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Sample records for heparin coupling efficiency

  1. Influence of spacer length on heparin coupling efficiency and fibrinogen adsorption of modified titanium surfaces

    Gbureck Uwe

    2007-07-01

    Full Text Available Abstract Background Chemical bonding of the drug onto surfaces by means of spacer molecules is accompanied with a reduction of the biological activity of the drug due to a constricted mobility since normally only short spacer molecule like aminopropyltrimethoxysilane (APMS are used for drug coupling. This work aimed to study covalent attachment of heparin to titanium(oxide surfaces by varying the length of the silane coupling agent, which should affect the biological potency of the drug due to a higher mobility with longer spacer chains. Methods Covalent attachment of heparin to titanium metal and TiO2 powder was carried out using the coupling agents 3-(Trimethoxysilyl-propylamine (APMS, N- [3-(Trimethoxysilylpropyl]ethylenediamine (Diamino-APMS and N1- [3-(Trimethoxy-silyl-propyl]diethylenetriamine (Triamino-APMS. The amount of bound coupling agent and heparin was quantified photometrically by the ninhydrin reaction and the tolidine-blue test. The biological potency of heparin was determined photometrically by the chromogenic substrate Chromozym TH and fibrinogen adsorption to the modified surfaces was researched using the QCM-D (Quartz Crystal Microbalance with Dissipation Monitoring technique. Results Zeta-potential measurements confirmed the successful coupling reaction; the potential of the unmodified anatase surface (approx. -26 mV shifted into the positive range (> + 40 mV after silanisation. Binding of heparin results in a strongly negatively charged surface with zeta-potentials of approx. -39 mV. The retaining biological activity of heparin was highest for the spacer molecule Triamino-APMS. QCM-D measurements showed a lower viscosity for adsorbed fibrinogen films on heparinised surfaces by means of Triamino-APMS. Conclusion The remaining activity of heparin was found to be highest for the covalent attachment with Triamino-APMS as coupling agent due to the long chain of this spacer molecule and therefore the highest mobility of the drug

  2. Simple and Efficient Purification of Recombinant Proteins Using the Heparin-Binding Affinity Tag.

    Jayanthi, Srinivas; Gundampati, Ravi Kumar; Kumar, Thallapuranam Krishnaswamy Suresh

    2017-11-01

    Heparin, a member of the glycosaminoglycan family, is known to interact with more than 400 different types of proteins. For the past few decades, significant progress has been made to understand the molecular details involved in heparin-protein interactions. Based on the structural knowledge available from the FGF1-heparin interaction studies, we have designed a novel heparin-binding peptide (HBP) affinity tag that can be used for the simple, efficient, and cost-effective purification of recombinant proteins of interest. HBP-tagged fusion proteins can be purified by heparin Sepharose affinity chromatography using a simple sodium chloride gradient to elute the bound fusion protein. In addition, owing to the high density of positive charges on the HBP tag, recombinant target proteins are preferably expressed in their soluble forms. The purification of HBP-fusion proteins can also be achieved in the presence of chemical denaturants, including urea. Additionally, polyclonal antibodies raised against the affinity tag can be used to detect HBP-fused target proteins with high sensitivity. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

  3. Qualitative and quantitative analysis of heparin and low molecular weight heparins using size exclusion chromatography with multiple angle laser scattering/refractive index and inductively coupled plasma/mass spectrometry detectors.

    Ouyang, Yilan; Zeng, Yangyang; Yi, Lin; Tang, Hong; Li, Duxin; Linhardt, Robert J; Zhang, Zhenqing

    2017-11-03

    Heparin, a highly sulfated glycosaminoglycan, has been used as a clinical anticoagulant over 80 years. Low molecular weight heparins (LMWHs), heparins partially depolymerized using different processes, are widely used as clinical anticoagulants. Qualitative molecular weight (MW) and quantitative mass content analysis are two important factors that contribute to LMWH quality control. Size exclusion chromatography (SEC), relying on multiple angle laser scattering (MALS)/refractive index (RI) detectors, has been developed for accurate analysis of heparin MW in the absence of standards. However, the cations, which ion-pair with the anionic polysaccharide chains of heparin and LMWHs, had not been considered in previous reports. In this study, SEC with MALS/RI and inductively coupled plasma/mass spectrometry detectors were used in a comprehensive analytical approach taking both anionic polysaccharide and ion-paired cations heparin products. This approach was also applied to quantitative analysis of heparin and LMWHs. Full profiles of MWs and mass recoveries for three commercial heparin/LMWH products, heparin sodium, enoxaparin sodium and nadroparin calcium, were obtained and all showed higher MWs than previously reported. This important improvement more precisely characterized the MW properties of heparin/LMWHs and potentially many other anionic polysaccharides. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Improving pancreatic islet in vitro functionality and transplantation efficiency by using heparin mimetic peptide nanofiber gels.

    Uzunalli, Gozde; Tumtas, Yasin; Delibasi, Tuncay; Yasa, Oncay; Mercan, Sercan; Guler, Mustafa O; Tekinay, Ayse B

    2015-08-01

    Pancreatic islet transplantation is a promising treatment for type 1 diabetes. However, viability and functionality of the islets after transplantation are limited due to loss of integrity and destruction of blood vessel networks. Thus, it is important to provide a proper mechanically and biologically supportive environment for enhancing both in vitro islet culture and transplantation efficiency. Here, we demonstrate that heparin mimetic peptide amphiphile (HM-PA) nanofibrous network is a promising platform for these purposes. The islets cultured with peptide nanofiber gel containing growth factors exhibited a similar glucose stimulation index as that of the freshly isolated islets even after 7 days. After transplantation of islets to STZ-induced diabetic rats, 28 day-long monitoring displayed that islets that were transplanted in HM-PA nanofiber gels maintained better blood glucose levels at normal levels compared to the only islet transplantation group. In addition, intraperitoneal glucose tolerance test revealed that animals that were transplanted with islets within peptide gels showed a similar pattern with the healthy control group. Histological assessment showed that islets transplanted within peptide nanofiber gels demonstrated better islet integrity due to increased blood vessel density. This work demonstrates that using the HM-PA nanofiber gel platform enhances the islets function and islet transplantation efficiency both in vitro and in vivo. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  5. The impact of preparation parameters on typical attributes of chitosan-heparin nanohydrogels: particle size, loading efficiency, and drug release.

    Shahbazi, Mohammad-Ali; Hamidi, Mehrdad

    2013-11-01

    Today, developing an optimized nanoparticle (NP) preparation procedure is of paramount importance in all nanoparticulate drug delivery researches, leading to expanding more operative and clinically validated nanomedicines. In this study, a one-at-a-time experimental approach was used for evaluating the effect of various preparation factors on size, loading, and drug release of hydrogel NPs prepared with ionotropic gelation between heparin and chitosan. The size, loading efficiency (LE) and drug release profile of the NPs were evaluated when the chitosan molecular weight, chitosan concentration, heparin addition time to chitosan solution, heparin concentration, pH value of chitosan solution, temperature, and mixing rate were changed separately while other factors were in optimum condition. The results displayed that size and LE are highly influenced by chitosan concentration, getting an optimum of 63 ± 0.57 and 75.19 ± 2.65, respectively, when chitosan concentration was 0.75 mg/ml. Besides, heparin addition time of 3 min leaded to 74.1 ± 0.79 % LE with no sensible effect on size and release profile. In addition, pH 5.5 showed a minimum size of 63 ± 1.87, maximum LE of 73.81 ± 3.13 and the slowest drug release with 63.71 ± 3.84 % during one week. Although LE was not affected by temperature, size and release reduced to 63 ± 0 and 74.21 ± 1.99% when temperature increased from 25°C to 55°C. Also, continuous increase of mixer rate from 500 to 3500 rpm resulted in constant enhancement of LE from 58.3 ± 3.6 to 74.4 ± 2.59 as well as remarkable decrease in size from 148 ± 4.88 to 63 ± 2.64.

  6. Heparin kinetics

    Swart, C.A.M. de.

    1983-01-01

    The author has studied the kinetics of heparin and heparin fractions after intravenous administration in humans and in this thesis the results of this study are reported. Basic knowledge about the physico-chemical properties of heparin and its interactions with proteins resulting in anticoagulant and lipolytic effects are discussed in a review (chapter II), which also comprises some clinical aspects of heparin therapy. In chapter III the kinetics of the anticoagulant effect are described after intravenous administration of five commercial heparin preparations. A mathematical model is presented that fits best to these kinetics. The kinetics of the anticoagulant and lipolytic effects after intravenous injection of various 35 S-radiolabelled heparin fractions and their relationship with the disappearance of the radiolabel are described in chapter IV. Chapter V gives a description of the kinetics of two radiolabels after injection of in vitro formed complexes consisting of purified, 125 I-radiolabelled antithrombin III and various 35 S-radiolabelled heparin fractions. (Auth.)

  7. Octasaccharide is the minimal length unit required for efficient binding of cyclophilin B to heparin and cell surface heparan sulphate.

    Vanpouille, Christophe; Denys, Agnès; Carpentier, Mathieu; Pakula, Rachel; Mazurier, Joël; Allain, Fabrice

    2004-09-01

    Cyclophilin B (CyPB) is a heparin-binding protein first identified as a receptor for cyclosporin A. In previous studies, we reported that CyPB triggers chemotaxis and integrin-mediated adhesion of T-lymphocytes by way of interaction with two types of binding sites. The first site corresponds to a signalling receptor; the second site has been identified as heparan sulphate (HS) and appears crucial to induce cell adhesion. Characterization of the HS-binding unit is critical to understand the requirement of HS in pro-adhesive activity of CyPB. By using a strategy based on gel mobility shift assays with fluorophore-labelled oligosaccharides, we demonstrated that the minimal heparin unit required for efficient binding of CyPB is an octasaccharide. The mutants CyPB(KKK-) [where KKK- refers to the substitutions K3A(Lys3-->Ala)/K4A/K5A] and CyPB(DeltaYFD) (where Tyr14-Phe-Asp16 has been deleted) failed to interact with octasaccharides, confirming that the Y14FD16 and K3KK5 clusters are required for CyPB binding. Molecular modelling revealed that both clusters are spatially arranged so that they may act synergistically to form a binding site for the octasaccharide. We then demonstrated that heparin-derived octasaccharides and higher degree of polymerization oligosaccharides inhibited the interaction between CyPB and fluorophore-labelled HS chains purified from T-lymphocytes, and strongly reduced the HS-dependent pro-adhesive activity of CyPB. However, oligosaccharides or heparin were unable to restore adhesion of heparinase-treated T-lymphocytes, indicating that HS has to be present on the cell membrane to support the pro-adhesive activity of CyPB. Altogether, these results demonstrate that the octasaccharide is likely to be the minimal length unit required for efficient binding of CyPB to cell surface HS and consequent HS-dependent cell responses.

  8. Improving plasmonic waveguides coupling efficiency using nanoantennas

    Andryieuski, Andrei; Malureanu, Radu; Bouillard, Jean-Sebastien

    2012-01-01

    . The classical dipole antenna scheme can be improved by changing the nanoantenna geometry, adding constructive elements such as reflecting bars and mirrors and using arrays of antennas. The modelling designates that the coupling efficiency from a vertical fiber to a plasmonic waveguide can be improved more than......Plasmonic waveguides bear a lot of potential for photonic applications. However, one of the challenges for implementing them in devices is the low coupling efficiency to and from optical fibers. We report on our approach to facilitate the coupling efficiency with the use of metallic nanoantennas...... in 180 times in comparison with a direct fiber-waveguide coupling. Pros and cons of each configuration are discussed. Fabrication and characterisation results are reported....

  9. Construction of mussel-inspired coating via the direct reaction of catechol and polyethyleneimine for efficient heparin immobilization

    Liu, Yujie [School of Material Science and Engineering, Southwest Jiaotong University, Chengdu 610031 (China); The Institute of Biomaterials and Surface Engineering, Southwest Jiaotong University, Chengdu 610031 (China); Luo, Rifang, E-mail: lrifang@126.com [School of Material Science and Engineering, Southwest Jiaotong University, Chengdu 610031 (China); The Institute of Biomaterials and Surface Engineering, Southwest Jiaotong University, Chengdu 610031 (China); Shen, Fangyu; Tang, Linlin [School of Material Science and Engineering, Southwest Jiaotong University, Chengdu 610031 (China); The Institute of Biomaterials and Surface Engineering, Southwest Jiaotong University, Chengdu 610031 (China); Wang, Jin, E-mail: jinxxwang@263.net [School of Material Science and Engineering, Southwest Jiaotong University, Chengdu 610031 (China); The Institute of Biomaterials and Surface Engineering, Southwest Jiaotong University, Chengdu 610031 (China); Huang, Nan [School of Material Science and Engineering, Southwest Jiaotong University, Chengdu 610031 (China); The Institute of Biomaterials and Surface Engineering, Southwest Jiaotong University, Chengdu 610031 (China)

    2015-02-15

    Highlights: • Catechol (CA) and PEI copolymerization was a mimetic and dopamine-like coating method. • CA/PEI film provided amine groups and was effective in heparin immobilization. • CA/PEI coating could inhibit smooth muscle cell proliferation. • CA/PEI coating did not show any significant cytotoxicity to endothelial cell. - Abstract: Dopamine could self-polymerize to form the coating on various substrates and the co-existence of catechols and amines was crucial in performing such polymerization process. In this work, a mimetic approach of coating formation was carried out based on the co-polymerization of catechol (CA) and polyethyleneimine (PEI). Mussel-inspired CA/PEI coating was deposited on 316L stainless steel (SS). Fourier transform infrared spectra (FTIR) and X-ray photoelectron spectroscopy (XPS) demonstrated the successful coating formation. QCM measurement showed good affinity of heparin immobilization on CA/PEI coating surface ascribed to the amine groups. Herein, vascular cell-material interactions like endothelial cells (ECs) and smooth muscle cells (SMCs) were also investigated. Interestingly, CA/PEI and heparin modified coatings presented no cytotoxicity to ECs, however to a certain extent, decreased SMCs proliferation. Moreover, heparin-binding surface presented significant anti-platelet adhesion and activation properties. These results effectively suggested that the mussel-inspired CA/PEI coating might be promising when served as a platform for biomolecule immobilization.

  10. Efficient shortcut techniques in evanescently coupled waveguides

    Paul, Koushik; Sarma, Amarendra K.

    2016-10-01

    Shortcut to Adiabatic Passage (SHAPE) technique, in the context of coherent control of atomic systems has gained considerable attention in last few years. It is primarily because of its ability to manipulate population among the quantum states infinitely fast compared to the adiabatic processes. Two methods in this regard have been explored rigorously, namely the transitionless quantum driving and the Lewis-Riesenfeld invariant approach. We have applied these two methods to realize SHAPE in adiabatic waveguide coupler. Waveguide couplers are integral components of photonic circuits, primarily used as switching devices. Our study shows that with appropriate engineering of the coupling coefficient and propagation constants of the coupler it is possible to achieve efficient and complete power switching. We also observed that the coupler length could be reduced significantly without affecting the coupling efficiency of the system.

  11. Distributed coupling high efficiency linear accelerator

    Tantawi, Sami G.; Neilson, Jeffrey

    2016-07-19

    A microwave circuit for a linear accelerator includes multiple monolithic metallic cell plates stacked upon each other so that the beam axis passes vertically through a central acceleration cavity of each plate. Each plate has a directional coupler with coupling arms. A first coupling slot couples the directional coupler to an adjacent directional coupler of an adjacent cell plate, and a second coupling slot couples the directional coupler to the central acceleration cavity. Each directional coupler also has an iris protrusion spaced from corners joining the arms, a convex rounded corner at a first corner joining the arms, and a corner protrusion at a second corner joining the arms.

  12. The heparin-binding domain of HB-EGF as an efficient cell-penetrating peptide for drug delivery.

    Luo, Zhao; Cao, Xue-Wei; Li, Chen; Wu, Miao-Dan; Yang, Xu-Zhong; Zhao, Jian; Wang, Fu-Jun

    2016-11-01

    Cell-penetrating peptides (CPPs) have been shown to be potential drug carriers for cancer therapy. The inherently low immunogenicity and cytotoxicity of human-derived CPPs make them more suitable for intracellular drug delivery compared to other delivery vehicles. In this work, the protein transduction ability of a novel CPP (termed HBP) derived from the heparin-binding domain of HB-EGF was evaluated. Our data shows, for the first time, that HBP possesses similar properties to typical CPPs and is a potent drug delivery vector for improving the antitumor activity of impermeable MAP30. The intrinsic bioactivities of recombinant MAP30-HBP were well preserved compared to those of free MAP30. Furthermore, HBP conjugated to the C-terminus of MAP30 promoted the cellular uptake of recombinant MAP30-HBP. Moreover, the fusion of HBP to MAP30 gave rise to significantly enhanced cytotoxic effects in all of the tumor cell lines tested. In HeLa cells, this cytotoxicity was mainly caused by the induction of cell apoptosis. Further investigation revealed that HBP enhanced MAP30-induced apoptosis through the activation of the mitochondrial- and death receptor-mediated signaling pathways. In addition, the MAP30-HBP fusion protein caused more HeLa cells to become arrested in S phase compared to MAP30 alone. These results highlight the MAP30-HBP fusion protein as a promising drug candidate for cancer therapy and demonstrate HBP, a novel CPP derived from human HB-EGF, as a new potential vector for antitumor drug delivery. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

  13. Heparin free dialysis in critically sick children using sustained low efficiency dialysis (SLEDD-f: A new hybrid therapy for dialysis in developing world.

    Sidharth Kumar Sethi

    Full Text Available In critically sick adults, sustained low efficiency dialysis [SLED] appears to be better tolerated hemodynamically and outcomes seem to be comparable to CRRT. However, there is paucity of data in critically sick children. In children, two recent studies from Taiwan (n = 11 and India (n = 68 showed benefits of SLED in critically sick children.The objective of the study was to look at the feasibility and tolerability of sustained low efficiency daily dialysis-filtration [SLEDD-f] in critically sick pediatric patients.Design: Retrospective study Inclusion criteria: All pediatric patients who had undergone heparin free SLEDD-f from January 2012 to October 2017. Measurements: Data collected included demographic details, vital signs, PRISM III at admission, ventilator parameters (where applicable, number of inotropes, blood gas and electrolytes before, during, and on conclusion of SLED therapy. Technical information was gathered regarding SLEDD-f prescription and complications.Between 2012-2017, a total of 242 sessions of SLEDD-f were performed on 70 patients, out of which 40 children survived. The median age of patients in years was 12 (range 0.8-17 years, and the median weight was 39 kg (range 8.5-66 kg. The mean PRISM score at admission was 8.77±7.22. SLEDD-f sessions were well tolerated, with marked improvement in fluid status and acidosis. Premature terminations had to be done in 23 (9.5% of the sessions. There were 21 sessions (8.6% terminated due to hypotension and 2 sessions (0.8% terminated due to circuit clotting. Post- SLEDD-f hypocalcemia occurred in 15 sessions (6.2%, post- SLEDD-f hypophosphatemia occurred in 1 session (0.4%, and post- SLEDD-f hypokalemia occurred in 17 sessions (7.0%.This study is the largest compiled data on pediatric SLEDD-f use in critically ill patients. Our study confirms the feasibility of heparin free SLEDD-f in a larger pediatric population, and even in children weighing <20 kg on inotropic support.

  14. High efficiency nebulization for helium inductively coupled plasma mass spectrometry

    Jorabchi, Kaveh; McCormick, Ryan; Levine, Jonathan A.; Liu Huiying; Nam, S.-H.; Montaser, Akbar

    2006-01-01

    A pneumatically-driven, high efficiency nebulizer is explored for helium inductively coupled plasma mass spectrometry. The aerosol characteristics and analyte transport efficiencies of the high efficiency nebulizer for nebulization with helium are measured and compared to the results obtained with argon. Analytical performance indices of the helium inductively coupled plasma mass spectrometry are evaluated in terms of detection limits and precision. The helium inductively coupled plasma mass spectrometry detection limits obtained with the high efficiency nebulizer at 200 μL/min are higher than those achieved with the ultrasonic nebulizer consuming 2 mL/min solution, however, precision is generally better with high efficiency nebulizer (1-4% vs. 3-8% with ultrasonic nebulizer). Detection limits with the high efficiency nebulizer at 200 μL/min solution uptake rate approach those using ultrasonic nebulizer upon efficient desolvation with a heated spray chamber followed by a Peltier-cooled multipass condenser

  15. Heparin and heparin-induced thrombocytopenia

    2007-06-15

    Jun 15, 2007 ... Heparin is one of the most widely used drugs. It is used routinely for treatment and thromboprophylaxis in a broad spectrum of conditions including venous thromboembolism, atrial fibrillation, acute coronary syndromes, peripheral vascular disease and to maintain the patency of indwelling catheters and ...

  16. Heparin pharmacovigilance in Brazil.

    Junqueira, Daniela Rezende Garcia; Viana, Thércia Guedes; Peixoto, Eliane R de M; Barros, Fabiana C R de; Carvalho, Maria das Graças; Perini, Edson

    2011-01-01

    To investigate the biological origin of injectable unfractioned heparin available in Brazilian market by discussing the impact of the profile of commercial products and the changes in heparin monograph on the drug safety. The Anvisa data base for the Registered Products of Pharmaceutical Companies and the Dictionary of Pharmaceutical Specialties (DEF 2008/2009) were searched. A survey with industries having an active permission for marketing the drug in Brazil was conducted. Five companies were granted a permission to market unfractioned heparin in Brazil. Three of them are porcine in origin and two of them are bovine in origin, with only one explicitly showing this information in the package insert. The effectiveness and safety of heparin studied in non-Brazilian populations may not represent the Brazilian reality, since most countries no longer produce bovine heparin. The currently marketed heparin has approximately 10% less anticoagulant activity than that previously produced and this change may have clinical implications. Evidence about the lack of dose interchangeability between bovine and porcine heparins and the unique safety profile of these drugs indicates the need to follow the treatment and the patients' response. Events threatening the patient's safety must be reported to the pharmacovigilance system in each particular country.

  17. N-Glycosylation of Human R-Spondin 1 Is Required for Efficient Secretion and Stability but Not for Its Heparin Binding Ability

    Chiung-Fang Chang

    2016-06-01

    Full Text Available R-spondin 1 (Rspo1 plays an essential role in stem cell biology by potentiating Wnt signaling activity. Despite the fact that Rspo1 holds therapeutic potential for a number of diseases, its biogenesis is not fully elucidated. All Rspo proteins feature two amino-terminal furin-like repeats, which are responsible for Wnt signal potentiation, and a thrombospondin type 1 (TSR1 domain that can provide affinity towards heparan sulfate proteoglycans. Using chemical inhibitors, deglycosylase and site-directed mutagenesis, we found that human Rspo1 and Rspo3 are both N-glycosylated at N137, a site near the C-terminus of the furin repeat 2 domain, and Rspo2 is N-glycosylated at N160, a position near the N-terminus of TSR1 domain. Elimination of N-glycosylation at these sites affects their accumulation in media but have no effect on the ability towards heparin. Introduction of the N-glycosylation site to Rspo2 mutant at the position homologous to N137 in Rspo1 restored full glycosylation and rescued the accumulation defect of nonglycosylated Rspo2 mutant in media. Similar effect can be observed in the N137 Rspo1 or Rspo3 mutant engineered with Rspo2 N-glycosylation site. The results highlight the importance of N-glycosylation at these two positions in efficient folding and secretion of Rspo family. Finally, we further showed that human Rspo1 is subjected to endoplasmic reticulum (ER quality control in N-glycan-dependent manner. While N-glycan of Rspo1 plays a role in its intracellular stability, it had little effect on secreted Rspo1. Our findings provide evidence for the critical role of N-glycosylation in the biogenesis of Rspo1.

  18. Heparin-Induced Thrombocytopenia

    ... HIT information card. Early identification of HIT and avoidance of inappropriate heparin therapy can help promote a ... Heart Association is a qualified 501(c)(3) tax-exempt organization. *Red Dress™ DHHS, Go Red™ AHA; ...

  19. Severe heparin osteoporosis in pregnancy.

    Griffiths, H. T.; Liu, D. T.

    1984-01-01

    A case of severe osteoporosis following administration of low dose subcutaneous heparin in pregnancy is reported. Possible reasons for the condition are suggested which caution against the indiscriminate use of subcutaneous heparin in pregnancy.

  20. Heparin for assisted reproduction.

    Akhtar, Muhammad A; Sur, Shyamaly; Raine-Fenning, Nick; Jayaprakasan, Kannamannadiar; Thornton, Jim G; Quenby, Siobhan

    2013-08-17

    Heparin as an adjunct in assisted reproduction (peri-implantation heparin) is given at or after egg collection or at embryo transfer during assisted reproduction. Heparin has been advocated to improve embryo implantation and clinical outcomes.  It has been proposed that heparin enhances the intra-uterine environment by improving decidualisation with an associated activation of growth factors and a cytokine expression profile in the endometrium that is favourable to pregnancy. To investigate whether the administration of heparin around the time of implantation (peri-implantation heparin) improves clinical outcomes in subfertile women undergoing assisted reproduction. A comprehensive and exhaustive search strategy was developed in consultation with the Trials Search Co-ordinator of the Cochrane Menstrual Disorders and Subfertility Group (MDSG). The strategy was used in an attempt to identify all relevant studies regardless of language or publication status (published, unpublished, in press, and in progress). Relevant trials were identified from both electronic databases and other resources (last search 6 May 2013). All randomised controlled trials (RCTs) were included where peri-implantation heparin was given during assisted reproduction. Peri-implantation low molecular weight heparin (LMWH) during IVF/ICSI was given at or after egg collection or at embryo transfer in the included studies. Live birth rate was the primary outcome. Two review authors independently assessed the eligibility and quality of trials and extracted relevant data. The quality of the evidence was evaluated using GRADE methods. Three RCTs (involving 386 women) were included in the review.Peri-implantation LMWH administration during assisted reproduction was associated with a significant improvement in live birth rate compared with placebo or no LMWH (odds ratio (OR) 1.77, 95% confidence interval (CI) 1.07 to 2.90, three studies, 386 women, I(2) = 51%, very low quality evidence with high

  1. Prophylaxis of postoperative thromboembolism with low molecular weight heparins

    Jørgensen, L N; Wille-Jørgensen, P; Hauch, O

    1993-01-01

    To evaluate the thromboprophylactic use of low molecular weight heparins (LMWHs), publications from 27 orthopaedic trials and 35 studies of patients undergoing general or gynaecological surgery were scrutinized and subjected to a partial meta-analysis. In orthopaedic surgery, LMWHs were superior...... to placebo or dextran and at least as efficient as unfractionated heparin in the prevention of deep vein thrombosis (DVT). Compared with unfractionated heparin, one of the LMWH preparations significantly reduced the total incidence of DVT. The rate of non-fatal pulmonary embolism was 0.49 per cent...

  2. Heparin: Past, Present, and Future.

    Oduah, Eziafa I; Linhardt, Robert J; Sharfstein, Susan T

    2016-07-04

    Heparin, the most widely used anticoagulant drug in the world today, remains an animal-derived product with the attendant risks of adulteration and contamination. A contamination crisis in 2007-2008 increased the impetus to provide non-animal-derived sources of heparin, produced under cGMP conditions. In addition, recent studies suggest that heparin may have significant antineoplastic activity, separate and distinct from its anticoagulant activity, while other studies indicate a role for heparin in treating inflammation, infertility, and infectious disease. A variety of strategies have been proposed to produce a bioengineered heparin. In this review, we discuss several of these strategies including microbial production, mammalian cell production, and chemoenzymatic modification. We also propose strategies for creating "designer" heparins and heparan-sulfates with various biochemical and physiological properties.

  3. Efficient synchronization of structurally adaptive coupled Hindmarsh-Rose neurons

    Moujahid, A.; D'Anjou, A.; Torrealdea, F.J.; Torrealdea, F.

    2011-01-01

    Highlights: → Neural activity might be constrained by a requirement of energy efficiency. → Signaling in synchrony is a normal way to propagate information between neurons. → Quality of synchrony affects the capacity to exchange information and the energy cost. → Adaptive mechanism leads to high degree of synchronization between nonidentical neurons. - Abstract: The use of spikes to carry information between brain areas implies complete or partial synchronization of the neurons involved. The degree of synchronization reached by two coupled systems and the energy cost of maintaining their synchronized behavior is highly dependent on the nature of the systems. For non-identical systems the maintenance of a synchronized regime is energetically a costly process. In this work, we study conditions under which two non-identical electrically coupled neurons can reach an efficient regime of synchronization at low energy cost. We show that the energy consumption required to keep the synchronized regime can be spontaneously reduced if the receiving neuron has adaptive mechanisms able to bring its biological parameters closer in value to the corresponding ones in the sending neuron.

  4. Highly sensitive ratiometric detection of heparin and its oversulfated chondroitin sulfate contaminant by fluorescent peptidyl probe.

    Mehta, Pramod Kumar; Lee, Hyeri; Lee, Keun-Hyeung

    2017-05-15

    The selective and sensitive detection of heparin, an anticoagulant in clinics as well as its contaminant oversulfated chondroitin sulfate (OSCS) is of great importance. We first reported a ratiometric sensing method for heparin as well as OSCS contaminants in heparin using a fluorescent peptidyl probe (Pep1, pyrene-GSRKR) and heparin-digestive enzyme. Pep1 exhibited a highly sensitive ratiometric response to nanomolar concentration of heparin in aqueous solution over a wide pH range (2~11) and showed highly selective ratiometric response to heparin among biological competitors such as hyaluronic acid and chondroitin sulfate. Pep1 showed a linear ratiometric response to nanomolar concentrations of heparin in aqueous solutions and in human serum samples. The detection limit for heparin was calculated to be 2.46nM (R 2 =0.99) in aqueous solutions, 2.98nM (R 2 =0.98) in 1% serum samples, and 3.43nM (R 2 =0.99) in 5% serum samples. Pep1 was applied to detect the contaminated OSCS in heparin with heparinase I, II, and III, respectively. The ratiometric sensing method using Pep1 and heparinase II was highly sensitive, fast, and efficient for the detection of OSCS contaminant in heparin. Pep1 with heparinase II could detect as low as 0.0001% (w/w) of OSCS in heparin by a ratiometric response. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Aerosol detection efficiency in inductively coupled plasma mass spectrometry

    Hubbard, Joshua A.; Zigmond, Joseph A.

    2016-05-01

    An electrostatic size classification technique was used to segregate particles of known composition prior to being injected into an inductively coupled plasma mass spectrometer (ICP-MS). Size-segregated particles were counted with a condensation nuclei counter as well as sampled with an ICP-MS. By injecting particles of known size, composition, and aerosol concentration into the ICP-MS, efficiencies of the order of magnitude aerosol detection were calculated, and the particle size dependencies for volatile and refractory species were quantified. Similar to laser ablation ICP-MS, aerosol detection efficiency was defined as the rate at which atoms were detected in the ICP-MS normalized by the rate at which atoms were injected in the form of particles. This method adds valuable insight into the development of technologies like laser ablation ICP-MS where aerosol particles (of relatively unknown size and gas concentration) are generated during ablation and then transported into the plasma of an ICP-MS. In this study, we characterized aerosol detection efficiencies of volatile species gold and silver along with refractory species aluminum oxide, cerium oxide, and yttrium oxide. Aerosols were generated with electrical mobility diameters ranging from 100 to 1000 nm. In general, it was observed that refractory species had lower aerosol detection efficiencies than volatile species, and there were strong dependencies on particle size and plasma torch residence time. Volatile species showed a distinct transition point at which aerosol detection efficiency began decreasing with increasing particle size. This critical diameter indicated the largest particle size for which complete particle detection should be expected and agreed with theories published in other works. Aerosol detection efficiencies also displayed power law dependencies on particle size. Aerosol detection efficiencies ranged from 10- 5 to 10- 11. Free molecular heat and mass transfer theory was applied, but

  6. Sterilization of heparinized cuprophan hemodialysis membranes

    ten Hoopen, Hermina W.M.; Hinrichs, W.L.J.; Hinrichs, W.L.J.; Engbers, G.H.M.; Feijen, Jan

    1996-01-01

    The effects of sterilization of dry heparinized Cuprophan hemodialysis membranes by means of ethylene oxide (EtO) exposure, gamma irradiation, or steam on the anticoagulant activity and chemical characteristics of immobilized heparin and the permeability of the membrane were investigated. Sterilization did not result in a release of heparin or heparin fragments from heparinized Cuprophan. Sterilization of heparinized Cuprophan by means of EtO exposure and gamma irradiation induced a slight, i...

  7. Different magnetospheric modes: solar wind driving and coupling efficiency

    N. Partamies

    2009-11-01

    Full Text Available This study describes a systematic statistical comparison of isolated non-storm substorms, steady magnetospheric convection (SMC intervals and sawtooth events. The number of events is approximately the same in each group and the data are taken from about the same years to avoid biasing by different solar cycle phase. The very same superposed epoch analysis is performed for each event group to show the characteristics of ground-based indices (AL, PCN, PC potential, particle injection at the geostationary orbit and the solar wind and IMF parameters. We show that the monthly occurrence of sawtooth events and isolated non-stormtime substorms closely follows maxima of the geomagnetic activity at (or close to the equinoxes. The most strongly solar wind driven event type, sawtooth events, is the least efficient in coupling the solar wind energy to the auroral ionosphere, while SMC periods are associated with the highest coupling ratio (AL/EY. Furthermore, solar wind speed seems to play a key role in determining the type of activity in the magnetosphere. Slow solar wind is capable of maintaining steady convection. During fast solar wind streams the magnetosphere responds with loading–unloading cycles, represented by substorms during moderately active conditions and sawtooth events (or other storm-time activations during geomagnetically active conditions.

  8. Covalently bound conjugates of albumin and heparin: Synthesis, fractionation and characterization

    Hennink, Wim E.; Feijen, Jan; Ebert, Charles D.; Kim, Sung Wan

    1983-01-01

    Covalently bound conjugates of human serum albumin and heparin were prepared as compounds which could improve the blood-compatibility of polymer surfaces either by preadsorption or by covalent coupling of the conjugates onto blood contacting surfaces. The conjugates (10–16 weight % of heparin) were

  9. Efficient solvers for coupled models in respiratory mechanics.

    Verdugo, Francesc; Roth, Christian J; Yoshihara, Lena; Wall, Wolfgang A

    2017-02-01

    We present efficient preconditioners for one of the most physiologically relevant pulmonary models currently available. Our underlying motivation is to enable the efficient simulation of such a lung model on high-performance computing platforms in order to assess mechanical ventilation strategies and contributing to design more protective patient-specific ventilation treatments. The system of linear equations to be solved using the proposed preconditioners is essentially the monolithic system arising in fluid-structure interaction (FSI) extended by additional algebraic constraints. The introduction of these constraints leads to a saddle point problem that cannot be solved with usual FSI preconditioners available in the literature. The key ingredient in this work is to use the idea of the semi-implicit method for pressure-linked equations (SIMPLE) for getting rid of the saddle point structure, resulting in a standard FSI problem that can be treated with available techniques. The numerical examples show that the resulting preconditioners approach the optimal performance of multigrid methods, even though the lung model is a complex multiphysics problem. Moreover, the preconditioners are robust enough to deal with physiologically relevant simulations involving complex real-world patient-specific lung geometries. The same approach is applicable to other challenging biomedical applications where coupling between flow and tissue deformations is modeled with additional algebraic constraints. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  10. Increasing Z-pinch vacuum hohlraum capsule coupling efficiency

    Callahan, Debbie; Vesey, Roger Alan; Cochrane, Kyle Robert; Nikroo, A.; Bennett, Guy R.; Schroen, Diana Grace; Ruggles, Laurence E.; Porter, John L.; Streit, Jon; Mehlhorn, Thomas Alan; Cuneo, Michael Edward

    2004-01-01

    Symmetric capsule implosions in the double-ended vacuum hohlraum (DEH) on Z have demonstrated convergence ratios of 14-21 for 2.15-mm plastic ablator capsules absorbing 5-7 kJ of x-rays, based on backlit images of the compressed ablator remaining at peak convergence (1). Experiments with DD-filled 3.3-mm diameter capsules designed to absorb 14 kJ of x-rays have begun as an integrated test of drive temperature and symmetry, complementary to thin-shell symmetry diagnostic capsules. These capsule implosions are characterized by excellent control of symmetry (< 3% time-integrated), but low hohlraum efficiency (< 2%). Possible methods to increase the capsule absorbed energy in the DEH include mixed-component hohlraums, large diameter foam ablator capsules, transmissive shine shields between the z-pinch and capsule, higher spoke electrode x-ray transmission, a double-sided power feed, and smaller initial radius z-pinch wire arrays. Simulations will explore the potential for each of these modifications to increase the capsule coupling efficiency for near-term experiments on Z and ZR

  11. Hydrolysis and Sulfation Pattern Effects on Release of Bioactive Bone Morphogenetic Protein-2 from Heparin-Based Microparticles.

    Tellier, Liane E; Miller, Tobias; McDevitt, Todd C; Temenoff, Johnna S

    2015-10-28

    Glycosaminoglycans (GAGs) such as heparin are promising materials for growth factor delivery due to their ability to efficiently bind positively charged growth factors including bone morphogenetic protein-2 (BMP-2) through their negatively charged sulfate groups. Therefore, the goal of this study was to examine BMP-2 release from heparin-based microparticles (MPs) after first, incorporating a hydrolytically degradable crosslinker and varying heparin content within MPs to alter MP degradation and second, altering the sulfation pattern of heparin within MPs to vary BMP-2 binding and release. Using varied MP formulations, it was found that the time course of MP degradation for 1 wt% heparin MPs was ~4 days slower than 10 wt% heparin MPs, indicating that MP degradation was dependent on heparin content. After incubating 100 ng BMP-2 with 0.1 mg MPs, most MP formulations loaded BMP-2 with ~50% efficiency and significantly more BMP-2 release (60% of loaded BMP-2) was observed from more sulfated heparin MPs (MPs with ~100% and 80% of native sulfation). Similarly, BMP-2 bioactivity in more sulfated heparin MP groups was at least four-fold higher than soluble BMP-2 and less sulfated heparin MP groups, as determined by an established C2C12 cell alkaline phosphatase (ALP) assay. Ultimately, the two most sulfated 10 wt% heparin MP formulations were able to efficiently load and release BMP-2 while enhancing BMP-2 bioactivity, making them promising candidates for future growth factor delivery applications.

  12. Collection of heparinized plasma by plasmapheresis

    van der Meer, P. F.; Vrielink, H.; Pietersz, R. N.; Dekker, W. J.; Reesink, H. W.

    1999-01-01

    BACKGROUND AND OBJECTIVES: Heparinized plasma can be used for exchange transfusions in neonates and is usually collected by drawing whole blood using heparin as anticoagulant. The heparinized red blood cells and buffy coat cannot be used and are therefore discarded. To collect heparinized plasma

  13. Intelligent sector coupling. Efficient energy transition; Intelligente Sektorkopplung. Effiziente Energiewende

    Kamphues, Stephan

    2017-04-15

    The transformation process of the German energy industry is advancing. The power line and storage infrastructure still appears to be very neglected. The 2050 climate protection plan, but also the EU winter package, is an all-electric approach despite sector-specific targets. In addition to the exorbitant expansion requirements for renewables, infrastructures with enormous transport and storage potential are ''given away''. As in the interview with OGE CEO Stephan Kamphues becomes clear, an efficient energy transition requires an intelligent coupling of different sectors and infrastructures, ultimately even perhaps network convergence. [German] Der Transformationsprozess der deutschen Energiewirtschaft schreitet voran. Immer noch stark vernachlaessigt erscheint die Leitungs- und Speicherinfrastruktur. Dem Klimaschutzplan 2050, aber auch dem EU-Winterpaket wohnt trotz sektorspezifischer Ziele ein all electric-Ansatz inne. Neben exorbitantem Ausbaubedarf an Erneuerbaren ''verschenkt'' man damit Infrastrukturen mit riesigem Transport- und Speicherpotenzial. Wie im Interview mit OGE-Geschaeftsfuehrer Stephan Kamphues deutlich wird, erfordert eine effiziente Energiewende eine intelligente Kopplung verschiedener Sektoren und Infrastrukturen, letztendlich vielleicht sogar Netzkonvergenz.

