The assay was equally sensitive to Mr 54,000 u-PA in the single chain or two-chain form but did not respond to Mr 33,000 urokinase. The lower limit of sensitivity of the assay was 0.1 ng/ml in buffer and 1 ng/ml in plasma. Coefficients of variation of the assay at physiological levels of u-PA were 6.5 percent within assays and 13 percent between assays. The level of u-PA in normal resting plasma was 1.9 ± 0.66 ng/ml (mean ± SD, n = 54). The assay can be performed within one working day and provides an efficient, reproducible, and stable means for the measurement of u-PA in biological fluids. As such it may facilitate physiological and pharmacological studies of urokinase-type plasminogen activators in man.
T-Cell Alterations in Hemophiliacs Treated with Commercial Clotting Factor Concentrates
Authors: Lechner K , Niessner H , Bettelheim P , Deutsch E , Fasching I , Fuhrmann M , Hinterberger W , Korninger C , Neumann E , Liszka K , Knapp W , Mayr W R , Stingl G , Zeitlhuber U
Published: July 2018

Various immunological parameters were determined in 46 patients with severe hemophilia A and in 9 patients with severe hemophilia B. All patients were treated over many years with commercial factor VIII or IX concentrates. Patients with severe classic hemophilia had a significantly reduced relative and absolute number of T-helper cells and a significantly increased relative and absolute number of T-suppressor cells. About half of these patients had an inverse T-helper/suppressor cell ratio. Patients with moderate hemophilia A and severe hemophilia B did not show these abnormalities. Hemophiliacs with an inverse ratio had a significantly higher concentration of serum total protein, IgG and IgM. No relationship between the amount of factor VIII concentrate administered, the HLA-type of the patient, the presence or absence of CMV-antibodies, hepatitis markers, thrombocytopenia and abnormal liver function tests to the T-cell abnormalities could be established. Lymphadenopathy was frequently associated with an inverse ratio. Indirect evidence suggests that the alterations of the immune system began in 1979/80.
Mechanisms of Vascular Damage in Gout and Oxalosis: Crystal Induced, Granulocyte Mediated, Endothelial Injury
Authors: Boogaerts M A , Hammerschmidt D E , Roelant C , Verwilghen R L , Jacob H S
Published: July 2018

Immune triggered granulocyte (PMN)-endothelial interactions have been implicated in the pathogenesis of vascular diseases. While hyperuricemia and gout are associated with an increased risk of atherogenesis, we studied the modulation by mono- sodiumurate (MSU) crystals of PMN-endothelial interactions in vitro. The relationship between calciumoxalate (COX) crystals - implicated in the vasculitis of primary oxalosis - and immunologically mediated endothelial injury was also explored.

Both MSU- and COX-crystals activate complement (C), as illustrated by the finding of strong PMN aggregating activity and large amounts of C3a and C5a-anaphylatoxin in MSU- and COX- crystal incubated sera.

MSU- and COX-crystal treated sera stimulate PMN to adhere to and induce significant 51Cr-release from endothelial cells in vitro. Platelets significantly increase crystal-triggered PMN endothelial cell adherence and 51Cr-release. This platelet augmenting effect depends on the release of platelet constituents (e. g. serotonin).

Microcrystalline material present in vessel walls, thus may cause C-activation and may trigger PMN and platelets to damage endothelium in vitro and in vivo. These findings may have relevance to the understanding of the accelerated atherogenesis of hyperuricemia and the fulminant vasculitis of oxalosis or ethylene glycol poisoning.
Individual Levels of Plasma α2-Antiplasmin and α2 Macroglobulin During the Normal Menstrual Cycle and in Women on Oral Contraceptives Low in Oestrogen
Authors: Jespersen Jørgen , Sidelmann Johannes
Published: July 2018

Determinations of α2-antiplasmin and α2-macroglobulin were made in plasma samples collected during one normal or hormone induced cycle in 15 normal women and 11 women using oral contraceptives containing 30 μg ethinyl oestradiol and 150 pg levo-norgestrel. The immediate plasmin inhibition test for determination of α2-antiplasmin was modified for application on a centrifugal analyser using the chromogenic peptide substrate Chromozym PL®. α2-Macroglobulin concentration was determined by radial-immunodiffusion. There were no differences between the two groups in the mean concentrations of α2- antiplasmin and α2-macroglobulin, but during the cycle a slight, and statistically significant fall occurred in the α2-antiplasmin concentration in both groups, while the fluctuations of α2- macroglobulin were small and insignificant. Distinctly individual levels of both inhibitors were found to exist. The variations in these during the periods of the cycle fluctuated within a much narrower range than the variation of the total average. The results stress the importance of determining the fluctuations in individual levels in longitudinal studies. These findings exclude variations in the concentrations of these inhibitors as possible sources of a change in the antithrombotic potential caused by oral contraceptives.
Factor XIII Levels in Five Families of Patients with Inherited Factor XIII Deficiency: Support for an Autosomal Recessive Inheritance
Authors: Fear J D , Miloszewski K J A , Losowsky M S
Published: July 2018

