bluuebunny/crossref_metadata_2025 huggingface dataset:
The Wiskott-Aldrich Syndrome (WAS): Studies On A Possible Defect In Mitochondrial ATP Regeneration In Platelets
Authors: van Brederode W , Gorter G , Akkerman J W N
Published: July 2018

WAS is a severe, X-linked disorder, characterized by eczema, immunodeficiency and an increased bleeding tendency caused by thrombocytopenia and platelet malfunction. There is a diminished epinephrine-induced aggregation response and an abnormal mitochondrial CO2 production during platelet activation. From this, Shapiro et al (The Lancet 1978) concluded that WAS-platelets have a defect in mitochondrial ATP regeneration, which could be employed for detection of WAS- carriers, who are clinically normal and have only minor platelet defects. The test consists of an epinephrine-induced aggregation in the presence of an inhibitor of glycolytic ATP production (deoxyglucose, 2 DG), and showed impaired second wave aggregation in obligate carriers but not in normal controls. We tested 4 unrelated obligate WAS-carriers and found impaired aggregations in all. Five out of 7 female relatives also showed aggregation abnormalities, suggestive for WAS-carriership. However, in 8 out of 15 normal controls (males and females) the test was also positive. The nature of a possible defect in mitochondrial ATP supply was further studied in gel-filtered platelets by analyzing the metabolic ATP level before and during epinephrine-induced aggregation in the presence of inhibitors of glycolysis and glycogenoly- sis and during incubation in substrate-depleted medium. These studies showed that mitochondrial energy generation depended on sugar supply either from glycolysis or glycoge- nolysis and was unable to maintain a normal metabolic ATP level when these pathways were inhibited. Incubation with 2DG led to a fall in metabolic ATP and - consequently - to an impaired epinephrine-induced aggregation. The fall of metabolic ATP (2DG present) was much steeper in platelets from 2 unrelated WAS-patients than in cells from normal controls; most (but not all) obligate carriers showed intermediate values. It is concluded that the impaired epinephrine-induced aggregation in the presence of 2DG in WAS reflects disturbances in ATP homeostasis, which are consistent with a mitochondrial defect.
Role Of α2-Macroglobulin /α2M/ In The Inhibition Of The Fibrinolytic System
Authors: Latallo Z S , Dudek-Wojciechowsk G , Kopeć M
Published: July 2018

Highly purified α2M, plasmin /PL/ and urokinase/UK/ preparations of human origin and synthetic chromogenic peptide substrates H-D-Val-Leu-Lys-pNA /S-225l/, < Glu-Gly-Arg-pNA /S-2444/, Tos-Gly-Pro-Lys-pNA ,/Chromozym PL/ were used in this study. PL was found to be completely bound to α2M within 15 min at 37° . Km values for the free and α2M-bound enzyme were almost identical 3.03 × l0-4mole/l and 3.30 × l0-4mole/l respectively /S-2251,0.15 M Tris-HC1,pH 7.4,37° /. The activity of α2M-PL complex was not inhibited by α2-anti- plasmin /oC2Ai>L/ and SBTI but decreased gradually in the presence of aprotinin depending upon the concentration of the latter and also with time. In contrast to PL, streptokinase-PL complex was inhibited by α2M only very slightly if at all. Heparin-free preparations of HMW /54,000/ and LMW /33 000/ of UK /Choay/ were found to have Km values of 7.81 × 10-5 and 7.14 × l0-5mole/l respectively /S-2444, 0.1M Tris-HCl pH 8.0 containing 0.05M NaCl,37°/. When calculated per mole their activities on S-2444 were almost identical. Although both types of UK formed complexes with α2M, completion of the reaction took 12-24 hrs. The rate of reaction with HMW was about double that of LMW. The results indicate that α2M does not play a significant role as an inhibitor of plasminogen activation. Its only important role in the inhibition of the fibrinolytic system appears to be its function as an overflow inhibitor of plasmin remaining after α2APL inhibition.
Evaluation Of Platelet Reactivity In Patients With Abnormal Heart Valves
Authors: Riddle J M , Magllligan D J , Stein P D
Published: July 2018

The reactivity of platelets from 57 patients was evaluated prior to removal of either an abnormal natural mitral or aortic valve or a degenerated porcine bioprosthetic valve. Thirty patients had aortic stenosis or insufficiency, 21 had mitral stenosis or insufficiency, and 6 underwent the removal of a long-term (4 to 7 years after insertion) Hancock porcine bioprosthetic valve. Transmission electron microscopy was used in a standardized in vitro method to evaluate these platelets. The degree of surface activation (cytoplasmic spreading by single platelets) and aggregate formation were both recorded. A hyperactive response was defined as >20% of the spread type platelet and/or an increased number of aggregates (>93 aggregates/100 single platelets). Hyperactive platelet populations were found in only 8% (6 of 72) of normal subjects. In contrast, 60% (18 of 30) of patients with aortic stenosis or insufficiency, 76%, (16 of 21) of patients with mitral stenosis or insufficiency, and 83%, (5 of 6) of patients with a degenerated porcine valve showed hyperactive platelets. The mean percentage of the spread type platelet for the various groups was 40, 38 and 30 respectively with corresponding mean values of 106, 124 and 102 for platelet aggregates. The reactivity of platelets from the normal group differed significantly from each group of patients with abnormal valves (P > 0.01). However, the level of platelet reactivity between the patient groups with abnormal valves did not differ significantly. Disturbed flow, high shear stresses and the exposure of potentially thrombotic materials are all features associated with abnormal natural heart valves as well as a degenerated bioprosthesis and may explain our finding of increased platelet reactivity in these patients.
Stabilization Of FVIII: C By Calcium
Authors: Cruickshank W H , Tackaberry E S , Palmer D S , Rock G A
Published: July 2018