  14. Interactions between nattokinase and heparin/GAGs.

    Zhang, Fuming; Zhang, Jianhua; Linhardt, Robert J

    2015-12-01

    Nattokinase (NK) is a serine protease extracted from a traditional Japanese food called natto. Due to its strong fibrinolytic and thrombolytic activity, NK is regarded as a valuable dietary supplement or nutraceutical for the oral thrombolytic therapy. In addition, NK has been investigated for some other medical applications including treatment of hypertension, Alzheimer's disease, and vitreoretinal disorders. The most widely used clinical anticoagulants are heparin and low molecular weight heparins. The interactions between heparin and proteins modulate diverse patho-physiological processes and heparin modifies the activity of serine proteases. Indeed, heparin plays important roles in almost all of NK's potential therapeutically applications. The current report relies on surface plasmon resonance spectroscopy to examine NK interacting with heparin as well as other glycosaminoglycans (GAGs). These studies showed that NK is a heparin binding protein with an affinity of ~250 nM. Examination with differently sized heparin oligosaccharides indicated that the interaction between NK and heparin is chain-length dependent and the minimum size for heparin binding is a hexasaccharide. Studies using chemically modified heparin showed the 6-O-sulfo as well as the N-sulfo groups but not the 2-O-sulfo groups within heparin, are essential for heparin's interaction with NK. Other GAGs (including HS, DS, and CSE) displayed modest binding affinity to NK. NK also interfered with other heparin-protein interactions, including heparin's interaction with antithrombin and fibroblast growth factors.

  15. How to give a heparin shot

    ... you put the injection. Storing Your Heparin and Supplies Ask your pharmacist how to store your heparin ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  16. A Path to High-Efficiency Optical Coupling for HIRMES

    Miller, Timothy M.; Brown, Ari-David; Costen, Nicholas; Franz, David; Kutyrev, Alexander; Mikula, Vilem; Miller, Kevin H.; Moseley, S. Harvey; Oxborrow, Joseph; Rostem, Karwan; Wollack, Edward J.

    2018-05-01

    The high-resolution mid-infrared spectrometer (HIRMES) under development for Stratospheric Observatory for Infrared Astronomy is an instrument operating in the 25-122 μm spectral range with a spectral resolution R = Δλ/λ 100,000 and has two absorber-coupled transition edge sensor bolometric detector focal planes. We have developed novel NbTiN low-stress absorber coatings which have the required optical impedance across the HIRMES operating band. The low intrinsic stress of these coatings allow for a peak-to-valley corrugation amplitude coupled bolometric detector applications, because it helps in controlling the optical loading from out-of-band radiation. We also discuss a novel method for integrating a wedged-reflective absorber termination to the detector array.

  17. Interference of heparin in carcinoembryonic antigen radioimmunoassays

    Wu, J.T.

    1983-01-01

    A false Roche carcinoembryonic antigen (CEA) activity could be detected in all commercial and noncommercial heparin preparations examined. The possibility of 'due to contamination' has been ruled out. Using the Roche procedure, heparin solutions, in the absence of CEA, gave positive CEA activity; on the other hand, no CEA activity was detected in solutions containing only heparin when the Abbott Kit was used. When heparin was present in specimens containing CEA, the Abbott Kit underestimated the CEA activity, whereas the Roche Kit gave false elevated values. However, the negative effect of heparin could be reduced by heat treatment in the presence of plasma proteins. (Auth.)

  18. Stochastic coupled cluster theory: Efficient sampling of the coupled cluster expansion

    Scott, Charles J. C.; Thom, Alex J. W.

    2017-09-01

    We consider the sampling of the coupled cluster expansion within stochastic coupled cluster theory. Observing the limitations of previous approaches due to the inherently non-linear behavior of a coupled cluster wavefunction representation, we propose new approaches based on an intuitive, well-defined condition for sampling weights and on sampling the expansion in cluster operators of different excitation levels. We term these modifications even and truncated selections, respectively. Utilising both approaches demonstrates dramatically improved calculation stability as well as reduced computational and memory costs. These modifications are particularly effective at higher truncation levels owing to the large number of terms within the cluster expansion that can be neglected, as demonstrated by the reduction of the number of terms to be sampled when truncating at triple excitations by 77% and hextuple excitations by 98%.

  19. Efficient frequency-transient co-simulation of coupled heat-electromagnetic problems

    Kaufmann, C.; Günther, M.; Klagges, D.; Knorrenschild, M.; Richwin, M.; Schöps, S.; Maten, ter E.J.W.

    2014-01-01

    Background With the recent advent of inductive charging systems all major automotive manufacturers develop concepts to wirelessly charge electric vehicles. Efficient designs require virtual prototyping that accounts for electromagnetic and thermal fields. The coupled simulations can be

  20. Terahertz Quantum Cascade Laser With Efficient Coupling and Beam Profile

    Chattopadhyay, Goutam; Kawamura, Jonathan H.; Lin, Robert H.; Williams, Benjamin

    2012-01-01

    Quantum cascade lasers (QCLs) are unipolar semiconductor lasers, where the wavelength of emitted radiation is determined by the engineering of quantum states within the conduction band in coupled multiple-quantum-well heterostructures to have the desired energy separation. The recent development of terahertz QCLs has provided a new generation of solid-state sources for radiation in the terahertz frequency range. Terahertz QCLs have been demonstrated from 0.84 to 5.0 THz both in pulsed mode and continuous wave mode (CW mode). The approach employs a resonant-phonon depopulation concept. The metal-metal (MM) waveguide fabrication is performed using Cu-Cu thermo-compression bonding to bond the GaAs/AlGaAs epitaxial layer to a GaAs receptor wafer.

  1. Coupled Triboelectric Nanogenerator Networks for Efficient Water Wave Energy Harvesting.

    Xu, Liang; Jiang, Tao; Lin, Pei; Shao, Jia Jia; He, Chuan; Zhong, Wei; Chen, Xiang Yu; Wang, Zhong Lin

    2018-02-27

    Water wave energy is a promising clean energy source, which is abundant but hard to scavenge economically. Triboelectric nanogenerator (TENG) networks provide an effective approach toward massive harvesting of water wave energy in oceans. In this work, a coupling design in TENG networks for such purposes is reported. The charge output of the rationally linked units is over 10 times of that without linkage. TENG networks of three different connecting methods are fabricated and show better performance for the ones with flexible connections. The network is based on an optimized ball-shell structured TENG unit with high responsivity to small agitations. The dynamic behavior of single and multiple TENG units is also investigated comprehensively to fully understand their performance in water. The study shows that a rational design on the linkage among the units could be an effective strategy for TENG clusters to operate collaboratively for reaching a higher performance.

  2. Analysis and characterization of heparin impurities.

    Beni, Szabolcs; Limtiaco, John F K; Larive, Cynthia K

    2011-01-01

    This review discusses recent developments in analytical methods available for the sensitive separation, detection and structural characterization of heparin contaminants. The adulteration of raw heparin with oversulfated chondroitin sulfate (OSCS) in 2007-2008 spawned a global crisis resulting in extensive revisions to the pharmacopeia monographs on heparin and prompting the FDA to recommend the development of additional physicochemical methods for the analysis of heparin purity. The analytical chemistry community quickly responded to this challenge, developing a wide variety of innovative approaches, several of which are reported in this special issue. This review provides an overview of methods of heparin isolation and digestion, discusses known heparin contaminants, including OSCS, and summarizes recent publications on heparin impurity analysis using sensors, near-IR, Raman, and NMR spectroscopy, as well as electrophoretic and chromatographic separations.

  3. Printed microfluidic filter for heparinized blood.

    Bilatto, Stanley E R; Adly, Nouran Y; Correa, Daniel S; Wolfrum, Bernhard; Offenhäusser, Andreas; Yakushenko, Alexey

    2017-05-01

    A simple lab-on-a-chip method for blood plasma separation was developed by combining stereolithographic 3D printing with inkjet printing, creating a completely sealed microfluidic device. In some approaches, one dilutes the blood sample before separation, reducing the concentration of a target analyte and increasing a contamination risk. In this work, a single drop (8  μ l) of heparinized whole blood could be efficiently filtered using a capillary effect without any external driving forces and without dilution. The blood storage in heparin tubes during 24 h at 4 °C initiated the formation of small crystals that formed auto-filtration structures in the sample upon entering the 3D-printed device, with pores smaller than the red blood cells, separating plasma from the cellular content. The total filtration process took less than 10 s. The presented printed plasma filtration microfluidics fabricated with a rapid prototyping approach is a miniaturized, fast and easy-to-operate device that can be integrated into healthcare/portable systems for point-of-care diagnostics.

  4. Energy efficient neural stimulation: coupling circuit design and membrane biophysics.

    Foutz, Thomas J; Ackermann, D Michael; Kilgore, Kevin L; McIntyre, Cameron C

    2012-01-01

    The delivery of therapeutic levels of electrical current to neural tissue is a well-established treatment for numerous indications such as Parkinson's disease and chronic pain. While the neuromodulation medical device industry has experienced steady clinical growth over the last two decades, much of the core technology underlying implanted pulse generators remain unchanged. In this study we propose some new methods for achieving increased energy-efficiency during neural stimulation. The first method exploits the biophysical features of excitable tissue through the use of a centered-triangular stimulation waveform. Neural activation with this waveform is achieved with a statistically significant reduction in energy compared to traditional rectangular waveforms. The second method demonstrates energy savings that could be achieved by advanced circuitry design. We show that the traditional practice of using a fixed compliance voltage for constant-current stimulation results in substantial energy loss. A portion of this energy can be recuperated by adjusting the compliance voltage to real-time requirements. Lastly, we demonstrate the potential impact of axon fiber diameter on defining the energy-optimal pulse-width for stimulation. When designing implantable pulse generators for energy efficiency, we propose that the future combination of a variable compliance system, a centered-triangular stimulus waveform, and an axon diameter specific stimulation pulse-width has great potential to reduce energy consumption and prolong battery life in neuromodulation devices.

  5. Energy efficient neural stimulation: coupling circuit design and membrane biophysics.

    Thomas J Foutz

    Full Text Available The delivery of therapeutic levels of electrical current to neural tissue is a well-established treatment for numerous indications such as Parkinson's disease and chronic pain. While the neuromodulation medical device industry has experienced steady clinical growth over the last two decades, much of the core technology underlying implanted pulse generators remain unchanged. In this study we propose some new methods for achieving increased energy-efficiency during neural stimulation. The first method exploits the biophysical features of excitable tissue through the use of a centered-triangular stimulation waveform. Neural activation with this waveform is achieved with a statistically significant reduction in energy compared to traditional rectangular waveforms. The second method demonstrates energy savings that could be achieved by advanced circuitry design. We show that the traditional practice of using a fixed compliance voltage for constant-current stimulation results in substantial energy loss. A portion of this energy can be recuperated by adjusting the compliance voltage to real-time requirements. Lastly, we demonstrate the potential impact of axon fiber diameter on defining the energy-optimal pulse-width for stimulation. When designing implantable pulse generators for energy efficiency, we propose that the future combination of a variable compliance system, a centered-triangular stimulus waveform, and an axon diameter specific stimulation pulse-width has great potential to reduce energy consumption and prolong battery life in neuromodulation devices.

  6. P-selectin- and heparanase-dependent antimetastatic activity of non-anticoagulant heparins.

    Hostettler, Nina; Naggi, Annamaria; Torri, Giangiacomo; Ishai-Michaeli, Riva; Casu, Benito; Vlodavsky, Israel; Borsig, Lubor

    2007-11-01

    Vascular cell adhesion molecules, P- and L-selectins, facilitate metastasis of cancer cells in mice by mediating interactions with platelets, endothelium, and leukocytes. Heparanase is an endoglycosidase that degrades heparan sulfate of extracellular matrix, thereby promoting tumor invasion and metastasis. Heparin is known to efficiently attenuate metastasis in different tumor models. Here we identified modified, nonanticoagulant species of heparin that specifically inhibit selectin-mediated cell-cell interactions, heparanase enzymatic activity, or both. We show that selective inhibition of selectin interactions or heparanase with specific heparin derivatives in mouse models of MC-38 colon carcinoma and B16-BL6 melanoma attenuates metastasis. Selectin-specific heparin derivatives attenuated metastasis of MC-38 carcinoma, but heparanase-specific derivatives had no effect, in accordance with the virtual absence of heparanase activity in these cells. Heparin derivatives had no further effect on metastasis in mice deficient in P- and L-selectin, indicating that selectins are the primary targets of heparin antimetastatic activity. Selectin-specific and heparanase-specific derivatives attenuated metastasis of B16-BL6 melanomas to a similar extent. When mice were injected with a derivative containing both heparanase and selectin inhibitory activity, no additional attenuation of metastasis could be observed. Thus, selectin-specific heparin derivatives efficiently attenuated metastasis of both tumor cell types whereas inhibition of heparanase led to reduction of metastasis only in tumor cells producing heparanase.

  7. High-efficiency resonant coupled wireless power transfer via tunable impedance matching

    Anowar, Tanbir Ibne; Barman, Surajit Das; Wasif Reza, Ahmed; Kumar, Narendra

    2017-10-01

    For magnetic resonant coupled wireless power transfer (WPT), the axial movement of near-field coupled coils adversely degrades the power transfer efficiency (PTE) of the system and often creates sub-resonance. This paper presents a tunable impedance matching technique based on optimum coupling tuning to enhance the efficiency of resonant coupled WPT system. The optimum power transfer model is analysed from equivalent circuit model via reflected load principle, and the adequate matching are achieved through the optimum tuning of coupling coefficients at both the transmitting and receiving end of the system. Both simulations and experiments are performed to evaluate the theoretical model of the proposed matching technique, and results in a PTE over 80% at close coil proximity without shifting the original resonant frequency. Compared to the fixed coupled WPT, the extracted efficiency shows 15.1% and 19.9% improvements at the centre-to-centre misalignment of 10 and 70 cm, respectively. Applying this technique, the extracted S21 parameter shows more than 10 dB improvements at both strong and weak couplings. Through the developed model, the optimum coupling tuning also significantly improves the performance over matching techniques using frequency tracking and tunable matching circuits.

  8. An efficient strongly coupled immersed boundary method for deforming bodies

    Goza, Andres; Colonius, Tim

    2016-11-01

    Immersed boundary methods treat the fluid and immersed solid with separate domains. As a result, a nonlinear interface constraint must be satisfied when these methods are applied to flow-structure interaction problems. This typically results in a large nonlinear system of equations that is difficult to solve efficiently. Often, this system is solved with a block Gauss-Seidel procedure, which is easy to implement but can require many iterations to converge for small solid-to-fluid mass ratios. Alternatively, a Newton-Raphson procedure can be used to solve the nonlinear system. This typically leads to convergence in a small number of iterations for arbitrary mass ratios, but involves the use of large Jacobian matrices. We present an immersed boundary formulation that, like the Newton-Raphson approach, uses a linearization of the system to perform iterations. It therefore inherits the same favorable convergence behavior. However, we avoid large Jacobian matrices by using a block LU factorization of the linearized system. We derive our method for general deforming surfaces and perform verification on 2D test problems of flow past beams. These test problems involve large amplitude flapping and a wide range of mass ratios. This work was partially supported by the Jet Propulsion Laboratory and Air Force Office of Scientific Research.

  9. In Vitro and In Vivo Biocompatibility Evaluation of Polyallylamine and Macromolecular Heparin Conjugates Modified Alginate Microbeads.

    Vaithilingam, Vijayaganapathy; Steinkjer, Bjørg; Ryan, Liv; Larsson, Rolf; Tuch, Bernard Edward; Oberholzer, Jose; Rokstad, Anne Mari

    2017-09-15

    Host reactivity to biocompatible immunoisolation devices is a major challenge for cellular therapies, and a human screening model would be of great value. We designed new types of surface modified barium alginate microspheres, and evaluated their inflammatory properties using human whole blood, and the intraperitoneal response after three weeks in Wistar rats. Microspheres were modified using proprietary polyallylamine (PAV) and coupled with macromolecular heparin conjugates (Corline Heparin Conjugate, CHC). The PAV-CHC strategy resulted in uniform and stable coatings with increased anti-clot activity and low cytotoxicity. In human whole blood, PAV coating at high dose (100 µg/ml) induced elevated complement, leukocyte CD11b and inflammatory mediators, and in Wistar rats increased fibrotic overgrowth. Coating of high dose PAV with CHC significantly reduced these responses. Low dose PAV (10 µg/ml) ± CHC and unmodified alginate microbeads showed low responses. That the human whole blood inflammatory reactions paralleled the host response shows a link between inflammatory potential and initial fibrotic response. CHC possessed anti-inflammatory activity, but failed to improve overall biocompatibility. We conclude that the human whole blood assay is an efficient first-phase screening model for inflammation, and a guiding tool in development of new generation microspheres for cell encapsulation therapy.

  10. Preparation and in vitro evaluation of heparin-loaded polymeric nanoparticles.

    Jiao, Y Y; Ubrich, N; Marchand-Arvier, M; Vigneron, C; Hoffman, M; Maincent, P

    2001-01-01

    Nanoparticles of a highly soluble macromolecular drug, heparin, were formulated with two biodegradable polymers (poly-E-caprolactone [PCL] and poly (D, L-lactic-co-glycolic-acid) 50/50 [PLAGA]) and two nonbiodegradable positively charged polymers (Eudragit RS and RL) by the double emulsion and solvent evaporation method, using a high-pressure homogenization device. The encapsulation efficiency and heparin release profiles were studied as a function of the type of polymers employed (alone or in combination) and the concentration of heparin. Optimal encapsulation efficiency was observed when 5000 IU of heparin were incorporated in the first emulsion. High drug entrapment efficiency was observed in both Eudragit RS and RL nanoparticles (60% and 98%, respectively), compared with PLAGA and PCL nanoparticles (PLAGA increased the encapsulation efficiency compared with these two biodegradable polymers used alone; however, the in vitro drug release was not modified and remained low. On the other hand, the addition of esterase to the dissolution medium resulted in a significant increase in heparin release. The in vitro biological activity of released heparin, evaluated by measuring the anti-Xa activity by a colorimetric assay, was conserved after the encapsulation process.

  11. Investigation of the heparin-thrombin interaction by dynamic force spectroscopy.

    Wang, Congzhou; Jin, Yingzi; Desai, Umesh R; Yadavalli, Vamsi K

    2015-06-01

    The interaction between heparin and thrombin is a vital step in the blood (anti)coagulation process. Unraveling the molecular basis of the interactions is therefore extremely important in understanding the mechanisms of this complex biological process. In this study, we use a combination of an efficient thiolation chemistry of heparin, a self-assembled monolayer-based single molecule platform, and a dynamic force spectroscopy to provide new insights into the heparin-thrombin interaction from an energy viewpoint at the molecular scale. Well-separated single molecules of heparin covalently attached to mixed self-assembled monolayers are demonstrated, whereby interaction forces with thrombin can be measured via atomic force microscopy-based spectroscopy. Further these interactions are studied at different loading rates and salt concentrations to directly obtain kinetic parameters. An increase in the loading rate shows a higher interaction force between the heparin and thrombin, which can be directly linked to the kinetic dissociation rate constant (koff). The stability of the heparin/thrombin complex decreased with increasing NaCl concentration such that the off-rate was found to be driven primarily by non-ionic forces. These results contribute to understanding the role of specific and nonspecific forces that drive heparin-thrombin interactions under applied force or flow conditions. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Study on efficiency of different topologies of magnetic coupled resonant wireless charging system

    Cui, S.; Liu, Z. Z.; Hou, Y. J.; Zeng, H.; Yue, Z. K.; Liang, L. H.

    2017-11-01

    This paper analyses the relationship between the output power, the transmission efficiency and the frequency, load and coupling coefficient of the four kinds of magnetic coupled resonant wireless charging system topologies. Based on mutual inductance principle, four kinds of circuit models are established, and the expressions of output power and transmission efficiency of different structures are calculated. The difference between the two power characteristics and efficiency characteristics is compared by simulating the SS (series-series) and SP (series-parallel) type wireless charging systems. With the same parameters of circuit components, the SS structure is usually suitable for small load resistance. The SP structure can be applied to large load resistors, when the transmission efficiency of the system is required to keep high. If the operating frequency deviates from the system resonance frequency, the SS type system has higher transmission efficiency than the SP type system.

  13. Low molecular weight heparin versus unfractionated heparin in the initial treatment of venous thromboembolism

    Hettiarachchi, R. J.; Prins, M. H.; Lensing, A. W.; Buller, H. R.

    1998-01-01

    In this review, we analyze data from randomized trials in which low molecular weight heparin was compared with unfractionated heparin, both to estimate the treatment effect of low molecular weight heparin in the initial treatment of venous thromboembolism and to evaluate the effect of the varied

  14. Analysis on the power and efficiency in wireless power transfer system via coupled magnetic resonances

    Liu, Mingjie

    2018-06-01

    The analysis of characteristics of the power and efficiency in wireless power transmission (WPT) system is the theoretical basis of magnetic coupling resonant wireless power transmission (MCR-WPT) technology. The electromagnetic field theory was employed to study the variation of the coupling degree of the two electromagnetic coils with the parameters of the coils. The equivalent circuit was used to analyze the influence of different factors on the transmission power and efficiency of the WPT system. The results show that there is an optimal radius ratio between the two coils, which makes the mutual inductance of the coils the largest. Moreover, when the WPT system operates in the under-coupling state, the transmission power of the system drops sharply, and there is a frequency splitting of the power when in the over-coupling state.

  15. Unfractionated heparin versus low molecular weight heparins for avoiding heparin-induced thrombocytopenia in postoperative patients.

    Junqueira, Daniela R; Zorzela, Liliane M; Perini, Edson

    2017-04-21

    Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction presenting as a prothrombotic disorder related to antibody-mediated platelet activation. It is a paradoxical immune reaction resulting in thrombin generation in vivo, which leads to a hypercoagulable state and the potential to initiate venous or arterial thrombosis. A number of factors are thought to influence the incidence of HIT including the type and preparation of heparin (unfractionated heparin (UFH) or low molecular weight heparin (LMWH)) and the heparin-exposed patient population, with the postoperative patient population at higher risk.Although LMWH has largely replaced UFH as a front-line therapy, there is evidence supporting a lack of superiority of LMWH compared with UFH regarding prevention of deep vein thrombosis and pulmonary embolism following surgery, and similar frequencies of bleeding have been described with LMWH and UFH. The decision as to which of these two preparations of heparin to use may thus be influenced by harmful effects such as HIT. We therefore sought to determine the relative impact of UFH and LMWH on HIT in postoperative patients receiving thromboembolism prophylaxis. This is an update of a review first published in 2012. The objective of this review was to compare the incidence of heparin-induced thrombocytopenia (HIT) and HIT complicated by venous thromboembolism in postoperative patients exposed to unfractionated heparin (UFH) versus low molecular weight heparin (LMWH). For this update, the Cochrane Vascular Information Specialist searched the Specialised Register (May 2016), CENTRAL (2016, Issue 4) and trials registries. The authors searched Lilacs (June 2016) and additional trials were sought from reference lists of relevant publications. We included randomised controlled trials (RCTs) in which participants were postoperative patients allocated to receive prophylaxis with UFH or LMWH, in a blinded or unblinded fashion. Studies were excluded if they did not use

  16. An efficient coupled polynomial interpolation scheme for shear mode sandwich beam finite element

    Litesh N. Sulbhewar

    Full Text Available An efficient piezoelectric sandwich beam finite element is presented here. It employs the coupled polynomial field interpolation scheme for field variables which incorporates electromechanical coupling at interpolation level itself; unlike conventional sandwich beam theory (SBT based formulations available in the literature. A variational formulation is used to derive the governing equations, which are used to establish the relationships between field variables. These relations lead to the coupled polynomial field descriptions of variables, unlike conventional SBT formulations which use assumed independent polynomials. The relative axial displacement is expressed only by coupled terms containing contributions from other mechanical and electrical variables, thus eliminating use of the transverse displacement derivative as a degree of freedom. A set of coupled shape function based on these polynomials has shown the improvement in the convergence characteristics of the SBT based formulation. This improvement in the performance is achieved with one nodal degree of freedom lesser than the conventional SBT formulations.

  17. Parent heparin and daughter LMW heparin correlation analysis using LC-MS and NMR

    Liu, Xinyue; St Ange, Kalib; Wang, Xiaohua; Lin, Lei; Zhang, Fuming

    2017-01-01

    Heparin is a structurally complex, polysaccharide anticoagulant derived from livestock, primarily porcine intestinal tissues. Low molecular weight (LMW) heparins are derived through the controlled partial depolymerization of heparin. Increased manufacturing and regulatory concerns have provided the motivation for the development of more sophisticated analytical methods for determining both their structure and pedigree. A strategy, for the comprehensive comparison of parent heparins and their LMW heparin daughters, is described that relies on the analysis of monosaccharide composition, disaccharide composition, and oligosaccharide composition. Liquid chromatography-mass spectrometry is rapid, robust, and amenable to automated processing and interpretation of both top-down and bottom-up analyses. Nuclear magnetic resonance spectroscopy provides complementary top-down information on the chirality of the uronic acid residues and glucosamine substitution. Principal component analysis (PCA) was applied to the normalized abundance of oligosaccharides, calculated in the bottom-up analysis, to show parent and daughter correlation in oligosaccharide composition. Using these approaches, six pairs of parent heparins and their daughter generic enoxaparins from two different manufacturers were comprehensively analyzed. Enoxaparin is the most widely used LMW heparin and is prepared through controlled chemical β-eliminative cleavage of porcine intestinal heparin. Lovenox"®, the innovator version of enoxaparin marketed in the US, was analyzed as a reference for the daughter LMW heparins. The results, show similarities between LMW heparins from two different manufacturers with Lovenox"®, excellent lot-to-lot consistency of products from each manufacturer, and detects a correlation between each parent heparin and daughter LMW heparin. - Highlights: • Low molecular weight heparins prepared from different heparin parents were analyzed. • An integrated analytical approach relied

  18. Parent heparin and daughter LMW heparin correlation analysis using LC-MS and NMR

    Liu, Xinyue, E-mail: liux22@rpi.edu [National Glycoengineering Research Center, Shandong Provincial Key Laboratory of Carbohydrate Chemistry and Glycobiology, State Key Laboratory of Microbial Technology, Shandong University, Jinan, Shandong, 250100 (China); Department of Chemistry and Chemical Biology, Department of Chemical and Biological Engineering, Department of Biology, Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, 12180 (United States); St Ange, Kalib, E-mail: stangk2@rpi.edu [Department of Chemistry and Chemical Biology, Department of Chemical and Biological Engineering, Department of Biology, Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, 12180 (United States); Wang, Xiaohua, E-mail: wangx35@rpi.edu [Department of Chemistry and Chemical Biology, Department of Chemical and Biological Engineering, Department of Biology, Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, 12180 (United States); School of Computer and Information, Hefei University of Technology, Hefei (China); Lin, Lei, E-mail: Linl5@rpi.edu [Department of Chemistry and Chemical Biology, Department of Chemical and Biological Engineering, Department of Biology, Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, 12180 (United States); Zhang, Fuming, E-mail: zhangf2@rpi.edu [Department of Chemistry and Chemical Biology, Department of Chemical and Biological Engineering, Department of Biology, Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, 12180 (United States); and others

    2017-04-08

    Heparin is a structurally complex, polysaccharide anticoagulant derived from livestock, primarily porcine intestinal tissues. Low molecular weight (LMW) heparins are derived through the controlled partial depolymerization of heparin. Increased manufacturing and regulatory concerns have provided the motivation for the development of more sophisticated analytical methods for determining both their structure and pedigree. A strategy, for the comprehensive comparison of parent heparins and their LMW heparin daughters, is described that relies on the analysis of monosaccharide composition, disaccharide composition, and oligosaccharide composition. Liquid chromatography-mass spectrometry is rapid, robust, and amenable to automated processing and interpretation of both top-down and bottom-up analyses. Nuclear magnetic resonance spectroscopy provides complementary top-down information on the chirality of the uronic acid residues and glucosamine substitution. Principal component analysis (PCA) was applied to the normalized abundance of oligosaccharides, calculated in the bottom-up analysis, to show parent and daughter correlation in oligosaccharide composition. Using these approaches, six pairs of parent heparins and their daughter generic enoxaparins from two different manufacturers were comprehensively analyzed. Enoxaparin is the most widely used LMW heparin and is prepared through controlled chemical β-eliminative cleavage of porcine intestinal heparin. Lovenox{sup ®}, the innovator version of enoxaparin marketed in the US, was analyzed as a reference for the daughter LMW heparins. The results, show similarities between LMW heparins from two different manufacturers with Lovenox{sup ®}, excellent lot-to-lot consistency of products from each manufacturer, and detects a correlation between each parent heparin and daughter LMW heparin. - Highlights: • Low molecular weight heparins prepared from different heparin parents were analyzed. • An integrated analytical

  19. Preparation of tin -heparin complex to be applied for myocardial infarct diagnosis

    Badi, J. M.; Al-Azzawi, H. A.; Resen, H. M.; Abed, I. G.; Owiad, H.; Manji, A. N.

    2012-12-01

    Tin-heparin complex has been prepared (liquid form) to be labeled with technetium-99 can be applied for diagnosis of myocardial infarcts vascular diseases and deep vein thrombosis. The preparation contents are 0.1mg tin chloride dehydrate and 1250 1.U of heparin. The results of the pH effect on the labeling yield indicated that high percentage of labeling yield (96.1%) was obtained in the optimal pH (5.50). The obtained results showed that the quantity of reducing agent (tin chloride dehydrate) and chelating agent (heparin) has no effect on the labeling yield. Results of radio analytical studies by paper chromatography technique wear confirmed by data obtained by Gel chromatography column scanning techniques. These techniques showed the high labeling yield of the tin-heparin complex. The persistence of high labeling yield for 8 hours is a good indication for its stability and efficiency for radio diagnosis examination in nuclear medicine centers. (Author)

  20. Sterilization of heparinized cuprophan hemodialysis membranes

    ten Hoopen, Hermina W.M.; Hinrichs, W.L.J.; Hinrichs, W.L.J.; Engbers, G.H.M.; Feijen, Jan

    1996-01-01

    The effects of sterilization of dry heparinized Cuprophan hemodialysis membranes by means of ethylene oxide (EtO) exposure, gamma irradiation, or steam on the anticoagulant activity and chemical characteristics of immobilized heparin and the permeability of the membrane were investigated.

  1. 21 CFR 864.7525 - Heparin assay.

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Heparin assay. 864.7525 Section 864.7525 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7525 Heparin assay. (a) Identification. A...

  2. Allergic anaphylaxis due to subcutaneously injected heparin

    Anders Diana

    2013-01-01

    Full Text Available Abstract Heparins are one of the most used class of anticoagulants in daily clinical practice. Despite their widespread application immune-mediated hypersensitivity reactions to heparins are rare. Among these, the delayed-type reactions to s.c. injected heparins are well-known usually presenting as circumscribed eczematous plaques at the injection sites. In contrast, potentially life-threatening systemic immediate-type anaphylactic reactions to heparins are extremely rare. Recently, some cases of non-allergic anaphylaxis could be attributed to undesirable heparin contaminants. A 43-year-old patient developed severe anaphylaxis symptoms within 5–10 minutes after s.c. injection of enoxaparin. Titrated skin prick testing with wheal and flare responses up to an enoxaparin dilution of 1:10.000 indicated a probable allergic mechanism of the enoxaparin-induced anaphylaxis. The basophil activation test as an additional in-vitro test method was negative. Furthermore, skin prick testing showed rather broad cross-reactivity among different heparin preparations tested. In the presented case, history, symptoms, and results of skin testing strongly suggested an IgE-mediated allergic hypersensitivity against different heparins. Therefore, as safe alternative anticoagulants the patient could receive beneath coumarins the hirudins or direct thrombin inhibitors. Because these compounds have a completely different molecular structure compared with the heparin-polysaccharides.

  3. Fe(HSO4)3 as an Efficient Catalyst for Diazotization and Diazo Coupling Reactions

    Rahimizadeh, Mohammad; Eshghi, Hossein; Shiri, Ali; Ghadamyari, Zohreh; Matin, Maryam M.; Pordeli, Parvaneh; Oroojalian, Fatemeh

    2012-01-01

    Diazo coupling reactions of aromatic amines with 2-naphthol in a green, efficient and easy procedure is described. Ferric hydrogensulfate catalyses this reaction in water at room temperature and short reaction time with high yields. The antibacterial activities of the synthesized compounds against four pathogenic bacteria are also investigated

  4. Efficient coupling of 527 nm laser beam power to a long scale-length plasma

    Moody, J.D.; Divol, L.; Glenzer, S.H.; MacKinnon, A.J.; Froula, D.H.; Gregori, G.; Kruer, W.L.; Meezan, N.B.; Suter, L.J.; Williams, E.A.; Bahr, R.; Seka, W.

    2006-01-01

    We experimentally demonstrate that application of laser smoothing schemes including smoothing by spectral dispersion (SSD) and polarization smoothing (PS) increases the intensity range for efficient coupling of frequency doubled (527 nm) laser light to a long scale-length plasma with n e /n cr equals 0.14 and T e equals 2 keV. (authors)

  5. Universality of energy conversion efficiency for optimal tight-coupling heat engines and refrigerators

    Sheng, Shiqi; Tu, Z C

    2013-01-01

    A unified χ-criterion for heat devices (including heat engines and refrigerators), which is defined as the product of the energy conversion efficiency and the heat absorbed per unit time by the working substance (de Tomás et al 2012 Phys. Rev. E 85 010104), is optimized for tight-coupling heat engines and refrigerators operating between two heat baths at temperatures T c and T h ( > T c ). By taking a new convention on the thermodynamic flux related to the heat transfer between two baths, we find that for a refrigerator tightly and symmetrically coupled with two heat baths, the coefficient of performance (i.e., the energy conversion efficiency of refrigerators) at maximum χ asymptotically approaches √(ε C ) when the relative temperature difference between two heat baths ε C -1 ≡(T h -T c )/T c is sufficiently small. Correspondingly, the efficiency at maximum χ (equivalent to maximum power) for a heat engine tightly and symmetrically coupled with two heat baths is proved to be η C /2+η C 2 /8 up to the second order term of η C ≡ (T h − T c )/T h , which reverts to the universal efficiency at maximum power for tight-coupling heat engines operating between two heat baths at small temperature difference in the presence of left–right symmetry (Esposito et al 2009 Phys. Rev. Lett. 102 130602). (fast track communication)

  6. Printed freeform lens arrays on multi-core fibers for highly efficient coupling in astrophotonic systems.

    Dietrich, Philipp-Immanuel; Harris, Robert J; Blaicher, Matthias; Corrigan, Mark K; Morris, Tim M; Freude, Wolfgang; Quirrenbach, Andreas; Koos, Christian

    2017-07-24

    Coupling of light into multi-core fibers (MCF) for spatially resolved spectroscopy is of great importance to astronomical instrumentation. To achieve high coupling efficiencies along with fill-fractions close to unity, micro-optical elements are required to concentrate the incoming light to the individual cores of the MCF. In this paper we demonstrate facet-attached lens arrays (LA) fabricated by two-photon polymerization. The LA provide close to 100% fill-fraction along with efficiencies of up to 73% (down to 1.4 dB loss) for coupling of light from free space into an MCF core. We show the viability of the concept for astrophotonic applications by integrating an MCF-LA assembly in an adaptive-optics test bed and by assessing its performance as a tip/tilt sensor.

  7. Achieving the classical Carnot efficiency in a strongly coupled quantum heat engine

    Xu, Y. Y.; Chen, B.; Liu, J.

    2018-02-01

    Generally, the efficiency of a heat engine strongly coupled with a heat bath is less than the classical Carnot efficiency. Through a model-independent method, we show that the classical Carnot efficiency is achieved in a strongly coupled quantum heat engine. First, we present the first law of quantum thermodynamics in strong coupling. Then, we show how to achieve the Carnot cycle and the classical Carnot efficiency at strong coupling. We find that this classical Carnot efficiency stems from the fact that the heat released in a nonequilibrium process is balanced by the absorbed heat. We also analyze the restrictions in the achievement of the Carnot cycle. The first restriction is that there must be two corresponding intervals of the controllable parameter in which the corresponding entropies of the work substance at the hot and cold temperatures are equal, and the second is that the entropy of the initial and final states in a nonequilibrium process must be equal. Through these restrictions, we obtain the positive work conditions, including the usual one in which the hot temperature should be higher than the cold, and a new one in which there must be an entropy interval at the hot temperature overlapping that at the cold. We demonstrate our result through a paradigmatic model—a two-level system in which a work substance strongly interacts with a heat bath. In this model, we find that the efficiency may abruptly decrease to zero due to the first restriction, and that the second restriction results in the control scheme becoming complex.

  8. Cutaneous reactions to heparin therapy: when are they caused by heparin allergy?

    Giuliana Zisa

    2013-03-01

    Full Text Available Introduction: Little is known about the incidence and causes of heparin-induced skin lesions. The most commonly reported causes are delayed-type hypersensitivity reactions. We describe 3 patients who were referred to our staff between March and October 2009 for suspected heparin allergies. All were scheduled to undergo major surgery (cardiovascular or orthopedic. Materials and methods: All 3 patients reported the development of itchy, erythematous rashes a few days after the subcutaneous administration of heparin (nadroparin calcium in cases 1 and 2, unspecified in case 3. Each of them underwent a diagnostic work-up for heparin allergy, which included prick and intradermal tests with commonly used heparins and patch testing with undiluted heparins and disinfectants. Results: Patch tests with disinfectants were negative in all 3 cases. In case 2, all allergological tests were negative. In cases 1 and 3, delayed positivity emerged for nadroparin calcium and at least one other heparin tested. Intravenous and/or subcutaneous provocation testing was done with an alternative heparin which produced negative results in skin tests (heparin sodium in case 1, pentasaccharide fondaparinux in case 3. In both cases the alternative drug was tolerated. After our evaluation, all 3 patients underwent surgery with no heparin-related complications. Discussion: The presenting clinical features in these 3 cases provided no information on which reactions were likely to be allergic: all 3 patients presented with similar local delayed reaction. The allergic reactions were identified only after cutaneous testing.

  9. Combined Conformal Strongly-Coupled Magnetic Resonance for Efficient Wireless Power Transfer

    Matjaz Rozman

    2017-04-01

    Full Text Available This paper proposes a hybrid circuit between a conformal strongly-coupled magnetic resonance (CSCMR and a strongly-coupled magnetic resonance (SCMR, for better wireless power transmission (WPT. This combination promises to enhance the flexibility of the proposed four-loop WPT system. The maximum efficiency at various distances is achieved by combining coupling-matching between the source and transmitting coils along with the coupling factor between the transmitting and receiving coils. Furthermore, the distance between transmitting and receiving coils is investigated along with the distance relationship between the source loop and transmission coil, in order to achieve the maximum efficiency of the proposed hybrid WPT system. The results indicate that the proposed approach can be effectively employed at distances comparatively smaller than the maximum distance without frequency matching. The achievable efficiency can be as high as 84% for the whole working range of the transmitter. In addition, the proposed hybrid system allows more spatial freedom compared to existing chargers.

  10. Induction-heating MOCVD reactor with significantly improved heating efficiency and reduced harmful magnetic coupling

    Li, Kuang-Hui; Alotaibi, Hamad S.; Sun, Haiding; Lin, Ronghui; Guo, Wenzhe; Torres-Castanedo, Carlos G.; Liu, Kaikai; Galan, Sergio V.; Li, Xiaohang

    2018-01-01

    In a conventional induction-heating III-nitride metalorganic chemical vapor deposition (MOCVD) reactor, the induction coil is outside the chamber. Therefore, the magnetic field does not couple with the susceptor well, leading to compromised heating efficiency and harmful coupling with the gas inlet and thus possible overheating. Hence, the gas inlet has to be at a minimum distance away from the susceptor. Because of the elongated flow path, premature reactions can be more severe, particularly between Al- and B-containing precursors and NH3. Here, we propose a structure that can significantly improve the heating efficiency and allow the gas inlet to be closer to the susceptor. Specifically, the induction coil is designed to surround the vertical cylinder of a T-shaped susceptor comprising the cylinder and a top horizontal plate holding the wafer substrate within the reactor. Therefore, the cylinder coupled most magnetic field to serve as the thermal source for the plate. Furthermore, the plate can block and thus significantly reduce the uncoupled magnetic field above the susceptor, thereby allowing the gas inlet to be closer. The results show approximately 140% and 2.6 times increase in the heating and susceptor coupling efficiencies, respectively, as well as a 90% reduction in the harmful magnetic flux on the gas inlet.

  11. Induction-heating MOCVD reactor with significantly improved heating efficiency and reduced harmful magnetic coupling

    Li, Kuang-Hui

    2018-02-23

    In a conventional induction-heating III-nitride metalorganic chemical vapor deposition (MOCVD) reactor, the induction coil is outside the chamber. Therefore, the magnetic field does not couple with the susceptor well, leading to compromised heating efficiency and harmful coupling with the gas inlet and thus possible overheating. Hence, the gas inlet has to be at a minimum distance away from the susceptor. Because of the elongated flow path, premature reactions can be more severe, particularly between Al- and B-containing precursors and NH3. Here, we propose a structure that can significantly improve the heating efficiency and allow the gas inlet to be closer to the susceptor. Specifically, the induction coil is designed to surround the vertical cylinder of a T-shaped susceptor comprising the cylinder and a top horizontal plate holding the wafer substrate within the reactor. Therefore, the cylinder coupled most magnetic field to serve as the thermal source for the plate. Furthermore, the plate can block and thus significantly reduce the uncoupled magnetic field above the susceptor, thereby allowing the gas inlet to be closer. The results show approximately 140% and 2.6 times increase in the heating and susceptor coupling efficiencies, respectively, as well as a 90% reduction in the harmful magnetic flux on the gas inlet.