Using quantitative methods, f.XIII activity and levels of subunits a and b have been measured in 5 families of 6 patients with inherited XIII deficiency, including 2 children of a XIII deficient male. The parents, as a group, and the children, individually, have low XIII activity and low levels of subunit A when compared to controls. These findings provide further support for an autosomal inheritance of f.XIII deficiency. The measurements, however, did not allow confident selection of individual heterozygotes as has been previously suggested and an explanation of this finding is offered.
Measurement of Crosslinked Fibrin Degradation Products – An Immunoassay Using Monoclonal Antibodies
Authors: Elms M J , Bunce I H , Bundesen P G , Rylatt D B , Webber A J , Masci P P , Whitaker A N
Published: July 2018

We have prepared a monoclonal antibody which recognises an antigenic determinant on D dimer, a specific fragment resulting from the degradation of crosslinked fibrin. This antibody has been used in the development of an enzyme-linked immunoassay for D dimer and related degradation products containing crosslinked gamma-gamma chains, to provide a simple assay of circulating crosslinked fibrin degradation products suitable for clinical use. Since these crosslinked fibrin degradation products are characteristic of fibrinolysis, as distinct from fibrinogenolysis, their measurement should aid in the diagnosis, evaluation and monitoring of thrombotic and thrombolytic states. In preliminary studies, low concentrations of crosslinked fibrin derivatives were detected in normal sera. High levels were found in 30/30 patients with disseminated intravascular coagulation .and in the majority of patients having deep venous thrombosis or pulmonary embolism.
Lipid Class Composition and Heparin Sensitivity in the Activated Partial Thromboplastin Time
Authors: Stevenson K J , Easton Ann C , Thomson Jean M , Poller L
Published: July 2018

In an APTT reagent, prepared from purified lipids, the role of phosphatidyl serine (PS) in determining the sensitivity of the APTT test system to measurement of the effect of heparin in plasma has been evaluated. As the concentration of PS decreases sensitivity to heparin increases but procoagulant activity decreases. Dilution of the test liposome over a wide range (1 g/1 to 30 mg/1) had a minimal effect on the clotting time. At levels below 30 mg/1, however, the amount of total lipid appeared to be rate limiting; a loss of procoagulant activity being paralleled by an increase in heparin sensitivity. Phosphatidyl inositol (PI) was not a satisfactory substitute for PS in the APTT method studied. The degree of unsaturation of test liposomes appeared to have no effect on either procoagulant activity or sensitivity to heparin at the lipid concentration employed.

In the light of these findings, a more critical appraisal of the phospholipid components of APTT reagents should facilitate the development of more reliable reagents for heparin control. A further benefit of this type of approach should be a reduction in the acknowledged wide variations in sensitivity to heparin which exist between available APTT reagents.
Adhesion and Aggregation of Thrombin Prestimulated Human Platelets on Surface-Bound Fibrinogen: Evidence for Involvement of ADP and Arachidonic Acid Pathways
Authors: Feuerstein I A , Dickson V M
Published: July 2018

The purpose of this study was to examine the influence of substances released from human platelets upon their accumulation on human fibrinogen-coated glass tubes. After prestimulation with thrombin for one minute or in the absence of prestimulation, washed human platelets suspended in Eagle’s medium with RBC were drawn through the tubes at 1 ml/min, 80 s-1, for 1, 2 or 6 min. Thrombin prestimulation (0.02,0.05 or 0.25 U/ml) was followed by inactivation with hirudin (0.1, 0.25 or 1.25 U/ml) before flow. Singly adherent platelets were observed in the absence of thrombin or with thrombin for exposure times of 1 and 2 min. At 6 min after at least 0.05 U/ml of thrombin, surface- bound aggregates were observed. The initial rate of adhesion increased with the amount of thrombin used for prestimulation. For adhesion to fibrinogen in the absence of prestimulation, platelet-derived ADP was a stimulator. Adhesion was shown to be independent of the ADP and arachidonic acid pathways in response to prestimulation with a low level of thrombin, 0.02 U/ml. For adhesion and cohesion, aggregation, in the presence of sufficient thrombin for prestimulation, 0.05 U/ml, ADP, serotonin and substances from arachidonic acid metabolism acted jointly to stimulate platelets.
The Effect of a Thromboxane Synthetase Inhibitor, Dazoxiben, and Acetylsalicylic Acid on Platelet Function and Prostaglandin Metabolism
Authors: Dale Jon , Thaulow Erik , Myhre Erik , Parry John
Published: July 2018

Twenty-four men received either placebo, 0.1 g of the thromboxane synthetase inhibitor dazoxiben, 0.25 or 1.0 g of acetylsalicylic acid (ASA). Dazoxiben reduced the maximal rate of collagen-induced platelet aggregation, but less than did ASA. ASA abolished secondary, ADP-induced aggregation, dazoxiben not. Both drugs prolonged the bleeding-time.

Plasma thromboxane B2 (TxB2) levels did not change significantly after dazoxiben, whereas the prostacyclin metabolite 6-keto-PGF1α rose. The larger dose of ASA reduced both TxB2 and 6-keto-PGF1α in plasma. Whole blood was allowed to clot in order to estimate prostaglandin metabolism. Both drugs prevented thromboxane production effectively. Formation of 6-keto-PGF1α decreased by 95 per cent after ASA but was more than doubled after dazoxiben.