The well-known two phase decay curve of Factor VIII which has been attributed to enzyme degradation is not altered by the addition of specific protease inhibitors. However, complete stability of Factor VIII, for at least 24 hours, is accomplished when physiological levels of calcium are maintained. Addition of calcium plus heparin to whole blood at 0, 2, and even 4 hours, effectively restores Factor VIII activity to 0 time values and maintains this activity throughout the next 24 hours. The restoration of activity noted after 2 and 4 hours.of incubation is very rapid with the Factor VIII activity increasing within 15 minutes of addition of calcium. Data obtained from column chromatography indicates that the molecular distribution of Factor VIII between high and low molecular weight forms is affected both by time and by the level of calcium present in blood. When blood is collected either into heparin or a mixture of CPD plus heparin plus calcium chloride, the elution profile indicates that Factor VIII activity is equally distributed between high and low molecular weight forms, both at 0 and 24 hours with the total activity remaining unchanged during this time interval. However, when Factor VIII activity at 0 time is in the high molecular weight form with less than 10% in the low molecular weight form. By 24 hours there is virtually no low molecular weight activity remaining in this citrated plasma. The data demonstrate an absolute requirement for calcium in the maintenance of Factor VIII: C activity and suggests that the relative lability of Factor VIII during the first phase of the decay curve is due to the loss of VIII: C activity when calcium is not present at physiological concentrations to stabilize the molecule.
Blood Group (BG) Prevalence In End-Stage (ES) Renal Disease (RD): Relationship To Ristocetin Willebrand Factor (VIII: RWF) And Platelet Survival (PS)
Authors: Torres V , Fuster V , Moore B , Donadio J , Kazmier F , Bowie E
Published: July 2018

BG 0 patients (pts) have lower risk for cardiovascular-thromboembolic disease than A-AB-B pts, particularly males. This might be related to blood hypocoagulability (lower Factor VIII). We report BG frequencies in our Caucasian renal transplant population divided in two groups, ES reflux nephropathy (RN) and ESRD of other etiologies excluding diabetes mellitus.

BG 0 male pts are protected, especially for ESRN. To determine whether this sex dependency could be related to different VIII: RWF levels or PS, VIII:RWF levels (n=82) and 51Cr-labelled PS (n=74) were analyzed in controls according to sex and BG.

VIII: RWF is sex independent and lower in BG 0. PS is BG independent and shortened in males. A hypercoagulable State reflected by high VIII: RWF and short PS might explain the increased risk of non-BG 0 males to develop ESRD. Non-BG 0 male pts with RN may be more susceptible to develop progressive RD.
The Use Of High Performance Liquid Chromatography In The Examination Of The Lipid Class Composition Of Thromboplastin Reference Preparations
Authors: Stevenson K J
Published: July 2018

A pressure liquid chromatographic method has been developed for separation and quantitation of lipid classes of reference thromboplastins.

The method employs a column of high capacity silica, eluted with a three-component gradient system. Detection is by a “moving-wire” flame ionization detector. Fractions of column effluent may be collected for further examination.

Three reference thromboplastins of rabbit, bovine and human (British Comparative Thromboplastin) origin have recently been prepared for the European Economic Community. Markedly contrasting lipid class compositions of these preparations have been detected with this method. The human preparation contains more lipid (13 g/1) than the rabbit (7 g/1) and bovine (3 g/1) preparations and less negatively-charged phospholipid (7.5% compared with 11% and 18% respectively). The animal preparations contained plasmalogens not found in the human material. The significance of these differences in terms of the predicted stability of these reference reagents is considered.
A Novel Animal Model For Plasma Hypercoagulability
Authors: Harenberg J , Stehle G , Haas R , Zimmermann R
Published: July 2018

A sensitive and reproducable animal model for plasma hypercoagulability has not been described so far. We report now on the determination of fi- brinopeptide A immunoreactivity (FPAi) in rabbit blood. Human FPA antiserum of the rabbit was used. The radioimmunological method with a high affinity second antibody was described previously.

The experiments were carried out in 90 rabbits, which were allocated randomly to one of the treatment groups. Normal FPAi in rabbits were 3-21 ng/ ml plasma (mean 12.5 ng/ml). In 12 rabbits only basline FPAi was determined. In 28 rabbits 6|ig, 3ug, 1.5μg sythetic FPA analog/kg bodyweight or saline were injected i.v. The elimination of FPA from blood followed a two phase kinetic without dose dependence. A t/2 of 20 sec was calculated for the a-phase and of 90 sec for the ß-phase. The in vivo recovery of FPA was more than 95%. After saline no changes of FPAi were measured. In 50 rabbits 10mg, 5mg, 2.5mg, 0.66mg phenprocoumon/kg bodyweight or saline were injected i.p. A standardized haematoma was obtained by puncture of the ear artery. After saline an increase of FPAi from 15.0 to 45.7 ng/ml was measured after three days. (p < 0.05). This increase could be inhibited by phenprocoumon in relation to the dose applied.