  12. More efficient second harmonic generation of whispering gallery modes by selective out-coupling

    Trainor, Luke S.; Sedlmeir, Florian; Peuntinger, Christian; Schwefel, Harald G. L.

    2017-01-01

    We demonstrate second harmonic generation (SHG) in an $x$-cut congruent lithium niobate (LN) whispering gallery mode resonator. We first show theoretically that independent control of the coupling of the pump and signal modes is optimal for high conversion rates. A scheme based on our earlier work in Ref. [1] is then implemented experimentally to verify this. Thereby we are able to improve on the efficiency of SHG by more than an order of magnitude by selectively out-coupling using a LN prism...

  13. Preparation and characterization of microspheres of albumin-heparin conjugates

    Kwon, Glen S.; Bae, You Han; Kim, Sung Wan; Cremers, Harry; Cremers, H.F.M.; Feijen, Jan

    1991-01-01

    Albumin-heparin microspheres have been prepared as a new drug carrier. A soluble albumin-heparin conjugate was synthesized by forming amide bonds between human serum albumin and heparin. After purification the albumin-heparin conjugate was crosslinked in a water-in-oil emulsion to form

  14. Click-coated, heparinized, decellularized vascular grafts.

    Dimitrievska, Sashka; Cai, Chao; Weyers, Amanda; Balestrini, Jenna L; Lin, Tylee; Sundaram, Sumati; Hatachi, Go; Spiegel, David A; Kyriakides, Themis R; Miao, Jianjun; Li, Guoyun; Niklason, Laura E; Linhardt, Robert J

    2015-02-01

    A novel method enabling the engineering of a dense and appropriately oriented heparin-containing layer on decellularized aortas has been developed. Amino groups of decellularized aortas were first modified to azido groups using 3-azidobenzoic acid. Azide-clickable dendrons were attached onto the azido groups through "alkyne-azide" click chemistry, affording a tenfold amplification of adhesions sites. Dendron end groups were finally decorated with end-on modified heparin chains. Heparin chains were oriented like heparan sulfate groups on native endothelial cells surface. X-ray photoelectron spectroscopy, nuclear magnetic resonance imaging, mass spectrometry and Fourier transform infrared FTIR spectroscopy were used to characterize the synthesis steps, building the final heparin layered coatings. The continuity of the heparin coating was verified using fluorescent microscopy and histological analysis. The efficacy of heparin linkage was demonstrated with factor Xa anti-thrombogenic assay and platelet adhesion studies. The results suggest that oriented heparin immobilization to decellularized aortas may improve the in vivo blood compatibility of decellularized aortas and vessels. Copyright © 2014 Acta Materialia Inc. All rights reserved.

  15. Heparin-based hydrogels with tunable sulfation & degradation for anti-inflammatory small molecule delivery.

    Peng, Yifeng; Tellier, Liane E; Temenoff, Johnna S

    2016-08-16

    Sustained release of anti-inflammatory agents remains challenging for small molecule drugs due to their low molecular weight and hydrophobicity. Therefore, the goal of this study was to control the release of a small molecule anti-inflammatory agent, crystal violet (CV), from hydrogels fabricated with heparin, a highly sulfated glycosaminoglycan capable of binding positively-charged molecules such as CV. In this system, both electrostatic interactions between heparin and CV and hydrogel degradation were tuned simultaneously by varying the level of heparin sulfation and varying the amount of dithiothreitol within hydrogels, respectively. It was found that heparin sulfation significantly affected CV release, whereby more sulfated heparin hydrogels (Hep and Hep(-N)) released CV with near zero-order release kinetics (R-squared values between 0.96-0.99). Furthermore, CV was released more quickly from fast-degrading hydrogels than slow-degrading hydrogels, providing a method to tune total CV release between 5-15 days while maintaining linear release kinetics. In particular, N-desulfated heparin hydrogels exhibited efficient CV loading (∼90% of originally included CV), near zero-order CV release kinetics, and maintenance of CV bioactivity after release, making this hydrogel formulation a promising CV delivery vehicle for a wide range of inflammatory diseases.

  16. Anticoagulation and endothelial cell behaviors of heparin-loaded graphene oxide coating on titanium surface

    Pan, Chang-Jiang, E-mail: panchangjiang@hyit.edu.cn [Jiangsu Provincial Key Laboratory for Interventional Medical Devices, Huaiyin Institute of Technology, Huai' an 223003 (China); Pang, Li-Qun [Department of General Surgery, Huai' an First People' s Hospital, Nanjing Medical University, Huai' an 223300 (China); Gao, Fei [Zhejiang Zylox Medical Devices Co., Ltd., Hangzhou 310000 (China); Wang, Ya-Nan; Liu, Tao; Ye, Wei; Hou, Yan-Hua [Jiangsu Provincial Key Laboratory for Interventional Medical Devices, Huaiyin Institute of Technology, Huai' an 223003 (China)

    2016-06-01

    Owing to its unique physical and chemical properties, graphene oxide (GO) has attracted tremendous interest in many fields including biomaterials and biomedicine. The purpose of the present study is to investigate the endothelial cell behaviors and anticoagulation of heparin-loaded GO coating on the titanium surface. To this end, the titanium surface was firstly covered by the polydopamine coating followed by the deposition of the GO coating. Heparin was finally loaded on the GO coating to improve the blood compatibility. The results of attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), Raman spectroscopy and X-ray photoelectron spectroscopy (XPS) indicated that the heparin-loaded GO coating was successfully created on the titanium surface. The scanning electron microscopy (SEM) images indicated that a relative uniform GO coating consisting of multilayer GO sheets was formed on the substrate. The hydrophilicity of the titanium surface was enhanced after the deposition of GO and further improved significantly by the loading heparin. The GO coating can enhance the endothelial cell adhesion and proliferation as compared with polydopamine coating and the blank titanium. Loading heparin on the GO coating can significantly reduce the platelet adhesion and prolong the activated partial thromboplastin time (APTT) while not influence the endothelial cell adhesion and proliferation. Therefore, the heparin-loaded GO coating can simultaneously enhance the cytocompatibility to endothelial cells and blood compatibility of biomaterials. Because the polydopamine coating can be easily prepared on most of biomaterials including polymer, ceramics and metal, thus the approach of the present study may open up a new window of promising an effective and efficient way to promote endothelialization and improve the blood compatibility of blood-contact biomedical devices such as intravascular stents. - Highlights: • Heparin-loaded graphene oxide coating was

  17. Oral heparin results in the appearance of heparin fragments in the plasma of rats

    Larsen, A.K.; Lund, D.P.; Langer, R.; Folkman, J.

    1986-01-01

    We have previously shown that angiogenesis inhibition and tumor regression can be accomplished by combinations of heparin or heparin fragments with cortisone. Oral heparin was also effective in combination with cortisone. We now show that a single oral dose of [ 35 S]heparin or [ 3 H]heparin (15,000 units/kg) results in continuous release of radioactive material into the bloodstream for at least 12 hr. This is associated with the presence of anti-factor Xa activity at a level of approximately equal to 0.1 unit/ml. The radioactive material is identified as oligo-, di-, and monosaccharides by its behavior in chromatographic systems, its possession of anti-factor Xa activity, and the effect of treatment with bacterial heparinase. The heparin fragments are extensively metabolized to fragments without anti-factor Xa activity that are readily subject to urinary excretion

  18. 77 FR 7584 - Draft Guidance for Industry on Heparin for Drug and Medical Device Use; Monitoring Crude Heparin...

    2012-02-13

    ... strategies to ensure that the heparin supply chain is not contaminated with OSCS or any non- porcine origin... device manufacturers of finished products, and others to the potential risk of crude heparin...) among patients injected with heparin sodium in 2008, FDA identified the contaminant OSCS in heparin API...

  19. 78 FR 38058 - Guidance for Industry on Heparin for Drug and Medical Device Use: Monitoring Crude Heparin for...

    2013-06-25

    ... public health. FDA developed this guidance to alert manufacturers to the risks of crude heparin contaminants and to recommend strategies to ensure that the heparin supply chain is not contaminated with OSCS... heparin sodium in 2008, FDA identified the contaminant OSCS in crude heparin sourced from China. FDA is...

  20. An Efficient Numerical Approach for Solving Nonlinear Coupled Hyperbolic Partial Differential Equations with Nonlocal Conditions

    A. H. Bhrawy

    2014-01-01

    Full Text Available One of the most important advantages of collocation method is the possibility of dealing with nonlinear partial differential equations (PDEs as well as PDEs with variable coefficients. A numerical solution based on a Jacobi collocation method is extended to solve nonlinear coupled hyperbolic PDEs with variable coefficients subject to initial-boundary nonlocal conservation conditions. This approach, based on Jacobi polynomials and Gauss-Lobatto quadrature integration, reduces solving the nonlinear coupled hyperbolic PDEs with variable coefficients to a system of nonlinear ordinary differential equation which is far easier to solve. In fact, we deal with initial-boundary coupled hyperbolic PDEs with variable coefficients as well as initial-nonlocal conditions. Using triangular, soliton, and exponential-triangular solutions as exact solutions, the obtained results show that the proposed numerical algorithm is efficient and very accurate.

  1. Optimization of output power and transmission efficiency of magnetically coupled resonance wireless power transfer system

    Yan, Rongge; Guo, Xiaoting; Cao, Shaoqing; Zhang, Changgeng

    2018-05-01

    Magnetically coupled resonance (MCR) wireless power transfer (WPT) system is a promising technology in electric energy transmission. But, if its system parameters are designed unreasonably, output power and transmission efficiency will be low. Therefore, optimized parameters design of MCR WPT has important research value. In the MCR WPT system with designated coil structure, the main parameters affecting output power and transmission efficiency are the distance between the coils, the resonance frequency and the resistance of the load. Based on the established mathematical model and the differential evolution algorithm, the change of output power and transmission efficiency with parameters can be simulated. From the simulation results, it can be seen that output power and transmission efficiency of the two-coil MCR WPT system and four-coil one with designated coil structure are improved. The simulation results confirm the validity of the optimization method for MCR WPT system with designated coil structure.

  2. Detection efficiencies in nano- and femtosecond laser ablation inductively coupled plasma mass spectrometry

    Waelle, M.; Koch, J.; Flamigni, L.; Heiroth, S.; Lippert, T.; Hartung, W.; Guenther, D.

    2009-01-01

    Detection efficiencies of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), defined as the ratio of ions reaching the detector and atoms released by LA were measured. For this purpose, LA of silicate glasses, zircon, and pure silicon was performed using nanosecond (ns) as well as femtosecond (fs) LA. For instance, ns-LA of silicate glass using helium as in-cell carrier gas resulted in detection efficiencies between approximately 1E-7 for low and 3E-5 for high mass range elements which were, in addition, almost independent on the laser wavelength and pulse duration chosen. In contrast, the application of argon as carrier gas was found to suppress the detection efficiencies systematically by a factor of up to 5 mainly due to a less efficient aerosol-to-ion conversion and ion transmission inside the ICP-MS

  3. Efficient Integration of Coupled Electrical-chemical Systems in Multiscale Neuronal Simulations

    Ekaterina Brocke

    2016-09-01

    Full Text Available Multiscale modeling and simulations in neuroscience is gaining scientific attention due to its growing importance and unexplored capabilities. For instance, it can help to acquire better understanding of biological phenomena that have important features at multiple scales of time and space. This includes synaptic plasticity, memory formation and modulation, homeostasis. There are several ways to organize multiscale simulations depending on the scientific problem and the system to be modeled. One of the possibilities is to simulate different components of a multiscale system simultaneously and exchange data when required. The latter may become a challenging task for several reasons. One of them is that the components of a multiscale system usually span different spatial and temporal scales, such that rigorous analysis of possible coupling solutions is required. For certain classes of problems a number of coupling mechanisms have been proposed and successfully used. However, a strict mathematical theory is missing in many cases. Recent work in the field has not so far investigated artifacts that may arise during coupled integration of different approximation methods. Moreover, the coupling of widely used numerical fixed step size solvers may lead to unexpected inefficiency. In this paper we address the question of possible numerical artifacts that can arise during the integration of a coupled system. We develop an efficient strategy to couple the components of a multiscale test system. We introduce an efficient coupling method based on the second-order backward differentiation formula numerical approximation. The method uses an adaptive step size integration with an error estimation proposed by Skelboe (2000. The method shows a significant advantage over conventional fixed step size solvers used for similar problems. We explore different coupling strategies that define the organization of computations between system components. We study the

  4. Heparin- induced thrombocytopenia (HIT: a case report of CABG patient

    Alireza Jahangirifard

    2016-08-01

    Full Text Available Heparin- induced thrombocytopenia (HIT is an antibody mediated adverse effect of heparin therapy which is classified into two subtypes, HITI which is non-immune, spontaneously reversible thrombocytopenia and; HITII which is an autoimmune-mediated adverse effect of heparin therapy. In this case report, we described a 65-year old male patient with HITII after coronary artery bypass grafting.Key words: Heparin- induced thrombocytopenia, Heparin- induced thrombosis, coronary artery bypass grafting.

  5. Highly Efficient Synthesis of 2-Aryl-3-methoxyacrylates via Suzuki-Miyaura Coupling Reaction

    Kim, Hyung Ho; Lee, Chun Ho; Song, Young Seob; Park, No Kyun; Kim, Bum Tae; Heo, Jung Nyoung [Korea Research Institute of Chemical Technology, Daejeon (Korea, Republic of)

    2006-02-15

    We have developed a highly efficient and convergent synthesis of 2-aryl-3-methoxyacrylates via the Suzuki-Miyaura coupling reaction of α-iodo-β-methoxy-acrylate with arylboronic acids. The biological activities of 2-aryl-3-methoxyacrylate derivatives will be reported in due course. The Suzuki-Miyaura coupling reaction provides a convenient access to the carbon-carbon bond formation with high efficiency. Recently, a number of 2-aryl-3-methoxy-acrylates served as a key scaffold for the development of biologically active pharmaceuticals and agrochemicals. Especially, the discovery of the naturally-occurring fungicides, such as strobilurin A and oudemansin A, possessing a β-methoxyacrylate moiety was immediately seized great attention by industrial research groups to open a new era of the strobilurin family including azoxy-strobin and picoxystrobin.

  6. Functionalization of chitosan/poly(lactic acid-glycolic acid) sintered microsphere scaffolds via surface heparinization for bone tissue engineering.

    Jiang, Tao; Khan, Yusuf; Nair, Lakshmi S; Abdel-Fattah, Wafa I; Laurencin, Cato T

    2010-06-01

    Scaffolds exhibiting biological recognition and specificity play an important role in tissue engineering and regenerative medicine. The bioactivity of scaffolds in turn influences, directs, or manipulates cellular responses. In this study, chitosan/poly(lactic acid-co-glycolic acid) (chitosan/PLAGA) sintered microsphere scaffolds were functionalized via heparin immobilization. Heparin was successfully immobilized on chitosan/PLAGA scaffolds with controllable loading efficiency. Mechanical testing showed that heparinization of chitosan/PLAGA scaffolds did not significantly alter the mechanical properties and porous structures. In addition, the heparinized chitosan/PLAGA scaffolds possessed a compressive modulus of 403.98 +/- 19.53 MPa and a compressive strength of 9.83 +/- 0.94 MPa, which are in the range of human trabecular bone. Furthermore, the heparinized chitosan/PLAGA scaffolds had an interconnected porous structure with a total pore volume of 30.93 +/- 0.90% and a median pore size of 172.33 +/- 5.89 mum. The effect of immobilized heparin on osteoblast-like MC3T3-E1 cell growth was investigated. MC3T3-E1 cells proliferated three dimensionally throughout the porous structure of the scaffolds. Heparinized chitosan/PLAGA scaffolds with low heparin loading (1.7 microg/scaffold) were shown to be capable of stimulating MC3T3-E1 cell proliferation by MTS assay and cell differentiation as evidenced by elevated osteocalcin expression when compared with nonheparinized chitosan/PLAGA scaffold and chitosan/PLAGA scaffold with high heparin loading (14.1 microg/scaffold). This study demonstrated the potential of functionalizing chitosan/PLAGA scaffolds via heparinization with improved cell functions for bone tissue engineering applications.

  7. Compact Printed Arrays with Embedded Coupling Mitigation for Energy-Efficient Wireless Sensor Networking

    Constantine G. Kakoyiannis

    2010-01-01

    Full Text Available Wireless sensors emerged as narrowband, resource-constrained devices to provide monitoring services over a wide life span. Future applications of sensor networks are multimedia-driven and include sensor mobility. Thus, sensors must combine small size, large bandwidth, and diversity capabilities. Compact arrays, offering transmit/receive diversity, suffer from strong mutual coupling (MC, which causes lower antenna efficiency, loss of bandwidth, and signal correlation. An efficient technique to reduce coupling in compact arrays is described herein: a defect was inserted in the ground plane (GNDP area between each pair of elements. The defect disturbed the GNDP currents and offered multidecibel coupling suppression, bandwidth recovery, and reduction of in-band correlation. Minimal pattern distortion was estimated. Computational results were supported by measurements. The bandwidth of unloaded arrays degraded gracefully from 38% to 28% with decreasing interelement distance (0.25 to 0.10. Defect-loaded arrays exhibited active impedance bandwidths 37–45%, respectively. Measured coupling was reduced by 15–20 dB.

  8. Theoretical and experimental investigations of efficient light coupling with spatially varied all dielectric striped waveguides

    Yilmaz, Y. A.; Tandogan, S. E.; Hayran, Z.; Giden, I. H.; Turduev, M.; Kurt, H.

    2017-07-01

    Integrated photonic systems require efficient, compact, and broadband solutions for strong light coupling into and out of optical waveguides. The present work investigates an efficient optical power transferring the problem between optical waveguides having different widths of in/out terminals. We propose a considerably practical and feasible concept to implement and design an optical coupler by introducing gradually index modulation to the coupler section. The index profile of the coupler section is modulated with a Gaussian function by the help of striped waveguides. The effective medium theory is used to replace the original spatially varying index profile with dielectric stripes of a finite length/width having a constant effective refractive index. 2D and 3D finite-difference time-domain analyzes are utilized to investigate the sampling effect of the designed optical coupler and to determine the parameters that play a crucial role in enhancing the optical power transfer performance. Comparing the coupling performance of conventional benchmark adiabatic and butt couplers with the designed striped waveguide coupler, the corresponding coupling efficiency increases from approximately 30% to 95% over a wide frequency interval. In addition, to realize the realistic optical coupler appropriate to integrated photonic applications, the proposed structure is numerically designed on a silicon-on-insulator wafer. The implemented SOI platform based optical coupler operates in the telecom wavelength regime (λ = 1.55 μm), and the dimensions of the striped coupler are kept as 9.77 μm (along the transverse to propagation direction) and 7.69 μm (along the propagation direction) where the unit distance is fixed to be 465 nm. Finally, to demonstrate the operating design principle, the microwave experiments are conducted and the spot size conversion ratio as high as 7.1:1 is measured, whereas a coupling efficiency over 60% in the frequency range of 5.0-16.0 GHz has been also

  9. Fiber-coupling efficiency of Gaussian-Schell model beams through an ocean to fiber optical communication link

    Hu, Beibei; Shi, Haifeng; Zhang, Yixin

    2018-06-01

    We theoretically study the fiber-coupling efficiency of Gaussian-Schell model beams propagating through oceanic turbulence. The expression of the fiber-coupling efficiency is derived based on the spatial power spectrum of oceanic turbulence and the cross-spectral density function. Our work shows that the salinity fluctuation has a greater impact on the fiber-coupling efficiency than temperature fluctuation does. We can select longer λ in the "ocean window" and higher spatial coherence of light source to improve the fiber-coupling efficiency of the communication link. We also can achieve the maximum fiber-coupling efficiency by choosing design parameter according specific oceanic turbulence condition. Our results are able to help the design of optical communication link for oceanic turbulence to fiber sensor.

  10. Cationization of heparin for film applications

    Šimkovic, I.; Mendichi, R.; Kelnar, Ivan; Filip, J.; Hricovíni, M.

    2015-01-01

    Roč. 115, 22 January (2015), s. 551-558 ISSN 0144-8617 Institutional support: RVO:61389013 Keywords : heparin * cationization * NMR Subject RIV: CD - Macromolecular Chemistry Impact factor: 4.219, year: 2015

  11. Hydrogen production methods efficiency coupled to an advanced high temperature accelerator driven system

    Rodríguez, Daniel González; Lira, Carlos Alberto Brayner de Oliveira

    2017-01-01

    The hydrogen economy is one of the most promising concepts for the energy future. In this scenario, oil is replaced by hydrogen as an energy carrier. This hydrogen, rather than oil, must be produced in volumes not provided by the currently employed methods. In this work two high temperature hydrogen production methods coupled to an advanced nuclear system are presented. A new design of a pebbled-bed accelerator nuclear driven system called TADSEA is chosen because of the advantages it has in matters of transmutation and safety. For the conceptual design of the high temperature electrolysis process a detailed computational fluid dynamics model was developed to analyze the solid oxide electrolytic cell that has a huge influence on the process efficiency. A detailed flowsheet of the high temperature electrolysis process coupled to TADSEA through a Brayton gas cycle was developed using chemical process simulation software: Aspen HYSYS®. The model with optimized operating conditions produces 0.1627 kg/s of hydrogen, resulting in an overall process efficiency of 34.51%, a value in the range of results reported by other authors. A conceptual design of the iodine-sulfur thermochemical water splitting cycle was also developed. The overall efficiency of the process was calculated performing an energy balance resulting in 22.56%. The values of efficiency, hydrogen production rate and energy consumption of the proposed models are in the values considered acceptable in the hydrogen economy concept, being also compatible with the TADSEA design parameters. (author)

  12. Hydrogen production methods efficiency coupled to an advanced high temperature accelerator driven system

    Rodríguez, Daniel González; Lira, Carlos Alberto Brayner de Oliveira [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Departamento de Energia Nuclear; Fernández, Carlos García, E-mail: danielgonro@gmail.com, E-mail: mmhamada@ipen.br [Instituto Superior de Tecnologías y Ciencias aplicadas (InSTEC), La Habana (Cuba)

    2017-07-01

    The hydrogen economy is one of the most promising concepts for the energy future. In this scenario, oil is replaced by hydrogen as an energy carrier. This hydrogen, rather than oil, must be produced in volumes not provided by the currently employed methods. In this work two high temperature hydrogen production methods coupled to an advanced nuclear system are presented. A new design of a pebbled-bed accelerator nuclear driven system called TADSEA is chosen because of the advantages it has in matters of transmutation and safety. For the conceptual design of the high temperature electrolysis process a detailed computational fluid dynamics model was developed to analyze the solid oxide electrolytic cell that has a huge influence on the process efficiency. A detailed flowsheet of the high temperature electrolysis process coupled to TADSEA through a Brayton gas cycle was developed using chemical process simulation software: Aspen HYSYS®. The model with optimized operating conditions produces 0.1627 kg/s of hydrogen, resulting in an overall process efficiency of 34.51%, a value in the range of results reported by other authors. A conceptual design of the iodine-sulfur thermochemical water splitting cycle was also developed. The overall efficiency of the process was calculated performing an energy balance resulting in 22.56%. The values of efficiency, hydrogen production rate and energy consumption of the proposed models are in the values considered acceptable in the hydrogen economy concept, being also compatible with the TADSEA design parameters. (author)

  13. High coupling efficiency of foam spherical hohlraum driven by 2ω laser light

    Chen, Yao-Hua; Lan, Ke; Zheng, Wanguo; Campbell, E. M.

    2018-02-01

    The majority of solid state laser facilities built for laser fusion research irradiate targets with third harmonic light (0.35 μm) up-converted from the fundamental Nd wavelength at 1.05 μm. The motivation for this choice of wavelength is improved laser-plasma coupling. Significant disadvantages to this choice of wavelength are the reduced damage threshold of optical components and the efficiency of energy conversion to third harmonic light. Both these issues are significantly improved if second harmonic (0.53 μm) radiation is used, but theory and experiments have shown lower optical to x-ray energy conversion efficiency and increased levels of laser-plasma instabilities, resulting in reduced laser-target coupling. In this letter, we propose to use a 0.53 μm laser for the laser ignition facilities and use a low density foam wall to increase the coupling efficiency from the laser to the capsule and present two-dimensional radiation-hydrodynamic simulations of 0.53 μm laser light irradiating an octahedral-spherical hohlraum with a low density foam wall. The simulations show that the reduced optical depth of the foam wall leads to an increased laser-light conversion into thermal x-rays and about 10% higher radiation flux on the capsule than that achieved with 0.35 μm light irradiating a solid density wall commonly used in laser indirect drive fusion research. The details of the simulations and their implications and suggestions for wavelength scaling coupled with innovative hohlraum designs will be discussed.

  14. Solving the Coupled System Improves Computational Efficiency of the Bidomain Equations

    Southern, J.A.; Plank, G.; Vigmond, E.J.; Whiteley, J.P.

    2009-01-01

    The bidomain equations are frequently used to model the propagation of cardiac action potentials across cardiac tissue. At the whole organ level, the size of the computational mesh required makes their solution a significant computational challenge. As the accuracy of the numerical solution cannot be compromised, efficiency of the solution technique is important to ensure that the results of the simulation can be obtained in a reasonable time while still encapsulating the complexities of the system. In an attempt to increase efficiency of the solver, the bidomain equations are often decoupled into one parabolic equation that is computationally very cheap to solve and an elliptic equation that is much more expensive to solve. In this study, the performance of this uncoupled solution method is compared with an alternative strategy in which the bidomain equations are solved as a coupled system. This seems counterintuitive as the alternative method requires the solution of a much larger linear system at each time step. However, in tests on two 3-D rabbit ventricle benchmarks, it is shown that the coupled method is up to 80% faster than the conventional uncoupled method-and that parallel performance is better for the larger coupled problem.

  15. Solving the Coupled System Improves Computational Efficiency of the Bidomain Equations

    Southern, J.A.

    2009-10-01

    The bidomain equations are frequently used to model the propagation of cardiac action potentials across cardiac tissue. At the whole organ level, the size of the computational mesh required makes their solution a significant computational challenge. As the accuracy of the numerical solution cannot be compromised, efficiency of the solution technique is important to ensure that the results of the simulation can be obtained in a reasonable time while still encapsulating the complexities of the system. In an attempt to increase efficiency of the solver, the bidomain equations are often decoupled into one parabolic equation that is computationally very cheap to solve and an elliptic equation that is much more expensive to solve. In this study, the performance of this uncoupled solution method is compared with an alternative strategy in which the bidomain equations are solved as a coupled system. This seems counterintuitive as the alternative method requires the solution of a much larger linear system at each time step. However, in tests on two 3-D rabbit ventricle benchmarks, it is shown that the coupled method is up to 80% faster than the conventional uncoupled method-and that parallel performance is better for the larger coupled problem.

  16. Computationally Efficient 2D DOA Estimation for L-Shaped Array with Unknown Mutual Coupling

    Yang-Yang Dong

    2018-01-01

    Full Text Available Although L-shaped array can provide good angle estimation performance and is easy to implement, its two-dimensional (2D direction-of-arrival (DOA performance degrades greatly in the presence of mutual coupling. To deal with the mutual coupling effect, a novel 2D DOA estimation method for L-shaped array with low computational complexity is developed in this paper. First, we generalize the conventional mutual coupling model for L-shaped array and compensate the mutual coupling blindly via sacrificing a few sensors as auxiliary elements. Then we apply the propagator method twice to mitigate the effect of strong source signal correlation effect. Finally, the estimations of azimuth and elevation angles are achieved simultaneously without pair matching via the complex eigenvalue technique. Compared with the existing methods, the proposed method is computationally efficient without spectrum search or polynomial rooting and also has fine angle estimation performance for highly correlated source signals. Theoretical analysis and simulation results have demonstrated the effectiveness of the proposed method.

  17. Demonstration of high coupling efficiency to Al capsule in rugby hohlraum on NIF

    Ping, Y.; Smalyuk, V.; Amendt, P.; Bennett, D.; Chen, H.; Dewald, E.; Goyon, C.; Graziani, F.; Johnson, S.; Khan, S.; Landen, O.; Nikroo, A.; Pino, J.; Ralph, J.; Seugling, R.; Strozzi, D.; Tipton, R.; Tommasini, R.; Wang, M.; Loomis, E.; Merritt, E.; Montgomery, D.

    2017-10-01

    A new design of the double-shell approach predicts a high coupling efficiency from the hohlraum to the capsule, with 700 kJ in the capsule instead of 200kJ in the conventional low-Z single-shell scheme, improving prospects of double-shell performance. A recent experiment on NIF has evaluated a first step toward this goal of energy coupling using 0.7x subscale Al capsule, Au rugby hohlraum and 1MJ drive. A shell velocity of 150 μm/ns was measured, DANTE peak temperature of 255 eV was measured, and shell kinetic energy of 36 kJ was inferred using a rocket model, all close to predictions and consistent with 330kJ of total energy coupled to the capsule. Data analysis and more results from subsequent experiments will be presented. In the next step, an additional 2x increase of total coupled energy up to 700 kJ is projected for full-scale 2-MJ drive in U Rugby hohlraum. This work was performed under DOE contract DE-AC52-07NA27344.

  18. An efficient protocol for the palladium-catalysed Suzuki-Miyaura cross-coupling

    Marziale, Alexander N.; Jantke, Dominik; Faul, Stefan Holger; Reiner, Thomas; Herdtweck, Eberhardt; Eppinger, Jö rg

    2011-01-01

    The palladacyclic catalyst precursor received by ortho-palladation of ([1,1′-biphenyl]-2-yloxy)diisopropyl-phosphine represents a highly active system for Suzuki-Miyaura cross-coupling reactions when used in neat water. An efficient, broadly applicable and sustainable aqueous protocol was developed using 2.5 eq. of Na2CO3 as base, allowing the reaction to be performed under air and at ambient temperature with Pd loadings of 0.04 mol%. Coupling products are obtained in high yields and excellent purity by simple filtration with no organic solvents needed throughout the whole reaction. A broad variety of functional groups are tolerated and a large number of substrates can be applied with this protocol. The crystal structure of the palladacyclic catalyst precursor is presented as well as investigations targeting the nature of catalyst activation and the active catalytic species. © 2011 The Royal Society of Chemistry.

  19. Analysis of the coupling efficiency of a tapered space receiver with a calculus mathematical model

    Hu, Qinggui; Mu, Yining

    2018-03-01

    We establish a calculus mathematical model to study the coupling characteristics of tapered optical fibers in a space communications system, and obtained the coupling efficiency equation. Then, using MATLAB software, the solution was calculated. After this, the sample was produced by the mature flame-brush technique. The experiment was then performed, and the results were in accordance with the theoretical analysis. This shows that the theoretical analysis was correct and indicates that a tapered structure could improve its tolerance with misalignment. Project supported by The National Natural Science Foundation of China (grant no. 61275080); 2017 Jilin Province Science and Technology Development Plan-Science and Technology Innovation Fund for Small and Medium Enterprises (20170308029HJ); ‘thirteen five’ science and technology research project of the Department of Education of Jilin 2016 (16JK009).

  20. An innovative computationally efficient hydromechanical coupling approach for fault reactivation in geological subsurface utilization

    Adams, M.; Kempka, T.; Chabab, E.; Ziegler, M.

    2018-02-01

    Estimating the efficiency and sustainability of geological subsurface utilization, i.e., Carbon Capture and Storage (CCS) requires an integrated risk assessment approach, considering the occurring coupled processes, beside others, the potential reactivation of existing faults. In this context, hydraulic and mechanical parameter uncertainties as well as different injection rates have to be considered and quantified to elaborate reliable environmental impact assessments. Consequently, the required sensitivity analyses consume significant computational time due to the high number of realizations that have to be carried out. Due to the high computational costs of two-way coupled simulations in large-scale 3D multiphase fluid flow systems, these are not applicable for the purpose of uncertainty and risk assessments. Hence, an innovative semi-analytical hydromechanical coupling approach for hydraulic fault reactivation will be introduced. This approach determines the void ratio evolution in representative fault elements using one preliminary base simulation, considering one model geometry and one set of hydromechanical parameters. The void ratio development is then approximated and related to one reference pressure at the base of the fault. The parametrization of the resulting functions is then directly implemented into a multiphase fluid flow simulator to carry out the semi-analytical coupling for the simulation of hydromechanical processes. Hereby, the iterative parameter exchange between the multiphase and mechanical simulators is omitted, since the update of porosity and permeability is controlled by one reference pore pressure at the fault base. The suggested procedure is capable to reduce the computational time required by coupled hydromechanical simulations of a multitude of injection rates by a factor of up to 15.

  1. Efficient Numerical Solution of Coupled Radial Differential Equations in Multichannel Scattering Problems

    Houfek, Karel

    2008-01-01

    Numerical solution of coupled radial differential equations which are encountered in multichannel scattering problems is presented. Numerical approach is based on the combination of the exterior complex scaling method and the finite-elements method with the discrete variable representation. This method can be used not only to solve multichannel scattering problem but also to find bound states and resonance positions and widths directly by diagonalization of the corresponding complex scaled Hamiltonian. Efficiency and accuracy of this method is demonstrated on an analytically solvable two-channel problem.

  2. A concise, efficient synthesis of sugar-based benzothiazoles through chemoselective intramolecular C-S coupling

    Shen, Chao

    2012-01-01

    Sugar-based benzothiazoles are a new class of molecules promising for many biological applications. Here, we have synthesized a wide range of sugar-based benzothiazoles from readily accessible glycosyl thioureas by chemoselective, palladium-catalyzed C-S coupling reactions. Corroborated by theoretical calculations, a mechanistic investigation indicates that the coordination to the palladium by a pivaloyl carbonyl group and the presence of intramolecular hydrogen bonding play important roles in the efficiency and chemoselectivity of reaction. These fluorescent glycoconjugates can be observed to readily enter mammalian tumor cells and exhibit potential in vitro antitumor activity. This journal is © The Royal Society of Chemistry 2012.

  3. An efficient method for hybrid density functional calculation with spin-orbit coupling

    Wang, Maoyuan; Liu, Gui-Bin; Guo, Hong; Yao, Yugui

    2018-03-01

    In first-principles calculations, hybrid functional is often used to improve accuracy from local exchange correlation functionals. A drawback is that evaluating the hybrid functional needs significantly more computing effort. When spin-orbit coupling (SOC) is taken into account, the non-collinear spin structure increases computing effort by at least eight times. As a result, hybrid functional calculations with SOC are intractable in most cases. In this paper, we present an approximate solution to this problem by developing an efficient method based on a mixed linear combination of atomic orbital (LCAO) scheme. We demonstrate the power of this method using several examples and we show that the results compare very well with those of direct hybrid functional calculations with SOC, yet the method only requires a computing effort similar to that without SOC. The presented technique provides a good balance between computing efficiency and accuracy, and it can be extended to magnetic materials.

  4. Computational model for a high temperature electrolyzer coupled to a HTTR for efficient nuclear hydrogen production

    Gonzalez, Daniel; Rojas, Leorlen; Rosales, Jesus; Castro, Landy; Gamez, Abel; Brayner, Carlos, E-mail: danielgonro@gmail.com [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil); Garcia, Lazaro; Garcia, Carlos; Torre, Raciel de la, E-mail: lgarcia@instec.cu [Instituto Superior de Tecnologias y Ciencias Aplicadas (InSTEC), La Habana (Cuba); Sanchez, Danny [Universidade Estadual de Santa Cruz (UESC), Ilheus, BA (Brazil)

    2015-07-01

    High temperature electrolysis process coupled to a very high temperature reactor (VHTR) is one of the most promising methods for hydrogen production using a nuclear reactor as the primary heat source. However there are not references in the scientific publications of a test facility that allow to evaluate the efficiency of the process and other physical parameters that has to be taken into consideration for its accurate application in the hydrogen economy as a massive production method. For this lack of experimental facilities, mathematical models are one of the most used tools to study this process and theirs flowsheets, in which the electrolyzer is the most important component because of its complexity and importance in the process. A computational fluid dynamic (CFD) model for the evaluation and optimization of the electrolyzer of a high temperature electrolysis hydrogen production process flowsheet was developed using ANSYS FLUENT®. Electrolyzer's operational and design parameters will be optimized in order to obtain the maximum hydrogen production and the higher efficiency in the module. This optimized model of the electrolyzer will be incorporated to a chemical process simulation (CPS) code to study the overall high temperature flowsheet coupled to a high temperature accelerator driven system (ADS) that offers advantages in the transmutation of the spent fuel. (author)

  5. Computational model for a high temperature electrolyzer coupled to a HTTR for efficient nuclear hydrogen production

    Gonzalez, Daniel; Rojas, Leorlen; Rosales, Jesus; Castro, Landy; Gamez, Abel; Brayner, Carlos; Garcia, Lazaro; Garcia, Carlos; Torre, Raciel de la; Sanchez, Danny

    2015-01-01

    High temperature electrolysis process coupled to a very high temperature reactor (VHTR) is one of the most promising methods for hydrogen production using a nuclear reactor as the primary heat source. However there are not references in the scientific publications of a test facility that allow to evaluate the efficiency of the process and other physical parameters that has to be taken into consideration for its accurate application in the hydrogen economy as a massive production method. For this lack of experimental facilities, mathematical models are one of the most used tools to study this process and theirs flowsheets, in which the electrolyzer is the most important component because of its complexity and importance in the process. A computational fluid dynamic (CFD) model for the evaluation and optimization of the electrolyzer of a high temperature electrolysis hydrogen production process flowsheet was developed using ANSYS FLUENT®. Electrolyzer's operational and design parameters will be optimized in order to obtain the maximum hydrogen production and the higher efficiency in the module. This optimized model of the electrolyzer will be incorporated to a chemical process simulation (CPS) code to study the overall high temperature flowsheet coupled to a high temperature accelerator driven system (ADS) that offers advantages in the transmutation of the spent fuel. (author)

  6. Tele-Coupling Energy Efficiency Polices in Europe: Showcasing the German Governance Arrangements

    Marc Ringel

    2018-05-01

    Full Text Available Climate change entails many situations of tele-coupling. We analyze an example in the field of European climate and energy policy. The EU aims at an almost full decarbonisation of its economy by 2050. Achieving this objective asks for transforming the energy sectors of EU Member States. These are responsible for 80% of carbon emissions. Further to this policy coupling, the EU transformation objectives have to be implemented by the Member States, regions and local actors. This proves especially complex in the field of energy efficiency. Here, a variety of policy instruments and actors are in place. In our contribution, we investigate in the question how multi-level governance arrangements in the energy efficiency field are designed. We focus on Germany as example for a federal state setting. Our review method comprises literature content analysis, primary sources, expert interviews and an in-depth screening of the German Sustainable Energy Action Plans. We find that formal vertical coordination has been successfully backed up by horizontal and especially informal governance mechanisms, leading to a model of polycentric governance. This model might serve as blueprint for other multi-level governance arrangements. Yet, we find that the “last mile” of this coordination still needs strengthening: Local actors need more active engaging and empowering to reap the full potential of the governance arrangements.

  7. DEGRADATION AND INTRAHEPATIC COMPATIBILITY OF ALBUMIN-HEPARIN CONJUGATE MICROSPHERES

    CREMERS, HFM; WOLF, RFE; BLAAUW, EH; SCHAKENRAAD, JM; LAM, KH; NIEUWENHUIS, P; VERRIJK, R; KWON, G; BAE, YH; KIM, SW; FEIJEN, J

    The in vitro degradation properties of glutaraldehyde cross-linked albumin and albumin-heparin conjugate microspheres (AMS and AHCMS respectively) were evaluated using light microscopy, turbidity measurements and heparin release determinations, showing that the microspheres are degraded by

  8. Structural characterization of pharmaceutical heparins prepared from different animal tissues.

    Fu, Li; Li, Guoyun; Yang, Bo; Onishi, Akihiro; Li, Lingyun; Sun, Peilong; Zhang, Fuming; Linhardt, Robert J

    2013-05-01

    Although most pharmaceutical heparin used today is obtained from porcine intestine, heparin has historically been prepared from bovine lung and ovine intestine. There is some regulatory concern about establishing the species origin of heparin. This concern began with the outbreak of mad cow disease in the 1990s and was exacerbated during the heparin shortage in the 2000s and the heparin contamination crisis of 2007-2008. Three heparins from porcine, ovine, and bovine were characterized through state-of-the-art carbohydrate analysis methods with a view profiling their physicochemical properties. Differences in molecular weight, monosaccharide and disaccharide composition, oligosaccharide sequence, and antithrombin III-binding affinity were observed. These data provide some insight into the variability of heparins obtained from these three species and suggest some analytical approaches that may be useful in confirming the species origin of a heparin active pharmaceutical ingredient. Copyright © 2013 Wiley Periodicals, Inc.