Dazoxiben is a selective and effective thromboxane synthetase inhibitor, but has a weaker effect on platelet reactivity than ASA, possibly because endoperoxide formation is not prevented.
An Enzyme Linked Immunosorbent Assay for Determination of Tissue Plasminogen Activator Applied to Patients with Thromboembolic Disease
Authors: Bergsdorf Nils , Nilsson Torbjörn , Wallén Per
Published: July 2018

Utilizing the immunoglobulin fraction from a goat antiserum against human uterine tissue plasminogen activator, an enzyme- linked immunoassay for tissue-type plasminogen activator in human plasma has been developed. With the new method, the concentration of t-PA in normal human acidified plasma is found to be 4.0 ± 1.8 (SD) ng/ml. It increases to 12 ng/ml after a tomiquet test, and to 14 ng/ml after strenous physical exercise. In a group of patients with idiopathic thromboembolic disease, the resting t-PA concentration was 5 ng/ml and the post-occlusion value 16 ng/ml. Furthermore, the patients also exhibited a normal post-occlusion rise in the concentration of plasmin-α2-antiplasmin complex. However, in 37% of the post-occlusion patient plasmas, virtually no increase in t-PA could be detected by a specific activity assay. The results indicate that the reason for a defective post-occlusion fibrinolytic activity in a majority of cases may be the presence of increased concentrations of a fast-acting specific t-PA inhibitor.
A Plasma Factor Enhances Activity of Vitamin K-Dependent Coagulation Proteins
Authors: Owens Michael R , Cimino Catherine D
Published: July 2018

A plasma factor, “coagulopoietin”, present in animals with depleted vitamin K-dependent coagulation factors, appears to enhance activity of these factors in normal animals. We have investigated the effects of “coagulopoietin” on synthesis of certain coagulation proteins by the isolated rat liver perfused for eight hours. Liver donor rats received plasma injections from vitamin K-deficient rats or from normal rats 24 hr before sacrifice. Coagulation activity of Factor VII and Factor II in liver perfusate samples was measured with a coagulation assay; Factor II synthesis was also measured by rocket immunoelectrophoresis and by activation with E. carinatus venom. Cumulative hepatic synthesis of. Factor VII coagulation activity was increased by 43% when rat liver donors received vitamin K-deficient rat plasma compared to normal rat plasma. Cumulative synthesis of Factor II coagulation activity was increased by 51%, but synthesis of the protein measured immunologically or by activation with venom was not affected. The “coagulopoietin” factor in these studies appears to increase measurable coagulation factor activity without increasing total protein synthesis.
Protective Effect of Warfarin in Arterial Thrombosis: Evidence from a Vascular Prosthesis Model in Rats
Authors: Reyers Ine , de Gaetano Giovanni , Benedetta Donati Maria
Published: July 2018

Three different schedules of treatment with warfarin were studied in rats bearing a polyethylene cannula in their abdominal aorta. The time of occlusion of the vascular prosthesis was significantly prolonged when warfarin was started 24 hr previously, at the time of loop insertion or 24 hr later. When the drug treatment was started 24 hr before insertion of the loop, however, a high degree of toxicity was observed. The animals of this group that died of hemorrhage had significantly lower mean thrombotest levels.

On the other hand, the correlation between occlusion of the loop and level of anticoagulation was not as simple as one might anticipate; on the one hand, severe anticoagulation did not protect all of the rats from loop occlusion, but, on the other hand, recovery from hypocoagulability was not always immediately followed by occlusion of the loop.

In order to better elucidate the mechanism of the antithrombotic effect of warfarin, we also assessed the effect of the drug on platelet-vessel wall interaction by the template bleeding time. A close association existed between warfarin-induced hypocoagulability and prolongation of the bleeding time.

These observations may constitute the experimental basis for a better understanding of the antithrombotic effect of warfarin in some arterial diseases and in myocardial infarction.
75Se-Seleno-Methionine-Actin as a Probe for Determination of Platelet Production Rate
Authors: Cardinaud R , Dassin E , Bourebia J
Published: July 2018

Synthesis of actin is a reasonably correct representation of the platelet production rate. Measurement of actin production obviates some of the drawbacks encountered in currently available methods. Platelet actin was characterized on polyacrylamide gel electrophoreses using methylated radioactive rabbit actin as a reference. Platelet actin was unambiguously identified by showing that it forms a complex with DNAase-I similar to the complex obtained with pure rabbit actin.

Six days after intravenous injection of 75Se-seleno-methionine actin was one of the most highly labelled platelet components. The platelet pellet (one rat per sample) was solubilized with 1% Triton X-100, 0.75 M guanidine-HCl and dialyzed in a medium containing 1% SDS (to eliminate Triton X-100 and guanidine-HCl). A carefully measured aliquot was deposited on a polyacrylamide gel. After electrophoresis in the presence of SDS the radioactivity of the actin band was measured and the ratio of the total actin radioactivity to the injected radioactivity was taken as a measure of platelet production.