The data indicate, that the animal model may be appropriate to induce plasma hypercoagulability and useful to investigate trigger mechanisms and the treatment of plasma hypercoagulability. Determination of FPAi in rabbits seem to be sensitive enough to study these problems as shown by the dose related decrease of FPAi under treatment with phenprocoumon after a standardized arterial lesion.
Prothrombin Frankfurt: A Dysfunctional Prothrombin Characterized by Substitution of Glu-466 by Ala
Authors: Friezner Degen Sandra J , McDowell Susan A , Sparks Leah M , Scharrer Inge
Published: July 2018

We have identified a patient with a dysfunctional prothrombin that we have designated Prothrombin Frankfurt. The proband was characterized by a prothrombin activity level of 13% and 20% compared to normal controls using two different assays with a normal prothrombin antigen level of 91% of normal controls. The genetic defect responsible for the abnormal prothrombin activity was determined by the polymerase chain reaction followed by single-strand conformation polymorphism (PCR-SSCP) analysis and by DNA sequence analysis of the human prothrombin gene. Substitution of a C for an A at nucleotide 10177 in the human prothrombin gene of the proband was identified, which results in the replacement of Glu-466 by Ala. The proband and one sister were homozygous for this mutation. Both parents, as well as one brother, were found to be heterozygous for this mutation. The same amino acid substitution was previously identified to be responsible for the dysfunctional protein Prothrombin Salakta and was hypothesized to result in altered substrate specificity. Four polymorphisms were also identified in the prothrombin gene from the proband when compared to the published sequence at nucleotides 554, 4048, 4272 and 10253.
Determinants of Plasminogen Activator Inhibitor-1 Activity in Survivors of Myocardial Infarction
Authors: Gray Rosaire P , Mohamed-Ali Vidya , Patterson David L H , Yudkin John S
Published: July 2018

A significant relationship has been described between plasminogen activator inhibitor-1 (PAI-1) and plasma insulin concentrations. However, most radioimmunoassays (RIA) substantially overestimate plasma insulin concentrations because of cross reaction with proinsulin-like molecules and it has been proposed that proinsulin-like molecules may be important determinants of PAI-1 activity. We measured fasting plasma immunoreactive insulin by conventional RIA, fasting plasma insulin (EIMA) by specific two site immuno-enzymometric assay, and intact proinsulin and des-31,32-proinsulin by two site immunoradiometric assay (IRMA) in 74 (50 nondiabetic and 24 diabetic) subjects who had survived a myocardial infarction between 6 and 24 months previously. In univariate analysis, PAI-1 activity correlated with serum triglycerides (rs=0.43; p <0.0001), insulin sensitivity (rs = -0.30; p = 0.004), and immunoreactive insulin (rs = 0.45; p <0.0001). However, the relationship between PAI-1 activity and plasma specific insulin (IEMA) was weaker (rs = 0.24; p = 0.019) than those with intact proinsulin (rs = 0.53; p <0.0001) and des-31,32-proinsulin (rs = 0.54; p <0.0001) despite the low concentrations of these proinsulin-like molecules. In multiple regression analysis, only des-31,32-proinsulin (p = 0.001) and serum triglycerides (p = 0.013) were significant determinants of PAI-1 activity. In conclusion, these results suggest that proinsulin-like molecules and serum triglycerides are important determinants of PAI-1 activity in survivors of myocardial infarction.
Factors that Contribute to Spontaneous Platelet Aggregation and Streptokinase-Induced Aggregation in Whole Blood
Authors: Armstrong Ruth , May Jane A , Lösche Wolfgang , Heptinstall Stan
Published: July 2018

When whole blood is stirred there is a “spontaneous” platelet aggregation (SPA) which is presumed to be caused by proaggregatory factors released from platelets and other blood cells. Adding streptokinase (SK) to stirred whole blood frequently increases the rate and extent of the platelet aggregation that occurs; this is likely to be via immune complex formation between SK and natural anti-SK antibodies leading to increased release of pro-aggregatory factors.

In this investigation we have examined the effects of several inhibitors and antagonists in an attempt to identify the proaggregatory factors that contribute to both SPA and SK-induced aggregation (SKA) and to evaluate different means of inhibiting both processes. The effects of the inhibitors/antagonists were determined in vitro after adding them to citrated whole blood obtained from healthy volunteers. Platelet aggregation was measured using a platelet counting technique.

Inhibition of both SPA and SKA by apyrase and by FPL 66096 (a P2T receptor antagonist) demonstrated the involvement of ADP in both processes. Inhibition by chlorpromazine indicated that the most likely source of the ADP is red cells. The effects of sulotroban (a TXA2 antagonist) indicated involvement of TXA2 in SKA but not in SPA. The lack of effect of specific antagonists at S2, α2 and PAF receptors suggested lack of involvement of serotonin, catecholamines and plateletactivating factor in either SPA or SKA. Both SPA and SKA were potently inhibited by low concentrations of iloprost (a PGI2 analogue), but a high concentration of SIN-1 (a NO donor) was much less effective. SPA and SKA were prevented by EDTA and by RGDS indicating the importance of divalent cations and of the RGD sequence in adhesive proteins in mediating the platelet aggregation that occurred.