  9. Fully etched apodized grating coupler on the SOI platform with −058 dB coupling efficiency

    Ding, Yunhong; Peucheret, Christophe; Ou, Haiyan

    2014-01-01

    We design and fabricate an ultrahigh coupling efficiency (CE) fully etched apodized grating coupler on the silicon- on-insulator (SOI) platform using subwavelength photonic crystals and bonded aluminum mirror. Fabrication error sensitivity andcoupling angle dependence are experimentally investiga......We design and fabricate an ultrahigh coupling efficiency (CE) fully etched apodized grating coupler on the silicon- on-insulator (SOI) platform using subwavelength photonic crystals and bonded aluminum mirror. Fabrication error sensitivity andcoupling angle dependence are experimentally...

  10. Palladium-catalyzed domino C,N-coupling/carbonylation/Suzuki coupling reaction: an efficient synthesis of 2-aroyl-/heteroaroylindoles.

    Arthuis, Martin; Pontikis, Renée; Florent, Jean-Claude

    2009-10-15

    A convenient one-pot synthesis of 2-aroylindoles using a domino palladium-catalyzed C,N-coupling/carbonylation/C,C-coupling sequence is described. The reaction involved easily prepared 2-gem-dibromovinylanilines and boronic acids under carbon monoxide. Optimized reaction conditions allowed the construction of a wide variety of highly functionalized 2-aroyl-/heteroaroylindoles in satisfactory yields.

  11. Endogenous heparin levels in the controlled asthmatic patient ...

    Background. Since heparin possesses anti-inflammatory properties, it is hypothesised that asthmatic patients have decreased levels of circulating heparin compared with healthy individuals. Design. We compared endogenous heparin levels in controlled asthmatic patients (53 adults) from the Asthma Clinic at ...

  12. Heparin increases food intake through AgRP neurons

    Although the widely used anticoagulant drug heparin has been shown to have many other biological functions independent of its anticoagulant role, its effects on energy homeostasis are unknown. Here, we demonstrate that heparin level is negatively associated with nutritional states and that heparin t...

  13. Human IGF-I propeptide A promotes articular chondrocyte biosynthesis and employs glycosylation-dependent heparin binding.

    Shi, Shuiliang; Kelly, Brian J; Wang, Congrong; Klingler, Ken; Chan, Albert; Eckert, George J; Trippel, Stephen B

    2018-03-01

    Insulin-like growth factor I (IGF-I) is a key regulator of chondrogenesis, but its therapeutic application to articular cartilage damage is limited by rapid elimination from the repair site. The human IGF-I gene gives rise to three IGF-I propeptides (proIGF-IA, proIGF-IB and proIGF-IC) that are cleaved to create mature IGF-I. In this study, we elucidate the processing of IGF-I precursors by articular chondrocytes, and test the hypotheses that proIGF-I isoforms bind to heparin and regulate articular chondrocyte biosynthesis. Human IGF-I propeptides and mutants were overexpressed in bovine articular chondrocytes. IGF-I products were characterized by ELISA, western blot and FPLC using a heparin column. The biosynthetic activity of IGF-I products on articular chondrocytes was assayed for DNA and glycosaminoglycan that the cells produced. Secreted IGF-I propeptides stimulated articular chondrocyte biosynthetic activity to the same degree as mature IGF-I. Of the three IGF-I propeptides, only one, proIGF-IA, strongly bound to heparin. Interestingly, heparin binding of proIGF-IA depended on N-glycosylation at Asn92 in the EA peptide. To our knowledge, this is the first demonstration that N-glycosylation determines the binding of a heparin-binding protein to heparin. The biosynthetic and heparin binding abilities of proIGF-IA, coupled with its generation of IGF-I, suggest that proIGF-IA may have therapeutic value for articular cartilage repair. These data identify human pro-insulin-like growth factor IA as a bifunctional protein. Its combined ability to bind heparin and augment chondrocyte biosynthesis makes it a promising therapeutic agent for cartilage damage due to trauma and osteoarthritis. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Broadband Light Collection Efficiency Enhancement of Carbon Nanotube Excitons Coupled to Metallo-Dielectric Antenna Arrays

    Shayan, Kamran [Department; Rabut, Claire [Department; Kong, Xiaoqing [Department; Li, Xiangzhi [Department; Luo, Yue [Department; Mistry, Kevin S. [National Renewable; Blackburn, Jeffrey L. [National Renewable; Lee, Stephanie S. [Department; Strauf, Stefan [Department

    2017-11-09

    The realization of on-chip quantum networks ideally requires lossless interfaces between photons and solid-state quantum emitters. We propose and demonstrate on-chip arrays of metallo-dielectric antennas (MDA) that are tailored toward efficient and broadband light collection from individual embedded carbon nanotube quantum emitters by trapping air gaps on chip that form cavity modes. Scalable implementation is realized by employing polymer layer dry-transfer techniques that avoid solvent incompatibility issues, as well as a planar design that avoids solid-immersion lenses. Cryogenic measurements demonstrate 7-fold enhanced exciton intensity when compared to emitters located on bare wafers, corresponding to a light collection efficiency (LCE) up to 92% in the best case (average LCE of 69%) into a narrow output cone of +/-15 degrees that enables a priori fiber-to-chip butt coupling. The demonstrated MDA arrays are directly compatible with other quantum systems, particularly 2D materials, toward enabling efficient on-chip quantum light sources or spin-photon interfaces requiring unity light collection, both at cryogenic or room temperature.

  15. Multigroup and coupled forward-adjoint Monte Carlo calculation efficiencies for secondary neutron doses from proton beams

    Kelsey IV, Charles T.; Prinja, Anil K.

    2011-01-01

    We evaluate the Monte Carlo calculation efficiency for multigroup transport relative to continuous energy transport using the MCNPX code system to evaluate secondary neutron doses from a proton beam. We consider both fully forward simulation and application of a midway forward adjoint coupling method to the problem. Previously we developed tools for building coupled multigroup proton/neutron cross section libraries and showed consistent results for continuous energy and multigroup proton/neutron transport calculations. We observed that forward multigroup transport could be more efficient than continuous energy. Here we quantify solution efficiency differences for a secondary radiation dose problem characteristic of proton beam therapy problems. We begin by comparing figures of merit for forward multigroup and continuous energy MCNPX transport and find that multigroup is 30 times more efficient. Next we evaluate efficiency gains for coupling out-of-beam adjoint solutions with forward in-beam solutions. We use a variation of a midway forward-adjoint coupling method developed by others for neutral particle transport. Our implementation makes use of the surface source feature in MCNPX and we use spherical harmonic expansions for coupling in angle rather than solid angle binning. The adjoint out-of-beam transport for organs of concern in a phantom or patient can be coupled with numerous forward, continuous energy or multigroup, in-beam perturbations of a therapy beam line configuration. Out-of-beam dose solutions are provided without repeating out-of-beam transport. (author)

  16. Effects of curcumin and ursolic acid on the mitochondrial coupling efficiency and hydrogen peroxide emission of intact skeletal myoblasts.

    Tueller, Daniel J; Harley, Jackson S; Hancock, Chad R

    2017-10-21

    Curcumin may improve blood glucose management, but the mechanism is not fully established. We demonstrated that curcumin (40 μM) reduced the mitochondrial coupling efficiency (percentage of oxygen consumption coupled to ATP synthesis) of intact skeletal muscle cells. A 30-minute pretreatment with curcumin reduced mitochondrial coupling efficiency by 17.0 ± 0.4% relative to vehicle (p Curcumin pretreatment also decreased the rate of hydrogen peroxide emission by 43 ± 13% compared to vehicle (p curcumin revealed a 40 ± 4% increase in the rate of oxygen consumption upon curcumin administration (p curcumin-pretreated cells after permeabilization of cell membranes (p > 0.7). The interaction between curcumin and ursolic acid, another natural compound that may improve blood glucose management, was also examined. Pretreatment with ursolic acid (0.12 μM) increased the mitochondrial coupling efficiency of intact cells by 4.1 ± 1.1% relative to vehicle (p curcumin when the two compounds were used in combination. The observed changes to mitochondrial coupling efficiency and hydrogen peroxide emission were consistent with the established effects of curcumin on blood glucose control. Our findings also show that changes to mitochondrial coupling efficiency after curcumin pretreatment may go undetected unless cells are assessed in the intact condition. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Enhancing the Out-Coupling Efficiency of Organic Light-Emitting Diodes Using Two-Dimensional Periodic Nanostructures

    Qingyang Yue

    2012-01-01

    Full Text Available The out-coupling efficiency of planar organic light emitting diodes (OLEDs is only about 20% due to factors, such as, the total internal reflection, surface plasmon coupling, and metal absorption. Two-dimensional periodic nanostructures, such as, photonic crystals (PhCs and microlenses arrays offer a potential method to improve the out-coupling efficiency of OLEDs. In this work, we employed the finite-difference time-domain (FDTD method to explore different mechanisms that embedded PhCs and surface PhCs to improve the out-coupling efficiency. The effects of several parameters, including the filling factor, the depth, and the lattice constant were investigated. The result showed that embedded PhCs play a key role in improving the out-coupling efficiency, and an enhancement factor of 240% was obtained in OLEDs with embedded PhCs, while the enhancement factor of OLEDs with surface PhCs was only 120%. Furthermore, the phenomena was analyzed using the mode theory and it demonstrated that the overlap between the mode and PhCs was related to the distribution of vertical mode profiles. The enhancement of the extraction efficiency in excess of 290% was observed for the optimized OLEDs structure with double PhCs. This proposed structure could be a very promising candidate for high extraction efficiency OLEDs.

  18. An efficient enzyme immunoassay for glutamate using glutaraldehyde coupling of the hapten to microtiter plates.

    Ordronneau, P; Abdullah, L H; Petrusz, P

    1991-09-13

    In order to coat microtiter plates for enzyme immunoassays (EIAs), amino acids and other haptens are usually coupled to larger protein molecules. The formation of such conjugates is not always reproducible. This may lead to inconsistent hapten-protein stoichiometries, unfavorable orientation of the hapten on the protein and/or well-to-well variation in the concentration of the available hapten. In the assay described here the excitatory amino acid (EAA) Glu is coupled directly to polystyrene microtiter wells with GA. Each step of the assay was tested for maximum efficiency. The resulting EIA with Glu as a competitor gave excellent reproducibility (coefficient of variation = 5.87%), an EC50 of 2.02 X 10(-5) M and a detection limit of 1.26 X 10(-6) M. This EIA method is generally useful for a variety of antisera to amino acids and small peptides and a wide range of competing substances. It can be used to characterize the conformational requirements for antigen binding, to assay for glutamate or to identify compounds with glutamate-like structure in unknown solutions.

  19. Characterization of heparin aerosols generated in jet and ultrasonic nebulizers

    Bendstrup, K.E.; Newhouse, M.T.; Pedersen, Ole Finn

    1999-01-01

    Inhaled heparin has been used for asthma treatment, but results have been inconsistent, probably due to highly varying lung doses. We determined the output per unit time and the particle size distributions of sodium heparin, calcium heparin, and low molecular weight (LMW) heparin formulations in ...... on the exhalation filter, and 15,000 IU was captured on the inhalation filter (inhaled mass). This corresponds to a respirable mass of 10,000 IU of heparin with a high probability of reaching the lower respiratory tract in normal healthy adults....

  20. Antiproliferative heparin (glycosaminoglycans) isolated from giant ...

    STORAGESEVER

    2009-05-18

    May 18, 2009 ... source of these sulfated polysaccharides (Nader and. Dietrich, 1989) and it often corresponds up to 90% of the total GAG content of these organisms. Heparin and heap- rin-like substances have a wide range of important biolo- gical activities including inhibition of pulmonary artery smooth muscle cell ...

  1. Biological distribution of 51Cr-heparin

    Almeida, M.A.T.M. de.

    1979-01-01

    The kinetics of heparin in normal Wistar rats using the radioactive tracer 51 Cr, has been studied. The labeled and purified 51 Cr-heparin was injected into rats intravenously and by intraperitoneal injection. In measuring the radioactivity of organs it was possible to conclude that the tissues rich in mast cells, liver and spleen, were found to take up the greater amounts of heparin. The curve that represents the logarithm of the concentration of heparin versus time is biexponential. The half-lives of the two exponential were determined. The volume of distribution, the rate constant and the renal clearance were determined by the values of the plasma levels and urinary excretions. The biological half-time, the turnover rate and the turnover time were determined by measuring the residual radioactivity of the total body and urinary excretions. With the data obtained from the mentioned experiments a compartmental model was performed in which the plasma is the central compartment for the distribution of the drug, exchanging with another extraplasmatic compartment and finally the drug being stored in reticulo endothelial system cells. (Author) [pt

  2. Optimization of an Efficient and Sustainable Sonogashira Cross-Coupling Protocol

    Walter, Philipp E.

    2012-12-01

    Cross coupling reactions are a well-established tool in modern organic synthesis and play a crucial role in the synthesis of a high number of organic compounds. Their importance is highlighted by the Nobel Prize in chemistry to Suzuki, Heck and Negishi in 2010. The increasing importance of sustainability requirements in chemical production has furthermore promoted the development of cross-coupling protocols that comply with the principles of “Green Chemistry”1. The Sonogashira reaction is today the most versatile and powerful way to generate aryl alkynes, a moiety recurring in many pharmaceutical and natural products. Despite many improvements to the original reaction, reports on generally applicable protocols that work under sustainable conditions are scarce. Our group recently reported an efficient protocol for a copperfree Sonogashira cross-coupling at low temperature, in aqueous medium and with no addition of organic solvents or additives2. The goal of this work was to further investigate the effects of different reaction parameters on the catalytic activity in order to optimize the protocol. Limitations of the protocol were tested in respect to reaction temperature, heating method, atmosphere, base type and amount, catalyst loading, reaction time and work up procedure. The reaction worked successfully under air and results were not affected by the presence of oxygen in the water phase. Among a variety of bases tested, triethylamine was confirmed to give the best results and its required excess could be reduced from nine to four equivalents. Catalyst loading could also be reduced by up to 90%: Good to near quantitative yields for a broad range of substrates were achieved using a catalyst concentration of 0.25mol% and 5 eq of Et3N at 50°C while more reactive substrates could be coupled with a catalyst concentration as low as 0.025mol%. Filtration experiments showed the possibility of a simplified work up procedure and a protocol completely free of organic

  3. Efficient Supercapacitor Energy Storage Using Conjugated Microporous Polymer Networks Synthesized from Buchwald-Hartwig Coupling.

    Liao, Yaozu; Wang, Haige; Zhu, Meifang; Thomas, Arne

    2018-03-01

    Supercapacitors have received increasing interest as energy storage devices due to their rapid charge-discharge rates, high power densities, and high durability. In this work, novel conjugated microporous polymer (CMP) networks are presented for supercapacitor energy storage, namely 3D polyaminoanthraquinone (PAQ) networks synthesized via Buchwald-Hartwig coupling between 2,6-diaminoanthraquinone and aryl bromides. PAQs exhibit surface areas up to 600 m 2 g -1 , good dispersibility in polar solvents, and can be processed to flexible electrodes. The PAQs exhibit a three-electrode specific capacitance of 576 F g -1 in 0.5 m H 2 SO 4 at a current of 1 A g -1 retaining 80-85% capacitances and nearly 100% Coulombic efficiencies (95-98%) upon 6000 cycles at a current density of 2 A g -1 . Asymmetric two-electrode supercapacitors assembled by PAQs show a capacitance of 168 F g -1 of total electrode materials, an energy density of 60 Wh kg -1 at a power density of 1300 W kg -1 , and a wide working potential window (0-1.6 V). The asymmetric supercapacitors show Coulombic efficiencies up to 97% and can retain 95.5% of initial capacitance undergo 2000 cycles. This work thus presents novel promising CMP networks for charge energy storage. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Study of the Efficacy, Safety and Tolerability of Low-Molecular-Weight Heparin vs. Unfractionated Heparin as Bridging Therapy in Patients with Embolic Stroke due to Atrial Fibrillation.

    Feiz, Farnia; Sedghi, Reyhane; Salehi, Alireza; Hatam, Nahid; Bahmei, Jamshid; Borhani-Haghighi, Afshin

    2016-06-01

    Anticoagulation with adjusted dose warfarin is a well-accepted treatment for the prevention of recurrent stroke in patients with atrial fibrillation. Meanwhile, using bridging therapy with heparin or heparinoids before warfarin for initiation of anticoagulation is a matter of debate. We compared safety, efficacy, and tolerability of low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) as a bridging method in patients with recent ischemic stroke due to atrial fibrillation. This study was a randomized single-blind controlled trial in patients with acute ischemic stroke due to atrial fibrillation who were eligible for receiving warfarin and were randomly treated with 60 milligrams (mg) of LMWH (enoxaparin) subcutaneously every 12 h, or 1000 units/h of continuous intravenous heparin. The primary efficacy endpoints were recurrence of new ischemic stroke, myocardial infarction and/or death. The primary safety endpoint was central nervous system and/or systemic bleeding. Seventy-four subjects were recruited. Baseline demographic and clinical characteristics of two groups were matched. Composite endpoint outcome of new ischemic stroke, myocardial infarction, and/or death in follow-up period was seen in 10 subjects (27.03%) in UFH group and in four subjects (10.81%) in LMWH group (p value: 0.136). All hemorrhages and symptomatic central nervous system (CNS) hemorrhages in follow-up period were in 7 (18.9%) and 4 (10.8%) patients in UFH group, in 5 (13.5%), and 3 (8.1%) patients in LMWH group (p values: 0.754 and 0.751), respectively. Drop out and major adverse-effects such as heparin-induced thrombocytopenia and drug hypersensitivity were not seen in any patient. Enoxaparin can be a safe and efficient alternative for UFH as bridging therapy.

  5. Efficiency droop suppression of distance-engineered surface plasmon-coupled photoluminescence in GaN-based quantum well LEDs

    Yufeng Li

    2017-11-01

    Full Text Available Ag coated microgroove with extreme large aspect-ratio of 500:1 was fabricated on p-GaN capping layer to investigate the coupling behavior between quantum wells and surface plasmon in highly spatial resolution. Significant photoluminescence enhancement was observed when the distance between Ag film and QWs was reduced from 220 nm to about 20 nm. A maximum enhancement ratio of 18-fold was achieved at the groove bottom where the surface plasmonic coupling was considered the strongest. Such enhancement ratio was found highly affected by the excitation power density. It also shows high correlation to the internal quantum efficiency as a function of coupling effect and a maximum Purcell Factor of 1.75 was estimated at maximum coupling effect, which matches number calculated independently from the time-resolved photoluminescence measurement. With such Purcell Factor, the efficiency was greatly enhanced and the droop was significantly suppressed.

  6. Couplings

    Stošić, Dušan; Auroux, Aline

    Basic principles of calorimetry coupled with other techniques are introduced. These methods are used in heterogeneous catalysis for characterization of acidic, basic and red-ox properties of solid catalysts. Estimation of these features is achieved by monitoring the interaction of various probe molecules with the surface of such materials. Overview of gas phase, as well as liquid phase techniques is given. Special attention is devoted to coupled calorimetry-volumetry method. Furthermore, the influence of different experimental parameters on the results of these techniques is discussed, since it is known that they can significantly influence the evaluation of catalytic properties of investigated materials.

  7. Structural and binding studies of SAP-1 protein with heparin.

    Yadav, Vikash K; Mandal, Rahul S; Puniya, Bhanwar L; Kumar, Rahul; Dey, Sharmistha; Singh, Sarman; Yadav, Savita

    2015-03-01

    SAP-1 is a low molecular weight cysteine protease inhibitor (CPI) which belongs to type-2 cystatins family. SAP-1 protein purified from human seminal plasma (HuSP) has been shown to inhibit cysteine and serine proteases and exhibit interesting biological properties, including high temperature and pH stability. Heparin is a naturally occurring glycosaminoglycan (with varied chain length) which interacts with a number of proteins and regulates multiple steps in different biological processes. As an anticoagulant, heparin enhances inhibition of thrombin by the serpin antithrombin III. Therefore, we have employed surface plasmon resonance (SPR) to improve our understanding of the binding interaction between heparin and SAP-1 (protease inhibitor). SPR data suggest that SAP-1 binds to heparin with a significant affinity (KD = 158 nm). SPR solution competition studies using heparin oligosaccharides showed that the binding of SAP-1 to heparin is dependent on chain length. Large oligosaccharides show strong binding affinity for SAP-1. Further to get insight into the structural aspect of interactions between SAP-1 and heparin, we used modelled structure of the SAP-1 and docked with heparin and heparin-derived polysaccharides. The results suggest that a positively charged residue lysine plays important role in these interactions. Such information should improve our understanding of how heparin, present in the reproductive tract, regulates cystatins activity. © 2014 John Wiley & Sons A/S.

  8. One click dataset transfer: toward efficient coupling of distributed storage resources and CPUs

    Zerola, Michal; Šumbera, Michal; Lauret, Jérôme; Barták, Roman

    2012-01-01

    The massive data processing in a multi-collaboration environment with geographically spread diverse facilities will be hardly 'fair' to users and hardly using network bandwidth efficiently unless we address and deal with planning and reasoning related to data movement and placement. The needs for coordinated data resource sharing and efficient plans solving the data transfer paradigm in a dynamic way are being more required. We will present the work which purpose is to design and develop an automated planning system acting as a centralized decision making component with emphasis on optimization, coordination and load-balancing. We will describe the most important optimization characteristic and modeling approach based on 'constraints'. Constraint-based approach allows for a natural declarative formulation of what must be satisfied, without expressing how. The architecture of the system, communication between components and execution of the plan by underlying data transfer tools will be shown. We will emphasize the separation of the planner from the 'executors' and explain how to keep the proper balance between being deliberative and reactive. The extension of the model covering full coupling and reasoning about computing resources will be shown. The system has been deployed within STAR experiment over several Tier sites and has been used for data movement in the favour of user analyses or production processing. We will present several real use-case scenario and performance of the system with a comparison to the 'traditional' - solved by hands methods. The benefits in terms of indispensable shorter data delivery time due to leveraging available network paths and intermediate caches will be revealed. Finally, we will outline several possible enhancements and avenues for future work.

  9. Novel high-frequency energy-efficient pulsed-dc generator for capacitively coupled plasma discharge

    Mamun, Md Abdullah Al; Furuta, Hiroshi; Hatta, Akimitsu

    2018-03-01

    The circuit design, assembly, and operating tests of a high-frequency and high-voltage (HV) pulsed dc generator (PDG) for capacitively coupled plasma (CCP) discharge inside a vacuum chamber are reported. For capacitive loads, it is challenging to obtain sharp rectangular pulses with fast rising and falling edges, requiring intense current for quick charging and discharging. The requirement of intense current generally limits the pulse operation frequency. In this study, we present a new type of PDG consisting of a pair of half-resonant converters and a constant current-controller circuit connected with HV solid-state power switches that can deliver almost rectangular high voltage pulses with fast rising and falling edges for CCP discharge. A prototype of the PDG is assembled to modulate from a high-voltage direct current (HVdc) input into a pulsed HVdc output, while following an input pulse signal and a set current level. The pulse rise time and fall time are less than 500 ns and 800 ns, respectively, and the minimum pulse width is 1 µs. The maximum voltage for a negative pulse is 1000 V, and the maximum repetition frequency is 500 kHz. During the pulse on time, the plasma discharge current is controlled steadily at the set value. The half-resonant converters in the PDG perform recovery of the remaining energy from the capacitive load at every termination of pulse discharge. The PDG performed with a high energy efficiency of 85% from the HVdc input to the pulsed dc output at a repetition rate of 1 kHz and with stable plasma operation in various discharge conditions. The results suggest that the developed PDG can be considered to be more efficient for plasma processing by CCP.

  10. Novel high-frequency energy-efficient pulsed-dc generator for capacitively coupled plasma discharge.

    Mamun, Md Abdullah Al; Furuta, Hiroshi; Hatta, Akimitsu

    2018-03-01

    The circuit design, assembly, and operating tests of a high-frequency and high-voltage (HV) pulsed dc generator (PDG) for capacitively coupled plasma (CCP) discharge inside a vacuum chamber are reported. For capacitive loads, it is challenging to obtain sharp rectangular pulses with fast rising and falling edges, requiring intense current for quick charging and discharging. The requirement of intense current generally limits the pulse operation frequency. In this study, we present a new type of PDG consisting of a pair of half-resonant converters and a constant current-controller circuit connected with HV solid-state power switches that can deliver almost rectangular high voltage pulses with fast rising and falling edges for CCP discharge. A prototype of the PDG is assembled to modulate from a high-voltage direct current (HVdc) input into a pulsed HVdc output, while following an input pulse signal and a set current level. The pulse rise time and fall time are less than 500 ns and 800 ns, respectively, and the minimum pulse width is 1 µs. The maximum voltage for a negative pulse is 1000 V, and the maximum repetition frequency is 500 kHz. During the pulse on time, the plasma discharge current is controlled steadily at the set value. The half-resonant converters in the PDG perform recovery of the remaining energy from the capacitive load at every termination of pulse discharge. The PDG performed with a high energy efficiency of 85% from the HVdc input to the pulsed dc output at a repetition rate of 1 kHz and with stable plasma operation in various discharge conditions. The results suggest that the developed PDG can be considered to be more efficient for plasma processing by CCP.

  11. Efficient pump module coupling >1kW from a compact detachable fiber

    Dogan, M.; Chin, R. H.; Fulghum, S.; Jacob, J. H.; Chin, A. K.

    2018-02-01

    In the most developed fiber amplifiers, optical pump power is introduced into the 400μm-diameter, 0.46NA first cladding of the double-clad, Yb-doped, gain fiber, using a (6+1):1 multi-mode fiber combiner. For this configuration, the core diameter and numerical aperture of the pump delivery fibers have maximum values of 225μm and 0.22, respectively. This paper presents the first fiber-coupled laser-diode pump module emitting more than 1kW of claddingmode- stripped power from a detachable 225μm, 0.22NA delivery fiber at 976nm. The electrical-to-optical power conversion efficiency at 1kW is 50%. The FWHM spectral width at 1kW output is 4nm and has an excellent overlap with the narrow absorption spectrum of ytterbium in glass. Six of these pump modules attached to a (6+1):1 multimode combiner enable a 5-6kW, single-mode, Yb-doped fiber amplifier.

  12. Cross-scale Efficient Tensor Contractions for Coupled Cluster Computations Through Multiple Programming Model Backends

    Ibrahim, Khaled Z. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Computational Research Division; Epifanovsky, Evgeny [Q-Chem, Inc., Pleasanton, CA (United States); Williams, Samuel W. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Computational Research Division; Krylov, Anna I. [Univ. of Southern California, Los Angeles, CA (United States). Dept. of Chemistry

    2016-07-26

    Coupled-cluster methods provide highly accurate models of molecular structure by explicit numerical calculation of tensors representing the correlation between electrons. These calculations are dominated by a sequence of tensor contractions, motivating the development of numerical libraries for such operations. While based on matrix-matrix multiplication, these libraries are specialized to exploit symmetries in the molecular structure and in electronic interactions, and thus reduce the size of the tensor representation and the complexity of contractions. The resulting algorithms are irregular and their parallelization has been previously achieved via the use of dynamic scheduling or specialized data decompositions. We introduce our efforts to extend the Libtensor framework to work in the distributed memory environment in a scalable and energy efficient manner. We achieve up to 240 speedup compared with the best optimized shared memory implementation. We attain scalability to hundreds of thousands of compute cores on three distributed-memory architectures, (Cray XC30&XC40, BlueGene/Q), and on a heterogeneous GPU-CPU system (Cray XK7). As the bottlenecks shift from being compute-bound DGEMM's to communication-bound collectives as the size of the molecular system scales, we adopt two radically different parallelization approaches for handling load-imbalance. Nevertheless, we preserve a uni ed interface to both programming models to maintain the productivity of computational quantum chemists.

  13. Sensitive detection of oversulfated chondroitin sulfate in heparin sodium or crude heparin with a colorimetric microplate based assay.

    Sommers, Cynthia D; Mans, Daniel J; Mecker, Laura C; Keire, David A

    2011-05-01

    In this work we describe a 96-well microplate assay for oversulfated chondroitin sulfate A (OSCS) in heparin, based on a water-soluble cationic polythiophene polymer (3-(2-(N-(N'-methylimidazole))ethoxy)-4-methylthiophene (LPTP)) and heparinase digestion of heparin. The assay takes advantage of several unique properties of heparin, OSCS, and LPTP, including OSCS inhibition of heparinase I and II activity, the molecular weight dependence of heparin-LPTP spectral shifts, and the distinct association of heparin fragments and OSCS to LPTP. These factors combine to enable detection of the presence of 0.003% w/w spiked OSCS in 10 μg of heparin sodium active pharmaceutical ingredient (API) using a plate reader and with visual detection to 0.1% levels. The same detection limit for OSCS was observed in the presence of 10% levels of dermatan sulfate (DS) or chondroitin sulfate A (CSA) impurities. In addition, we surveyed a selection of crude heparin samples received by the agency in 2008 and 2009 to determine average and extreme DS, CSA, and galactosamine weight percent levels. In the presence of these impurities and the variable heparin content in the crude heparin samples, spiked OSCS was reliably detected to the 0.1% w/w level using a plate reader. Finally, authentically OSCS contaminated heparin sodium API and crude samples were distinguished visually by color from control samples using the LPTP/heparinase test.

  14. A spectroscopic study of interaction of cationic dyes with heparin

    R. Nandini

    2010-01-01

    Full Text Available The interaction of two cationic dyes namely, acridine orange and pinacyanol chloride with an anionic polyelectrolyte, heparin, has been investigated by spectrophotometric method.The polymer induced metachromasy in the dyes resulting in the shift of the absorption maxima of the dyes towards shorter wavelengths. The stability of the complexes formed between acridine orange and heparin was found to be lesser than that formed between pinacyanol chloride and heparin. This fact was further confirmed by reversal studies using alcohols, urea and surfactants. The interaction of acridine orange with heparin has also been investigated fluorimetrically.The interaction parameters revealed that binding between acridine orange and heparin arises due to electrostatic interaction while that between pinacyanol chloride and heparin is found to involve both electrostatic and hydrophobic forces. The effect of the structure of the dye in inducing metachromasy has also been discussed.

  15. A sensitive competitive binding assay for exogenous and endogenous heparins

    Dawes, J.; Pepper, D.S.

    1982-01-01

    A new type of assay for heparins has been devised, in which the test material competes with 125 I-labelled heparin for binding to protamine-Sepharose. The assay is very sensitive and will measure heparin concentrations down to 10 ng ml-1. It responds to both the degree of sulphation and the molecular weight of acidic polysaccharides, but is independent of their biological activities. It can be used to quantitate heparins in biological fluids after pretreatment of the samples with protease. In this way endogenous heparins were measured in normal human serum, plasma and urine. The assay is extremely versatile and has great potential for the investigation of endogenous and exogenous heparins

  16. Electrophoresis for the analysis of heparin purity and quality.

    Volpi, Nicola; Maccari, Francesca; Suwan, Jiraporn; Linhardt, Robert J

    2012-06-01

    The adulteration of raw heparin with oversulfated chondroitin sulfate (OSCS) in 2007-2008 produced a global crisis resulting in extensive revisions to the pharmacopeia monographs and prompting the FDA to recommend the development of additional methods for the analysis of heparin purity. As a consequence, a wide variety of innovative analytical approaches have been developed for the quality assurance and purity of unfractionated and low-molecular-weight heparins. This review discusses recent developments in electrophoresis techniques available for the sensitive separation, detection, and partial structural characterization of heparin contaminants. In particular, this review summarizes recent publications on heparin quality and related impurity analysis using electrophoretic separations such as capillary electrophoresis (CE) of intact polysaccharides and hexosamines derived from their acidic hydrolysis, and polyacrylamide gel electrophoresis (PAGE) for the separation of heparin samples without and in the presence of its relatively specific depolymerization process with nitrous acid treatment. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. A novel efficient coupled polynomial field interpolation scheme for higher order piezoelectric extension mode beam finite elements

    Sulbhewar, Litesh N; Raveendranath, P

    2014-01-01

    An efficient piezoelectric smart beam finite element based on Reddy’s third-order displacement field and layerwise linear potential is presented here. The present formulation is based on the coupled polynomial field interpolation of variables, unlike conventional piezoelectric beam formulations that use independent polynomials. Governing equations derived using a variational formulation are used to establish the relationship between field variables. The resulting expressions are used to formulate coupled shape functions. Starting with an assumed cubic polynomial for transverse displacement (w) and a linear polynomial for electric potential (φ), coupled polynomials for axial displacement (u) and section rotation (θ) are found. This leads to a coupled quadratic polynomial representation for axial displacement (u) and section rotation (θ). The formulation allows accommodation of extension–bending, shear–bending and electromechanical couplings at the interpolation level itself, in a variationally consistent manner. The proposed interpolation scheme is shown to eliminate the locking effects exhibited by conventional independent polynomial field interpolations and improve the convergence characteristics of HSDT based piezoelectric beam elements. Also, the present coupled formulation uses only three mechanical degrees of freedom per node, one less than the conventional formulations. Results from numerical test problems prove the accuracy and efficiency of the present formulation. (paper)

  18. Fe(HSO{sub 4}){sub 3} as an Efficient Catalyst for Diazotization and Diazo Coupling Reactions

    Rahimizadeh, Mohammad; Eshghi, Hossein; Shiri, Ali; Ghadamyari, Zohreh; Matin, Maryam M.; Pordeli, Parvaneh [Ferdowsi Univ. of Mashhad, Mashhad (Iran, Islamic Republic of); Oroojalian, Fatemeh [Univ. of Tehran, Tehran (Iran, Islamic Republic of)

    2012-12-15

    Diazo coupling reactions of aromatic amines with 2-naphthol in a green, efficient and easy procedure is described. Ferric hydrogensulfate catalyses this reaction in water at room temperature and short reaction time with high yields. The antibacterial activities of the synthesized compounds against four pathogenic bacteria are also investigated.

  19. Exploiting level anti-crossings for efficient and selective transfer of hyperpolarization in coupled nuclear spin systems

    Pravdivtsev, A.N.; Yurkovskaya, A.V.; Kaptein, R.; Miesel, K.; Vieth, H.-M.; Ivanov, K.L.

    2013-01-01

    Spin hyperpolarization can be coherently transferred to other nuclei in field-cycling NMR experiments. At low magnetic fields spin polarization is redistributed in a strongly coupled network of spins. Polarization transfer is most efficient at fields where level anti-crossings (LACs) occur for the

  20. Efficiency of a closed-coupled solar pasteurization system in treating roof harvested rainwater.

    Dobrowsky, P H; Carstens, M; De Villiers, J; Cloete, T E; Khan, W

    2015-12-01

    Many studies have concluded that roof harvested rainwater is susceptible to chemical and microbial contamination. The aim of the study was thus to conduct a preliminary investigation into the efficiency of a closed-coupled solar pasteurization system in reducing the microbiological load in harvested rainwater and to determine the change in chemical components after pasteurization. The temperature of the pasteurized tank water samples collected ranged from 55 to 57°C, 64 to 66°C, 72 to 74°C, 78 to 81°C and 90 to 91°C. Cations analyzed were within drinking water guidelines, with the exception of iron [195.59 μg/L (55°C)-170.1 μg/L (91°C)], aluminum [130.98 μg/L (78°C)], lead [12.81 μg/L (55°C)-13.2 μg/L (91°C)] and nickel [46.43 μg/L (55°C)-32.82 μg/L (78°C)], which were detected at levels above the respective guidelines in the pasteurized tank water samples. Indicator bacteria including, heterotrophic bacteria, Escherichia coli and total coliforms were reduced to below the detection limit at pasteurization temperatures of 72°C and above. However, with the use of molecular techniques Yersinia spp., Legionella spp. and Pseudomonas spp. were detected in tank water samples pasteurized at temperatures greater than 72°C. The viability of the bacteria detected in this study at the higher temperature ranges should thus be assessed before pasteurized harvested rainwater is used as a potable water source. In addition, it is recommended that the storage tank of the pasteurization system be constructed from an alternative material, other than stainless steel, in order for a closed-coupled pasteurization system to be implemented and produce large quantities of potable water from roof harvested rainwater. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Does ′heparin-induced thrombocytopenia′ hit our minds?

    Arun R Thangavel

    2016-01-01

    Full Text Available Unfractionated heparin is a widely used drug to prevent deep vein thrombosis and pulmonary emboli in patients at risk. With the advent of newer anticoagulants having lesser side effects, its use has diminished but not out of service. Here, we report a case of deep venous thrombosis, in a patient on prophylactic dose of heparin, which was later found to be a manifestation of heparin-induced thrombocytopenia (HIT. Thrombosis in the presence of heparin prophylaxis should be considered as HIT rather than a failure of anticoagulation.

  2. Immunomodulating effects of heparin on human B cell proliferation

    Wasik, Maria; Stepien-Sopniewska, Barbara; Gorski, Andrzej

    1993-01-01

    Recent data indicate that heparin may act as an immunomodulator. In this paper we have analyzed the effect of this agent on human B cell proliferation ''in vitro'' induced by ''S. aureus'' Cowan. The action of heparin is complex, but there was a trend for inhibition of B cell responses obtained from defibrinated but not heparinized blood samples. This suggest that heparin interacts with platelet products (growth factors, cytokines) and the results of such interactions determine the final effect. (author). 6 refs, 4 figs

  3. An efficient coupled polynomial interpolation scheme to eliminate material-locking in the Euler-Bernoulli piezoelectric beam finite element

    Litesh N. Sulbhewar

    Full Text Available The convergence characteristic of the conventional two-noded Euler-Bernoulli piezoelectric beam finite element depends on the configuration of the beam cross-section. The element shows slower convergence for the asymmetric material distribution in the beam cross-section due to 'material-locking' caused by extension-bending coupling. Hence, the use of conventional Euler-Bernoulli beam finite element to analyze piezoelectric beams which are generally made of the host layer with asymmetrically surface bonded piezoelectric layers/patches, leads to increased computational effort to yield converged results. Here, an efficient coupled polynomial interpolation scheme is proposed to improve the convergence of the Euler-Bernoulli piezoelectric beam finite elements, by eliminating ill-effects of material-locking. The equilibrium equations, derived using a variational formulation, are used to establish relationships between field variables. These relations are used to find a coupled quadratic polynomial for axial displacement, having contributions from an assumed cubic polynomial for transverse displacement and assumed linear polynomials for layerwise electric potentials. A set of coupled shape functions derived using these polynomials efficiently handles extension-bending and electromechanical couplings at the field interpolation level itself in a variationally consistent manner, without increasing the number of nodal degrees of freedom. The comparison of results obtained from numerical simulation of test problems shows that the convergence characteristic of the proposed element is insensitive to the material configuration of the beam cross-section.

  4. Battery Coupling Impact on the Antenna Efficiency in a Small Wearable Device

    Ruaro, Andrea; Thaysen, Jesper; Jakobsen, Kaj Bjarne

    2015-01-01

    Wearable electronics is often challenged by the extremely reduced space available to the antenna design. This study assesses the impact that the coupling to a large battery has on a small antenna for wearable devices. The coupling mechanism and its potential risks for the Electromagnetic...

  5. Efficient coupling of a single diamond color center to propagating plasmonic gap modes

    Kumar, Shailesh; Huck, Alexander; Andersen, Ulrik L

    2013-01-01

    We report on coupling of a single nitrogen-vacancy (NV) center in a nanodiamond to the propagating gap mode of two parallel placed chemically grown silver nanowires. The coupled NV-center nanowire system is made by manipulating nanodiamonds and nanowires with the tip of an atomic force microscope...