The validity of the actin probe was tested with populations of normal animals. The specific radioactivity of actin was proportional to the injected dose of 75Se-seleno-methionine up to 1 mCi/ kg animal. A semi-log plot of actin specific radioactivity vs time exhibited a pseudo-first order decrease. Another constituent with a high specific radioactivity (XM) was excluded as a suitable probe because it was shown to be an adsorbed plasma protein.
Platelet Adhesion in Polytetrafluoroethylene (PTFE) Vascular Grafts In Vivo and the Influence of Increased Intramuscular Pressure-An Experimental Model
Authors: Christenson J T , Qvarfordt P , Strand S-E , Arvidsson D , Sjöberg T , Olsson P-I
Published: July 2018

Thrombogenicity of graft material is involved in early graft failure in small diameter grafts. The frequently seen postoperative swelling of the leg after distal revascularization may cause an increased intramuscular pressure and early graft failure.

Pairs of 4 mm polytetrafluoroethylene (PTFE) grafts were implanted. Autologous platelets were labeled with mIn-oxine. Platelet adhesiveness onto the grafts were analyzed from gamma camera images. Intramuscular pressures were measured with wick technique. Blood flow was measured. One graft served as control the other as test graft. Ninety minutes after declamping the i. m. pressure was increased in the test-leg to 30 mmHg, and later to 60 mmHg.

In the control-graft platelet uptake increased to a maximum 60 min after declamping. Blood flow and i.m. pressure remained uneffected. The test-grafts were initially similar but when i.m. pressure was increased to 30 mmHg activity in the grafts increased significantly. Blood flow decreased with 12% of initial flow. When i. m. pressure was raised to 60 mmHg platelet uptake continued to increase.

An increased intramuscular pressure of 30 mmHg or more significantly increase the amount of platelets adhering onto PTFE grafts, emphasizing the need for measuring intramuscular pressures after lower limb vascular revascularizations.
Glucocorticoids Inhibit Plasminogen Activator Production by Endothelial Cells
Authors: Laug Walter E
Published: July 2018

Confluent cultures of bovine aortic endothelial cells (BEC) were found to secrete both tissue type plasminogen activator (t- PA) and urokinase type plasminogen activator (u-PA). Exposure of the cultures to increasing concentrations of dexamethasone resulted in a time and concentration dependent inhibition of cellular and secreted u-PA. Complete inhibition of u-PA production and secretion was found at dexamethasone concentrations of 10-8 molar or higher. Several distinct PA forms with molecular weights ranging from 10,000-20,000 to >200,000 were found in the conditioned medium of untreated BEC cultures. After addition of dexamethasone (10-7 molar) to the culture medium the PAs with molecular weights of 117,000, 58,000,47,000, were absent suggesting that they were u-PAs, whereas the PAs with molecular weights of >200,000 and 75,000 remained unchanged suggesting their t-PA origins. The PAs with lower molecular weights of 35,000, 28,000 and 10,000 to 20,000 were most likely generated from the higher molecular weight forms by limited proteolysis since they were absent when the medium was conditioned in the presence of the protease inhibitor Trasylol.

The two PA types may therefore be independently regulated in BEC.
Mechanical Heart Valve Replacement in a Low-Middle Income Region in the Modern Era: Midterm Results from a Sub-Saharan Center
Authors: Mve Mvondo Charles , Pugliese Marta , Ambassa Jean Claude , Giamberti Alessandro , Bovio Emanuele , Dailor Ellen
Published: July 2018

Background The management of patients with mechanical heart valves remains a major concern in populations with limited resources and medical facilities. This study reports the clinical outcomes of patients who underwent mechanical valve implantation in a sub-Saharan center over an 8-year period.

Methods A total of 291 mechanical valves were implanted in 233 patients in our institution between February 2008 and June 2016. A total of 117 patients underwent mitral valve replacement (MVR, 50.2%), 57 had aortic valve replacement (AVR, 24.4%), and 59 underwent both AVR and MVR (double valve replacement [DVR], 25.7%). The mean age at surgery was 27.6 ± 13.4 years (range, 7–62 years). Rheumatic etiology was found in 80.6% of the patients. Hospital mortality, late deaths, and valve-related events were reviewed at follow-up (839 patient-years, range: 1–9.4 years, complete in 93%).

Results The 30-day mortality was 4.7% (11/233). The overall survival at 1 and 6 years for the whole cohort was 88.8 ± 2.1% and 78.7 ± 3.3%, respectively. The 6-year survival for AVR, MVR, and DVR was 89.3 ± 4.8%, 73.2 ± 5.4%, and 79.3 ± 5.8%, respectively (p = 0.15). The freedom from neurologic events and anticoagulation-related bleeding at 6 years was 93.1 ± 2.1% and 78.9 ± 3.7%, respectively. No patient had reoperation at follow-up. No case of prosthetic valve thrombosis was identified. Eight full-term pregnancies were reported.