We also determined the effects on SPA and SKA of adding MgCl2 to whole blood. In this case we used blood containing hirudin as anticoagulant. MgCl2 (1 mM) appeared to delay the onset of SPA and markedly inhibited SKA.
Comparison of the Pharmacokinetic Profiles of Three Low Molecular Mass Heparins – Dalteparin, Enoxaparin and Nadroparin – Administered Subcutaneously in Healthy Volunteers (Doses for Prevention of Thromboembolism)
Authors: Collignon F , Frydman A , Caplain H , Ozoux M L , Roux Y Le , Bouthier J , Thébault J J
Published: July 2018

The present trial was designed to comparatively investigate the pharmacokinetic profile and evaluate the apparent bioavailability pattern of three already marketed low molecular mass heparins (LMMHs): dalteparin (Fragmin®), nadroparin (Fraxiparin®), and enoxaparin (Love- nox®) given by subcutaneous route. The study was carried out in 20 healthy young volunteers given, according to a cross over design, a single subcutaneous injection of the doses recommended for the prophylaxis of deep vein thrombosis (commercial preparations, prefilled syringes): dalteparin 2,500 IU (= 2,500 IU anti-Xa), nadroparin 7,500 ICU (= 3,075 IU anti-Xa), enoxaparin 20 mg (= 2,000 IU anti-Xa) and enoxaparin 40 mg (= 4,000 IU anti-Xa). Of the markers used, activated partial thromboplastin time (APTT), thrombin clotting time (TCT), Heptest®, anti-thrombin (aIIa) activity and anti-Xa (aXa) activity, the most pertinent parameter (from a biodynamic viewpoint) is plasma aXa activity. We demonstrated that dalteparin, nadroparin and enoxaparin exhibit statistically significantly different pharmacokinetic and overall disposition patterns. Normalized to the same injected dose (1,000 IU aXa), the relative actual amount of plasma anti-Xa activity generated by enoxaparin is 1.48 times greater (p < 0.001) than that of nadroparin and 2.28 times greater (p < 0.001) than that of dalteparin while the plasma amount induced by nadroparin is 1.54 times greater (p < 0.001) than that of dalteparin. The apparent total body clearance of enoxaparin doses (CL/F = 16.7 ± 5.5 and 13.8 ± 3.2 ml/min) is significantly smaller than those of nadroparin (CL/F = 21.4 ± 7.0 ml/min ; p < 0.01) and dalteparin (CL/F = 33.3 ±11.8 ml/min ; p < 0.001) while dalteparin apparent clearance is about 1.5-fold greater (p < 0.001) than that of nadroparin. These LMMHs also differ by their renal excretion pattern : more fragments exhibiting an anti-Xa activity are recovered in urine following enoxaparin doses (6.4 and 8.7 % of the dose, respectively) than following nadroparin (3.9 %) and dalteparin (3.4 %) injection. These differences in the disposition profiles explain why the apparent elimination half life t1/2 values of the LMMHs compared here are different: dalteparin: 2.8 h; nadroparin: 3.7 h; and enoxaparin: 4.1 h. Whether or not these differences may contribute to explain the different safety/efficacy balance of each of these antithrombotic medications remains to be discussed and needs further studies.
Homozygous APC-resistance Combined with Inherited Type I Protein S Deficiency in a Young Boy with Severe Thrombotic Disease
Authors: Zöller Bengt , He Xuhua , Dahlbäck Björn
Published: July 2018

Inherited resistance to activated protein C (APC) is a frequent cause of familial thrombosis. It is associated with a factor V gene point mutation replacing arginine506 in the APC-cleavage site with a glutamine. Thrombotic events are rare during childhood even in patients with homozygous APC-resistance. We now wish to report on a case of severe venous thrombosis, in a 10-year-old boy. He was found to have pronounced APC-resistance due to homozygous factor V gene mutation in combination with inherited type I protein S deficiency. The two traits were independently inherited in the family. The APC-resistance was partially corrected by adding factor V, whereas added protein S was without effect. This is the first reported case of homozygous APC-resistance combined with another inherited prothrombotic disorder. It illustrates how multiple genetic defects may provoke thrombosis at young age and emphasizes the need of complete evaluation of thrombotic patients in order to determine whether multiple risk factors exist.
Properties of a Recombinant Chimeric Protein in which the gamma-Carboxyglutamic Acid and Helical Stack Domains of Human Anticoagulant Protein C Are Replaced by those of Human Coagulation Factor VII
Authors: Geng Jie-Ping , Castellino Francis J
Published: July 2018

A chimeric cDNA, encoding residues 1-46 (the γ-carboxyglutamic acid module and its trailing helical stack) of human coagulant factor (f) VII, bound to residues 47-419 of human anticoagulant protein C (PC), was constructed and expressed. The resulting protein, r-[∆GD-HSPC/∇GD-HSfVII]PC, was properly processed with regard to signal/ propeptide release, cleavage of the K156R dipeptide, Gla and Hya contents, and the presence of glycosylation.

The mutant protein displayed normal dependencies on Ca2+ for adoption of its metal ion-dependent conformation and for binding to acidic phospholipid vesicles. The chimera failed to recognize a monoclonal antibody (MAb) specific for the Ca2+-induced conformation of the Gla domain (GD) of PC, but did react with another MAb directed in part to the Ca2+-dependent conformation of the GD of fVII. Further, this chimeric protein possessed similar steady state constants as wild-type r-PC toward activation by thrombin and thrombin/thrombomodulin. The activated form of the chimera was very similar to that of its wild- type counterpart in its whole plasma anticoagulant activity, as well as its activity toward inactivation of coagulation factor VIII. The chimeric protein did not bind to the fVII cofactor, tissue factor, showing that the GD/HS domain region of fVII is insufficient for that particular interaction.