  6. Optimal elastic coupling in form of one mechanical spring to improve energy efficiency of walking bipedal robots

    Bauer, Fabian; Römer, Ulrich, E-mail: ulrich.roemer@kit.edu; Fidlin, Alexander; Seemann, Wolfgang [Institute of Engineering Mechanics, Karlsruhe Institute of Technology (Germany)

    2016-11-15

    This paper presents a method to optimize the energy efficiency of walking bipedal robots by more than 80 % in a speed range from 0.3 to 2.3 m/s using elastic couplings—mechanical springs with movement speed independent parameters. The considered planar robot consists of a trunk, two two-segmented legs, two actuators in the hip joints, two actuators in the knee joints and an elastic coupling between the shanks. It is modeled as underactuated system to make use of its natural dynamics and feedback controlled via input–output linearization. A numerical optimization of the joint angle trajectories as well as the elastic couplings is performed to minimize the average energy expenditure over the whole speed range. The elastic couplings increase the swing leg motion’s natural frequency thus making smaller steps more efficient which reduce the impact loss at the touchdown of the swing leg. The process of energy turnover is investigated in detail for the robot with and without elastic coupling between the shanks. Furthermore, the influences of the elastic couplings’ topology and of joint friction are analyzed. It is shown that the optimization of the robot’s motion and elastic coupling towards energy efficiency leads to a slightly slower convergence rate of the controller, yet no loss of stability, but a lower sensitivity with respect to disturbances. The optimal elastic coupling discovered via numerical optimization is a linear torsion spring with transmissions between the shanks. A design proposal for this elastic coupling—which does not affect the robot’s trunk and parallel shank motion and can be used to enhance an existing robot—is given for planar as well as spatial robots.

  7. Biochemical and microscopic evidence for the internalization and degradation of heparin-containing mast cell granules by bovine endothelial cells

    Atkins, F.M.; Friedman, M.M.; Metcalfe, D.D.

    1985-01-01

    Incubation of [ 35 S]heparin-containing mast cell granules with cultured bovine endothelial cells was followed by the appearance of 35 S-granule-associated radioactivity within the endothelial cells and a decrease in radioactivity in the extracellular fluid. These changes occurred during the first 24 hours of incubation and suggested ingestion of the mast cell granules by the endothelial cells. Periodic electron microscopic examination of the monolayers confirmed this hypothesis by demonstrating apposition of the granules to the plasmalemma of endothelial cells, which was followed by the engulfment of the granules by cytoplasmic projections. Under light microscopic examination, mast cell granules within endothelial cells then appeared to undergo degradation. The degradation of [ 35 S]heparin in mast cell granules was demonstrated by a decrease in the amount of intracellular [ 35 S]heparin proteoglycan after 24 hours and the appearance of free [ 35 S]sulfate in the extracellular compartment. Intact endothelial cells were more efficient at degrading [ 35 S]heparin than were cell lysates or cell supernatants. These data provide evidence of the ability of endothelial cells to ingest mast cell granules and degrade native heparin that is presented as a part of the mast cell granule

  8. Efficient simulations of fluid flow coupled with poroelastic deformations in pleated filters

    Calo, Victor M.; Iliev, Dimitar; Iliev, Oleg; Kirsch, Ralf; Lakdawala, Zahra; Printsypar, Galina

    2015-01-01

    model describes a free fluid flow coupled with a flow in porous media in a domain that contains the filtering media. To discretize the complex computational domain we use quadrilateral boundary fitted grids which resolve porous-fluid interfaces

  9. Efficient fiber-coupled single-photon sources based on quantum dots

    Daveau, Raphaël Sura

    refrigeration with coupled quantum wells. Many photonic quantum information processing applications would benet from a highbrightness, ber-coupled source of triggered single photons. This thesis presents a study of such sources based on quantum dots coupled to unidirectional photonic-crystal waveguide devices.......6 %. This latter method opens a promising future for increasing the eciency and reliability of planar chip-based single-photon sources. Refrigeration of a solid-state system with light has potential applications for cooling small-scale electronic and photonic circuits. We show theoretically that two coupled...... semiconductor quantum wells are ecient cooling media because they support long-lived indirect electron-hole pairs. These pairs can be thermally excited to distinct higher-energy states with faster radiative recombination, thereby creating an ecient escape channel to remove thermal energy from the system. From...

  10. SPECIFIC ASPECTS OF INTERACTION OF PLATELETS WITH THE HEPARINIZED MATERIALS

    E.A. Nemets

    2012-01-01

    Full Text Available Comparative analysis of anticoagulant nature on medical materials testing was done. It was found that change of citrate by heparin is accompanied by significant changes in platelet adhesion and activation. This results allowed us to arrive at a conclusion about reasonability of heparin usage as anticoagulant in in vitro testing. 

  11. 99m Tc-labeled heparin test in orthopaedic surgery

    Bouvier, J.F.; Lafon, J.C.; Colin, M.; Chatelut, J.; Beaubatie, F.

    1983-01-01

    99m Tc-labeled heparin test was performed for early detection of phlebitis or pulmonary embolism after orthopaedic prothesis. Heparinic treatment and surgery per se were demonstrated to have no effect on the results. If this test demonstrates a statistical difference for pathologic patients, it is of greater value to consider ratio between rates before and after intervention [fr

  12. Citrate Anticoagulation for CRRT in Children: Comparison with Heparin

    Sara Nicole Fernández

    2014-01-01

    Full Text Available Regional anticoagulation with citrate is an alternative to heparin in continuous renal replacement therapies, which may prolong circuit lifetime and decrease hemorrhagic complications. A retrospective comparative cohort study based on a prospective observational registry was conducted including critically ill children undergoing CRRT. Efficacy, measured as circuit survival, and secondary effects of heparin and citrate were compared. 12 patients on CRRT with citrate anticoagulation and 24 patients with heparin anticoagulation were analyzed. Median citrate dose was 2.6 mmol/L. Median calcium dose was 0.16 mEq/kg/h. Median heparin dose was 15 UI/kg/h. Median circuit survival was 48 hours with citrate and 31 hours with heparin (P=0.028. 66.6% of patients treated with citrate developed mild metabolic alkalosis, which was directly related to citrate dose. There were no cases of citrate intoxication: median total calcium/ionic calcium index (CaT/I of 2.16 and a maximum CaT/I of 2.33, without metabolic acidosis. In the citrate group, 45.5% of patients developed hypochloremia and 27.3% hypomagnesemia. In the heparin group, 27.8% developed hypophosphatemia. Three patients were moved from heparin to citrate to control postoperatory bleeding. In conclusion citrate is a safe and effective anticoagulation method for CRRT in children and it achieves longer circuit survival than heparin.

  13. Heparin release from thermosensitive polymer coatings: in vivo studies

    Gutowska, Anna; Bae, You Han; Jacobs, Harvey; Mohammad, Fazal; Mix, Donald; Feijen, Jan; Kim, Sung Wan

    1995-01-01

    Biomer/poly(N-isopropylacrylamide)/[poly(NiPAAm)] thermosensitive polymer blends were prepared and their application as heparin-releasing polymer coatings for the prevention of surface-induced thrombosis was examined. The advantage of using poly(NiPAAm)-based coatings as heparin-releasing polymers

  14. Heparin-induced thrombocytopenia: real-world issues.

    Linkins, Lori-Ann; Warkentin, Theodore E

    2011-09-01

    Heparin-induced thrombocytopenia (HIT) is a prothrombotic drug reaction caused by platelet-activating antibodies. HIT sera often activate platelets without needing heparin-such heparin-"independent" platelet activation can be associated with HIT beginning or worsening despite stopping heparin ("delayed-onset HIT"). We address important issues in HIT diagnosis and therapy, using a recent cohort of HIT patients to illustrate influences of heparin type; triggers for HIT investigation; serological features of heparin-independent platelet activation; and treatment. In our cohort of recent HIT cases ( N = 13), low-molecular-weight heparin (dalteparin) was a common causative agent ( N = 8, 62%); most patients were diagnosed after HIT-thrombosis had occurred; and danaparoid was the most frequently selected treatment. Heparin-independent platelet activation was common (7/13 [54%]) and predicted slower platelet count recovery (>1 week) among evaluable patients (5/5 vs 1/6; P = 0.015). In our experience with argatroban-treated patients, HIT-associated consumptive coagulopathy confounds anticoagulant monitoring. Our observations provide guidance on practical aspects of HIT diagnosis and management. Thieme Medical Publishers.

  15. Anticoagulant effect of low molecular weight heparin on central ...

    Purpose: To analyse the effect of low molecular weight heparin on venous catheters in haemodialysis patients. Methods: This study included 140 eligible patients who were randomly and evenly divided into two groups, viz, a study group that received low molecular weight heparin and a control group that received ...

  16. Experimental realization of highly efficient broadband coupling of single quantum dots to a photonic crystal waveguide

    Lund-Hansen, Toke; Stobbe, Søren; Julsgaard, Brian

    2008-01-01

    We present time-resolved spontaneous emission measurements of single quantum dots embedded in photonic crystal waveguides. Quantum dots that couple to a photonic crystal waveguide are found to decay up to 27 times faster than uncoupled quantum dots. From these measurements -factors of up to 0.89 ...... taking into account that the light-matter coupling is strongly enhanced due to the significant slow-down of light in the photonic crystal waveguides....

  17. Efficient spin filtering in a disordered semiconductor superlattice in the presence of Dresselhaus spin-orbit coupling

    Khayatzadeh Mahani, Mohammad Reza; Faizabadi, Edris

    2008-01-01

    The influence of the Dresselhaus spin-orbit coupling on spin polarization by tunneling through a disordered semiconductor superlattice was investigated. The Dresselhaus spin-orbit coupling causes the spin polarization of the electron due to transmission possibilities difference between spin up and spin down electrons. The electron tunneling through a zinc-blende semiconductor superlattice with InAs and GaAs layers and two variable distance In x Ga (1-x) As impurity layers was studied. One hundred percent spin polarization was obtained by optimizing the distance between two impurity layers and impurity percent in disordered layers in the presence of Dresselhaus spin-orbit coupling. In addition, the electron transmission probability through the mentioned superlattice is too much near to one and an efficient spin filtering was recommended

  18. A 65 nm CMOS high efficiency 50 GHz VCO with regard to the coupling effect of inductors

    Ye Yu; Tian Tong

    2013-01-01

    A 50 GHz cross-coupled voltage controlled oscillator (VCO) considering the coupling effect of inductors based on a 65 nm standard complementary metal oxide semiconductor (CMOS) technology is reported. A pair of inductors has been fabricated, measured and analyzed to characterize the coupling effects of adjacent inductors. The results are then implemented to accurately evaluate the VCO's LC tank. By optimizing the tank voltage swing and the buffer's operation region, the VCO achieves a maximum efficiency of 11.4% by generating an average output power of 2.5 dBm while only consuming 19.7 mW (including buffers). The VCO exhibits a phase noise of −87 dBc/Hz at 1 MHz offset, leading to a figure of merit (FoM) of −167.5 dB/Hz and a tuning range of 3.8% (from 48.98 to 50.88 GHz). (semiconductor integrated circuits)

  19. Efficient modeling of reactive transport phenomena by a multispecies random walk coupled to chemical equilibrium

    Pfingsten, W.

    1996-01-01

    Safety assessments for radioactive waste repositories require a detailed knowledge of physical, chemical, hydrological, and geological processes for long time spans. In the past, individual models for hydraulics, transport, or geochemical processes were developed more or less separately to great sophistication for the individual processes. Such processes are especially important in the near field of a waste repository. Attempts have been made to couple at least two individual processes to get a more adequate description of geochemical systems. These models are called coupled codes; they couple predominantly a multicomponent transport model with a chemical reaction model. Here reactive transport is modeled by the sequentially coupled code MCOTAC that couples one-dimensional advective, dispersive, and diffusive transport with chemical equilibrium complexation and precipitation/dissolution reactions in a porous medium. Transport, described by a random walk of multispecies particles, and chemical equilibrium calculations are solved separately, coupled only by an exchange term. The modular-structured code was applied to incongruent dissolution of hydrated silicate gels, to movement of multiple solid front systems, and to an artificial, numerically difficult heterogeneous redox problem. These applications show promising features with respect to applicability to relevant problems and possibilities of extensions

  20. Numerical modelling of methane oxidation efficiency and coupled water-gas-heat reactive transfer in a sloping landfill cover.

    Feng, S; Ng, C W W; Leung, A K; Liu, H W

    2017-10-01

    Microbial aerobic methane oxidation in unsaturated landfill cover involves coupled water, gas and heat reactive transfer. The coupled process is complex and its influence on methane oxidation efficiency is not clear, especially in steep covers where spatial variations of water, gas and heat are significant. In this study, two-dimensional finite element numerical simulations were carried out to evaluate the performance of unsaturated sloping cover. The numerical model was calibrated using a set of flume model test data, and was then subsequently used for parametric study. A new method that considers transient changes of methane concentration during the estimation of the methane oxidation efficiency was proposed and compared against existing methods. It was found that a steeper cover had a lower oxidation efficiency due to enhanced downslope water flow, during which desaturation of soil promoted gas transport and hence landfill gas emission. This effect was magnified as the cover angle and landfill gas generation rate at the bottom of the cover increased. Assuming the steady-state methane concentration in a cover would result in a non-conservative overestimation of oxidation efficiency, especially when a steep cover was subjected to rainfall infiltration. By considering the transient methane concentration, the newly-modified method can give a more accurate oxidation efficiency. Copyright © 2017. Published by Elsevier Ltd.

  1. Use of heparin in the investigation of obscure gastrointestinal bleeding

    Mernagh, J.R.; O'Donovan, N.; Somers, S.; Gill, G.; Sridhar, S.

    2001-01-01

    To determine if the administration of heparin improves the predictive value of angiography in the investigation of obscure gastrointestinal (GI) bleeding. 18 patients with a history of chronic GI bleeding were investigated with angiography. For 6 patients, the cause of GI bleeding was established with angiography; the 12 patients who had negative results were given heparin for 24 h and were reassessed with angiography. After heparin administration, the source of GI bleeding was determined with angiography for 6 of the remaining 12 patients. Thus, heparinization increased diagnostic yield from 33% (6 of 18) to 67% (12 of 18). No significant complications, such as uncontrolled GI bleeding, occurred. Heparinization improves the diagnostic yield of angiography when obscure GI bleeding is being investigated. (author)

  2. Interface COMSOL-PHREEQC (iCP), an efficient numerical framework for the solution of coupled multiphysics and geochemistry

    Nardi, Albert; Idiart, Andrés; Trinchero, Paolo; de Vries, Luis Manuel; Molinero, Jorge

    2014-08-01

    This paper presents the development, verification and application of an efficient interface, denoted as iCP, which couples two standalone simulation programs: the general purpose Finite Element framework COMSOL Multiphysics® and the geochemical simulator PHREEQC. The main goal of the interface is to maximize the synergies between the aforementioned codes, providing a numerical platform that can efficiently simulate a wide number of multiphysics problems coupled with geochemistry. iCP is written in Java and uses the IPhreeqc C++ dynamic library and the COMSOL Java-API. Given the large computational requirements of the aforementioned coupled models, special emphasis has been placed on numerical robustness and efficiency. To this end, the geochemical reactions are solved in parallel by balancing the computational load over multiple threads. First, a benchmark exercise is used to test the reliability of iCP regarding flow and reactive transport. Then, a large scale thermo-hydro-chemical (THC) problem is solved to show the code capabilities. The results of the verification exercise are successfully compared with those obtained using PHREEQC and the application case demonstrates the scalability of a large scale model, at least up to 32 threads.

  3. Efficiency of conscious access improves with coupling of slow and fast neural oscillations.

    Nakatani, Chie; Raffone, Antonino; van Leeuwen, Cees

    2014-05-01

    Global workspace access is considered as a critical factor for the ability to report a visual target. A plausible candidate mechanism for global workspace access is coupling of slow and fast brain activity. We studied coupling in EEG data using cross-frequency phase-amplitude modulation measurement between delta/theta phases and beta/gamma amplitudes from two experimental sessions, held on different days, of a typical attentional blink (AB) task, implying conscious access to targets. As the AB effect improved with practice between sessions, theta-gamma and theta-beta coupling increased generically. Most importantly, practice effects observed in delta-gamma and delta-beta couplings were specific to performance on the AB task. In particular, delta-gamma coupling showed the largest increase in cases of correct target detection in the most challenging AB conditions. All these practice effects were observed in the right temporal region. Given that the delta band is the main frequency of the P3 ERP, which is a marker of global workspace activity for conscious access, and because the gamma band is involved in visual object processing, the current results substantiate the role of phase-amplitude modulation in conscious access to visual target representations.

  4. An efficient hydro-mechanical model for coupled multi-porosity and discrete fracture porous media

    Yan, Xia; Huang, Zhaoqin; Yao, Jun; Li, Yang; Fan, Dongyan; Zhang, Kai

    2018-02-01

    In this paper, a numerical model is developed for coupled analysis of deforming fractured porous media with multiscale fractures. In this model, the macro-fractures are modeled explicitly by the embedded discrete fracture model, and the supporting effects of fluid and fillings in these fractures are represented explicitly in the geomechanics model. On the other hand, matrix and micro-fractures are modeled by a multi-porosity model, which aims to accurately describe the transient matrix-fracture fluid exchange process. A stabilized extended finite element method scheme is developed based on the polynomial pressure projection technique to address the displacement oscillation along macro-fracture boundaries. After that, the mixed space discretization and modified fixed stress sequential implicit methods based on non-matching grids are applied to solve the coupling model. Finally, we demonstrate the accuracy and application of the proposed method to capture the coupled hydro-mechanical impacts of multiscale fractures on fractured porous media.

  5. XGC developments for a more efficient XGC-GENE code coupling

    Dominski, Julien; Hager, Robert; Ku, Seung-Hoe; Chang, Cs

    2017-10-01

    In the Exascale Computing Program, the High-Fidelity Whole Device Modeling project initially aims at delivering a tightly-coupled simulation of plasma neoclassical and turbulence dynamics from the core to the edge of the tokamak. To permit such simulations, the gyrokinetic codes GENE and XGC will be coupled together. Numerical efforts are made to improve the numerical schemes agreement in the coupling region. One of the difficulties of coupling those codes together is the incompatibility of their grids. GENE is a continuum grid-based code and XGC is a Particle-In-Cell code using unstructured triangular mesh. A field-aligned filter is thus implemented in XGC. Even if XGC originally had an approximately field-following mesh, this field-aligned filter permits to have a perturbation discretization closer to the one solved in the field-aligned code GENE. Additionally, new XGC gyro-averaging matrices are implemented on a velocity grid adapted to the plasma properties, thus ensuring same accuracy from the core to the edge regions.

  6. Efficient frequency-transient co-simulation of coupled heat-electromagnetic problems

    Kaufmann, C.; Günther, M.; Klagges, D.; Knorrenschild, M.; Richwin, M.; Schöps, S.; Maten, ter E.J.W.

    2012-01-01

    Background: With the recent advent of inductive charging systems all major automotive manufacturers develop concepts to wirelessly charge electric vehicles. E¿cient designs require virtual prototyping that accounts for electromagnetic and thermal ¿elds. The coupled simulations can be computationally

  7. Highly efficient hybrid energy generator: coupled organic photovoltaic device and randomly oriented electrospun poly(vinylidene fluoride) nanofiber.

    Park, Boongik; Lee, Kihwan; Park, Jongjin; Kim, Jongmin; Kim, Ohyun

    2013-03-01

    A hybrid architecture consisting of an inverted organic photovoltaic device and a randomly-oriented electrospun PVDF piezoelectric device was fabricated as a highly-efficient energy generator. It uses the inverted photovoltaic device with coupled electrospun PVDF nanofibers as tandem structure to convert solar and mechanical vibrations energy to electricity simultaneously or individually. The power conversion efficiency of the photovoltaic device was also significantly improved up to 4.72% by optimized processes such as intrinsic ZnO, MoO3 and active layer. A simple electrospinning method with the two electrode technique was adopted to achieve a high voltage of - 300 mV in PVDF piezoelectric fibers. Highly-efficient HEG using voltage adder circuit provides the conceptual possibility of realizing multi-functional energy generator whenever and wherever various energy sources are available.

  8. Bioinspired Heparin Nanosponge Prepared by Photo-crosslinking for Controlled Release of Growth Factors

    Choi, Won Il; Sahu, Abhishek; Vilos, Cristian

    2017-01-01

    to overcome these limitations. Herein, we have developed a thermosensitive heparin nanosponge (Hep-NS) by a one step photopolymerization reaction between diacrylated pluronic and thiolated heparin molecules. The amount of heparin in Hep-NS was precisely controlled by varying the heparin amount in the reaction...

  9. Energy Efficiency of an Intracavity Coupled, Laser-Driven Linear Accelerator Pumped by an External Laser

    Neil Na, Y.C.; Siemann, R.H.; SLAC; Byer, R.L.; Stanford U., Phys. Dept.

    2005-01-01

    We calculate the optimum energy efficiency of a laser-driven linear accelerator by adopting a simple linear model. In the case of single bunch operation, the energy efficiency can be enhanced by incorporating the accelerator into a cavity that is pumped by an external laser. In the case of multiple bunch operation, the intracavity configuration is less advantageous because the strong wakefield generated by the electron beam is also recycled. Finally, the calculation indicates that the luminosity of a linear collider based on such a structure is comparably small if high efficiency is desired

  10. Influence of heparin on radioimmunological assay of ACTH

    Dupouy, J.P.; Godaut, M.; Chatelain, A.

    1986-01-01

    1 - Heparin traps plasma ACTH, promoting the formation of aggregates with apparent high molecular weight as shown by chromatography on Sephadex G 50 fine columns. The percentage of 125 I-ACTH which appeared in the void volume of the column, increased linearly with the log. dose of heparin. 2 - Heparin at concentrations of up to 100 IU/ml does not impair ACTH adsorption on either silicic acid or Quso G 32 as well as further elution by acetic acid/acetone/water (I: 40: 59; V/V) or HCl O.I N. Silicic acid traps selectively ACTH but not heparin. 3 - Heparin interferes with direct RIA-ACTH in the plasma by decreasing 125 I-ACTH binding to the antibodies and modifying the slope of the standard curve. Unsuitable artefacts induced by heparin, as overestimation or underestimation of plasma ACTH levels by RIA, can be avoid by previous hormone extraction from heparinized plasmas. Such results emphasized the importance of the sample preparation in order to obtain consistent results [fr

  11. Heparin-associated thrombocytopenia: antibody binding specificity to platelet antigens.

    Lynch, D M; Howe, S E

    1985-11-01

    Sera from four patients with heparin-associated thrombocytopenia (HAT) were evaluated by a quantitative enzyme-linked immunosorbent assay (ELISA) to detect heparin-dependent serum platelet-bindable immunoglobulin (S-PBIg) and by Western blotting and immunoprecipitation to investigate the specificity of the antibody binding. All HAT sera showed mildly increased S-PBIg (mean, 7.8 fg per platelet; normal, less than 6.0 fg per platelet) to intact target platelets in the ELISA, which was markedly increased in the presence of heparin (mean, 20.9 fg per platelet). This increase was 20-fold greater than normal control sera, which showed a mean differential increase of only 0.5 fg per platelet. Immunoglobulin binding specificity to platelet antigens was investigated using sodium dodecyl sulfate-polyacrylamide gel electrophoresis of platelet lysate with transfer of the platelet fractions onto nitrocellulose strips (Western blotting) and subsequent immunoassay using HAT and normal sera. In the presence of heparin, the four HAT patients demonstrated increased binding of immunoglobulin to platelet antigens of apparent molecular weights of 180, 124, and 82 kd. Radiolabeled heparin when incubated with HAT sera, normal sera, or albumin blanks bound to platelet proteins of the same apparent molecular weights. These observations are consistent with current hypotheses suggesting that HAT antibody is directed to heparin-platelet complexes or, alternatively, that heparin induces conformational change of antigenic sites on the platelet membrane.

  12. A concise, efficient synthesis of sugar-based benzothiazoles through chemoselective intramolecular C-S coupling

    Shen, Chao; Xia, Haijun; Yan, Hua; Chen, Xinzhi; Ranjit, Sadananda; Xie, Xiaoji; Tan, Davin; Lee, Richmond; Yang, Yanmei; Xing, Bengang; Huang, Kuo-Wei; Zhang, Pengfei; Liu, Xiaogang

    2012-01-01

    in the efficiency and chemoselectivity of reaction. These fluorescent glycoconjugates can be observed to readily enter mammalian tumor cells and exhibit potential in vitro antitumor activity. This journal is © The Royal Society of Chemistry 2012.

  13. Effects of heparin on insulin binding and biological activity

    Kriauciunas, K.M.; Grigorescu, F.; Kahn, C.R.

    1987-01-01

    The effect of heparin, a polyanionic glycosaminoglycan known to alter the function of many proteins, on insulin binding and bioactivity was studied. Cultured human lymphocytes (IM-9) were incubated with varying concentrations of heparin, then extensively washed, and 125 I-labeled insulin binding was measured. Heparin at concentrations used clinically for anticoagulation (1-50 U/ml) inhibited binding in a dose-dependent manner; 50% inhibition of binding occurred with 5-10 U/ml. Scatchard analysis indicated that the decrease in binding was due to a decrease in both the affinity and the apparent number of available insulin receptors. The effect occurred within 10 min at 22 degrees C and persisted even after the cells were extensively washed. Inhibition of insulin binding also occurred when cells were preincubated with heparinized plasma or heparinized serum but not when cells were incubated with normal serum or plasma from blood anticoagulated with EDTA. By contrast, other polyanions and polycations, e.g., poly-L-glutamic acid, poly-L-lysine, succinylated poly-L-lysine, and histone, did not inhibit binding. Heparin also inhibited insulin binding in Epstein-Barr (EB) virus-transformed lymphocytes but had no effect on insulin binding to isolated adipocytes, human erythrocytes, or intact hepatoma cells. When isolated adipocytes were incubated with heparin, there was a dose-dependent inhibition of insulin-stimulated glucose oxidation and, to a lesser extent, of basal glucose oxidation. Although heparin has no effect on insulin binding to intact hepatoma cells, heparin inhibited both insulin binding and insulin-stimulated autophosphorylation in receptors solubilized from these cells

  14. Current Trends in Heparin Use During Arterial Vascular Interventional Radiology

    Durran, Alexandra C.; Watts, Christopher

    2012-01-01

    Purpose: This study was designed to assess the current use of heparinized saline and bolus doses of heparin in non-neurological interventional radiology and to determine whether consensus could be reached to produce guidance for heparin use during arterial vascular intervention. Methods: An interactive electronic questionnaire was distributed to members of the British Society of Interventional Radiology regarding their current practice in the use, dosage, and timing of heparin boluses and heparinized flushing solutions.ResultsA total of 108 completed questionnaires were received. More than 80% of respondents used heparinized saline with varying concentrations; the most prevalent was 1,000 IU/l (international units of heparin per liter) and 5,000 IU/l. Fifty-one percent of interventionalists use 3,000 IU as their standard bolus dose; however, the respondents were split regarding the timing of bolus dose with ∼60% administering it after arterial access is obtained and 40% after crossing the lesion. There was no consensus on altering dose according to body weight, and only 4% monitored clotting parameters. Conclusions: There seems to be some coherence among practicing interventionalists regarding heparin administration. We hypothesize that heparinized saline should be used at a recognized standard concentration of 1,000 IU/l as a flushing concentration in all arterial vascular interventions and that 3,000 IU bolus is considered the standard dose for straightforward therapeutic procedures and 5000 IU for complex, crural, and endovascular aneurysm repair work. The bolus should be given after arterial access is obtained to allow time for optimal anticoagulation to be achieved by the time of active intervention and stenting. Further research into clotting abnormalities following such interventional procedures would be an interesting quantifiable follow-up to this initial survey of opinions and practice.

  15. Out-coupling membrane for large-size organic light-emitting panels with high efficiency and improved uniformity

    Ding, Lei, E-mail: dinglei@sust.edu.cn [College of Electrical and Information Engineering, Shaanxi University of Science and Technology, Xi’an, Shaanxi 710021 (China); Wang, Lu-Wei [College of Electrical and Information Engineering, Shaanxi University of Science and Technology, Xi’an, Shaanxi 710021 (China); Zhou, Lei, E-mail: zhzhlei@gmail.com [Faculty of Mathematics and Physics, Huaiyin Institute of Technology, Huai' an 223003 (China); Zhang, Fang-hui [College of Electrical and Information Engineering, Shaanxi University of Science and Technology, Xi’an, Shaanxi 710021 (China)

    2016-12-15

    Highlights: • An out-coupling membrane embedded with a scattering film of SiO{sub 2} spheres and polyethylene terephthalate (PET) plastic was successfully developed for 150 × 150 mm{sup 2} OLEDs. • Remarkable enhancement in efficiency was achieved from the OLEDs with out- coupling membrane. • The uniformity of large-size GOLED lighting panel is remarkably improved. - Abstract: An out-coupling membrane embedded with a scattering film of SiO{sub 2} spheres and polyethylene terephthalate (PET) plastic was successfully developed for 150 × 150 mm{sup 2} green OLEDs. Comparing with a reference OLED panel, an approximately 1-fold enhancement in the forward emission was obtained with an out-coupling membrane adhered to the surface of the external glass substrate of the panel. Moreover, it was verified that the emission color at different viewing angles can be stabilized without apparent spectral distortion. Particularly, the uniformity of the large-area OLEDs was greatly improved. Theoretical calculation clarified that the improved performance of the lighting panels is primarily attributed to the effect of particle scattering.

  16. Efficient Substrate Noise Coupling Verification and Failure Analysis Methodology for Smart Power ICs in Automotive Applications

    Moursy , Yasser; Zou , Hao; Khalil , Raouf; Iskander , Ramy; Tisserand , Pierre; Ton , Dieu-My; Pasetti , Giuseppe; Louërat , Marie-Minerve

    2016-01-01

    International audience; This paper presents a methodology to analyze the substrate noise coupling and reduce their effects in smart power integrated circuits. This methodology considers the propagation of minority carriers in the substrate. Hence, it models the lateral bipolar junction transistors that are layout dependent and are not modeled in conventional substrate extraction tools. It allows the designer to simulate substrate currents and check their effects on circuits functionality. The...

  17. Analyses of Interactions Between Heparin and the Apical Surface Proteins of Plasmodium falciparum

    Kobayashi, Kyousuke; Takano, Ryo; Takemae, Hitoshi; Sugi, Tatsuki; Ishiwa, Akiko; Gong, Haiyan; Recuenco, Frances C.; Iwanaga, Tatsuya; Horimoto, Taisuke; Akashi, Hiroomi; Kato, Kentaro

    2013-11-01

    Heparin, a sulfated glycoconjugate, reportedly inhibits the blood-stage growth of the malaria parasite Plasmodium falciparum. Elucidation of the inhibitory mechanism is valuable for developing novel invasion-blocking treatments based on heparin. Merozoite surface protein 1 has been reported as a candidate target of heparin; however, to better understand the molecular mechanisms involved, we characterized the molecules that bind to heparin during merozoite invasion. Here, we show that heparin binds only at the apical tip of the merozoite surface and that multiple heparin-binding proteins localize preferentially in the apical organelles. To identify heparin-binding proteins, parasite proteins were fractionated by means of heparin affinity chromatography and subjected to immunoblot analysis with ligand-specific antibodies. All tested members of the Duffy and reticulocyte binding-like families bound to heparin with diverse affinities. These findings suggest that heparin masks the apical surface of merozoites and blocks interaction with the erythrocyte membrane after initial attachment.

  18. Simulation studies on the effect of positioning tolerances on optical coupling efficiency

    Pamidighantam, Ramana V.; Yeo, Yongkee; Sudharsanam, Krishnamachari; Lee, Sik Pong; Iyer, Mahadevan K.

    2002-08-01

    The development of Optoelectronic components for communications is converging towards access networks where device cost makes a significant impact on the market acceptance. Thus, the device design engineer needs to input assembly, fabrication and process constraints into the design at an early stage. The present study is part of a Project on Packaging of Optical Components that IME, Singapore has initiated as part of an ongoing Electronics Packaging Research Consortium with industry partnership. In the present study, the coupling of optical radiation from a laser diode to optical fiber is simulated for a fiber optic transmitter component development project. Different optical configurations based on direct coupling, spherical ball lenses, integral lensed fibers and thermally expanded fibers are created within the commercially available transmitter package space. The effect of optical element variables on the placement tolerance is analyzed and will be reported. The effect of alignment tolerances on the optical coupling is analyzed. Simulation results are presented recommending realizable alignment and placement tolerances to develop a low cost short range link distance transmitter.

  19. Increased accuracy in heparin and protamine administration decreases bleeding

    Runge, Marx; Møller, Christian H; Steinbrüchel, Daniel A

    2009-01-01

    Three to 5 percent of the patients undergoing cardiac surgery are reoperated because of bleeding. When a surgical cause can be excluded, heparin/protamine mismatch may be considered. Insufficient reversal of heparin and overdosing of protamine may cause postoperative bleeding. The purpose......). A reduced number of patients needed blood transfusions in the RxDx group, although this was not statistically significant (19% vs. 38%, respectively; p = .13). Initial heparin dose was significantly reduced in the RxDx group (250 mg; range, 100-375 mg) compared with the control group (300 mg; range, 200...

  20. A monomeric G protein-coupled receptor isolated in a high-density lipoprotein particle efficiently activates its G protein

    Whorton, Matthew R; Bokoch, Michael P; Rasmussen, Søren Gøgsig Faarup

    2007-01-01

    G protein-coupled receptors (GPCRs) respond to a diverse array of ligands, mediating cellular responses to hormones and neurotransmitters, as well as the senses of smell and taste. The structures of the GPCR rhodopsin and several G proteins have been determined by x-ray crystallography, yet...... the organization of the signaling complex between GPCRs and G proteins is poorly understood. The observations that some GPCRs are obligate heterodimers, and that many GPCRs form both homo- and heterodimers, has led to speculation that GPCR dimers may be required for efficient activation of G proteins. However......, technical limitations have precluded a definitive analysis of G protein coupling to monomeric GPCRs in a biochemically defined and membrane-bound system. Here we demonstrate that a prototypical GPCR, the beta2-adrenergic receptor (beta2AR), can be incorporated into a reconstituted high-density lipoprotein...

  1. Layer-by-Layer Heparinization of the Cell Surface by Using Heparin-Binding Peptide Functionalized Human Serum Albumin.

    Song, Guowei; Hu, Yaning; Liu, Yusheng; Jiang, Rui

    2018-05-20

    Layer-by-layer heparinization of therapeutic cells prior to transplantation is an effective way to inhibit the instant blood-mediated inflammatory reactions (IBMIRs), which are the major cause of early cell graft loss during post-transplantation. Here, a conjugate of heparin-binding peptide (HBP) and human serum albumin (HSA), HBP-HSA, was synthesized by using heterobifunctional crosslinker. After the first heparin layer was coated on human umbilical vein endothelial cells (HUVECs) by means of the HBP-polyethylene glycol-phospholipid conjugate, HBP-HSA and heparin were then applied to the cell surface sequentially to form multiple layers. The immobilization and retention of heparin were analyzed by confocal microscopy and flow cytometry, respectively, and the cytotoxity of HBP-HSA was further evaluated by cell viability assay. Results indicated that heparin was successfully introduced to the cell surface in a layer-by-layer way and retained for at least 24 h, while the cytotoxity of HBP-HSA was negligible at the working concentration. Accordingly, this conjugate provides a promising method for co-immobilization of heparin and HSA to the cell surface under physiological conditions with improved biocompatibility.

  2. Results of the HepZero study comparing heparin-grafted membrane and standard care show that heparin-grafted dialyzer is safe and easy to use for heparin-free dialysis

    Laville, Maurice; Dorval, Marc; Ros, Joan Fort; Fay, Renaud; Cridlig, Joelle; Nortier, Joelle L.; Juillard, Laurent; Debska-Slizien, Alicja; Lorente, Loreto Fernandez; Thibaudin, Damien; Franssen, Casper; Schulz, Michael; Moureau, Frederique; Loughraieb, Nathalie; Rossignol, Patrick

    2014-01-01

    Heparin is used to prevent clotting during hemodialysis, but heparin-free hemodialysis is sometimes needed to decrease the risk of bleeding. The HepZero study is a randomized, multicenter international controlled open-label trial comparing no-heparin hemodialysis strategies designed to assess

  3. Quantitative description of thermodynamic and kinetic properties of the platelet factor 4/heparin bonds

    Nguyen, Thi-Huong; Greinacher, Andreas; Delcea, Mihaela

    2015-05-01

    Heparin is the most important antithrombotic drug in hospitals. It binds to the endogenous tetrameric protein platelet factor 4 (PF4) forming PF4/heparin complexes which may cause a severe immune-mediated adverse drug reaction, so-called heparin-induced thrombocytopenia (HIT). Although new heparin drugs have been synthesized to reduce such a risk, detailed bond dynamics of the PF4/heparin complexes have not been clearly understood. In this study, single molecule force spectroscopy (SMFS) is utilized to characterize the interaction of PF4 with heparins of defined length (5-, 6-, 8-, 12-, and 16-mers). Analysis of the force-distance curves shows that PF4/heparin binding strength rises with increasing heparin length. In addition, two binding pathways in the PF4/short heparins (=8-mers) are identified. We provide a model for the PF4/heparin complexes in which short heparins bind to one PF4 tetramer, while long heparins bind to two PF4 tetramers. We propose that the interaction between long heparins and PF4s is not only due to charge differences as generally assumed, but also due to hydrophobic interaction between two PF4s which are brought close to each other by long heparin. This complicated interaction induces PF4/heparin complexes more stable than other ligand-receptor interactions. Our results also reveal that the boundary between antigenic and non-antigenic heparins is between 8- and 12-mers. These observations are particularly important to understand processes in which PF4-heparin interactions are involved and to develop new heparin-derived drugs.Heparin is the most important antithrombotic drug in hospitals. It binds to the endogenous tetrameric protein platelet factor 4 (PF4) forming PF4/heparin complexes which may cause a severe immune-mediated adverse drug reaction, so-called heparin-induced thrombocytopenia (HIT). Although new heparin drugs have been synthesized to reduce such a risk, detailed bond dynamics of the PF4/heparin complexes have not been clearly

  4. Mapping of low molecular weight heparins using reversed phase ion pair liquid chromatography-mass spectrometry.

    Li, Daoyuan; Chi, Lequan; Jin, Lan; Xu, Xiaohui; Du, Xuzhao; Ji, Shengli; Chi, Lianli

    2014-01-01

    Low molecular weight heparins (LMWHs) are structurally complex, highly sulfated and negatively charged, linear carbohydrate polymers prepared by chemical or enzymatic depolymerization of heparin. They are widely used as anticoagulant drugs possessing better bioavailability, longer half-life, and lower side effects than heparin. Comprehensive structure characterization of LMWHs is important for drug quality assurance, generic drug application, and new drug research and development. However, fully characterization of all oligosaccharide chains in LMWHs is not feasible for current available analytical technologies due to their structure complexity and heterogeneity. Fingerprinting profiling is an efficient way for LMWHs' characterization and comparison. In this work, we present a simple, sensitive, and powerful analytical approach for structural characterization of LMWHs. Two different LMWHs, enoxaparin and nadroparin, were analyzed using reversed phase ion pair electrospray ionization mass spectrometry (RPIP-ESI-MS). More than 200 components were identified, including major structures, minor structures, and process related impurities. This approach is robust for high resolution and complementary fingerprinting analysis of LMWHs. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Photovoltaic efficiency of intermediate band solar cells based on CdTe/CdMnTe coupled quantum dots

    Prado, Silvio J.; Marques, Gilmar E.; Alcalde, Augusto M.

    2017-11-01

    In this work we show the calculation of optimized efficiencies of intermediate band solar cells (IBSCs) based on Mn-doped II-VI CdTe/CdMnTe coupled quantum dot (QD) structures. We focus our attention on the combined effects of geometrical and Mn-doping parameters on optical properties and solar cell efficiency. In the framework of {k \\cdot p} theory, we accomplish detailed calculations of electronic structure, transition energies, optical selection rules and their corresponding intra- and interband oscillator strengths. With these results and by following the intermediate band model, we have developed a strategy which allows us to find optimal photovoltaic efficiency values. We also show that the effects of band admixture which can lead to degradation of optical transitions and reduction of efficiency can be partly minimized by a careful selection of the structural parameters and Mn-concentration. Thus, the improvement of band engineering is mandatory for any practical implementation of QD systems as IBSC hardware. Finally, our calculations show that it is possible to reach significant efficiency, up to  ∼26%, by selecting a restricted space of parameters such as quantum dot size and shape and Mn-concentration effects, to improve the modulation of optical absorption in the structures.

  6. Efficient genome editing by FACS enrichment of paired D10A Cas9 nickases coupled with fluorescent proteins.

    Gopalappa, Ramu; Song, Myungjae; Chandrasekaran, Arun Pandian; Das, Soumyadip; Haq, Saba; Koh, Hyun Chul; Ramakrishna, Suresh

    2018-05-31

    Targeted genome editing by clustered regularly interspaced short palindromic repeats (CRISPR-Cas9) raised concerns over off-target effects. The use of double-nicking strategy using paired Cas9 nickase has been developed to minimize off-target effects. However, it was reported that the efficiency of paired nickases were comparable or lower than that of either corresponding nuclease alone. Recently, we conducted a systematic comparison of the efficiencies of several paired Cas9 with their corresponding Cas9 nucleases and showed that paired D10A Cas9 nickases are sometimes more efficient than individual nucleases for gene disruption. However, sometimes the designed paired Cas9 nickases exhibited significantly lower mutation frequencies than nucleases, hampering the generation of cells containing paired Cas9 nickase-induced mutations. Here we implemented IRES peptide-conjugation of fluorescent protein to Cas9 nickase and subjected for fluorescence-activated cell sorting. The sorted cell populations are highly enriched with cells containing paired Cas9 nickase-induced mutations, by a factor of up to 40-fold as compared with the unsorted population. Furthermore, gene-disrupted single cell clones using paired nickases followed by FACS sorting strategy were generated highly efficiently, without compromising with its low off-target effects. We envision that our fluorescent protein coupled paired nickase-mediated gene disruption, facilitating efficient and highly specific genome editing in medical research.