Conclusion This preliminary experience reports acceptable midterm results after mechanical heart valve implantation in our region. Both accurate surgical evaluation and strategies, either financial or social, facilitating patient's education and medical assistance are crucial to ensure good results. Long-term follow-up and further studies comparing current nonthrombogenic options are warranted to draw reliable conclusions.
Number of Risk Factors in Down Syndrome Pregnancies
Authors: Hussamy Deana , Herrera Christina , Twickler Diane , Mcintire Donald , Dashe Jodi
Published: July 2018

Objective The objective of this study was to evaluate risk factor prevalence in pregnancies with fetal Down syndrome, in an effort to characterize efficacy of population-based screening.

Study Design Retrospective review of singleton pregnancies with delivery of live born or stillborn infant with Down syndrome from 2009 through 2015. Risk factor categories included maternal age ≥35 years, abnormal serum screening, identification of ≥1 ultrasound marker at 16 to 22 weeks (nuchal thickness ≥6 mm, echogenic intracardiac focus, echogenic bowel, renal pelvis dilatation, femur length <third percentile), and detection of a major fetal anomaly. Statistical analyses included χ2 test and Mantel–Haenszel χ2 test.

Results Down syndrome infants represented 1:428 singleton births. All risk categories were assessed in 125 pregnancies and included abnormal serum screen in 110 (88%), ≥1 ultrasound marker in 66 (53%), and ≥1 anomaly in 41 (34%). The calculated risk was at least 1:270 in 93% of Down syndrome pregnancies. More pregnancies had multiple risk factors than had a single risk factor, 90 (72%) versus 30 (24%), p < 0.001. An abnormal ultrasound marker or anomaly was identified in >50% of fetuses in women <35 years and in >75% of those 35 years and older.

Conclusion In a population-based cohort, sensitivity of second-trimester Down syndrome screening was 93%, with multiple risk factors present in nearly three-fourths of cases.
Interdelivery Interval and Medically Indicated Preterm Delivery
Authors: Grobman William , Dude Annie
Published: July 2018

Objective The objective of this study was to examine whether a medically indicated preterm delivery is relatively more likely following longer interdelivery intervals.

Study Design This is a case–control study of women with two consecutive deliveries of a live singleton at the same institution between 2005 and 2015, with the subsequent delivery occurring preterm. Preterm deliveries were classified as spontaneous if women delivered following preterm labor, preterm premature rupture of membranes, or placental abruption. Preterm deliveries were classified as medically indicated if women underwent delivery for fetal or maternal medical indications. Interdelivery interval was categorized as < 18, 18 to 59, and 60 months or more. Characteristics of women who had a medically indicated versus spontaneous preterm delivery were compared.

Results Of the 1,276 women, 25.6% had a medically indicated preterm delivery and 74.4% had a spontaneous preterm delivery. Compared with women with an interdelivery interval of 18 to 59 months (of whom 25.7% had a preterm delivery for medical indications), women with a shorter interdelivery interval were less likely (19.3%), while women with a longer interdelivery interval were more likely (37.4%; p = 0.003) to have a medically indicated preterm delivery. This relationship persisted even when accounting for other factors.

Conclusion Preterm deliveries are more likely to be medically indicated as the interdelivery interval lengthens.
Interfacial oxidation kinetics at SiO2/Si(001) mediated by the generation of point defects: Effect of raising O2 pressure
Authors: Ogawa Shuichi , Takakuwa Yuji
Published: July 2018

In the thermal oxidation reaction of Si, point defects (emitted Si atoms and its vacancies) occur owing to oxidation-induced strain. These point defects become not only charge traps that degrade device characteristics but also oxidation reaction sites. However, a reaction rate equation of a model in which point defects are regarded as reaction sites has not yet been proposed. We investigated the O2 pressure dependence of the initial interfacial oxidation rate Ri(0) after the oxidation of an Si(001) surface using real-time Auger electron spectroscopy to establish the reaction rate equation based on the point defect generation model. We found that Ri(0) was proportional to the square root of the O2 pressure, and the initial deceleration of the interfacial oxidation rate was proportional to the O2 pressure. Using the result of the pressure dependence of Ri(0), we derived the reaction rate equation based on the Si oxidation model in which O2 dissociation preferentially occurs at vacancies resulting from Si atom emission at the SiO2/Si(001) interface. The prediction of the O2 pressure dependence of the initial deceleration of the interfacial oxidation rate shows good agreement with the experimental results. In addition, we predicted that there were two kinds of vacancies at the SiO2/Si(001) interface to dissociate the O2 molecules.
Improved thermoelectric properties of nanostructured composites out of Bi1−xSbx nanoparticles and carbon phases
Authors: Güneş Ekrem , Wickleder Mathias S. , Müller Eckhard , Elm Matthias T. , Klar Peter J.
Published: July 2018