The results demonstrate that the GD/HS of fVII, when present in the PC and APC background, serves to maintain the Ca2+/PL-related functions of these latter proteins, and suggest that the Ca2+ and PL- dependent interactions of the GD-HS of PC are sufficiently general in nature such that the GD-HS regions of other proteins of this type can satisfy most of the requirements of PC and APC. The data presented also offer support for the independent nature of the domain unit consisting of the GD/HS module.
Distribution of Phenylindanedione in Blood and Tissues after Oral and Intravenous Administration
Authors: Millar G. J , Mersereau Mary Ogilvie , Lowenthal J , Jaques L. B
Published: July 2018

The absorption spectrum and Polarographie behaviour are described for phenylindanedione. The drug may be estimated by measuring the optical density at 338 nιμ or the Polarographie reduction ware in a phosphate buffer at pH 11.8. For the estimation of the drug in tissue and plasma, the substance is extracted with toluene, taken up in alkali and estimated spectrometrically. For red cells, it is necessary to extract with acetone and after evaporation, take up the residue in water and determine the phenylindanedione polarographically. Blood and tissue levels were determined after administration to rabbits and dogs. Phenylindanedione disappeared from the plasma after intravenous injection much more rapidly than dicumarol. Considerable amounts of the drug were detected in liver and intestine one hour later. On oral administration, after 4—6 hours 50°/o was still recovered from the intestine, while 10—20% was found in the liver. Phenylindanedione and / or its metabolic derivative could be detected in the erythrocytes of rabbits but not in those of dogs.
Blood Viscosity and Haemostasis in the Nephrotic Syndrome
Authors: McGinley E , Lowe G D O , Boulton-Jones M , Forbes C D , Prentice C R M
Published: July 2018

Blood viscosity and its major determinants (haematocrit, plasma viscosity and fibrinogen) as well as several haemostatic variables were measured in 21 patients with the nephrotic syndrome, and 21 controls matched for age, sex, smoking habit and serum creatinine. Blood viscosity was significantly increased in the nephrotic group, measured at a low shear rate (mean increase 41%, p<0.01) and at a high shear rate (mean increase 25%, p <0.01). Haematocrit was not significantly increased, but plasma viscosity was significantly higher (p <0.01), associated with increased plasma macroglobulins especially fibrinogen, which was increased to double the plasma concentration of the control group (p <0.01). Nephrotic subjects also had increased plasma levels of a2-macroglobulin, factor VIII activity, factor VIC antigen and beta-thromboglobulin; differences in antithrombin ID, fibrin degradation products, plasminogen, and platelet count were not significant.

We suggest that increased blood and plasma viscosity may play a role in the vascular complications of the nephrotic syndrome.
Simulation in Neuroanesthesia: How Much to Learn?
Authors: Bhatt Rashmi , Khanna Puneet
Published: July 2018

Taking a cue from the aviation industry, medicine took upon itself the responsibility to improve patient safety. The cause was championed by anesthesia that became a pioneer in using simulation-based training to improve the nontechnical skills, at every level of clinical training. The needs have been understood by evolving subspecialties such as neuroanesthesia as well, where a fewer number of patients and reduced margin of safety have propelled the development of simulation modules specific to requirements. The constant, ongoing advances and improvement in simulation practices have contributed immensely to the betterment of patient safety, and a significant dent in surgical morbidity and mortality probably explains why simulation-based training programs are being incorporated into teaching curriculum across the world.
Pharming animals: a global history of antibiotics in food production (1935–2017)
Authors: Kirchhelle Claas
Published: July 2018

Since their advent during the 1930s, antibiotics have not only had a dramatic impact on human medicine, but also on food production. On farms, whaling and fishing fleets as well as in processing plants and aquaculture operations, antibiotics were used to treat and prevent disease, increase feed conversion, and preserve food. Their rapid diffusion into nearly all areas of food production and processing was initially viewed as a story of progress on both sides of the Iron Curtain. However, from the mid-1950s onwards, agricultural antibiotic use also triggered increasing conflicts about drug residues and antimicrobial resistance (AMR). Significantly, antibiotic concerns did not develop evenly but instead gave rise to an international patchwork of different regulatory approaches. During a time of growing concerns about AMR and a post-antibiotic age, this article reconstructs the origins, global proliferation, and international regulation of agricultural antibiotics. It argues that policymakers need to remember the long history of regulatory failures that has resulted in current antibiotic infrastructures. For effective international stewardship to develop, it is necessary to address the economic dependencies, deep-rooted notions of development, and fragmented cultural understandings of risk, which all contribute to drive global antibiotic consumption and AMR.
Linear waves at a surfactant-contaminated interface separating two fluids: Dispersion and dissipation of capillary-gravity waves
Authors: Rajan Girish K. , Henderson Diane M.
Published: July 2018

Two-dimensional linear waves at a contaminated interface separating two infinitely deep fluids of arbitrary densities and viscosities are investigated. The contamination is modeled as a massless monolayer, which may result from insoluble surfactants, and introduces interfacial elasticity. Thus, the interface supports two wave modes: transverse, capillary-gravity waves (CG-waves) and longitudinal, Marangoni waves (M-waves). A comprehensive dispersion relation is derived; it can be solved numerically to obtain the complex-valued frequency as a function of the irrotational wavenumber for the CG-waves and for the M-waves. The CG-waves are analyzed in this paper; the M-waves are analyzed in a separate work. The main result here is the derivation of an operational approximate formula for the temporal decay rate of the CG-waves. Its predictions are compared to the available measurements of (laboratory) gravity waves, ocean swell, and (laboratory) capillary waves. It is shown that the previously published decay rate models, which include either the effects due to an upper fluid or those due to interfacial contamination (but not both), are limiting cases of the present model. A parametric study of decay rate predictions shows that there are systems including ocean swell for which the influence of both the dynamics of the upper fluid and of the contamination are significant.
Invited Article: Comparison of hyperspectral coherent Raman scattering microscopies for biomedical applications
Authors: Bocklitz T. , Meyer T. , Schmitt M. , Rimke I. , Hoffmann F. , von Eggeling F. , Ernst G. , Guntinas-Lichius O. , Popp J.
Published: July 2018