  7. Photovoltaic efficiency of intermediate band solar cells based on CdTe/CdMnTe coupled quantum dots.

    Prado, Silvio J; Marques, Gilmar E; Alcalde, Augusto M

    2017-11-08

    In this work we show the calculation of optimized efficiencies of intermediate band solar cells (IBSCs) based on Mn-doped II-VI CdTe/CdMnTe coupled quantum dot (QD) structures. We focus our attention on the combined effects of geometrical and Mn-doping parameters on optical properties and solar cell efficiency. In the framework of [Formula: see text] theory, we accomplish detailed calculations of electronic structure, transition energies, optical selection rules and their corresponding intra- and interband oscillator strengths. With these results and by following the intermediate band model, we have developed a strategy which allows us to find optimal photovoltaic efficiency values. We also show that the effects of band admixture which can lead to degradation of optical transitions and reduction of efficiency can be partly minimized by a careful selection of the structural parameters and Mn-concentration. Thus, the improvement of band engineering is mandatory for any practical implementation of QD systems as IBSC hardware. Finally, our calculations show that it is possible to reach significant efficiency, up to  ∼26%, by selecting a restricted space of parameters such as quantum dot size and shape and Mn-concentration effects, to improve the modulation of optical absorption in the structures.

  8. Accuracy and Efficiency of a Coupled Neutronics and Thermal Hydraulics Model

    Pope, Michael A.; Mousseau, Vincent A.

    2009-01-01

    The accuracy requirements for modern nuclear reactor simulation are steadily increasing due to the cost and regulation of relevant experimental facilities. Because of the increase in the cost of experiments and the decrease in the cost of simulation, simulation will play a much larger role in the design and licensing of new nuclear reactors. Fortunately as the work load of simulation increases, there are better physics models, new numerical techniques, and more powerful computer hardware that will enable modern simulation codes to handle this larger workload. This manuscript will discuss a numerical method where the six equations of two-phase flow, the solid conduction equations, and the two equations that describe neutron diffusion and precursor concentration are solved together in a tightly coupled, nonlinear fashion for a simplified model of a nuclear reactor core. This approach has two important advantages. The first advantage is a higher level of accuracy. Because the equations are solved together in a single nonlinear system, the solution is more accurate than the traditional 'operator split' approach where the two-phase flow equations are solved first, the heat conduction is solved second and the neutron diffusion is solved third, limiting the temporal accuracy to 1st order because the nonlinear coupling between the physics is handled explicitly. The second advantage of the method described in this manuscript is that the time step control in the fully implicit system can be based on the timescale of the solution rather than a stability-based time step restriction like the material Courant. Results are presented from a simulated control rod movement and a rod ejection that address temporal accuracy for the fully coupled solution and demonstrate how the fastest timescale of the problem can change between the state variables of neutronics, conduction and two-phase flow during the course of a transient.

  9. Accuracy and Efficiency of a Coupled Neutronics and Thermal Hydraulics Model

    Vincent A. Mousseau; Michael A. Pope

    2007-01-01

    The accuracy requirements for modern nuclear reactor simulation are steadily increasing due to the cost and regulation of relevant experimental facilities. Because of the increase in the cost of experiments and the decrease in the cost of simulation, simulation will play a much larger role in the design and licensing of new nuclear reactors. Fortunately as the work load of simulation increases, there are better physics models, new numerical techniques, and more powerful computer hardware that will enable modern simulation codes to handle the larger workload. This manuscript will discuss a numerical method where the six equations of two-phase flow, the solid conduction equations, and the two equations that describe neutron diffusion and precursor concentration are solved together in a tightly coupled, nonlinear fashion for a simplified model of a nuclear reactor core. This approach has two important advantages. The first advantage is a higher level of accuracy. Because the equations are solved together in a single nonlinear system, the solution is more accurate than the traditional 'operator split' approach where the two-phase flow equations are solved first, the heat conduction is solved second and the neutron diffusion is solved third, limiting the temporal accuracy to 1st order because the nonlinear coupling between the physics is handled explicitly. The second advantage of the method described in this manuscript is that the time step control in the fully implicit system can be based on the timescale of the solution rather than a stability-based time step restriction like the material Courant. Results are presented from a simulated control rod movement and a rod ejection that address temporal accuracy for the fully coupled solution and demonstrate how the fastest timescale of the problem can change between the state variables of neutronics, conduction and two-phase flow during the course of a transient

  10. Efficient simulations of fluid flow coupled with poroelastic deformations in pleated filters

    Calo, Victor M.

    2015-04-27

    Pleated filters are broadly used for various applications. In certain cases, especially in solid-liquid separation case, the filtering media may get deflected and that may change the overall performance characteristics of the filter. From the modeling point of view, this is a challenging multiphysics problem, namely the interaction of the fluid with a so-called poroelastic structure. This work focuses on the development of an algorithm for the simulation of the Fluid Porous Structure Interaction (FPSI) problem in the case of pleated filtering media. The first part of the work is concerned with the development of a robust and accurate numerical method for solving the Stokes-Brinkman system of equations on quadrilateral grids. The mathematical model describes a free fluid flow coupled with a flow in porous media in a domain that contains the filtering media. To discretize the complex computational domain we use quadrilateral boundary fitted grids which resolve porous-fluid interfaces. The Stokes-Brinkman system of equations is discretized here using a sophisticated finite volume method, namely multi-point flux approximation (MPFA) O-method. MPFA is widely used, e.g., in solving scalar elliptic equations with full tensor and highly varying coefficients and/or solving on heterogeneous non-orthogonalgrids. Up to the authors’ knowledge, there was no investigation of MPFA discretization for Stokes-Brinkman problems, and this study aims to fill this gap. Some numerical experiments are presented in order to demonstrate the robustness of the proposed numerical algorithm[1]. The second part of this study focuses on the coupling of the flow model with the deflection of the filtering media. For the consideration of the FPSI problem in 3D, the classical Biot system describes coupled flow and deformations in a porous body due to difference in the upstream and downstream pressures. Solving the Biot system of equations is complicated and requires a significant amount of

  11. Efficient full wave code for the coupling of large multirow multijunction LH grills.

    Preinhaelter, Josef; Hillairet, J.; Milanesio, D.; Maggiora, R.; Urban, Jakub; Vahala, L.; Vahala, G.

    2017-01-01

    Roč. 57, č. 11 (2017), č. článku 116060. ISSN 0029-5515 R&D Projects: GA MŠk(CZ) 8D15001; GA MŠk(CZ) LM2015045 Institutional support: RVO:61389021 Keywords : lower hybrid waves * coupling * large multirow multijunction grills * tokamak * full-wave Subject RIV: BL - Plasma and Gas Discharge Physics OBOR OECD: Fluids and plasma physics (including surface physics) Impact factor: 3.307, year: 2016 http://iopscience.iop.org/article/10.1088/1741-4326/aa7f4f/meta

  12. Cosmic Microwave Background Polarization Detector with High Efficiency, Broad Bandwidth, and Highly Symmetric Coupling to Transition Edge Sensor Bolometers

    Wollack, E.; Cao, N.; Chuss, D.; Denis, K.; Hsieh, W.-T.; Moseley, S. Harvey; Schneider, G.; Stevenson, T.; Travers, D.; U-yen, K.

    2008-01-01

    Four probe antennas transfer signals from waveguide to microstrip lines. The probes not only provide broadband impedance matching, but also thermally isolate waveguide and detector. In addition, we developed a new photonic waveguide choke joint design, with four-fold symmetry, to suppress power leakage at the interface. We have developed facilities to test superconducting circuit elements using a cryogenic microwave probe station, and more complete systems in waveguide. We used the ring resonator shown below to measure a dielectric loss tangent 99% coupling efficiency over 30% fractional bandwidth.

  13. Efficient Geometry and Data Handling for Large-Scale Monte Carlo - Thermal-Hydraulics Coupling

    Hoogenboom, J. Eduard

    2014-06-01

    Detailed coupling of thermal-hydraulics calculations to Monte Carlo reactor criticality calculations requires each axial layer of each fuel pin to be defined separately in the input to the Monte Carlo code in order to assign to each volume the temperature according to the result of the TH calculation, and if the volume contains coolant, also the density of the coolant. This leads to huge input files for even small systems. In this paper a methodology for dynamical assignment of temperatures with respect to cross section data is demonstrated to overcome this problem. The method is implemented in MCNP5. The method is verified for an infinite lattice with 3x3 BWR-type fuel pins with fuel, cladding and moderator/coolant explicitly modeled. For each pin 60 axial zones are considered with different temperatures and coolant densities. The results of the axial power distribution per fuel pin are compared to a standard MCNP5 run in which all 9x60 cells for fuel, cladding and coolant are explicitly defined and their respective temperatures determined from the TH calculation. Full agreement is obtained. For large-scale application the method is demonstrated for an infinite lattice with 17x17 PWR-type fuel assemblies with 25 rods replaced by guide tubes. Again all geometrical detailed is retained. The method was used in a procedure for coupled Monte Carlo and thermal-hydraulics iterations. Using an optimised iteration technique, convergence was obtained in 11 iteration steps.

  14. A modified CAS-CI approach for an efficient calculation of magnetic exchange coupling constants

    Fink, Karin; Staemmler, Volker

    2013-09-01

    A modification of the conventional wavefunction-based CAS-CI method for the calculation of magnetic exchange coupling constants J in small molecules and transition metal complexes is presented. In general, CAS-CI approaches yield much too small values for J since the energies of the important charge transfer configurations are calculated with the ground state orbitals and are therefore much too high. In the present approach we improve these energies by accounting for the relaxation of the orbitals in the charge transfer configurations. The necessary relaxation energies R can be obtained in separate calculations using mononuclear or binuclear model systems. The method is applied to a few examples, small molecules, binuclear transition metal complexes, and bulk NiO. It allows to obtaining fairly reliable estimates for J at costs that are not higher than those of conventional CAS-CI calculations. Therefore, extended and very time-consuming perturbation theory (PT2), configuration interaction (CI), or coupled cluster (CC) schemes on top of the CAS-CI calculation can be avoided and the modified CAS-CI (MCAS-CI) approach can be applied to rather large systems.

  15. Magnetic exchange couplings from constrained density functional theory: an efficient approach utilizing analytic derivatives.

    Phillips, Jordan J; Peralta, Juan E

    2011-11-14

    We introduce a method for evaluating magnetic exchange couplings based on the constrained density functional theory (C-DFT) approach of Rudra, Wu, and Van Voorhis [J. Chem. Phys. 124, 024103 (2006)]. Our method shares the same physical principles as C-DFT but makes use of the fact that the electronic energy changes quadratically and bilinearly with respect to the constraints in the range of interest. This allows us to use coupled perturbed Kohn-Sham spin density functional theory to determine approximately the corrections to the energy of the different spin configurations and construct a priori the relevant energy-landscapes obtained by constrained spin density functional theory. We assess this methodology in a set of binuclear transition-metal complexes and show that it reproduces very closely the results of C-DFT. This demonstrates a proof-of-concept for this method as a potential tool for studying a number of other molecular phenomena. Additionally, routes to improving upon the limitations of this method are discussed. © 2011 American Institute of Physics

  16. Coupling molecular catalysts with nanostructured surfaces for efficient solar fuel production

    Jin, Tong

    Solar fuel generation via carbon dioxide (CO2) reduction is a promising approach to meet the increasing global demand for energy and to minimize the impact of energy consumption on climate change. However, CO2 is thermodynamically stable; its activation often requires the use of appropriate catalysts. In particular, molecular catalysts with well-defined structures and tunability have shown excellent activity in photochemical CO2 reduction. These homogenous catalysts, however, suffer from poor stability under photochemical conditions and difficulty in recycling from the reaction media. Heterogenized molecular catalysts, particularly those prepared by coupling molecular catalysts with solid-state surfaces, have attracted more attention in recent years as potential solutions to address the issues associated with molecular catalysts. In this work, solar CO2 reduction is investigated using systems coupling molecular catalysts with robust nanostructured surfaces. In Chapter 2, heterogenization of macrocyclic cobalt(III) and nickel (II) complexes on mesoporous silica surface was achieved by different methods. Direct ligand derivatization significantly lowered the catalytic activity of Co(III) complex, while grafting the Co(III) complex onto silica surface through Si-O-Co linkage resulted in hybrid catalysts with excellent activity in CO2 reduction in the presence of p-terphenyl as a molecular photosensitizer. An interesting loading effect was observed, in which the optimal activity was achieved at a medium Co(III) surface density. Heterogenization of the Ni(II) complex on silica surface has also been implemented, the poor photocatalytic activity of the hybrid catalyst can be attributed to the intrinsic nature of the homogeneous analogue. This study highlighted the importance of appropriate linking strategies in preparing functional heterogenized molecular catalysts. Coupling molecular complexes with light-harvesting surfaces could avoid the use of expensive molecular

  17. Heparin: The Silver Bullet of Aneurysmal Subarachnoid Hemorrhage?

    Nicolas K. Khattar

    2018-03-01

    Full Text Available Various neurological diseases have recently been associated with neuroinflammation and worsening outcomes. Subarachnoid hemorrhage has been shown to generate a potent neuroinflammatory response. Heparin is a potential effective anti-inflammatory agent to prevent initial injury as well as delayed neurological decline. Different mechanisms of action for heparin have been proposed including, but not limited to the binding and neutralization of oxyhemoglobin, decreased transcription and signal transduction of endothelin-1, inhibition of binding to vessel wall selectins and vascular leakage into the subarachnoid space as well as direct binding and neutralization of inflammatory molecules. With a reasonably safe side-effect profile, heparin has shown significant promise in small series in human studies of aneurysmal subarachnoid hemorrhage in decreasing both initial and delayed neurological injury. Further studies are needed to validate various neuroprotective features of heparin in subarachnoid hemorrhage as well as other disease states.

  18. Clinical effects of low-molecular-weight heparin combined with ...

    Tropical Journal of Pharmaceutical Research August 2016; 15 (8): 1787-1792 ... Keywords: Acute pancreatitis, Low-molecular-weight heparin, Multiple organ function syndrome,. APACHE II score ... mediators by lowering the expression of.

  19. Polymer optical fiber compound parabolic concentrator tip for enhanced coupling efficiency for fluorescence based glucose sensors

    Hassan, Hafeez Ul; Nielsen, Kristian; Aasmul, Søren

    2015-01-01

    We demonstrate that the light excitation and capturing efficiency of fluorescence based fiber-optical sensors can be significantly increased by using a CPC (Compound Parabolic Concentrator) tip instead of the standard plane-cut tip. We use Zemax modelling to find the optimum CPC tip profile...... and fiber length of a polymer optical fiber diabetes sensor for continuous monitoring of glucose levels. We experimentally verify the improved performance of the CPC tipped sensor and the predicted production tolerances. Due to physical size requirements when the sensor has to be inserted into the body...... a non-optimal fiber length of 35 mm is chosen. For this length an average improvement in efficiency of a factor of 1.7 is experimentally demonstrated and critically compared to the predicted ideal factor of 3 in terms of parameters that should be improved through production optimization....

  20. Limiting efficiency of generalized realistic c-Si solar cells coupled to ideal up-converters

    Johnson, Craig M.; Conibeer, Gavin J.

    2012-11-01

    The detailed balance model of photovoltaic up-conversion is revised for the specific case of a c-Si solar cell under the AM1.5G solar spectrum. The limiting efficiency of an ideal solar cell with a band gap of 1.117 eV may be increased from approximately 33% to 40% with ideal up-conversion. However, real solar cells do not demonstrate the step-function absorption characteristic assumed in the standard detailed balance model. Here, we use tabulated Si refractive index data to develop a generalized model of a realistic conventional c-Si solar cell. The model incorporates optical design and material parameters such as free carrier absorption that have a non-trivial impact on the operation of the up-conversion layer. While these modifications are shown to decrease the absolute limiting efficiency, the benefit of up-conversion is shown to be relatively greater.

  1. Polymer optical fiber compound parabolic concentrator tip for enhanced coupling efficiency for fluorescence based glucose sensors.

    Hassan, Hafeez Ul; Nielsen, Kristian; Aasmul, Soren; Bang, Ole

    2015-12-01

    We demonstrate that the light excitation and capturing efficiency of fluorescence based fiber-optical sensors can be significantly increased by using a CPC (Compound Parabolic Concentrator) tip instead of the standard plane-cut tip. We use Zemax modelling to find the optimum CPC tip profile and fiber length of a polymer optical fiber diabetes sensor for continuous monitoring of glucose levels. We experimentally verify the improved performance of the CPC tipped sensor and the predicted production tolerances. Due to physical size requirements when the sensor has to be inserted into the body a non-optimal fiber length of 35 mm is chosen. For this length an average improvement in efficiency of a factor of 1.7 is experimentally demonstrated and critically compared to the predicted ideal factor of 3 in terms of parameters that should be improved through production optimization.

  2. Study of ICRF wave propagation and plasma coupling efficiency in a linear magnetic mirror device

    Peng, S.Y.

    1991-07-01

    Ion Cyclotron Range of Frequency (ICRF) wave propagation in an inhomogeneous axial magnetic field in a cylindrical plasma-vacuum system has historically been inadequately modelled. Previous works either sacrifice the cylindrical geometry in favor of a simpler slab geometry, concentrate on the resonance region, use a single mode to represent the entire field structure, or examine only radial propagation. This thesis performs both analytical and computational studies to model the ICRF wave-plasma coupling and propagation problem. Experimental analysis is also conducted to compare experimental results with theoretical predictions. Both theoretical as well as experimental analysis are undertaken as part of the thesis. The theoretical studies simulate the propagation of ICRF waves in an axially inhomogeneous magnetic field and in cylindrical geometry. Two theoretical analysis are undertaken - an analytical study and a computational study. The analytical study treats the inhomogeneous magnetic field by transforming the (r,z) coordinate into another coordinate system (ρ,ξ) that allows the solution of the fields with much simpler boundaries. The plasma fields are then Fourier transformed into two coupled convolution-integral equations which are then differenced and solved for both the perpendicular mode number α as well as the complete EM fields. The computational study involves a multiple eigenmode computational analysis of the fields that exist within the plasma-vacuum system. The inhomogeneous axial field is treated by dividing the geometry into a series of transverse axial slices and using a constant dielectric tensor in each individual slice. The slices are then connected by longitudinal boundary conditions

  3. Heparin conjugated quantum dots for in vitro imaging applications.

    Maguire, Ciaran Manus; Mahfoud, Omar Kazem; Rakovich, Tatsiana; Gerard, Valerie Anne; Prina-Mello, Adriele; Gun'ko, Yurii; Volkov, Yuri

    2014-11-01

    In this work heparin-gelatine multi-layered cadmium telluride quantum dots (QDgel/hep) were synthesised using a novel 'one-pot' method. The QDs produced were characterised using various spectroscopic and physiochemical techniques. Suitable QDs were then selected and compared to thioglycolic acid stabilised quantum dots (QDTGA) and gelatine coated quantum dots (QDgel) for utilisation in in vitro imaging experiments on live and fixed permeabilised THP-1, A549 and Caco-2 cell lines. Exposure of live THP-1 cells to QDgel/hep resulted in localisation of the QDs to the nucleus of the cells. QDgel/hep show affinity for the nuclear compartment of fixed permeabilised THP-1 and A549 cells but remain confined to cytoplasm of fixed permeabilised Caco-2 cells. It is postulated that heparin binding to the CD11b receptor facilitates the internalisation of the QDs into the nucleus of THP-1 cells. In addition, the heparin layer may reduce the unfavourable thrombogenic nature of quantum dots observed in vivo. In this study, heparin conjugated quantum dots were found to have superior imaging properties compared to its native counterparts. The authors postulate that heparin binding to the CD11b receptor facilitates QD internalization to the nucleus, and the heparin layer may reduce the in vivo thrombogenic properties of quantum dots. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Travelling Wave Pulse Coupled Oscillator (TWPCO) Using a Self-Organizing Scheme for Energy-Efficient Wireless Sensor Networks.

    Al-Mekhlafi, Zeyad Ghaleb; Hanapi, Zurina Mohd; Othman, Mohamed; Zukarnain, Zuriati Ahmad

    2017-01-01

    Recently, Pulse Coupled Oscillator (PCO)-based travelling waves have attracted substantial attention by researchers in wireless sensor network (WSN) synchronization. Because WSNs are generally artificial occurrences that mimic natural phenomena, the PCO utilizes firefly synchronization of attracting mating partners for modelling the WSN. However, given that sensor nodes are unable to receive messages while transmitting data packets (due to deafness), the PCO model may not be efficient for sensor network modelling. To overcome this limitation, this paper proposed a new scheme called the Travelling Wave Pulse Coupled Oscillator (TWPCO). For this, the study used a self-organizing scheme for energy-efficient WSNs that adopted travelling wave biologically inspired network systems based on phase locking of the PCO model to counteract deafness. From the simulation, it was found that the proposed TWPCO scheme attained a steady state after a number of cycles. It also showed superior performance compared to other mechanisms, with a reduction in the total energy consumption of 25%. The results showed that the performance improved by 13% in terms of data gathering. Based on the results, the proposed scheme avoids the deafness that occurs in the transmit state in WSNs and increases the data collection throughout the transmission states in WSNs.

  5. Travelling Wave Pulse Coupled Oscillator (TWPCO) Using a Self-Organizing Scheme for Energy-Efficient Wireless Sensor Networks

    Hanapi, Zurina Mohd; Othman, Mohamed; Zukarnain, Zuriati Ahmad

    2017-01-01

    Recently, Pulse Coupled Oscillator (PCO)-based travelling waves have attracted substantial attention by researchers in wireless sensor network (WSN) synchronization. Because WSNs are generally artificial occurrences that mimic natural phenomena, the PCO utilizes firefly synchronization of attracting mating partners for modelling the WSN. However, given that sensor nodes are unable to receive messages while transmitting data packets (due to deafness), the PCO model may not be efficient for sensor network modelling. To overcome this limitation, this paper proposed a new scheme called the Travelling Wave Pulse Coupled Oscillator (TWPCO). For this, the study used a self-organizing scheme for energy-efficient WSNs that adopted travelling wave biologically inspired network systems based on phase locking of the PCO model to counteract deafness. From the simulation, it was found that the proposed TWPCO scheme attained a steady state after a number of cycles. It also showed superior performance compared to other mechanisms, with a reduction in the total energy consumption of 25%. The results showed that the performance improved by 13% in terms of data gathering. Based on the results, the proposed scheme avoids the deafness that occurs in the transmit state in WSNs and increases the data collection throughout the transmission states in WSNs. PMID:28056020

  6. A highly efficient surface plasmon polaritons excitation achieved with a metal-coupled metal-insulator-metal waveguide

    Hongyan Yang

    2014-12-01

    Full Text Available We propose a novel metal-coupled metal-insulator-metal (MC-MIM waveguide which can achieve a highly efficient surface plasmon polaritons (SPPs excitation. The MC-MIM waveguide is formed by inserting a thin metal film in the insulator of an MIM. The introduction of the metal film, functioning as an SPPs coupler, provides a space for the interaction between SPPs and a confined electromagnetic field of the intermediate metal surface, which makes energy change and phase transfer in the metal-dielectric interface, due to the joint action of incomplete electrostatic shielding effect and SPPs coupling. Impacts of the metal film with different materials and various thickness on SPPs excitation are investigated. It is shown that the highest efficient SPPs excitation is obtained when the gold film thickness is 60 nm. The effect of refractive index of upper and lower symmetric dielectric layer on SPPs excitation is also discussed. The result shows that the decay value of refractive index is 0.3. Our results indicate that this proposed MC-MIM waveguide may offer great potential in designing a new SPPs source.

  7. Surface biomimetic modification with laminin-loaded heparin/poly-L-lysine nanoparticles for improving the biocompatibility

    Liu, Tao, E-mail: 11140021@hyit.edu.cn [Jiangsu Provincial Key Laboratory for Interventional Medical Devices, Huaiyin Institute of Technology, Huai' an (China); Hu, Youdong [Department of Geriatrics, The Affiliated Huai' an Hospital of Xuzhou Medical College, Huai' an (China); Tan, Jianying [Key Lab. of Advanced Technology for Materials of Chinese Education Ministry, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu (China); Liu, Shihui [Jiangsu Provincial Key Laboratory for Interventional Medical Devices, Huaiyin Institute of Technology, Huai' an (China); Chen, Junying [Key Lab. of Advanced Technology for Materials of Chinese Education Ministry, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu (China); Guo, Xin; Pan, Changjiang [Jiangsu Provincial Key Laboratory for Interventional Medical Devices, Huaiyin Institute of Technology, Huai' an (China); Li, Xia, E-mail: xial_li@qq.com [Department of Geriatrics, The Affiliated Huai' an Hospital of Xuzhou Medical College, Huai' an (China)

    2017-02-01

    Late thrombus and restenosis caused by delayed endothelialization and insufficient biocompatibility of polymer coating continue to be the greatest limitations of drug-eluting stents. In this study, based on the specific structure of vascular basement membrane, a novel biomimetic nano-coating was constructed by incorporating laminin into electrostatic-assembled heparin/poly-L-lysine nanoparticles. Alteration of heparin and poly-L-lysine concentration ratio in a certain range has no significantly influence nanoparticle size, uniformity and stability, but may affect the chemical property and subsequently the binding efficiency to dopamine-coated titanium surface. By use of this feature, four different nanoparticles were synthesized and immobilized on titanium surface for creating gradient nanoparticle binding density. According to in vitro biocompatibility evaluation, the nanoparticle modified surfaces were found to effectively block coagulation pathway and reduce thrombosis formation. Moreover, NP10L and NP15L modified surface with relatively low heparin exposing density (4.9 to 7.1 μg/cm2) showed beneficial effect in selective promoting EPCs and ECs proliferation, as well as stimulating cell migration and NO synthesis. - Highlights: • A novel laminin-loaded anticoagulant nanoparticle was prepared and used for titanium surface modification. • The nanoparticle binding density was adjustable by alteration the concentration ratio of heparin and poly-L-lysine. • In a certain range of NPs density, the surface was found to selectively direct platelet and vascular cells behavior.

  8. Surface biomimetic modification with laminin-loaded heparin/poly-L-lysine nanoparticles for improving the biocompatibility

    Liu, Tao; Hu, Youdong; Tan, Jianying; Liu, Shihui; Chen, Junying; Guo, Xin; Pan, Changjiang; Li, Xia

    2017-01-01

    Late thrombus and restenosis caused by delayed endothelialization and insufficient biocompatibility of polymer coating continue to be the greatest limitations of drug-eluting stents. In this study, based on the specific structure of vascular basement membrane, a novel biomimetic nano-coating was constructed by incorporating laminin into electrostatic-assembled heparin/poly-L-lysine nanoparticles. Alteration of heparin and poly-L-lysine concentration ratio in a certain range has no significantly influence nanoparticle size, uniformity and stability, but may affect the chemical property and subsequently the binding efficiency to dopamine-coated titanium surface. By use of this feature, four different nanoparticles were synthesized and immobilized on titanium surface for creating gradient nanoparticle binding density. According to in vitro biocompatibility evaluation, the nanoparticle modified surfaces were found to effectively block coagulation pathway and reduce thrombosis formation. Moreover, NP10L and NP15L modified surface with relatively low heparin exposing density (4.9 to 7.1 μg/cm2) showed beneficial effect in selective promoting EPCs and ECs proliferation, as well as stimulating cell migration and NO synthesis. - Highlights: • A novel laminin-loaded anticoagulant nanoparticle was prepared and used for titanium surface modification. • The nanoparticle binding density was adjustable by alteration the concentration ratio of heparin and poly-L-lysine. • In a certain range of NPs density, the surface was found to selectively direct platelet and vascular cells behavior.

  9. Coupling R and PHREEQC: an interactive and extensible environment for efficient programming of geochemical models

    De Lucia, Marco; Kühn, Michael

    2013-04-01

    PHREEQC [1] is a widely used non-interactive open source software for speciation, batch-reactions, one-dimensional transport, and inverse geochemical caclulations. It represents the tool of choice for many researchers and practicioners for a broad set of geochemical problems, underground CO2 storage among others. Its open source nature, the flexibility to program arbitrary kinetic laws for the chemical reactions, as well as a thorough implementation of the Pitzer formalism explain its success and longevity. However, its non-interactive architecture make it cumbersome to couple PHREEQC to transport programs to achieve reactive transport simulations [2], but also to overcome the limitations of PHREEQC itself regarding the setup of large numbers of simulations - for example exploring wide ranges of conditions - and the graphical evaluation of the results. This has been the main motivation leading to the development of an interface with the high level language and environment for statistical computing and graphics GNU R [3]. The interface consists of minor modifications in PHREEQC's C source code, only affecting data I/O, plus on the R side a bunch of helper functions used to setup the simulations - basically automated manipulation of PHREEQC's input files, which are text files - and to collect and visualize the results. The most relevant subset of PHREEQC's capabilities and features are fully usable through the interface. Illustratory examples for the utility of this programmable interface were given in the framework of the research project this developement originated from: CLEAN [4], a project investigating the feasibility of enhanced gas recovery combined with CO2 storage. This interface allowed us to successfully and easily manipulate, compare and refit chemical databases, perform sensitivity analysis by combinatory variations of parameters, and all that in an environment which is both scriptable and interactive, with all results directly available for further

  10. Advanced nanocarriers based on heparin and its derivatives for cancer management.

    Yang, Xiaoye; Du, Hongliang; Liu, Jiyong; Zhai, Guangxi

    2015-02-09

    To obtain a satisfying anticancer effect, rationally designed nanocarriers are intensively studied. In this field, heparin and its derivatives have been widely attempted recently as potential component of nanocarriers due to their unique biological and physiochemical features, especially the anticancer activity. This review focuses on state-of-the-art nanocarriers with heparin/heparin derivatives as backbone or coating material. At the beginning, the unique advantages of heparin used in cancer nanotechnology are discussed. After that, different strategies of heparin chemical modification are reviewed, laying the foundation of developing various nanocarriers. Then a systematic summary of diverse nanoparticles with heparin as component is exhibited, involving heparin-drug conjugate, polymeric nanoparticles, nanogels, polyelectrolyte complex nanoparticles, and heparin-coated organic and inorganic nanoparticles. The application of these nanoparticles in various novel cancer therapy (containing targeted therapy, magnetic therapy, photodynamic therapy, and gene therapy) will be highlighted. Finally, future challenges and opportunities of heparin-based biomaterials in cancer nanotechnology are discussed.

  11. In vivo studies on the binding of heparin and its fractions with platelet factor 4

    Walz, D.A.; Hung, G.L.

    1985-01-01

    PF4 has a half-life in plasma of less than 3 minutes, and its rapid clearance appears to be a function of binding to the vascular endothelium. Once bound to the endothelium, PF4 can be released by heparin in a time-dependent manner; recovery is greater the sooner heparin is administered following PF4 infusion. This heparin-induced release of PF4 can be abolished if the heparin is first complexed with hexadimethrine bromide. Likewise, this heparin-induced release of PF4 is dependent upon the type of heparin used; low molecular weight heparin fractions and fragments do not cause the PF4 rebound seen with intact heparin. Thus, it would appear that low molecular weight forms of heparin are advantageous in that their in vivo administration would not be mediated by such platelet modulators as PF4

  12. An Efficient Explicit Finite-Difference Scheme for Simulating Coupled Biomass Growth on Nutritive Substrates

    G. F. Sun

    2015-01-01

    Full Text Available A novel explicit finite-difference (FD method is presented to simulate the positive and bounded development process of a microbial colony subjected to a substrate of nutrients, which is governed by a nonlinear parabolic partial differential equations (PDE system. Our explicit FD scheme is uniquely designed in such a way that it transfers the nonlinear terms in the original PDE into discrete sets of linear ones in the algebraic equation system that can be solved very efficiently, while ensuring the stability and the boundedness of the solution. This is achieved through (1 a proper design of intertwined FD approximations for the diffusion function term in both time and spatial variations and (2 the control of the time-step through establishing theoretical stability criteria. A detailed theoretical stability analysis is conducted to reveal that our FD method is indeed stable. Our examples verified the fact that the numerical solution can be ensured nonnegative and bounded to simulate the actual physics. Numerical examples have also been presented to demonstrate the efficiency of the proposed scheme. The present scheme is applicable for solving similar systems of PDEs in the investigation of the dynamics of biological films.

  13. Asymmetric flow field-flow fractionation coupled to inductively coupled plasma mass spectrometry for the quantification of quantum dots bioconjugation efficiency.

    Menéndez-Miranda, Mario; Encinar, Jorge Ruiz; Costa-Fernández, José M; Sanz-Medel, Alfredo

    2015-11-27

    Hyphenation of asymmetric flow field-flow fractionation (AF4) to an on-line elemental detection (inductively coupled plasma-mass spectrometry, ICP-MS) is proposed as a powerful diagnostic tool for quantum dots bioconjugation studies. In particular, conjugation effectiveness between a "model" monoclonal IgG antibody (Ab) and CdSe/ZnS core-shell Quantum Dots (QDs), surface-coated with an amphiphilic polymer, has been monitored here by such hybrid AF4-ICP-MS technique. Experimental conditions have been optimized searching for a proper separation between the sought bioconjugates from the eventual free reagents excesses employed during the bioconjugation (QDs and antibodies). Composition and pH of the carrier have been found to be critical parameters to ensure an efficient separation while ensuring high species recovery from the AF4 channel. An ICP-MS equipped with a triple quadropole was selected as elemental detector to enable sensitive and reliable simultaneous quantification of the elemental constituents, including sulfur, of the nanoparticulated species and the antibody. The hyphenated technique used provided nanoparticle size-based separation, elemental detection, and composition analysis capabilities that turned out to be instrumental in order to investigate in depth the Ab-QDs bioconjugation process. Moreover, the analytical strategy here proposed allowed us not only to clearly identify the bioconjugation reaction products but also to quantify nanoparticle:antibodies bioconjugation efficiency. This is a key issue in future development of analytical and bioanalytical photoluminescent QDs applications. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Tomato Yield and Water Use Efficiency - Coupling Effects between Growth Stage Specific Soil Water Deficits

    Chen, Si; Zhenjiang, Zhou; Andersen, Mathias Neumann

    2015-01-01

    To investigate the sensitivity of tomato yield and water use efficiency (WUE) to soil water content at different growth stages, the central composite rotatable design (CCRD) was employed in a five-factor-five-level pot experiment under regulated deficit irrigation. Two regression models concerning...... the effects of stage-specific soil water content on tomato yield and WUE were established. The results showed that the lowest available soil water (ASW) content (around 28%) during vegetative growth stage (here denoted θ1) resulted in high yield and WUE. Moderate (around 69% ASW) during blooming and fruit...... effects of ASW in two growth stages were between θ2 and θ5, θ3. In both cases a moderate θ2 was a precondition for maximum yield response to increasing θ5 and θ3. Sensitivity analysis revealed that yield was most sensitive to soil water content at fruit maturity (θ5). Numerical inspection...

  15. In vitro anticoagulation monitoring of low-molecular-weight heparin

    WANG Jian-qi; SHI Xu-bo; YANG Jin-gang; HU Da-yi

    2009-01-01

    Background Although low-molecular-weight heparin has replaced unfractionated heparin to become the primary anticoagulation drug for treatment of acute coronary syndrome, there is no convenient bedside monitoring method. We explored the best laboratory monitoring method of low-molecular-weight heparins (enoxapadn, dalteparin, and nadroparin) by use of the Sonoclot coagulation analyzer to monitor the activated clotting time.Methods Atotal of 20 healthy volunteers were selected and 15 ml of fasting venous blood samples were collected and incubated. Four coagulants, kaolin, diatomite, glass bead, and magnetic stick, were used to determine the activated clotting time of the low-molecular-weight heparins at different in vitro anti-Xa factor concentrations. A correlation analysis was made to obtain the regression equation. The activated clotting time of the different low-molecular-weight heparins with the same anti-Xa factor concentration was monitored when the coagulant glass beads were applied. Results The activated clotting time measured using the glass beads, diatomite, kaolin, and magnetic stick showed a linear correlation with the concentration of nadroparin (r= 0.964, 0.966, 0.970, and 0.947, respectively). The regression equation showed that the linear slopes of different coagulants were significantly different (glass beads 230.03 s/IU,diatomite 89.91 s/IU, kaolin 50.87 s/IU, magnetic stick could not be calculated). When the concentration of the anti-Xa factor was the same for different low-molecular-weight heparins, the measured activated clotting time was different after the application of the glass bead coagulant.Conclusions The glass bead coagulant is most feasible for monitoring the in vitro anticoagulation activity of nadroparin.The different effects of different low-molecular-weight heparins on the activated clotting time may be related to the different anti-Ila activities.

  16. Profiling Heparin-Chemokine Interactions Using Synthetic Tools

    de Paz, Jose L.; Moseman, E. Ashley; Noti, Christian; Polito, Laura; von Andrian, Ulrich H.; Seeberger, Peter H.

    2009-01-01

    Glycosaminoglycans (GAGs), such as heparin or heparan sulfate, are required for the in vivo function of chemokines. Chemokines play a crucial role in the recruitment of leukocyte subsets to sites of inflammation and lymphocytes trafficking. GAG-chemokine interactions mediate cell migration and determine which leukocyte subsets enter tissues. Identifying the exact GAC sequences that bind to particular chemokines is key to understand chemokine function at the molecular level and develop strategies to interfere with chemokine-mediated processes. Here, we characterize the heparin binding profiles of eight chemokines (CCL21, IL-8, CXCL12, CXCL13, CCL19, CCL25, CCL28, and CXCL16) by employing heparin microarrays containing a small library of synthetic heparin oligosaccharides. The chemokines differ significantly in their interactions with heparin oligosaccharides: While some chemokines, (e.g., CCL21) strongly bind to a hexasaccharide containing the GlcNSO3(6-OSO3)-IdoA(2-OSO3) repeating unit, CCL19 does not bind and CXCL12 binds only weakly. The carbohydrate microarray binding results were validated by surface plasmon resonance experiments. In vitro chemotaxis assays revealed that dendrimers coated with the fully sulfated heparin hexasaccharide inhibit lymphocyte migration toward CCL21. Migration toward CXCL12 or CCL19 was not affected. These in vitro homing assays indicate that multivalent synthetic heparin dendrimers inhibit the migration of lymphocytes toward certain chemokine gradients by blocking the formation of a chemokine concentration gradient on GAG endothelial chains. These findings are in agreement with preliminary in vivo measurements of circulating lymphocytes. The results presented here contribute to the understanding of GAG-chemokine interactions, a first step toward the design of novel drugs that modulate chemokine activity. PMID:18030990

  17. An efficient spectrofluorimetric method adopts doxazosin, terazosin and alfuzosin coupling with orthophthalaldehyde: Application in human plasma

    Omar, Mahmoud A.; Mohamed, Abdel-Maaboud I.; Derayea, Sayed M.; Hammad, Mohamed A.; Mohamed, Abobakr A.

    2018-04-01

    A new, selective and sensitive spectrofluorimetric method was designed for the quantitation of doxazosin (DOX), terazosin (TER) and alfuzosin (ALF) in their dosage forms and human plasma. The method adopts efficient derivatization of the studied drugs with ortho-phthalaldehyde (OPA), in the presence of 2-mercaptoethanol in borate buffer (pH 9.7) to generate a highly fluorescent isoindole derivatives, which can strongly enhance the fluorescence intensities of the studied drugs, allowing their sensitive determination at 430 nm after excitation at 337 nm. The fluorescence-concentration plots were rectilinear over the ranges (10.0-400.0) ng/mL. Detection and quantification limits were found to be (0.52-3.88) and (1.59-11.76) ng/mL, respectively. The proposed method was validated according to ICH guidelines, and successfully applied for the determination of pharmaceutical preparations of the studied drugs. Moreover, the high sensitivity of the proposed method permits its successful application to the analysis of the studied drugs in spiked human plasma with % recovery (96.12 ± 1.34-100.66 ± 0.57, n = 3). A proposal for the reaction mechanism was presented.