Thermoelectric figures of merit of ZT ≈ 0.4 at room temperature were achieved in nanostructured composite materials prepared by uniaxial pressing of Bi1−xSbx nanoparticles and 0.3 wt.% of a carbon phase. This constitutes a significant improvement of the low-temperature thermoelectric material Bi1−xSbx and strongly suggests the possibility of employing these materials in efficient thermoelectric devices working at room temperature. Interestingly, the beneficial effect of the carbon phase added to nanostructured Bi1−xSbx is the same for either carbon nanotubes or active carbon. This finding is attributed, on the one hand, to a combination of electronic band gap engineering due to nanostructuring and energy filtering due to graphene-like interlayers between Bi1−xSbx grains and, on the other hand, to modified phonon scattering at the grain boundaries and additional phonon scattering by agglomeration sites of carbon material on the μm scale.
A tunable time-resolved spontaneous Raman spectroscopy setup for probing ultrafast collective excitation and quasiparticle dynamics in quantum materials
Authors: Versteeg R. B. , Zhu J. , Padmanabhan P. , Boguschewski C. , German R. , Goedecke M. , Becker P. , van Loosdrecht P. H. M.
Published: July 2018

We present a flexible and efficient ultrafast time-resolved spontaneous Raman spectroscopy setup to study collective excitation and quasi-particle dynamics in quantum materials. The setup has a broad energy tuning range extending from the visible to near infrared spectral regions for both the pump excitation and Raman probe pulses. Additionally, the balance between energy and time-resolution can be controlled. A high light collecting efficiency is realized by high numerical aperture collection optics and a high-throughput flexible spectrometer. We demonstrate the functionality of the setup with a study of the zone-center longitudinal optical phonon and hole continuum dynamics in silicon and discuss the role of the Raman tensor in time-resolved Raman scattering. In addition, we show an evidence for unequal phonon softening rates at different high symmetry points in the Brillouin zone of silicon by means of detecting pump-induced changes in the two-phonon overtone spectrum. Demagnetization dynamics in the helimagnet Cu2OSeO3 is studied by observing softening and broadening of a magnon after photo-excitation, underlining the unique power of measuring transient dynamics in the frequency domain, and the feasibility to study phase transitions in quantum materials.
An integrated genetic approach to provenancing and establishment of founding individuals for restoration in the semiarid midwest region of Western Australia
Authors: Millar Melissa A. , Coates David J. , Byrne Margaret , Roberts J. Dale
Published: July 2018

An increasingly important practical application of the analysis of spatial genetic structure and life history traits of plant species is to aid the design of seed sourcing scenarios that provide for long-term successful restoration. Despite this, there are few practical recommendations on how to use empirical knowledge of genetic structure and life history traits to design appropriate seed sourcing regimes and planting designs. We identified potential divergent lineages within species as an important first step in determining appropriate areas in which to source seeds. We then used a modelling approach for restoration based on patterns of genetic structure and life history traits that affect demography, dispersal and gene flow to inform the impact of number and spatial positioning of founder individuals, as well as different seed sourcing scenarios, on population growth and the initial capture and long-term maintenance of genetic diversity for restored populations. The approach is illustrated using datasets for four perennial plant species associated with the Banded Iron Formations of the semiarid midwest region of Western Australia. The approach can be tailored to any restoration site and applied to a range of species with differing patterns of genetic structure and differing life history traits.
Atom Transfer Radical Polymerization Functionalization on Polypropylene Films for Immobilizing Active Compounds
Authors: Contreras Cintia B. , Toselli Ricardo , Strumia Miriam C.
Published: July 2018

This work proposes the surface chemical modification of polypropylene films (PP) by atom transfer radical polymerization (ATRP) using glycidyl methacrylate (GMA) as the graft monomer. At a later stage, the epoxy groups of PP-g-PGMA were used for covalent binding of glucose oxidase (GOD) to obtain an active material (PP-g-PGMA-GOD) with 9.38 ± 0.06 mg cm−2 of enzyme bonded on the surface of PP. Preliminary microbiological studies have shown that this methodology of covalent binding of the enzyme onto the PP surface allowed its activity to be maintained. Therefore, this advantage would give to PP-g-PGMA-GOD films a potential use as an active packaging material if further specific studies on their antimicrobial properties can be verified.
Single-cell RNA sequencing reveals distinct gene expression patterns in glucose metabolism of human preimplantation embryos
Authors: Zhao Di-Cheng , Li Yu-Mei , Ma Jie-Liang , Yi Ning , Yao Zhong-Yuan , Li Yan-Ping , Quan Yi , Li Xin-Ning , Xu Chang-Long , Qiu Ying , Wu Ling-Qian
Published: July 2018