Raman scattering based imaging represents a very powerful optical tool for biomedical diagnostics. Different Raman signatures obtained by distinct tissue structures and disease induced changes provoke sophisticated analysis of the hyperspectral Raman datasets. While the analysis of linear Raman spectroscopic tissue data is quite established, the evaluation of hyperspectral nonlinear Raman data has not yet been evaluated in great detail. The two most common nonlinear Raman methods are CARS (coherent anti-Stokes Raman scattering) and SRS (stimulated Raman scattering) spectroscopy. Specifically the linear concentration dependence of SRS as compared to the quadratic dependence of CARS has fostered the application of SRS tissue imaging. Here, we applied spectral processing to hyperspectral SRS and CARS data for tissue characterization. We could demonstrate for the first time that similar cluster distributions can be obtained for multispectral CARS and SRS data but that clustering is based on different spectral features due to interference effects in CARS and the different concentration dependence of CARS and SRS. It is shown that a direct combination of CARS and SRS data does not improve the clustering results.
Photon-added and photon-subtracted coherent states on a sphere
Authors: Mahdifar A. , Amooghorban E. , Jafari M.
Published: July 2018

In this paper, we construct the m-photon-added and m-photon-subtracted coherent states on a sphere. These states are shown to satisfy the usual conditions of continuity in the label, normalizability, and the resolution of identity. The preparation of the constructed states, as the states of the radiation field, is considered. We examine and analyze the nonclassical properties of these states, including the photon mean number, Mandel parameter, and quadrature squeezing. We find that these states are sub-Poissonian in nature, whereas the degree of squeezing is reduced (enhanced) by increasing m for the photon-added (photon-subtracted) coherent states on a sphere. The results also exhibit that the curvature of the sphere contributes to the enhancement of nonclassical behavior of the photon-added and photon-subtracted coherent states on the sphere.
Mesoscopic effects on shock initiation of multi-component plastic bonded explosives
Authors: Li Shurui , Duan Zhuoping , Wen Lijing , Bai Zhiling , Ou Zhuocheng , Huang Fenglei
Published: July 2018

A series of one-dimensional Lagrangian tests have been performed to examine model parameters in the mesoscopic reaction rate model for shock initiation of multi-component plastic bonded explosives (PBXs) for two multi-component plastic bonded explosives PBXC03 (87% HMX (octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazoncine), 7% TATB (triaminotrinitrobenzene), and 6% binder by weight) and PBXC10 (25% HMX, 70% TATB, and 5% binder by weight). As the numerical results are in good agreement with experimental data, the model parameters have been used to predict the effects of variations in mesoscopic properties (the particle size, initial density, binder strength, and content) on the shock initiation characteristics of PBXC03 and PBXC10. It is found that the time to detonation for PBXC03 increases with all these mesoscopic properties, while the time to detonation for PBXC10 is basically independent of its mesoscopic properties. Thus, PBXC03 is sensitive to mesoscopic properties, but PBXC10 is not. Moreover, it is also found that the pressure-history curves behind the initial shock wave in PBXC03 have different trends from PBXC10, which implies different chemical reaction mechanisms. Further analysis reveals that it arises from the different hot spot ignition processes due to their different threshold initiation pressures. The hot spots are ignited gradually and almost simultaneously in PBXC03 and PBXC10, respectively.
Plasma-surface interactions in atmospheric pressure plasmas: In situ measurements of electron heating in materials
Authors: Walton S. G. , Foley B. M. , Tomko J. , Boris D. R. , Gillman E. D. , Hernández S. C. , Giri A. , Petrova Tz. B. , Hopkins P. E.
Published: July 2018

The energy flux to a surface during plasma exposure and the associated surface heating are of long standing interest as they contribute to the physico-chemical changes that occur during plasma-based materials synthesis and processing. Indeed, the energy delivered to the surface, via a flux of particles and photons, in concert with a flux of reactive species serves to chemically modify, etch, and/or deposit materials, with an efficacy that depends on the plasma processing environment. A unique feature of plasma synthesis and processing is that most of the delivered energy is absorbed at or very near the surface over short (picosecond) time scales. The dissipation of thermal energy proceeds through electron-electron and/or electron-phonon interactions as they propagate through the material, with relaxation time scales that can be orders of magnitude slower. Typically then, the surface is not in thermal equilibrium with the bulk material. Fast, surface-sensitive techniques are thus required to fully appreciate the dynamics of the plasma-surface interaction. In this work, we employ pump-probe Time-Domain Thermoreflectance, a surface sensitive technique typically used to measure thermal properties of thin films, to determine electron heating of thin metal films during exposure to an atmospheric pressure plasma jet. The results, in conjunction with current measurements, are used to develop a first order understanding of plasma jet-surface interactions. The results show that the energy delivered by the plasma jet causes a localized increase in electron energy within the thin film over an area commensurate with the plasma jet radius.
Comparative study of Ar-implanted Ti-Zr-V non-evaporable getter films on the Al-alloy substrate
Authors: Wu Ling-Hui , Lin Ting-Chun , Cheng Chia-Mu , Chang Chin-Chun , Chan Che-Kai , Perng Shen-Yaw , Sheng I-Ching
Published: July 2018