  18. Disappearance of a low molecular weight heparin fraction (CY 216) differs from standard heparin in rabbits

    Boneu, B.; Buchanan, M.R.; Caranobe, C.; Gabaig, A.M.; Dupouy, D.; Sie, P.; Hirsh, J.

    1987-01-01

    In previous studies, we have reported that standard heparin (SH) was cleared by two mechanisms, a saturable mechanism which predominated at low doses (less than 100 anti-factor Xa U/kg) and a non-saturable mechanism which predominated at higher doses, when the first mechanism became saturated. In this study, we examined the importance of these two mechanisms in the disappearance of a low molecular weight heparin fraction (LMWH) (CY 216), by comparing the pharmacokinetics and the pharmacodynamics of a wide range of doses of SH and CY 216 (1.5 to 500 anti-factor Xa U/kg). Pharmacokinetics was measured as the disappearance of 125 I-radiolabelled SH or CY 216. Pharmacodynamics was measured as the disappearance of the anti-factor Xa activity of SH and CY 216. We found that the saturable mechanism contributed little to the disappearance of CY 216 and that it was cleared predominantly by the non-saturable mechanism at all doses tested. Thus, at low doses (less than 100 anti-factor Xa U/kg), SH was cleared more rapidly than CY 216, whereas at higher doses, CY 216 was cleared more rapidly than SH. We conclude that the mechanism of disappearance of LMWH's differ significantly from those of SH, and that this difference may explain the apparent prolonged anticoagulant activity of LMWH's within the therapeutic range doses

  19. Heparin induces an accumulation of atherogenic lipoproteins during hemodialysis in normolipidemic end-stage renal disease patients.

    Barbagallo, Carlo M; Noto, Davide; Cefalù, Angelo B; Ganci, Antonia; Giammarresi, Carlo; Panno, Donata; Cusumano, Gaspare; Greco, Massimiliano; Di Gaudio, Francesca; Averna, Maurizio R

    2015-07-01

    Dyslipidemias may account for the excess of cardiovascular mortality in end-stage renal disease (ESRD). Lipoprotein studies in ESRD patients are usually relative to prehemodialysis samples even if significative changes may occur after dialysis. In this study, we aimed to investigate the effects of ESRD on triglyceride-rich lipoproteins (TRL) subpopulations distribution and acute change following hemodialytic procedures, including the relative contribution of heparin administration. We selected a group of normolipidemic male middle-aged ESRD patients free of any concomitant disease affecting lipoprotein remnant metabolism compared with controls. We separated TRL subfractions according to density and apoE content and evaluated the changes of these particles after hemodialytic procedures with or without heparin. ESRD subjects had higher TRL subfractions, with the exception of apoE-rich particles, lower high-density lipoprotein (HDL) largest subclasses, and a smaller low-density lipoprotein peak particle size than controls. After a hemodialytic standard procedure with heparin, we demonstrated a significant reduction of triglyceride, an increase of HDL-cholesterol levels, and a raise of small very-low-density lipoprotein, intermediate-density lipoproteins (IDL), apoE-rich particles, and non-HDL-cholesterol levels. When hemodialysis was performed without heparin, no significant changes were observed. In the absence of concomitant hyperlipidemic triggers, ESRD patients show significant lipoprotein abnormalities before dialysis, but without any increased remnant particles concentrations. We speculate that hemodialysis, in particular heparin administration during this procedure, leads to a massive atherogenic TRLs production because of the acute stimulation of the dysfunctional lipolytic system not followed by an efficient removal, determining a recurrent lipoprotein remnant accumulation. © 2014 International Society for Hemodialysis.

  20. Veno-venous bypass without systemic heparinization using a centrifugal pump: a blind comparison of a heparin bonded circuit versus a non heparin bonded circuit

    van der Hulst, V. P.; Henny, C. P.; Moulijn, A. C.; Engbers, G.; ten Cate, H.; Gründeman, P. F.; Klopper, P. J.

    1989-01-01

    Veno-venous bypass without the use of systemic heparinization has recently become of increasing interest for application during liver transplantation and surgery on the large abdominal veins. However, possible adverse effects on blood components as demonstrated by means of hematologic and hemostatic

  1. Coupled orbit-attitude motion of high area-to-mass ratio (HAMR) objects including efficient self-shadowing

    Früh, Carolin; Jah, Moriba K.

    2014-02-01

    This paper shows the effect of self-shadowing on the coupled attitude-orbit dynamics of objects with high area-to-mass ratios (HAMR) in simulating standard multi layer insulation materials (MLI) as tilted single rigid sheets. Efficient and computationally fast self-shadowing methods have been developed. This includes an approximate self-shadowing method and a rapid exact self-shadowing method. Accuracy considerations are made and the effect of a chosen tessellation is shown. The coupled orbit-attitude perturbations of solar radiation pressure and Earth gravity field are taken into account. The results are compared to the attitude-orbit dynamics, when neglecting self-shadowing effects. An averaged physical shadow-map model is developed and compared to the full self-shadowing simulation. The combined effect of solar radiation pressure and self-shadowing leads to a rapid spin-up of the objects, even though they have uniform reflection properties. As a result, the observed brightness of these objects is subject to rapid changes.

  2. Energy-efficient pulse-coupled synchronization strategy design for wireless sensor networks through reduced idle listening

    Wang, Yongqiang; Núñez, Felipe; Doyle, Francis J.

    2013-01-01

    Synchronization is crucial to wireless sensor networks due to their decentralized structure. We propose an energy-efficient pulse-coupled synchronization strategy to achieve this goal. The basic idea is to reduce idle listening by intentionally introducing a large refractory period in the sensors’ cooperation. The large refractory period greatly reduces idle listening in each oscillation period, and is analytically proven to have no influence on the time to synchronization. Hence, it significantly reduces the total energy consumption in a synchronization process. A topology control approach tailored for pulse-coupled synchronization is given to guarantee a k-edge strongly connected interaction topology, which is tolerant to communication-link failures. The topology control approach is totally decentralized and needs no information exchange among sensors, and it is applicable to dynamic network topologies as well. This facilitates a completely decentralized implementation of the synchronization strategy. The strategy is applicable to mobile sensor networks, too. QualNet case studies confirm the effectiveness of the synchronization strategy. PMID:24307831

  3. Spectrometric performances of high quantum efficiency multi and single anode PMTs coupled to LaBr3(Ce) crystal

    Cinti, Maria Nerina, E-mail: marianerina.cinti@uniroma1.it [Department of Molecular Medicine, Sapienza University of Rome, Rome 00161 (Italy); INFN Rome 1 Section, Rome (Italy); Pani, Roberto; Pellegrini, Rosanna [Department of Molecular Medicine, Sapienza University of Rome, Rome 00161 (Italy); INFN Rome 1 Section, Rome (Italy); Bennati, Paolo [Department of Molecular Medicine, Sapienza University of Rome, Rome 00161 (Italy); Orlandi, Chiara [Medical Physics Post Graduate School, Sapienza University of Rome, Rome 00161 (Italy); Fabbri, Andrea [Department of Physics, Roma Tre University, Rome (Italy); INFN Rome 3 Section, Rome (Italy); Ridolfi, Stefano; Scafè, Raffaele [Department of Molecular Medicine, Sapienza University of Rome, Rome 00161 (Italy)

    2013-10-01

    High quantum efficiency semiconductor photodetectors have recently drawn the attention of the scientific community for their potential in the realization of a new class of scintillation imagers with very high energy and spatial resolution performance. However, this goal does not seem within easy reach, due to various technological issues such as, for example, the difficulty to scale the characteristics of a single detector to an imager with suitable dimensions. Lately a definite technical improvement in increasing quantum efficiency up to 42% for position sensitive photomultipliers was achieved. The aim of this work is thus to test this new technological progress and to study the possible implications in imaging applications. Four Hamamatsu PMTs were tested: two multi anode photomultipliers, one with a bialkali (27% quantum efficiency) and the other one with a super-bialkali photocathode (38% quantum efficiency), and two 1×1 in. PMTs, both equipped with an ultra bialkali photocathode (42% quantum efficiency). In particular one of the ultra bialkali PMT has also an increased efficiency of first dynode charge collection. The results were compared with the ones obtained with a reference PMT (Hamamatsu R6231), mainly used in spectroscopy. The PMTs were coupled to LaBr3(Ce), NaI(Tl) and LSO(Ce) continuous scintillation crystals. The tests were done using two independent electronic chains: one dedicated for spectroscopic application and a second one, using a multi wire 64 channel readout, for imaging applications. The super-bialkali MA-PMTs have shown high energy resolution, both with spectroscopic and imaging setup, highlighting the appropriateness of these devices for the development of imaging devices with high spectroscopic performance. -- Highlights: • A study of energy resolution results coming from position sensitive photomultipliers are proposed. • The study is also extended on mono- anode photomultiplier. • The selected scintillation crystal is LeBr3(Ce

  4. Pharmacokinetics of heparin and related polysaccharides

    Boneu, B.; Dol, F.; Caranobe, C.; Sie, P.; Houin, G.

    1989-01-01

    The pharmacodynamic profile of standard heparin (SH), a low molecular weight derivative (CY 216) and of dermatan sulfate (DS), a new potential antithrombotic drug, was investigated in the rabbit over a large range of doses. After bolus i.v. injection of low doses, the biological activity of SH disappeared exponentially; however, its half-life was prolonged when the dose injected increased, and over 158 micrograms/kg (100 anti-factor Xa U/kg) the biological activity disappeared as a concave-convex curve. CY 216 disappeared more slowly than SH at low doses but faster than SH at higher doses. More than 90% of the DS biological activity present 1 minute after the i.v. injection disappeared exponentially without dose-dependent effects. Increasing doses of the three drugs were then delivered for 5 h under continuous infusions. Below 500 micrograms/kg/h the DS and CY 216 plateau concentrations were higher than that of SH while above this dose the SH concentration was higher than that of DS and CY 216. These observations may be explained by the results of pharmacokinetics experiments where 125 I-labeled compounds were delivered by bolus i.v. injection in association with increasing doses of their unlabeled counterparts. For SH there was a 10-fold difference between the half-life of the lower dose (32 micrograms/kg or 5 anti-factor Xa U/kg) and that of the higher dose (3200 micrograms/kg); it was demonstrated that the half-life of SH continuously shortened as its plasma concentration decreased. In contrast the CY 216 and DS half-lives were very close, independent of the dose delivered, and therefore longer than that of SH at low doses and shorter than that of SH at higher doses

  5. Nuclear androgen receptors in human prostatic tissue. Extraction with heparin and estimation of the number of binding sites with different methods

    Foekens, J.A.; Bolt-de Vries, J.; Mulder, E.; Blankenstein, M.A.; Schroeder, F.H.; Molen, H.J. van der

    1981-01-01

    A procedure for the estimation of nuclear androgen receptors in benign prostatic hyperplastic tissue is described, which employs extraction of receptors from nuclei with buffers containing heparin. Extraction of a nuclear pellet with a heparin-containing (1 g/l) buffer appeared to have definite advantages over 0.4 mol/l KCl extraction. Heparin appeared to be twice as efficient in extracting androgen receptors. In addition aggregated receptor proteins, formed after storage at -80 0 C, were partly deaggregated by heparin. Specific isolation of the androgen receptor was performed using either agar gel electrophoresis, protamine sulphate precipitation or LH-20 gel filtration. A comparison was made between the amounts of estimated receptors with these different techniques. Protamine sulphate precipitation resulted in the highest estimates of receptor-bound 5α-[ 3 H]dihydrotestosterone ( 3 H-DHT). Treatment of the labelled nuclear extracts with a charcoal suspension prior to the receptor assay resulted in lower amounts of estimated androgen receptors. A method for routine evaluation of nuclear androgen receptors in prostatic tissue has been evaluated, which involves extraction of nuclear pellets with a heparin-containing (1 g/l) buffer, exchange labelling of the nuclear extracts for 20 h at 10 0 C and quantification of the receptors with protamine sulphate precipitation. (Auth.)

  6. Endothelial cell capture of heparin-binding growth factors under flow.

    Bing Zhao

    2010-10-01

    Full Text Available Circulation is an important delivery method for both natural and synthetic molecules, but microenvironment interactions, regulated by endothelial cells and critical to the molecule's fate, are difficult to interpret using traditional approaches. In this work, we analyzed and predicted growth factor capture under flow using computer modeling and a three-dimensional experimental approach that includes pertinent circulation characteristics such as pulsatile flow, competing binding interactions, and limited bioavailability. An understanding of the controlling features of this process was desired. The experimental module consisted of a bioreactor with synthetic endothelial-lined hollow fibers under flow. The physical design of the system was incorporated into the model parameters. The heparin-binding growth factor fibroblast growth factor-2 (FGF-2 was used for both the experiments and simulations. Our computational model was composed of three parts: (1 media flow equations, (2 mass transport equations and (3 cell surface reaction equations. The model is based on the flow and reactions within a single hollow fiber and was scaled linearly by the total number of fibers for comparison with experimental results. Our model predicted, and experiments confirmed, that removal of heparan sulfate (HS from the system would result in a dramatic loss of binding by heparin-binding proteins, but not by proteins that do not bind heparin. The model further predicted a significant loss of bound protein at flow rates only slightly higher than average capillary flow rates, corroborated experimentally, suggesting that the probability of capture in a single pass at high flow rates is extremely low. Several other key parameters were investigated with the coupling between receptors and proteoglycans shown to have a critical impact on successful capture. The combined system offers opportunities to examine circulation capture in a straightforward quantitative manner that

  7. Evaluation of power transfer efficiency for a high power inductively coupled radio-frequency hydrogen ion source

    Jain, P.; Recchia, M.; Cavenago, M.; Fantz, U.; Gaio, E.; Kraus, W.; Maistrello, A.; Veltri, P.

    2018-04-01

    Neutral beam injection (NBI) for plasma heating and current drive is necessary for International Thermonuclear Experimental reactor (ITER) tokamak. Due to its various advantages, a radio frequency (RF) driven plasma source type was selected as a reference ion source for the ITER heating NBI. The ITER relevant RF negative ion sources are inductively coupled (IC) devices whose operational working frequency has been chosen to be 1 MHz and are characterized by high RF power density (˜9.4 W cm-3) and low operational pressure (around 0.3 Pa). The RF field is produced by a coil in a cylindrical chamber leading to a plasma generation followed by its expansion inside the chamber. This paper recalls different concepts based on which a methodology is developed to evaluate the efficiency of the RF power transfer to hydrogen plasma. This efficiency is then analyzed as a function of the working frequency and in dependence of other operating source and plasma parameters. The study is applied to a high power IC RF hydrogen ion source which is similar to one simplified driver of the ELISE source (half the size of the ITER NBI source).

  8. Inductively and capacitively coupled plasmas at interface: A comparative study towards highly efficient amorphous-crystalline Si solar cells

    Guo, Yingnan; Ong, Thiam Min Brian; Levchenko, I.; Xu, Shuyan

    2018-01-01

    A comparative study on the application of two quite different plasma-based techniques to the preparation of amorphous/crystalline silicon (a-Si:H/c-Si) interfaces for solar cells is presented. The interfaces were fabricated and processed by hydrogen plasma treatment using the conventional plasma-enhanced chemical vacuum deposition (PECVD) and inductively coupled plasma chemical vapour deposition (ICP-CVD) methods The influence of processing temperature, radio-frequency power, treatment duration and other parameters on interface properties and degree of surface passivation were studied. It was found that passivation could be improved by post-deposition treatment using both ICP-CVD and PECVD, but PECVD treatment is more efficient for the improvement on passivation quality, whereas the minority carrier lifetime increased from 1.65 × 10-4 to 2.25 × 10-4 and 3.35 × 10-4 s after the hydrogen plasma treatment by ICP-CVD and PECVD, respectively. In addition to the improvement of carrier lifetimes at low temperatures, low RF powers and short processing times, both techniques are efficient in band gap adjustment at sophisticated interfaces.

  9. The intracellular uptake and protracted release of exogenous heparins by cultured endothelial cells

    Hiebert, L.M.; McDuffie, N.M.

    1989-01-01

    Heparins from bovine or porcine sources were fed in media for 48 hrs to cultured porcine aortic and human umbilical vein endothelial cells. Heparin was found in pericellular and cellular fractions after extraction by chemical methods and 125 I radiolabelled heparins were recovered when radiolabelled heparin was included in the feed. Even after washing and media changes heparin was detected in media and cell fractions up to 6 days post feeding. Metachromatic vacuoles within cells were demonstrated histologically up to 7 days post feeding after staining with toluidine blue. This is the first report of protracted internalization of exogenous heparin by cultured endothelial cells with concurrent prolonged release of the heparin to the media. This clearly demonstrates that the endothelium plays an important role in the distribution and metabolism of heparin

  10. Stochastic analysis of the efficiency of coupled hydraulic-physical barriers to contain solute plumes in highly heterogeneous aquifers

    Pedretti, Daniele; Masetti, Marco; Beretta, Giovanni Pietro

    2017-10-01

    The expected long-term efficiency of vertical cutoff walls coupled to pump-and-treat technologies to contain solute plumes in highly heterogeneous aquifers was analyzed. A well-characterized case study in Italy, with a hydrogeological database of 471 results from hydraulic tests performed on the aquifer and the surrounding 2-km-long cement-bentonite (CB) walls, was used to build a conceptual model and assess a representative remediation site adopting coupled technologies. In the studied area, the aquifer hydraulic conductivity Ka [m/d] is log-normally distributed with mean E (Ya) = 0.32 , variance σYa2 = 6.36 (Ya = lnKa) and spatial correlation well described by an exponential isotropic variogram with integral scale less than 1/12 the domain size. The hardened CB wall's hydraulic conductivity, Kw [m/d], displayed strong scaling effects and a lognormal distribution with mean E (Yw) = - 3.43 and σYw2 = 0.53 (Yw =log10Kw). No spatial correlation of Kw was detected. Using this information, conservative transport was simulated across a CB wall in spatially correlated 1-D random Ya fields within a numerical Monte Carlo framework. Multiple scenarios representing different Kw values were tested. A continuous solute source with known concentration and deterministic drains' discharge rates were assumed. The efficiency of the confining system was measured by the probability of exceedance of concentration over a threshold (C∗) at a control section 10 years after the initial solute release. It was found that the stronger the aquifer heterogeneity, the higher the expected efficiency of the confinement system and the lower the likelihood of aquifer pollution. This behavior can be explained because, for the analyzed aquifer conditions, a lower Ka generates more pronounced drawdown in the water table in the proximity of the drain and consequently a higher advective flux towards the confined area, which counteracts diffusive fluxes across the walls. Thus, a higher σYa2 results

  11. Quantitation of heparosan with heparin lyase III and spectrophotometry.

    Huang, Haichan; Zhao, Yingying; Lv, Shencong; Zhong, Weihong; Zhang, Fuming; Linhardt, Robert J

    2014-02-15

    Heparosan is Escherichia coli K5 capsule polysaccharide, which is the key precursor for preparing bioengineered heparin. A rapid and effective quantitative method for detecting heparosan is important in the large-scale production of heparosan. Heparin lyase III (Hep III) effectively catalyzes the heparosan depolymerization, forming unsaturated disaccharides that are measurable using a spectrophotometer at 232 nm. We report a new method for the quantitative detection of heparosan with heparin lyase III and spectrophotometry that is safer and more specific than the traditional carbazole assay. In an optimized detection system, heparosan at a minimum concentration of 0.60 g/L in fermentation broth can be detected. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Heparin-Based Nanoparticles: An Overview of Their Applications

    Maria del Pilar Rodriguez-Torres

    2018-01-01

    Full Text Available This review deals with nanoparticles synthesized using heparin. Such nanoparticles have been widely studied since a long time ago, obtaining satisfactory outcomes. An outstanding aspect of these nanoparticles is that they possess good biocompatible characteristics, and since heparin is produced in the human body within the mast cells, this makes these nanoparticles useful for future applications like imaging, disease and cancer treatment, and antibacterial activity. They can also be used for applications that are not oriented directly to the medical and biological areas such as in the case of analyte detection in aqueous solution, although such studies are very few. These nanoparticles synthesis is mainly through wet chemistry methods, using heparin that could have been modified or not.

  13. Highly Efficient and Scalable Compound Decomposition of Two-Electron Integral Tensor and Its Application in Coupled Cluster Calculations

    Peng, Bo [William R. Wiley Environmental; Kowalski, Karol [William R. Wiley Environmental

    2017-08-11

    The representation and storage of two-electron integral tensors are vital in large- scale applications of accurate electronic structure methods. Low-rank representation and efficient storage strategy of integral tensors can significantly reduce the numerical overhead and consequently time-to-solution of these methods. In this paper, by combining pivoted incomplete Cholesky decomposition (CD) with a follow-up truncated singular vector decomposition (SVD), we develop a decomposition strategy to approximately represent the two-electron integral tensor in terms of low-rank vectors. A systematic benchmark test on a series of 1-D, 2-D, and 3-D carbon-hydrogen systems demonstrates high efficiency and scalability of the compound two-step decomposition of the two-electron integral tensor in our implementation. For the size of atomic basis set N_b ranging from ~ 100 up to ~ 2, 000, the observed numerical scaling of our implementation shows O(N_b^{2.5~3}) versus O(N_b^{3~4}) of single CD in most of other implementations. More importantly, this decomposition strategy can significantly reduce the storage requirement of the atomic-orbital (AO) two-electron integral tensor from O(N_b^4) to O(N_b^2 log_{10}(N_b)) with moderate decomposition thresholds. The accuracy tests have been performed using ground- and excited-state formulations of coupled- cluster formalism employing single and double excitations (CCSD) on several bench- mark systems including the C_{60} molecule described by nearly 1,400 basis functions. The results show that the decomposition thresholds can be generally set to 10^{-4} to 10^{-3} to give acceptable compromise between efficiency and accuracy.

  14. Changes in heparin dose response slope during cardiac surgery: possible result in inaccuracy in predicting heparin bolus dose requirement to achieve target ACT.

    Ichikawa, Junko; Mori, Tetsu; Kodaka, Mitsuharu; Nishiyama, Keiko; Ozaki, Makoto; Komori, Makiko

    2017-09-01

    The substantial interpatient variability in heparin requirement has led to the use of a heparin dose response (HDR) technique. The accuracy of Hepcon-based heparin administration in achieving a target activated clotting time (ACT) using an HDR slope remains controversial. We prospectively studied 86 adult patients scheduled for cardiac surgery requiring cardiopulmonary bypass. The total dose of calculated heparin required for patient and pump priming was administered simultaneously to achieve a target ACT of 450 s for HDR on the Hepcon HMS system. Blood samples were obtained after the induction of anesthesia, at 3 min after heparin administration and after the initiation of CPB to measure kaolin ACT, HDR slope, whole-blood heparin concentration based on the HDR slope and anti-Xa heparin concentration, antithrombin and complete blood count. The target ACT of 450 s was not achieved in 68.6% of patients. Compared with patients who achieved the target ACT, those who failed to achieve their target ACT had a significantly higher platelet count at baseline. Correlation between the HDR slope and heparin sensitivity was poor. Projected heparin concentration and anti-Xa heparin concentration are not interchangeable based on the Bland-Altman analysis. It can be hypothesized that the wide discrepancy in HDR slope versus heparin sensitivity may be explained by an inaccurate prediction of the plasma heparin level and/or the change in HDR of individual patients, depending on in vivo factors such as extravascular sequestration of heparin, decreased intrinsic antithrombin activity level and platelet count and/or activity.

  15. Histones Differentially Modulate the Anticoagulant and Profibrinolytic Activities of Heparin, Heparin Derivatives, and Dabigatran.

    Ammollo, Concetta Tiziana; Semeraro, Nicola; Carratù, Maria Rosaria; Colucci, Mario; Semeraro, Fabrizio

    2016-02-01

    The antithrombin activity of unfractionated heparin (UFH) is offset by extracellular histones, which, along with DNA, represent a novel mediator of thrombosis and a structural component of thrombi. Here, we systematically evaluated the effect of histones, DNA, and histone-DNA complexes on the anticoagulant and profibrinolytic activities of UFH, its derivatives enoxaparin and fondaparinux, and the direct thrombin inhibitor dabigatran. Thrombin generation was assessed by calibrated automated thrombinography, inhibition of factor Xa and thrombin by synthetic substrates, tissue plasminogen activator-mediated clot lysis by turbidimetry, and thrombin-activatable fibrinolysis inhibitor (TAFI) activation by a functional assay. Histones alone delayed coagulation and slightly stimulated fibrinolysis. The anticoagulant activity of UFH and enoxaparin was markedly inhibited by histones, whereas that of fondaparinux was enhanced. Histones neutralized both the anti-Xa and anti-IIa activities of UFH and preferentially blocked the anti-IIa activity of enoxaparin. The anti-Xa activity of fondaparinux was not influenced by histones when analyzed by chromogenic substrates, but was potentiated in a plasma prothrombinase assay. Histones inhibited the profibrinolytic activity of UFH and enoxaparin and enhanced that of fondaparinux by acting on the modulation of TAFI activation by anticoagulants. Histone H1 was mainly responsible for these effects. Histone-DNA complexes, as well as intact neutrophil extracellular traps, impaired the activities of UFH, enoxaparin, and fondaparinux. Dabigatran was not noticeably affected by histones and/or DNA, whatever the assay performed. In conclusion, histones and DNA present in the forming clot may variably influence the antithrombotic activities of anticoagulants, suggesting a potential therapeutic advantage of dabigatran and fondaparinux over heparins. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  16. The effect of different forms of heparin on point-of-care blood gas ...

    and heparin vacutainers on blood gas and electrolyte analysis and ... This prospective, cross-sectional study took place in the ED of a ... the effect of two concentrations of liquid heparin and the use of heparin vacutainers on the reliability of blood gas ... Germany) and (iv) a 2 mL plastic syringe (BD) washed with 5 000 IU/.

  17. Coexistence of Antiphospholipid Syndrome and Heparin-Induced Thrombocytopenia in a Patient with Recurrent Venous Thromboembolism

    Samuel Adediran

    2017-01-01

    Full Text Available Heparin-induced thrombocytopenia (HIT is a prothrombotic adverse drug reaction in which heparin forms complexes with platelet factor 4 forming neoantigens that are recognized by autoantibodies. Antiphospholipid syndrome (APS is similar to HIT in that it is mediated by autoantibodies that are also prothrombotic. We present a case of rare coexistence of antiphospholipid antibody syndrome and heparin-induced thrombocytopenia.

  18. A genome-wide association study of heparin-induced thrombocytopenia using an electronic medical record

    Karnes, Jason H; Cronin, Robert M; Rollin, Jerome

    2015-01-01

    Heparin-induced thrombocytopenia (HIT) is an unpredictable, potentially catastrophic adverse effect of heparin treatment resulting from an immune response to platelet factor 4 (PF4)/heparin complexes. No genome-wide evaluations have been performed to identify potential genetic influences on HIT. ...

  19. Automated system for efficient microwave power coupling in an S-band ECR ion source driven under different operating conditions

    Muguira, L., E-mail: lmuguira@essbilbao.org [ESS-Bilbao, Edificio Rectorado, Vivero de Empresas, 48940 Leioa (Bizkaia) (Spain); Portilla, J. [University of Basque Country (UPV/EHU), Department of Electricity and Electronics, Science and Technology Faculty, 48940 Leioa (Bizkaia) (Spain); Gonzalez, P.J.; Garmendia, N.; Feuchtwanger, J. [ESS-Bilbao, Edificio Rectorado, Vivero de Empresas, 48940 Leioa (Bizkaia) (Spain); Etxebarria, V. [University of Basque Country (UPV/EHU), Department of Electricity and Electronics, Science and Technology Faculty, 48940 Leioa (Bizkaia) (Spain); Eguiraun, M.; Arredondo, I.; Miracoli, R.; Belver, D. [ESS-Bilbao, Edificio Rectorado, Vivero de Empresas, 48940 Leioa (Bizkaia) (Spain)

    2014-03-21

    This article presents an automated system for optimizing the microwave power coupling to the plasma generated in a proton/deuteron Electron Cyclotron Resonance (ECR) source, based on a specific model of a rectangular waveguide triple-stub tuner and the integrated measurement and control electronics, helping to get stable plasma states. The control and improvement of the RF power absorption into the plasma is a complex process, essential for the ion source development and optimization under different operating conditions. A model and a matching algorithm for the triple-stub tuner have been developed and, besides, different methods to accurately measure the power transfer in a waveguide RF system have been studied and deployed in the ESS-Bilbao ion source system. The different parts have been integrated through a controller, which allows to run an automatic plasma matching system in closed loop. The behavior of the system implemented for low and high power regimes has been tested under different conditions: with several load impedances, with plasma inside the chamber, in continuous wave and pulsed wave operation modes, demonstrating power absorption typically over 90% in all the ion source configurations. The developed system allows to achieve significant improvement in the ECR ion source power absorption efficiency, both in continuous and pulsed mode. The automatic tuning unit enhances the system operation finding an optimum solution much faster than manually, also behaving as an adaptive system able to respond in few pulses to ion source configuration changes to maintain the power coupling as high as possible. - Highlights: • An automated system optimizing plasma and microwave power interaction is presented. • A model and a matching algorithm for the triple-stub tuner have been developed. • Different methods to measure the power transfer have been studied and deployed. • The system works for low or high power regimes under different ion source conditions.

  20. Automated system for efficient microwave power coupling in an S-band ECR ion source driven under different operating conditions

    Muguira, L.; Portilla, J.; Gonzalez, P.J.; Garmendia, N.; Feuchtwanger, J.; Etxebarria, V.; Eguiraun, M.; Arredondo, I.; Miracoli, R.; Belver, D.

    2014-01-01

    This article presents an automated system for optimizing the microwave power coupling to the plasma generated in a proton/deuteron Electron Cyclotron Resonance (ECR) source, based on a specific model of a rectangular waveguide triple-stub tuner and the integrated measurement and control electronics, helping to get stable plasma states. The control and improvement of the RF power absorption into the plasma is a complex process, essential for the ion source development and optimization under different operating conditions. A model and a matching algorithm for the triple-stub tuner have been developed and, besides, different methods to accurately measure the power transfer in a waveguide RF system have been studied and deployed in the ESS-Bilbao ion source system. The different parts have been integrated through a controller, which allows to run an automatic plasma matching system in closed loop. The behavior of the system implemented for low and high power regimes has been tested under different conditions: with several load impedances, with plasma inside the chamber, in continuous wave and pulsed wave operation modes, demonstrating power absorption typically over 90% in all the ion source configurations. The developed system allows to achieve significant improvement in the ECR ion source power absorption efficiency, both in continuous and pulsed mode. The automatic tuning unit enhances the system operation finding an optimum solution much faster than manually, also behaving as an adaptive system able to respond in few pulses to ion source configuration changes to maintain the power coupling as high as possible. - Highlights: • An automated system optimizing plasma and microwave power interaction is presented. • A model and a matching algorithm for the triple-stub tuner have been developed. • Different methods to measure the power transfer have been studied and deployed. • The system works for low or high power regimes under different ion source conditions.

  1. The Efficiency of Quartz Particles Evaporation in the Argon Plasma Flow of the RF Inductively Coupled Plasma Torch

    Yu. M. Grishin

    2017-01-01

    Full Text Available Owing to high-power density and high-purity plasma, a RF inductively coupled plasma torch (ICPT is widely used both in research laboratory and in industry. The potential RF ICPT application areas are powders spheroidisation, waste treatment, thermal spraying, etc.In the last decade the investigation was focused on the treatment processes of quartz into polycrystalline silicon. An analysis of these results has shown that the increasing productivity and producing high-purity silicon can be achieved only when using the electrodeless radio-frequency induction plasma torches and in case the optimum conditions for evaporation of SiO2solid particles are realized.Optimization of the RF ICPT design and power parameters calls for a wide range of computational studies. In spite of the fact that to date a large number of efforts to calculate the evaporation efficiency of powder materials have been made, a number of issues, as applied to the problem of obtaining silicon, require further research.In this paper, we present the results of a two-dimensional numerical simulation of the heating and evaporation of quartz particles in the RF ICPT channel with axial flow of gases. The main aim is to determine how the axial position of the central tube (through which the particles are injected into the discharge zone, the dispersion of the quartz powder, the amplitude of the discharge current (and, respectively, flow regimes impact on the evaporation efficiency of quartz particles.The paper presented the numerical modeling results of heating and evaporation processes of quartz particles supplied by transporting gas to the RF ICPT channel with axial gas flow (argon. Defined the impact of the axial position of the central tube, the plasma flow regime, the discharge current, the flow rate of transporting gas, and other parameters on the evaporation efficiency of quartz particles.It is shown that the evaporation efficiency of particles reaches its maximum when their

  2. Self-Assembled Lipid Nanoparticles for Oral Delivery of Heparin-Coated Iron Oxide Nanoparticles for Theranostic Purposes.

    Truzzi, Eleonora; Bongio, Chiara; Sacchetti, Francesca; Maretti, Eleonora; Montanari, Monica; Iannuccelli, Valentina; Vismara, Elena; Leo, Eliana

    2017-06-09

    Recently, solid lipid nanoparticles (SLNs) have attracted increasing attention owing to their potential as an oral delivery system, promoting intestinal absorption in the lymphatic circulation which plays a role in disseminating metastatic cancer cells and infectious agents throughout the body. SLN features can be exploited for the oral delivery of theranostics. Therefore, the aim of this work was to design and characterise self-assembled lipid nanoparticles (SALNs) to encapsulate and stabilise iron oxide nanoparticles non-covalently coated with heparin (Fe@hepa) as a model of a theranostic tool. SALNs were characterised for physico-chemical properties (particle size, surface charge, encapsulation efficiency, in vitro stability, and heparin leakage), as well as in vitro cytotoxicity by methyl thiazole tetrazolium (MTT) assay and cell internalisation in CaCo-2, a cell line model used as an indirect indication of intestinal lymphatic absorption. SALNs of about 180 nm, which are stable in suspension and have a high encapsulation efficiency (>90%) were obtained. SALNs were able to stabilise the heparin coating of Fe@hepa, which are typically unstable in physiological environments. Moreover, SALNs-Fe@hepa showed no cytotoxicity, although their ability to be internalised into CaCo-2 cells was highlighted by confocal microscopy analysis. Therefore, the results indicated that SALNs can be considered as a promising tool to orally deliver theranostic Fe@hepa into the lymphatic circulation, although further in vivo studies are needed to comprehend further potential applications.

  3. 12500 E heparin and 12500 E of a semisynthetic heparin analogue (SSHA) in preventing thrombosis during radiotherapy of gynaecological carcinomas

    Hilscher, T.M.

    1983-01-01

    The effects of 12500 E calcium heparin given once daily were contrasted with those seen under daily treatment with 12500 E of a semisynthetic heparin analogue (SSHA) and evaluated using iodine-125-labelled fibrinogen. The study included 80 patients, who were randomly assigned to the two treatment groups on a 1:1 basis. The findings revealed here led to the conclusion that both drugs, administered once daily by the subcutaneous route, were effective in preventing the occurrence of thrombosis during radiation treatment of gynaecological tumours. (orig./MG) [de

  4. Decomplexation efficiency and mechanism of Cu(II)-EDTA by H2O2 coupled internal micro-electrolysis process.

    Zhou, Dongfang; Hu, Yongyou; Guo, Qian; Yuan, Weiguang; Deng, Jiefan; Dang, Yapan

    2016-12-29

    Internal micro-electrolysis (IE) coupled with Fenton oxidation (IEF) was a very effective technology for copper (Cu)-ethylenediaminetetraacetic acid (EDTA) wastewater treatment. However, the mechanisms of Cu 2+ removal and EDTA degradation were scarce and lack persuasion in the IEF process. In this paper, the decomplexation and removal efficiency of Cu-EDTA and the corresponding mechanisms during the IEF process were investigated by batch test. An empirical equation and the oxidation reduction potential (ORP) index were proposed to flexibly control IE and the Fenton process, respectively. The results showed that Cu 2+ , total organic carbon (TOC), and EDTA removal efficiencies were 99.6, 80.3, and 83.4%, respectively, under the proper operation conditions of iron dosage of 30 g/L, Fe/C of 3/1, initial pH of 3.0, Fe 2+ /H 2 O 2 molar ratio of 1/4, and reaction time of 20 min, respectively for IE and the Fenton process. The contributions of IE and Fenton to Cu 2+ removal were 91.2 and 8.4%, respectively, and those to TOC and EDTA removal were 23.3, 25.1, and 57, 58.3%, respectively. It was found that Fe 2+ -based replacement-precipitation and hydroxyl radical (•OH) were the most important effects during the IEF process. •OH played an important role in the degradation of EDTA, whose yield and productive rate were 3.13 mg/L and 0.157 mg/(L min -1 ), respectively. Based on the intermediates detected by GC-MS, including acetic acid, propionic acid, pentanoic acid, amino acetic acid, 3-(diethylamino)-1,2-propanediol, and nitrilotriacetic acid (NTA), a possible degradation pathway of Cu-EDTA in the IEF process was proposed. Graphical abstract The mechanism diagram of IEF process.

  5. Efficient fiber-coupled single-photon source based on quantum dots in a photonic-crystal waveguide

    Daveau, Raphaël S.; Balram, Krishna C.; Pregnolato, Tommaso

    2017-01-01

    Many photonic quantum information processing applications would benefit from a high brightness, fiber-coupled source of triggered single photons. Here, we present a fiber-coupled photonic-crystal waveguide (PCWG) singlephoton source relying on evanescent coupling of the light field from a tapered...

  6. Coupling Modern Portfolio Theory and Marxan enhances the efficiency of Lesser White-fronted Goose's (Anser erythropus) habitat conservation.

    Liang, Jie; Gao, Xiang; Zeng, Guangming; Hua, Shanshan; Zhong, Minzhou; Li, Xiaodong; Li, Xin

    2018-01-09

    Climate change and human activities cause uncertain changes to species biodiversity by altering their habitat. The uncertainty of climate change requires planners to balance the benefit and cost of making conservation plan. Here optimal protection approach for Lesser White-fronted Goose (LWfG) by coupling Modern Portfolio Theory (MPT) and Marxan selection were proposed. MPT was used to provide suggested weights of investment for protected area (PA) and reduce the influence of climatic uncertainty, while Marxan was utilized to choose a series of specific locations for PA. We argued that through combining these two commonly used techniques with the conservation plan, including assets allocation and PA chosing, the efficiency of rare bird's protection would be enhanced. In MPT analyses, the uncertainty of conservation-outcome can be reduced while conservation effort was allocated in Hunan, Jiangxi and Yangtze River delta. In Marxan model, the optimal location for habitat restorations based on existing nature reserve was identified. Clear priorities for the location and allocation of assets could be provided based on this research, and it could help decision makers to build conservation strategy for LWfG.

  7. Modulation transfer function and detective quantum efficiency of electron bombarded charge coupled device detector for low energy electrons

    Horacek, Miroslav

    2005-01-01

    The use of a thinned back-side illuminated charge coupled device chip as two-dimensional sensor working in direct electron bombarded mode at optimum energy of the incident signal electrons is demonstrated and the measurements of the modulation transfer function (MTF) and detective quantum efficiency (DQE) are described. The MTF was measured for energy of electrons 4 keV using an edge projection method and a stripe projection method. The decrease of the MTF for a maximum spatial frequency of 20.8 cycles/mm, corresponding to the pixel size 24x24 μm, is 0.75≅-2.5 dB, and it is approximately the same for both horizontal and vertical directions. DQE was measured using an empty image and the mixing factor method. Empty images were acquired for energies of electrons from 2 to 5 keV and for various doses, ranging from nearly dark image to a nearly saturated one. DQE increases with increasing energy of bombarded electrons and reaches 0.92 for electron energy of 5 keV. For this energy the detector will be used for the angle- and energy-selective detection of signal electrons in the scanning low energy electron microscope

  8. Iron control on global productivity: an efficient inverse model of the ocean's coupled phosphate and iron cycles.

    Pasquier, B.; Holzer, M.; Frants, M.

    2016-02-01

    We construct a data-constrained mechanistic inverse model of the ocean's coupled phosphorus and iron cycles. The nutrient cycling is embedded in a data-assimilated steady global circulation. Biological nutrient uptake is parameterized in terms of nutrient, light, and temperature limitations on growth for two classes of phytoplankton that are not transported explicitly. A matrix formulation of the discretized nutrient tracer equations allows for efficient numerical solutions, which facilitates the objective optimization of the key biogeochemical parameters. The optimization minimizes the misfit between the modelled and observed nutrient fields of the current climate. We systematically assess the nonlinear response of the biological pump to changes in the aeolian iron supply for a variety of scenarios. Specifically, Green-function techniques are employed to quantify in detail the pathways and timescales with which those perturbations are propagated throughout the world oceans, determining the global teleconnections that mediate the response of the global ocean ecosystem. We confirm previous findings from idealized studies that increased iron fertilization decreases biological production in the subtropical gyres and we quantify the counterintuitive and asymmetric response of global productivity to increases and decreases in the aeolian iron supply.