Precise regulation of glucose metabolism-related genes is essential for early embryonic development. Although previous research has yielded detailed information on the biochemical processes, little is yet known of the dynamic gene expression profiles in glucose metabolism of preimplantation embryos at a single-cell resolution. In the present study, we performed integrated analysis of single-cell RNA sequencing (scRNA-seq) data of human preimplantation embryos that had been cultured in sequential medium. Different cells in the same embryo have similar gene expression patterns in glucose metabolism. During the switch from the cleavage to morula stage, the expression of glycolysis-related genes, such as glucose transporter genes (solute carrier family 2 (facilitated glucose transporter), member 1 (SLC2A1) and solute carrier family 2 (facilitated glucose transporter), member 3 (SLC2A3) and genes encoding hexokinase, phosphofructokinase, pyruvate kinase and lactate dehydrogenase, is increased. The genes involved in the pentose phosphate pathway are highly expressed at the cleavage stage, generating the reducing power to balance oxidative stress derived from biosynthesis. Expression of the genes involved in the biosynthesis of glycerophospholipids is increased after the morula stage. Nevertheless, the expression of tricarboxylic acid-related genes remains relatively unchanged during the preimplantation stages. In conclusion, we discovered that the gene expression profiles are dynamic according to glucose utilisation in the embryos at different stages, which contributes to our understanding of regulatory mechanisms of glucose metabolism-related genes in human preimplantation embryos.
Neutral Spaces and Topological Explanations in Evolutionary Biology: Lessons from Some Landscapes and Mappings
Authors: Huneman Philippe
Published: July 2018

I consider recent uses of the notion of neutrality in evolutionary biology and ecology, questioning their relevance to the kind of explanation recently labeled ‘topological explanation’. Focusing on fitness landscapes and genotype-phenotype maps, I explore the explanatory uses of neutral subspaces, as modeled in two perspectives: hyperdimensional fitness landscapes and RNA sequence-structure maps. I argue that topological properties of such spaces account for features of evolutionary systems: respectively, capacity for adaptive evolution toward global optima and mutational robustness of genotypes. Thus many models appealing to “neutral” manifolds provide topological alternatives to hypothetical mechanisms.
Runge tubes in Stein manifolds with the density property
Authors: Forstnerič Franc , Wold Erlend
Published: July 2018

In this paper we give a simple proof of the existence and plenitude of Runge tubes in

C

n

\mathbb {C}^n

(
n
>
1
)

(n>1)

and, more generally, in Stein manifolds with the density property. We show in particular that for any algebraic submanifold

X
X

of codimension at least two in a complex Euclidean space

C

n

\mathbb {C}^n

, the normal bundle of

X
X

admits a holomorphic embedding onto a Runge domain in

C

n

\mathbb {C}^n

which agrees with the inclusion map

X
↪

C

n

X\hookrightarrow \mathbb {C}^n

on the zero section.
SKEMPI 2.0: an updated benchmark of changes in protein–protein binding energy, kinetics and thermodynamics upon mutation
Authors: Jankauskaitė Justina , Jiménez-García Brian , Dapkūnas Justas , Fernández-Recio Juan , Moal Iain H
Published: July 2018

Motivation

Understanding the relationship between the sequence, structure, binding energy, binding kinetics and binding thermodynamics of protein–protein interactions is crucial to understanding cellular signaling, the assembly and regulation of molecular complexes, the mechanisms through which mutations lead to disease, and protein engineering.

Results

We present SKEMPI 2.0, a major update to our database of binding free energy changes upon mutation for structurally resolved protein–protein interactions. This version now contains manually curated binding data for 7085 mutations, an increase of 133%, including changes in kinetics for 1844 mutations, enthalpy and entropy changes for 443 mutations, and 440 mutations, which abolish detectable binding.

Availability and implementation

The database is available as supplementary data and at https://life.bsc.es/pid/skempi2/.

Supplementary information

Supplementary data are available at Bioinformatics online.
Heritability estimation and differential analysis of count data with generalized linear mixed models in genomic sequencing studies
Authors: Sun Shiquan , Zhu Jiaqiang , Mozaffari Sahar , Ober Carole , Chen Mengjie , Zhou Xiang
Published: July 2018

Motivation

Genomic sequencing studies, including RNA sequencing and bisulfite sequencing studies, are becoming increasingly common and increasingly large. Large genomic sequencing studies open doors for accurate molecular trait heritability estimation and powerful differential analysis. Heritability estimation and differential analysis in sequencing studies requires the development of statistical methods that can properly account for the count nature of the sequencing data and that are computationally efficient for large datasets.

Results

Here, we develop such a method, PQLseq (Penalized Quasi-Likelihood for sequencing count data), to enable effective and efficient heritability estimation and differential analysis using the generalized linear mixed model framework. With extensive simulations and comparisons to previous methods, we show that PQLseq is the only method currently available that can produce unbiased heritability estimates for sequencing count data. In addition, we show that PQLseq is well suited for differential analysis in large sequencing studies, providing calibrated type I error control and more power compared to the standard linear mixed model methods. Finally, we apply PQLseq to perform gene expression heritability estimation and differential expression analysis in a large RNA sequencing study in the Hutterites.

Availability and implementation

PQLseq is implemented as an R package with source code freely available at www.xzlab.org/software.html and https://cran.r-project.org/web/packages/PQLseq/index.html.

Supplementary information

Supplementary data are available at Bioinformatics online.
BIPSPI: a method for the prediction of partner-specific protein–protein interfaces
Authors: Sanchez-Garcia Ruben , Sorzano C O S , Carazo J M , Segura Joan
Published: July 2018

Motivation

Protein–Protein Interactions (PPI) are essentials for most cellular processes and thus, unveiling how proteins interact is a crucial question that can be better understood by identifying which residues are responsible for the interaction. Computational approaches are orders of magnitude cheaper and faster than experimental ones, leading to proliferation of multiple methods aimed to predict which residues belong to the interface of an interaction.