Original and Ar-implanted Ti-Zr-V non-evaporable getter (NEG) films were characterized using scanning electron microscope, X-ray diffractometer, electron spectroscopy for chemical analysis, and transmission electron microscopy. Similar properties and results were observed in the surface morphology, the composition, and the crystalline structure for original and implanted Ti-Zr-V films. However, the thermal activation temperature were increased for implanted films. The analysis of implanted Ti-Zr-V films revealed that defects formed in the upper layers of the films can trap diffused gaseous atoms from the surface into the Ti-Zr-V films. Therefore, the thermal activation reaction of Ti-Zr-V films would be affected due to implantation-induced defects in the films. We show directly that the thermal activation reaction of Ti-Zr-V films are changed by the existence of defects in the getter films.
The new magnetic diagnostics in the WEST tokamak
Authors: Moreau P. , Le-Luyer A. , Spuig P. , Malard P. , Saint-Laurent F. , Artaud J. F. , Morales J. , Faugeras B. , Heumann H. , Cantone B. , Moreau M. , Brun C. , Nouailletas R. , Nardon E. , Santraine B. , Berne A. , Kumari P. , Belsare S. ,   WEST Team
Published: July 2018

The WEST tokamak consists of a major upgrade of the superconducting medium size tokamak Tore Supra aiming at testing ITER divertor components. Such modification has required rebuilding a full set of magnetic diagnostics. The project was started in 2013 and completed in 2016. The diagnostic consists of a set of 469 sensors (421 pick-up coils, 36 flux loops, and 12 Rogowski coils) installed in the WEST vacuum vessel. New analog integrators have been developed in order to obtain the magnetic field and flux from the raw signal of the sensors. During the startup phase of WEST, plasma currents of the order of a few kilo amperes were measured despite much larger current of the order of hundreds of kilo amperes flowing in nearby conducting structures. The diagnostic is now fully operational and exhibits a noise level of about 0.5 mT on the magnetic field, and 2.0 mWb on flux loops allowing identifying the plasma boundary with an accuracy of a few millimeters on a 2 ms time cycle.
Two-step photon absorption in InP/InGaP quantum dot solar cells
Authors: Kum Hyun , Dai Yushuai , Aihara Taketo , Slocum Michael A. , Tayagaki Takeshi , Fedorenko Anastasiia , Polly Stephen J. , Bittner Zachary , Sugaya Takeyoshi , Hubbard Seth M.
Published: July 2018

Intermediate band solar cells promise improved efficiencies beyond the Shockley-Queisser limit by utilizing an intermediate band formed within the bandgap of a single junction solar cell. InP quantum dots (QDs) in an In0.49Ga0.51P host are a promising material system for this application, but two-step photon absorption has not yet been demonstrated. InP QDs were grown via metalorganic chemical vapor deposition, and a density, a diameter, and a height of 0.7 × 1010 cm−2, 56 ± 10 nm, and 18 ± 2.8 nm, respectively, were achieved. Time-resolved photoluminescence measurements show a long carrier lifetime of 240 ns, indicating a type-II band alignment of these InP quantum dots. Several n-i-p In0.49Ga0.51P solar cells were grown with both 3 and 5 layers of InP QDs in the i-region. While the solar cells showed an overall loss in short circuit current compared to reference cells due to emitter degradation, a sub-bandgap enhancement of 0.11 mA/cm2 was clearly observed, due to absorption and collection from the InP QDs. Finally, two-step photon absorption experiments have shown unambiguous photocurrent generation involving an intermediate band within the bandgap at temperatures up to 250 K.
Residual-free reactive ion etching of gold layers
Authors: Franz Gerhard , Oberhausen Wolfhard , Meyer Ralf , Amann Markus-Christian
Published: July 2018

Metal contacts on semiconductors devices are normally defined by lift-off process, because no well-defined etch processes exist for some rare metals. In this work, an RIE process for gold contacts is introduced which requires a high-density plasma, generated by electron cyclotron resonance. The proof is given by the residual-free etching without fence-generation and micromasking in the vicinity of the mask.
Influence of Ni-Zn-Cu-ferrite on electroactive β-phase in poly(vinylidene fluoride)-Ni-Zn-Cu-ferrite nanocomposite film: Unique metamaterial for enhanced microwave absorption
Authors: Saha Papiya , Das Sukhen , Sutradhar Soumyaditya
Published: July 2018

In search of a new radar absorbing material for microwave applications, the nanoparticles of Ni0.40Zn0.40Cu0.20Fe2O4 (NZCF) are successfully incorporated in the matrix of poly(vinylidene fluoride) (PVDF), and this NZCF-PVDF nanocomposite system has evolved as the potential one for absorbing radiations in the microwave/GHz frequency range. The enhancement of electroactive β-phase of PVDF has been observed in the NZCF-PVDF nanocomposite system due to the formation of NZCF-PVDF interfaces. Also, the magnetic dipoles of ferrite nanoparticles are present in the same resultant nanocomposite system. Both these factors play a significant role in the interaction of microwave radiation with the medium of the nanocomposite system. The optimization of wave matter interaction leads to the superior reflection loss property of the NZCF-PVDF nanocomposite system. The mutual contributions of both magnetic nano-fillers and electroactive PVDF polymers make this NZCF-PVDF nanocomposite system a unique metamaterial for enhanced microwave absorption. Many articles have been published on polymer-ferrite systems but in true sense the involvement of NZCF-PVDF interfaces as active centres during wave matter interactions has not been considered by anyone else. Reflection loss property of all the NZCF-PVDF nanocomposite films has been observed, and a maximum of −49.7 dB at 13.2 GHz is obtained for 10 wt. % of NZCF loaded PVDF nanocomposite films. This is the highest reflection loss ever found in these types of polymer based metamaterials. Also, the high reflection loss in NZCF-PVDF nanocomposite films (X and Ku bands) makes it the most suitable one for the applications in the area of microwave devices.
Photoelectron spectroscopy studies of PTCDI on Ag/Si(111)-3×3
Authors: Emanuelsson C. , Johansson L. S. O. , Zhang H. M.
Published: July 2018

3,4,9,10-perylene tetracarboxylic diimide molecules were evaporated onto a Ag/Si(111)-3×3 surface and studied using photoelectron spectroscopy and near edge X-ray absorption fine structure (NEXAFS). All core levels related to the imide group of the molecules showed a partial shift to lower binding energies at low coverages. In NEXAFS spectra, the first transitions to the unoccupied states were weaker at low coverages compared to thicker films. Also, extra states in the valence band between the regular highest occupied molecular orbital and the Fermi level were found at low coverages. These changes were explained by two types of molecules. Due to charge transfer from the surface, these two types have different interactions between the imide group and the substrate. As a result, one type has a partially filled lowest unoccupied molecular orbital while the other type does not.
Nearly 40% outcoupling efficiency in OLEDs with all-metal electrodes
Authors: Brodeur Julien , Arguel Romain , Hafezian Soroush , Barachati Fábio , Kéna-Cohen Stéphane
Published: July 2018

Due to its high transparency and low sheet resistance, indium tin oxide (ITO) has been the material of choice for transparent anodes in organic light-emitting diodes (OLEDs). Indium tin oxide, however, is a source of outcoupling loss due to waveguiding and reduced mechanical stability on flexible/stretchable substrates due to its brittle nature. We demonstrate that highly efficient ITO-free OLEDs can be achieved using high quality silver electrodes and horizontally aligned dipole emitters to avoid plasmonic losses. Using an ultrathin Ag/MPTMS anode and a partially aligned phosphorescent emitter, we demonstrate OLEDs with 30% EQE, luminous efficiency exceeding 130 lm/W, and low leakage current. In addition, we demonstrate OLEDs with an optimized structure showing a 36.1% outcoupling efficiency. Theoretical calculations show that our approach can yield up to 48.4% outcoupling efficiency for perfect horizontal alignment, which exceeds the maximum achievable with ITO. The combination of a silver anode and a horizontal phosphorescent emitter is promising for the future design of ultra-efficient flexible OLEDs.
Theory of ion dynamics and heating by magnetic pumping in FRC plasma
Authors: Egedal J. , Monkhorst H. J. , Lichko E. , Montag P.
Published: July 2018

A new mathematical framework is developed for efficient evaluation of ion heating during magnetic pumping of field-reversed configuration (FRC) plasmas. The topology of ion trajectories is examined through the use of action variables applied to a typical FRC equilibrium. Orbit bifurcations are identified and characterized analytically. These bifurcations are associated with the breakdown of the action variables as adiabatic invariants. The associated pitch-angle-mixing is important to the efficiency of magnetic pumping and is included in a new model for the kinetic behavior of the ions during the heating process.
Triggering of flow asymmetry by anisotropic deflection of lamella during the impact of a drop onto superhydrophobic surfaces
Authors: Regulagadda Kartik , Bakshi Shamit , Das Sarit Kumar
Published: July 2018

A water drop impacting a superhydrophobic surface (SHS) rebounds completely with remarkable elasticity. For a given drop size, the time of contact on a flat SHS remains constant. However, recent studies show that the contact time can be reduced further by triggering an asymmetry in the hydrodynamics of impact. This can be achieved in different ways; an example being the impact on a cylindrical SHS with a curvature comparable to the drop. Here, the anisotropic flow generated from the tangential momentum and elliptical footprint of the drop before the crash leads to the formation of lobes. In the present work, we perform drop impact experiments on a bathtub-like SHS and show that the radial anisotropy can be triggered even in the absence of both the tangential momentum and non-circular footprint. This is shown to be a consequence of lamella deflection during the drop spreading. The reduction in contact time is quite clearly evident in this experimental regime.
Overcoming network resilience to synchronization through non-fast stochastic broadcasting
Authors: Jeter Russell , Porfiri Maurizio , Belykh Igor
Published: July 2018

Stochastic broadcasting is an important and understudied paradigm for controlling networks. In this paper, we examine the feasibility of on-off broadcasting from a single reference node to induce synchronization in a target network with connections from the reference node that stochastically switch in time with an arbitrary switching period. Internal connections within the target network are static and promote the network’s resilience to externally induced synchronization. Through rigorous mathematical analysis, we uncover a complex interplay between the network topology and the switching period of stochastic broadcasting, fostering or hindering synchronization to the reference node. We derive a criterion which reveals an explicit dependence of induced synchronization on the properties of the network (the Laplacian spectrum) and the switching process (strength of broadcasting, switching period, and switching probabilities). With coupled chaotic tent maps as our test-bed, we prove the emergence of “windows of opportunity” where only non-fast switching periods are favorable to synchronization. The size of these windows of opportunity is shaped by the Laplacian spectrum such that the switching period needs to be manipulated accordingly to induce synchronization. Surprisingly, only the zero and the largest eigenvalues of the Laplacian matrix control these windows of opportunities for tent maps within a wide parameter region.