Results

We present BIPSPI, a new machine learning-based method for the prediction of partner-specific PPI sites. Contrary to most binding site prediction methods, the proposed approach takes into account a pair of interacting proteins rather than a single one in order to predict partner-specific binding sites. BIPSPI has been trained employing sequence-based and structural features from both protein partners of each complex compiled in the Protein–Protein Docking Benchmark version 5.0 and in an additional set independently compiled. Also, a version trained only on sequences has been developed. The performance of our approach has been assessed by a leave-one-out cross-validation over different benchmarks, outperforming state-of-the-art methods.

Availability and implementation

BIPSPI web server is freely available at http://bipspi.cnb.csic.es. BIPSPI code is available at https://github.com/bioinsilico/BIPSPI. Docker image is available at https://hub.docker.com/r/bioinsilico/bipspi/.

Supplementary information

Supplementary data are available at Bioinformatics online.
Scaling read aligners to hundreds of threads on general-purpose processors
Authors: Langmead Ben , Wilks Christopher , Antonescu Valentin , Charles Rone
Published: July 2018

Motivation

General-purpose processors can now contain many dozens of processor cores and support hundreds of simultaneous threads of execution. To make best use of these threads, genomics software must contend with new and subtle computer architecture issues. We discuss some of these and propose methods for improving thread scaling in tools that analyze each read independently, such as read aligners.

Results

We implement these methods in new versions of Bowtie, Bowtie 2 and HISAT. We greatly improve thread scaling in many scenarios, including on the recent Intel Xeon Phi architecture. We also highlight how bottlenecks are exacerbated by variable-record-length file formats like FASTQ and suggest changes that enable superior scaling.

Availability and implementation

Experiments for this study: https://github.com/BenLangmead/bowtie-scaling.

Bowtie

http://bowtie-bio.sourceforge.net .

Bowtie 2

http://bowtie-bio.sourceforge.net/bowtie2 .

HISAT

http://www.ccb.jhu.edu/software/hisat

Supplementary information

Supplementary data are available at Bioinformatics online.
Current status of stationary fuel cells for coal power generation
Authors: Zhang Xing
Published: July 2018

Fuel cells electrochemically convert chemical energy in fuels into electrical energy (and heat) and so can produce power efficiently with low environmental impact. Applications of fuel cells include stationary power generation, distributed combined heat and power (CHP) and portable power. Recently, research has been conducted on direct carbon fuel cell (DCFC) technology that converts the chemical energy in solid carbon directly into electricity. This article discusses these technologies and their development status. For small- to medium-sized stationary power systems and CHP, the USA ranks first for fuel cell capacity and Japan leads for delivery systems. South Korea is home to the world’s largest fuel cell power plant: the 59-MW Gyeonggi Green Energy park in Hwasung City. Deployment of fuel cell systems is driven by support from governments in the form of tax credits and other incentives. For large stationary power generation, current interest is in integrating a coal gasification process with high-temperature fuel cells (IGFC) to create ultra-high-efficiency, low-emissions power generation systems. The first IGFC demonstration plant with CCS may be in Japan in 2021 as a result of the CoolGen project. DCFC is still in its infancy and far from demonstration. The overall challenges for stationary fuel cells are cost and cell durability. Experience gained from research, designing, building and operating commercially available systems and the IGFC demonstration plant should lead to further development of the technologies and reduced costs, making them a realistic option for power generation.
Species specialization limits movement ability and shapes ecological networks: the case study of 2 forest mammals
Authors: Dondina Olivia , Orioli Valerio , Chiatante Gianpasquale , Meriggi Alberto , Bani Luciano
Published: July 2018

To counteract the negative effects of forest fragmentation on wildlife, it is crucial to maintain functional ecological networks. We identified the ecological networks for 2 mammals with very different degrees of forest specialization, the European badger Meles meles and the Roe deer Capreolus capreolus, by differentiating 4 agroforestry elements as either nodes or connectivity elements, and by defining the distance that provides the functional connectivity between fragments. Species occurrence data were collected in a wide agroecosystem in northern Italy. To test the role of hedgerows, traditional poplar cultivations, short rotation coppices, and reforestations as ecological network elements for the 2 species we applied the method of simulated species perceptions of the landscape (SSPL), comparing the ability of different SSPLs to explain the observed species distribution. All analyses were repeated considering different scenarios of species movement ability through the matrix. Model outputs seem to show that the specialist and highly mobile Roe deer has the same movement ability throughout the matrix (2 km) as the European badger, a smaller, but generalist species. The ecological network identified for the European badger was widespread throughout the area and was composed of woodlands, poplar cultivations and hedgerows as nodes and short rotation coppices as connectivity elements. Conversely, the ecological network of the Roe deer was mostly limited to the main forest areas and was composed of woodlands, poplar cultivations and reforestations as nodes and short rotation coppices and hedgerows as connectivity elements. The degree of forest specialization strongly affects both species perception of habitat and movement ability throughout the matrix, regardless of species size. This has important implications for species conservation.