  9. Insulin acutely improves mitochondrial function of rat and human skeletal muscle by increasing coupling efficiency of oxidative phosphorylation.

    Nisr, Raid B; Affourtit, Charles

    2014-02-01

    Insulin is essential for the regulation of fuel metabolism and triggers the uptake of glucose by skeletal muscle. The imported glucose is either stored or broken down, as insulin stimulates glycogenesis and ATP synthesis. The mechanism by which ATP production is increased is incompletely understood at present and, generally, relatively little functional information is available on the effect of insulin on mitochondrial function. In this paper we have exploited extracellular flux technology to investigate insulin effects on the bioenergetics of rat (L6) and human skeletal muscle myoblasts and myotubes. We demonstrate that a 20-min insulin exposure significantly increases (i) the cell respiratory control ratio, (ii) the coupling efficiency of oxidative phosphorylation, and (iii) the glucose sensitivity of anaerobic glycolysis. The improvement of mitochondrial function is explained by an insulin-induced immediate decrease of mitochondrial proton leak. Palmitate exposure annuls the beneficial mitochondrial effects of insulin. Our data improve the mechanistic understanding of insulin-stimulated ATP synthesis, and reveal a hitherto undisclosed insulin sensitivity of cellular bioenergetics that suggests a novel way of detecting insulin responsiveness of cells. © 2013.

  10. Insulin acutely improves mitochondrial function of rat and human skeletal muscle by increasing coupling efficiency of oxidative phosphorylation☆

    Nisr, Raid B.; Affourtit, Charles

    2014-01-01

    Insulin is essential for the regulation of fuel metabolism and triggers the uptake of glucose by skeletal muscle. The imported glucose is either stored or broken down, as insulin stimulates glycogenesis and ATP synthesis. The mechanism by which ATP production is increased is incompletely understood at present and, generally, relatively little functional information is available on the effect of insulin on mitochondrial function. In this paper we have exploited extracellular flux technology to investigate insulin effects on the bioenergetics of rat (L6) and human skeletal muscle myoblasts and myotubes. We demonstrate that a 20-min insulin exposure significantly increases (i) the cell respiratory control ratio, (ii) the coupling efficiency of oxidative phosphorylation, and (iii) the glucose sensitivity of anaerobic glycolysis. The improvement of mitochondrial function is explained by an insulin-induced immediate decrease of mitochondrial proton leak. Palmitate exposure annuls the beneficial mitochondrial effects of insulin. Our data improve the mechanistic understanding of insulin-stimulated ATP synthesis, and reveal a hitherto undisclosed insulin sensitivity of cellular bioenergetics that suggests a novel way of detecting insulin responsiveness of cells. PMID:24212054

  11. N-doped graphene coupled with Co nanoparticles as an efficient electrocatalyst for oxygen reduction in alkaline media

    Zhang, Geng; Lu, Wangting; Cao, Feifei; Xiao, Zhidong; Zheng, Xinsheng

    2016-01-01

    Development of low-cost and highly efficient electrocatalysts for oxygen reduction reaction (ORR) is still a great challenge for the large-scale application of fuel cells and metal-air batteries. Herein, a noble metal-free ORR electrocatalyst in the form of N-doped graphene coupled with part of Co nanoparticles encased in N-doped graphitic shells (named as SUCo-0.03-800) is prepared by facile one-step pyrolysis of the mixture of sucrose, urea and cobalt nitrate. The novel structure is confirmed by High Resolution-TEM, XRD, XPS and Raman spectroscopy. SUCo-0.03-800 presents comparable ORR catalytic activity to commercial Pt/C catalyst with a dominating four-electron pathway under alkaline conditions, and both of its mass activity and volume activity also outperform Co-free N-doped graphene and other Co/N-C hybrids with higher Co content, which may probably be ascribed to the high specific surface area, novel structure and synergistic effect between encased Co nanoparticles and N-doped graphitic shell. Additionally, SUCo-0.03-800 also shows outstanding stability and improved selectivity towards ORR, making it a promising alternative to Pt with potential application in fuel cells and metal-air batteries.

  12. Improved assay for measuring heparin binding to bull sperm

    Miller, D.J.; Ax, R.L.

    1988-01-01

    The binding of heparin to sperm has been used to study capacitation and to rank relative fertility of bulls. Previous binding assays were laborious, used 10 7 sperm per assay point, and required large amounts of radiolabeled heparin. A modified heparin-binding assay is described that used only 5 x 10 4 cells per incubation well and required reduced amounts of [ 3 H] heparin. The assay was performed in 96-well Millititer plates, enabling easy incubation and filtering. Dissociation constants and concentrations of binding sites did not differ if analyzed by Scatchard plots, Woolf plots, or by log-logit transformed weighted nonlinear least squares regression, except in the case of outliers. In such cases, Scatchard analysis was more sensitive to outliers. Nonspecific binding was insignificant using nonlinear logistic fit regression and a proportion graph. The effects were tested of multiple free-thawing of sperm in either a commercial egg yolk extender, 40 mM Tris buffer with 8% glycerol, or 40 mM Tris buffer without glycerol. Freeze-thawing in extender did not affect the dissociation constant or the concentration of binding sites. However, freeze-thawing three times in 40 mM Tris reduced the concentration of binding sites and lowered the dissociation constant (raised the affinity). The inclusion of glycerol in the 40 mM Tris did not significantly affect the estimated dissociation constant or the concentration of binding sites as compared to 40 mM Tris without glycerol

  13. Cyclic Voltammetry of Biopolymer Heparin at PVC Plasticized Liquid Membrane

    Samec, Zdeněk; Trojánek, Antonín; Langmaier, Jan; Samcová, E.

    2003-01-01

    Roč. 5, - (2003), s. 867-870 ISSN 1388-2481 R&D Projects: GA ČR GA203/04/0424 Institutional research plan: CEZ:AV0Z4040901 Keywords : cyclic voltammetry * PVC plasticized liquit membrane * heparin Subject RIV: CG - Electrochemistry Impact factor: 2.300, year: 2003

  14. The Effect of Low Molecular Weight Heparins on Fracture Healing.

    Kapetanakis, Stylianos; Nastoulis, Evangelos; Demesticha, Theano; Demetriou, Thespis

    2015-01-01

    Venous Thromboembolism is a serious complication in the trauma patient. The most commonly studied and used anticoagulant treatment in prophylaxis of thrombosis is heparin. The prolonged use of unfractionated heparin has been connected with increased incidence of osteoporotic fractures. Low molecular-weight-heparins (LMWHs) have been the golden rule in antithrombotic therapy during the previous two decades as a way to overcome the major drawbacks of unfractioned heparin. However there are few studies reporting the effects of LMWHs on bone repair after fractures. This review presents the studies about the effects of LMWHs on bone biology (bone cells and bone metabolism) and underlying the mechanisms by which LMWHs may impair fracture healing process. The authors' research based on literature concluded that there are no facts and statistics for the role of LMWHs on fracture healing process in humans and the main body of evidence of their role comes from in vitro and animal studies. Further large clinical studies designed to compare different types of LMWHs, in different dosages and in different patient or animal models are needed for exploring the effects of LMWHs on fracture healing process.

  15. Proteomic analysis of heparin-binding proteins from human seminal ...

    Prakash

    (MALDI TOF/MS) for protein analysis of human HBPs. We resolved 70 ... Thus, the combined effects of seminal plasma components support the survival of ...... The BBXB motif of RANTES is the principal site for heparin binding and controls ...

  16. 21 CFR 864.5680 - Automated heparin analyzer.

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Automated heparin analyzer. 864.5680 Section 864.5680 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Automated and Semi-Automated Hematology Devices § 864...

  17. Clinical effects of low-molecular-weight heparin combined with ...

    Purpose: To explore the clinical effects of low-molecular-weight heparin (LMWH) combined with ulinastatin (UTI) in children with acute pancreatitis. Methods: In total, 560 patients with severe acute pancreatitis treated at Binzhou People's Hospital, Shandong, China, from April 2012 to June 2014 were enrolled in this study.

  18. Alternative method for determination of contaminated heparin using chiral recognition.

    Szekely, J; Collins, M; Currie, C A

    2014-05-15

    Since 2008 a significant amount of work has focused on the development of methods to analyze contaminated heparin. This work focuses on utilizing heparin's ability to serve as a chiral selector as a means for determining contamination. Specifically, the effect of contamination on the separation of pheniramine and chloroquine enantiomers was explored. Separations were conducted using heparin contaminated with chondroitin sulfate at varying levels. For each pair of enantiomers, electrophoretic mobility and resolution were calculated. For pheniramine enantiomers, an increase in contamination leads to a decrease in the electrophoretic mobility and resolution. A linear relationship between contamination level and electrophoretic mobility of the pheniramine enantiomers was observed for the entire contamination range. A linear relationship was also found between contamination level and resolution of the enantiomers between 0 and 70 percent contamination. For the separation of chloroquine enantiomers, it was found that at low levels of contamination, the resolution of enantiomers was increased due to the secondary interaction between the chloroquine enantiomers and the chondroitin sulfate. Results of this study illustrate the potential of using chiral recognition as a means to determine heparin contamination as well as the improvement of the chiral resolution of chloroquine with the additional of low levels of chondroitin sulfate A. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Dansyl (5-dimethylaminonaphthalene-1-sulphonyl)-heparin binds antithrombin III and platelet factor 4 at separate sites

    Piepkorn, Michael W.

    1981-01-01

    Antithrombin III binds to, and thereby augments the fluorescence of, dansyl-(5-dimethylaminonaphthalene-1-sulphonyl)-heparin; platelet factor 4 binding to the fluorescent heparin has little of this effect. Competition studies in which antithrombin III competes with platelet factor 4 for heparin binding demonstrate that heparin can simultaneously bind both proteins. PMID:7317004

  20. Efficient and accurate local approximations to coupled-electron pair approaches: An attempt to revive the pair natural orbital method.

    Neese, Frank; Wennmohs, Frank; Hansen, Andreas

    2009-03-21

    Coupled-electron pair approximations (CEPAs) and coupled-pair functionals (CPFs) have been popular in the 1970s and 1980s and have yielded excellent results for small molecules. Recently, interest in CEPA and CPF methods has been renewed. It has been shown that these methods lead to competitive thermochemical, kinetic, and structural predictions. They greatly surpass second order Moller-Plesset and popular density functional theory based approaches in accuracy and are intermediate in quality between CCSD and CCSD(T) in extended benchmark studies. In this work an efficient production level implementation of the closed shell CEPA and CPF methods is reported that can be applied to medium sized molecules in the range of 50-100 atoms and up to about 2000 basis functions. The internal space is spanned by localized internal orbitals. The external space is greatly compressed through the method of pair natural orbitals (PNOs) that was also introduced by the pioneers of the CEPA approaches. Our implementation also makes extended use of density fitting (or resolution of the identity) techniques in order to speed up the laborious integral transformations. The method is called local pair natural orbital CEPA (LPNO-CEPA) (LPNO-CPF). The implementation is centered around the concepts of electron pairs and matrix operations. Altogether three cutoff parameters are introduced that control the size of the significant pair list, the average number of PNOs per electron pair, and the number of contributing basis functions per PNO. With the conservatively chosen default values of these thresholds, the method recovers about 99.8% of the canonical correlation energy. This translates to absolute deviations from the canonical result of only a few kcal mol(-1). Extended numerical test calculations demonstrate that LPNO-CEPA (LPNO-CPF) has essentially the same accuracy as parent CEPA (CPF) methods for thermochemistry, kinetics, weak interactions, and potential energy surfaces but is up to 500

  1. Heparin and Heparin-Derivatives in Post-Subarachnoid Hemorrhage Brain Injury: A Multimodal Therapy for a Multimodal Disease

    Erik G. Hayman

    2017-05-01

    Full Text Available Pharmacologic efforts to improve outcomes following aneurysmal subarachnoid hemorrhage (aSAH remain disappointing, likely owing to the complex nature of post-hemorrhage brain injury. Previous work suggests that heparin, due to the multimodal nature of its actions, reduces the incidence of clinical vasospasm and delayed cerebral ischemia that accompany the disease. This narrative review examines how heparin may mitigate the non-vasospastic pathological aspects of aSAH, particularly those related to neuroinflammation. Following a brief review of early brain injury in aSAH and heparin’s general pharmacology, we discuss potential mechanistic roles of heparin therapy in treating post-aSAH inflammatory injury. These roles include reducing ischemia-reperfusion injury, preventing leukocyte extravasation, modulating phagocyte activation, countering oxidative stress, and correcting blood-brain barrier dysfunction. Following a discussion of evidence to support these mechanistic roles, we provide a brief discussion of potential complications of heparin usage in aSAH. Our review suggests that heparin’s use in aSAH is not only safe, but effectively addresses a number of pathologies initiated by aSAH.

  2. Efficient C1-continuous phase-potential upwind (C1-PPU) schemes for coupled multiphase flow and transport with gravity

    Jiang, Jiamin; Younis, Rami M.

    2017-10-01

    In the presence of counter-current flow, nonlinear convergence problems may arise in implicit time-stepping when the popular phase-potential upwinding (PPU) scheme is used. The PPU numerical flux is non-differentiable across the co-current/counter-current flow regimes. This may lead to cycles or divergence in the Newton iterations. Recently proposed methods address improved smoothness of the numerical flux. The objective of this work is to devise and analyze an alternative numerical flux scheme called C1-PPU that, in addition to improving smoothness with respect to saturations and phase potentials, also improves the level of scalar nonlinearity and accuracy. C1-PPU involves a novel use of the flux limiter concept from the context of high-resolution methods, and allows a smooth variation between the co-current/counter-current flow regimes. The scheme is general and applies to fully coupled flow and transport formulations with an arbitrary number of phases. We analyze the consistency property of the C1-PPU scheme, and derive saturation and pressure estimates, which are used to prove the solution existence. Several numerical examples for two- and three-phase flows in heterogeneous and multi-dimensional reservoirs are presented. The proposed scheme is compared to the conventional PPU and the recently proposed Hybrid Upwinding schemes. We investigate three properties of these numerical fluxes: smoothness, nonlinearity, and accuracy. The results indicate that in addition to smoothness, nonlinearity may also be critical for convergence behavior and thus needs to be considered in the design of an efficient numerical flux scheme. Moreover, the numerical examples show that the C1-PPU scheme exhibits superior convergence properties for large time steps compared to the other alternatives.

  3. Fully-etched apodized fiber-to-chip grating coupler on the SOI platform with -0.78 dB coupling efficiency using photonic crystals and bonded Al mirror

    Ding, Yunhong; Ou, Haiyan; Peucheret, Christophe

    2014-01-01

    We design and fabricate an ultra-high coupling efficiency fully-etched apodized grating coupler on the SOI platform using photonic crystals and bonded aluminum mirror. Ultra-high coupling efficiency of -0.78 dB with a 3 dB bandwidth of 74 nm are demonstrated.......We design and fabricate an ultra-high coupling efficiency fully-etched apodized grating coupler on the SOI platform using photonic crystals and bonded aluminum mirror. Ultra-high coupling efficiency of -0.78 dB with a 3 dB bandwidth of 74 nm are demonstrated....

  4. The regulatory role of heparin on c-Met signaling in hepatocellular carcinoma cells.

    İşcan, Evin; Güneş, Aysim; Korhan, Peyda; Yılmaz, Yeliz; Erdal, Esra; Atabey, Neşe

    2017-06-01

    The role of heparin as an anticoagulant is well defined; however, its role in tumorigenesis and tumor progression is not clear yet. Some studies have shown that anticoagulant treatment in cancer patients improve overall survival, however, recent clinical trials have not shown a survival benefit in cancer patients receiving heparin treatment. In our previous studies we have shown the inhibitory effects of heparin on Hepatocyte Growth Factor (HGF)-induced invasion and migration in hepatocellular carcinoma (HCC) cells. In this study, we showed the differential effects of heparin on the behaviors of HCC cells based on the presence or absence of HGF. In the absence of HGF, heparin activated HGF/c-Met signaling and promoted motility and invasion in HCC cells. Heparin treatment led to c-Met receptor dimerization and activated c-Met signaling in an HGF independent manner. Heparin-induced c-Met activation increased migration and invasion through ERK1/2, early growth response factor 1 (EGR1) and Matrix Metalloproteinases (MMP) axis. Interestingly, heparin modestly decreased the proliferation of HCC cells by inhibiting activatory phosphorylation of Akt. The inhibition of c-Met signaling reversed heparin-induced increase in motility and invasion and, proliferation inhibition. Our study provides a new perspective into the role of heparin on c-Met signaling in HCC.

  5. Determining the microwave coupling and operational efficiencies of a microwave plasma assisted chemical vapor deposition reactor under high pressure diamond synthesis operating conditions

    Nad, Shreya [Department of Electrical and Computer Engineering, Michigan State University, East Lansing, Michigan 48824 (United States); Department of Physics and Astronomy, Michigan State University, East Lansing, Michigan 48824 (United States); Gu, Yajun; Asmussen, Jes [Department of Electrical and Computer Engineering, Michigan State University, East Lansing, Michigan 48824 (United States)

    2015-07-15

    The microwave coupling efficiency of the 2.45 GHz, microwave plasma assisted diamond synthesis process is investigated by experimentally measuring the performance of a specific single mode excited, internally tuned microwave plasma reactor. Plasma reactor coupling efficiencies (η) > 90% are achieved over the entire 100–260 Torr pressure range and 1.5–2.4 kW input power diamond synthesis regime. When operating at a specific experimental operating condition, small additional internal tuning adjustments can be made to achieve η > 98%. When the plasma reactor has low empty cavity losses, i.e., the empty cavity quality factor is >1500, then overall microwave discharge coupling efficiencies (η{sub coup}) of >94% can be achieved. A large, safe, and efficient experimental operating regime is identified. Both substrate hot spots and the formation of microwave plasmoids are eliminated when operating within this regime. This investigation suggests that both the reactor design and the reactor process operation must be considered when attempting to lower diamond synthesis electrical energy costs while still enabling a very versatile and flexible operation performance.

  6. Direct comparison of the electronic coupling efficiency of sulfur and selenium alligator clips for molecules adsorbed onto gold electrodes

    Patrone, L.; Palacin, S.; Bourgoin, J.P.

    2003-01-01

    Scanning tunneling microscopy experiments have been performed to compare the electronic coupling provided by S and by Se used as alligator clips for bisthiol- and biselenol-terthiophene molecules adsorbed onto gold. The molecules were inserted in a dodecanethiol (DT) self-assembled monolayer. Their apparent height above the dodecanethiol matrix was used as a measure of the electronic coupling strength corresponding to S and Se, respectively. We show that the insertion behaviors of the two molecules are qualitatively the same, and that Se provides systematically a better coupling link than S, whatever the tunneling conditions

  7. Voltammetric determination of heparin based on its interaction with ...

    ... with the linear regression equation as ∆ip″ (nA) = 360.19 C (mg/L) + 178.88 (n = 15, γ = 0.998) and the detection limit as 0.28 mg/L (3σ). The effects of coexisting substances such as metal ions, amino acids on the determination of heparin were investigated and the results showed that this method had good selectivity.

  8. Protein interactions with quaternized chitosan/heparin multilayers

    Kumorek, Marta M.; Kubies, Dana; Riedel, Tomáš

    2016-01-01

    Roč. 65, Suppl. 2 (2016), S253-S261 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) LQ1604 Institutional support: RVO:61389013 Keywords : heparin * chitosan * protein Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.461, year: 2016 http://www.biomed.cas.cz/physiolres/pdf/65%20Suppl%202/65_S253.pdf

  9. Acid-citrate-dextrose compared with heparin in the preparation of in vivo/in vitro technetium-99m red blood cells

    Porter, W.C.; Dees, S.M.; Freitas, J.E.; Dworkin, H.J.

    1983-01-01

    Red blood cells labeled in vivo/in vitro with Tc-99m (Tc-99m RBC) were prepared in a series of 21 patients and two normal volunteers. In each subject both heparin and acid-citrate-dextrose (ACD) solutions were used to label tandem blood samples. The immediate preinjection binding efficiency (BE) was then determined. In each of the 23 studies, the ACD preparation yielded superior BE. The average BE was 93.47% (+/- 3.78) with ACD and 87.23% (+/- 4.29) with heparin. With the ACD method the effect of carrier Tc-99 may be as great as a 24% reduction in BE observed when initial eluates from long-ingrowth-time generators were used. Improved image quality with minimal renal and urinary-bladder activity results with ACD labeling. It is concluded that the use of ACD results in superior RBC labeling with less nontarget activity relative to heparin and is preferred over heparin for preparing in vivo/in vitro Tc-99m RBC

  10. Heparin defends against the toxicity of circulating histones in sepsis.

    Wang, Feifei; Zhang, Naipu; Li, Biru; Liu, Lanbo; Ding, Lei; Wang, Ying; Zhu, Yimin; Mo, Xi; Cao, Qing

    2015-06-01

    Although circulating histones were demonstrated as major mediators of death in septic mice models, their roles in septic patients are not clarified. The present study sought to evaluate the clinical relevance of the circulating histone levels in septic children, and the antagonizing effects of heparin on circulating histones. Histone levels in the plasma of septic children were significantly higher than healthy controls, and positively correlated with disease severity. Histone treatment could activate NF-κB pathway of the endothelial cells and induce the secretion of large amount of cytokines that further amplify inflammation, subsequently leading to organ damage. Co-injection of low dose heparin with lethal dose histones could protect mouse from organ damage and death by antagonizing circulating histones, and similar effects were also observed in other septic models. Collectively, these findings indicated that circulating histones might serve as key factors in the pathogenesis of sepsis and their levels in plasma might be a marker for disease progression and prognosis. Furthermore, low dose heparin might be an effective therapy to hamper sepsis progression and reduce the mortality.

  11. The Use of Heparin during Endovascular Peripheral Arterial Interventions: A Synopsis

    Arno M. Wiersema

    2016-01-01

    Full Text Available A large variety exists for many aspects of the use of heparin as periprocedural prophylactic antithrombotics (PPAT during peripheral arterial interventions (PAI. This variation is present, not only within countries, but also between them. Due to a lack of (robust data, no systematic review on the use of heparin during PAI could be justified. A synopsis of all available literature on heparin during PAI describes that heparin is used on technical equipment to reduce the thrombogenicity and in the flushing solution with saline. Heparin could have a cumulative anticoagulant effect when used in combination with ionic contrast medium. No level-1 evidence exists on the use of heparin. A measurement of actual anticoagulation status by means of an activated clotting time should be mandatory.

  12. Removal of glycosaminoglycans from bovine granulosa cells contributes to increased binding of hydrogen-3 heparin

    Ax, R.L.; Stodd, C.M.; Boehm, S.K.; Bellin, M.E.

    1986-02-01

    Granulosa cells from small or large bovine follicles were pretreated with enzymes that hydrolyze various glycosaminoglycans, and binding of (/sup 3/H)-heparin to the granulosa was measured. Binding of (/sup 3/H) heparin increased significantly after enzymatic pretreatments with chondroitinase ABC and fungal hyaluronidase, and similar results were obtained with granulosa from small and large follicles. No changes in binding of (/sup 3/H) heparin were detected after hydrolyses with chondroitinase AC and heparinase in either follicle size. Heparitinase, which hydrolyzes heparan sulfate, led to a significant 50% increase in binding of (/sup 3/H) heparin to granulosa from large follicles but was without effect in small follicles. These results suggest that the lower binding of (/sup 3/H) heparin, which has been reported with follicular enlargement, may be due to heparan sulfate occupying or obstructing binding sites for heparin on granulosa from large follicles.

  13. Extending the magnetoelectric efficiency of an MFC/brass/NdFeB energy harvester by coupling a pair of movable magnets

    Leung, Chung Ming; Wang, Ya

    2017-10-01

    In this letter, an MFC/brass/NdFeB tip magnet three-phase cantilever beam was coupled with a pair of movable magnets to harness energy from alternating magnetic fields. By coupling with a pair of moveable magnets, both bandwidth and magnetoelectric (ME) voltage coefficient (α\\text{V}) were largely increased by 25% and 87.5%, respectively, in comparison with the same harvester coupled with stationary magnets. Such improvements were attributed to magnetic energy introduced by the moving magnets. Experiments also revealed the boundary positions of external magnets (movable and stationary) where the repulsive magnetic forces jumped to the attractive ones, and the stiffness hardening switched to the softening process. These results provided a wide-band nonlinear approach to efficiently harvest/detect the low-frequency alternating magnetic field energies.

  14. High efficiency all-optical plasmonic diode based on a nonlinear side-coupled waveguide-cavity structure with broken symmetry

    Liang, Hong-Qin; Liu, Bin; Hu, Jin-Feng; He, Xing-Dao

    2018-05-01

    An all-optical plasmonic diode, comprising a metal-insulator-metal waveguide coupled with a stub cavity, is proposed based on a nonlinear Fano structure. The key technique used is to break structural spatial symmetry by a simple reflector layer in the waveguide. The spatial asymmetry of the structure gives rise to the nonreciprocity of coupling efficiencies between the Fano cavity and waveguides on both sides of the reflector layer, leading to a nonreciprocal nonlinear response. Transmission properties and dynamic responses are numerically simulated and investigated by the nonlinear finite-difference time-domain method. In the proposed structure, high-efficiency nonreciprocal transmission can be achieved with a low power threshold and an ultrafast response time (subpicosecond level). A high maximum transmittance of 89.3% and an ultra-high transmission contrast ratio of 99.6% can also be obtained. The device can be flexibly adjusted for working wavebands by altering the stub cavity length.

  15. One-pot solvothermal synthesis of highly efficient, daylight active and recyclable Ag/AgBr coupled photocatalysts with synergistic dual photoexcitation

    Zhang, Caihong; Ai, Lunhong; Li, Lili; Jiang, Jing

    2014-01-01

    Highlights: • Ag/AgBr photocatalysts were controllably synthesized by solvothermal process. • Ag/AgBr composites showed excellent daylight driven photocatalytic activity. • The remarkable activity is attributed to the synergistic dual photoexcitation. -- Abstract: Efficient light harvesting has been considered to be critical for manipulating the photocatalytic behavior of photocatalysts, because it directly determines the generation of reactive redox charge carriers involved in photoreaction process. In this study, we present a successful example on efficient conversion of solar energy by Ag/AgBr coupled photocatalysts that hold unique synergistic dual photoexcitation. A series of Ag/AgBr coupled photocatalysts were controllably synthesized by an easily manipulated mild solvothermal process. The physicochemical properties of the as-prepared Ag/AgBr coupled photocatalysts were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), X-ray energy dispersive spectroscopy (EDS) and UV–vis diffuse reflectance spectroscopy (DRS). The results showed the solvothermal reaction time played key role for control of crystalline structure, morphology, composition, and visible light absorption ability of the resulting photocatalysts. The as-prepared Ag/AgBr coupled photocatalysts exhibited remarkable photocatalytic performance and good reusability for decomposing organic dyes in aqueous solution under the irradiation of commercial 20 W cool daylight fluorescent lamp, owing to the synergistic dual photoexcitation cooperating between plasmonic Ag nanoparticles and narrow-band-gap AgBr

  16. Qualitative and Quantitative Analysis of Heparin during Precipitation by Near-Infrared Spectroscopy

    Lian Li; Jinfeng Wang; Hengchang Zang; Hui Zhang; Wei Jiang; Shang Chen; Fengshan Wang

    2016-01-01

    Heparin is a glycosaminoglycan (GAG) that plays an important role in the blood coagulation system. Its quality is of great importance, so it is necessary to develop a fast analytical method during the manufacture process to analyse the quality of heparin produced. In this study, the heparin contents of 80 samples collected from five batches during the precipitation process were analysed using nearinfrared (NIR) spectroscopy and a chemometrics approach. This was done in order to improve the ef...

  17. Proposal for efficient mode converter based on cavity quantum electrodynamics dark mode in a semiconductor quantum dot coupled to a bimodal microcavity

    Li, Jiahua [School of Physics, Huazhong University of Science and Technology, Wuhan 430074 (China); Key Laboratory of Fundamental Physical Quantities Measurement of Ministry of Education, Wuhan 430074 (China); Yu, Rong, E-mail: yurong321@126.com [School of Science, Hubei Province Key Laboratory of Intelligent Robot, Wuhan Institute of Technology, Wuhan 430073 (China); Ma, Jinyong; Wu, Ying, E-mail: yingwu2@163.com [School of Physics, Huazhong University of Science and Technology, Wuhan 430074 (China)

    2014-10-28

    The ability to engineer and convert photons between different modes in a solid-state approach has extensive technological implications not only for classical communication systems but also for future quantum networks. In this paper, we put forward a scheme for coherent mode conversion of optical photons by utilizing the intermediate coupling between a single quantum dot and a bimodal photonic crystal microcavity via a waveguide. Here, one mode of the photonic crystal microcavity is coherently driven by an external single-frequency continuous-wave laser field and the two cavity modes are not coupled to each other due to their orthogonal polarizations. The undriven cavity mode is thus not directly coupled to the input driving laser and the only way it can get light is via the quantum dot. The influences of the system parameters on the photon-conversion efficiency are analyzed in detail in the limit of weak probe field and it is found that high photon-conversion efficiency can be achieved under appropriate conditions. It is shown that the cavity dark mode, which is a superposition of the two optical modes and is decoupled from the quantum dot, can appear in such a hybrid optical system. We discuss the properties of the dark mode and indicate that the formation of the dark mode enables the efficient transfer of optical fields between the two cavity modes.

  18. From Farm to Pharma: An Overview of Industrial Heparin Manufacturing Methods.

    van der Meer, Jan-Ytzen; Kellenbach, Edwin; van den Bos, Leendert J

    2017-06-21

    The purification of heparin from offal is an old industrial process for which commercial recipes date back to 1922. Although chemical, chemoenzymatic, and biotechnological alternatives for this production method have been published in the academic literature, animal-tissue is still the sole source for commercial heparin production in industry. Heparin purification methods are closely guarded industrial secrets which are not available to the general (scientific) public. However by reviewing the academic and patent literature, we aim to provide a comprehensive overview of the general methods used in industry for the extraction of heparin from animal tissue.

  19. Heparin and insulin in the management of hypertriglyceridemia-associated pancreatitis: case series and literature review.

    Kuchay, Mohammad Shafi; Farooqui, Khalid J; Bano, Tarannum; Khandelwal, Manoj; Gill, Harmandeep; Mithal, Ambrish

    2017-01-01

    Severe hypertriglyceridemia accounts for up to 7% of all cases of acute pancreatitis. Heparin and insulin activate lipoprotein lipase (LPL), thereby reducing plasma triglyceride levels. However, the safety and efficacy of heparin and insulin in the treatment of hypertriglyceridemia-associated acute pancreatitis have not been well established yet. We successfully used heparin and insulin as first-line therapy in four consecutive patients with acute pancreatitis secondary to hypertriglyceridemia. In a literature search, we revised almost all reports published to date of patients managed successfully with this combination. Heparin and insulin appear to be a safe, effective, and inexpensive first-line therapy for hypertriglyceridemia-associated acute pancreatitis.

  20. Evidence-based algorithm for heparin dosing before cardiopulmonary bypass. Part 1: Development of the algorithm.

    McKinney, Mark C; Riley, Jeffrey B

    2007-12-01

    The incidence of heparin resistance during adult cardiac surgery with cardiopulmonary bypass has been reported at 15%-20%. The consistent use of a clinical decision-making algorithm may increase the consistency of patient care and likely reduce the total required heparin dose and other problems associated with heparin dosing. After a directed survey of practicing perfusionists regarding treatment of heparin resistance and a literature search for high-level evidence regarding the diagnosis and treatment of heparin resistance, an evidence-based decision-making algorithm was constructed. The face validity of the algorithm decisive steps and logic was confirmed by a second survey of practicing perfusionists. The algorithm begins with review of the patient history to identify predictors for heparin resistance. The definition for heparin resistance contained in the algorithm is an activated clotting time 450 IU/kg heparin loading dose. Based on the literature, the treatment for heparin resistance used in the algorithm is anti-thrombin III supplement. The algorithm seems to be valid and is supported by high-level evidence and clinician opinion. The next step is a human randomized clinical trial to test the clinical procedure guideline algorithm vs. current standard clinical practice.

  1. Identification of a novel structure in heparin generated by potassium permanganate oxidation

    Beccati, Daniela; Roy, Sucharita; Yu, Fei; Gunay, Nur Sibel; Capila, Ishan; Lech, Miroslaw; Linhardt, Robert J.; Venkataraman, Ganesh

    2012-01-01

    The worldwide heparin contamination crisis in 2008 led health authorities to take fundamental steps to better control heparin manufacture, including implementing appropriate analytical and bio-analytical methods to ensure production and release of high quality heparin sodium product. Consequently, there is an increased interest in the identification and structural elucidation of unusually modified structures that may be present in heparin. Our study focuses on the structural elucidation of species that give rise to a signal observed at 2.10 ppm in the N-acetyl region of the 1H NMR spectrum of some pharmaceutical grade heparin preparations. Structural elucidation experiments were carried out using homonuclear (COSY, TOSCY and NOESY) and heteronuclear (HSQC, HSQC-DEPT, HMQC-COSY, HSQC-TOCSY, and HMBC) 2D NMR spectroscopy on both heparin as well as heparin-like model compounds. Our results identify a novel type of oxidative modification of the heparin chain that results from a specific step in the manufacturing process used to prepare heparin. PMID:25147414

  2. Natural phosphate-supported palladium: A highly efficient and recyclable catalyst for the suzuki-miyaura coupling under microwave irradiation

    Hassine, Ayoub; Bouhrara, Mohamed; Sebti, Said; Solhy, Abderrahim; Mahfouz, Remi; Luart, Denis; Lene, Christophe; Fihri, Aziz

    2015-01-01

    This report explores Suzuki-Miyaura coupling under microwave irradiation, using a new generation of catalyst that is based on natural phosphate (NP) impregnated by palladium. This catalyst was prepared by the treatment of natural phosphate with bis(benzonitrile)palladium(II) chloride in acetone at room temperature. The catalyst displayed high catalytic activity for the Suzuki-Miyaura coupling of aryl bromides and chlorides with aryl boronic acids in pure water and with the use of microwave irradiation. The low-cost and availability of the solid support, mild reaction conditions, high yields of desired products, recyclability of the catalyst and short reaction times are the notable features of these methods.

  3. Natural phosphate-supported palladium: A highly efficient and recyclable catalyst for the suzuki-miyaura coupling under microwave irradiation

    Hassine, Ayoub

    2015-01-19

    This report explores Suzuki-Miyaura coupling under microwave irradiation, using a new generation of catalyst that is based on natural phosphate (NP) impregnated by palladium. This catalyst was prepared by the treatment of natural phosphate with bis(benzonitrile)palladium(II) chloride in acetone at room temperature. The catalyst displayed high catalytic activity for the Suzuki-Miyaura coupling of aryl bromides and chlorides with aryl boronic acids in pure water and with the use of microwave irradiation. The low-cost and availability of the solid support, mild reaction conditions, high yields of desired products, recyclability of the catalyst and short reaction times are the notable features of these methods.

  4. Investigation of High-Efficiency Wireless Power Transfer Criteria of Resonantly-Coupled Loops and Dipoles through Analysis of the Figure of Merit

    Charles Moorey

    2015-10-01

    Full Text Available The efficiency of a Wireless Power Transfer (WPT system is greatly dependent on both the geometry and operating frequency of the transmitting and receiving structures. By using Coupled Mode Theory (CMT, the figure of merit is calculated for resonantly-coupled loop and dipole systems. An in-depth analysis of the figure of merit is performed with respect to the key geometric parameters of the loops and dipoles, along with the resonant frequency, in order to identify the key relationships leading to high-efficiency WPT. For systems consisting of two identical single-turn loops, it is shown that the choice of both the loop radius and resonant frequency are essential in achieving high-efficiency WPT. For the dipole geometries studied, it is shown that the choice of length is largely irrelevant and that as a result of their capacitive nature, low-MHz frequency dipoles are able to produce significantly higher figures of merit than those of the loops considered. The results of the figure of merit analysis are used to propose and subsequently compare two mid-range loop and dipole WPT systems of equal size and operating frequency, where it is shown that the dipole system is able to achieve higher efficiencies than the loop system of the distance range examined.

  5. Debye potentials, electromagnetic reciprocity and impedance boundary conditions for efficient analytic approximation of coupling impedances in complex heterogeneous accelerator pipes

    Petracca, S [Salerno Univ. (Italy)

    1996-08-01

    Debye potentials, the Lorentz reciprocity theorem, and (extended) Leontovich boundary conditions can be used to obtain simple and accurate analytic estimates of the longitudinal and transverse coupling impedances of (piecewise longitudinally uniform) multi-layered pipes with non simple transverse geometry and/or (spatially inhomogeneous) boundary conditions. (author)

  6. Efficient production of acetone-butanol-ethanol (ABE) from cassava by a fermentation-pervaporation coupled process.

    Li, Jing; Chen, Xiangrong; Qi, Benkun; Luo, Jianquan; Zhang, Yuming; Su, Yi; Wan, Yinhua

    2014-10-01

    Production of acetone-butanol-ethanol (ABE) from cassava was investigated with a fermentation-pervaporation (PV) coupled process. ABE products were in situ removed from fermentation broth to alleviate the toxicity of solvent to the Clostridium acetobutylicum DP217. Compared to the batch fermentation without PV, glucose consumption rate and solvent productivity increased by 15% and 21%, respectively, in batch fermentation-PV coupled process, while in continuous fermentation-PV coupled process running for 304 h, the substrate consumption rate, solvent productivity and yield increased by 58%, 81% and 15%, reaching 2.02 g/Lh, 0.76 g/Lh and 0.38 g/g, respectively. Silicalite-1 filled polydimethylsiloxane (PDMS)/polyacrylonitrile (PAN) membrane modules ensured media recycle without significant fouling, steadily generating a highly concentrated ABE solution containing 201.8 g/L ABE with 122.4 g/L butanol. After phase separation, a final product containing 574.3g/L ABE with 501.1g/L butanol was obtained. Therefore, the fermentation-PV coupled process has the potential to decrease the cost in ABE production. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. The efficient synthesis of 2-arylpyrimidine acyclic nucleoside phosphonates using Liebeskind-Srogl cross-coupling reaction

    Břehová, Petra; Česnek, Michal; Dračínský, Martin; Holý, Antonín; Janeba, Zlatko

    2011-01-01

    Roč. 67, č. 38 (2011), s. 7379-7385 ISSN 0040-4020 R&D Projects: GA MŠk 1M0508 Institutional research plan: CEZ:AV0Z40550506 Keywords : Liebeskind-Srogl cross - coupling * acyclic nucleoside phosphonates * pyrimidines * arylboronic acids * microwave Subject RIV: CC - Organic Chemistry Impact factor: 3.025, year: 2011

  8. An efficient protocol for copper-free palladium-catalyzed Sonogashira cross-coupling in aqueous media at low temperatures

    Marziale, Alexander N.; Schlü ter, Johannes; Eppinger, Jö rg

    2011-01-01

    A thorough study on copper-free Sonogashira cross-couplings in water was carried out using the palla-dacycle, [{Pd(μ-Cl){K2-P,C-P(iPr) 2(OC6H3-2-Ph)}}2] as pre-catalyst with different bases and palladium concentrations. The highly active pre

  9. Clinical effectiveness of a Bayesian algorithm for the diagnosis and management of heparin-induced thrombocytopenia.

    Raschke, R A; Gallo, T; Curry, S C; Whiting, T; Padilla-Jones, A; Warkentin, T E; Puri, A

    2017-08-01

    Essentials We previously published a diagnostic algorithm for heparin-induced thrombocytopenia (HIT). In this study, we validated the algorithm in an independent large healthcare system. The accuracy was 98%, sensitivity 82% and specificity 99%. The algorithm has potential to improve accuracy and efficiency in the diagnosis of HIT. Background Heparin-induced thrombocytopenia (HIT) is a life-threatening drug reaction caused by antiplatelet factor 4/heparin (anti-PF4/H) antibodies. Commercial tests to detect these antibodies have suboptimal operating characteristics. We previously developed a diagnostic algorithm for HIT that incorporated 'four Ts' (4Ts) scoring and a stratified interpretation of an anti-PF4/H enzyme-linked immunosorbent assay (ELISA) and yielded a discriminant accuracy of 0.97 (95% confidence interval [CI], 0.93-1.00). Objectives The purpose of this study was to validate the algorithm in an independent patient population and quantitate effects that algorithm adherence could have on clinical care. Methods A retrospective cohort comprised patients who had undergone anti-PF4/H ELISA and serotonin release assay (SRA) testing in our healthcare system from 2010 to 2014. We determined the algorithm recommendation for each patient, compared recommendations with the clinical care received, and enumerated consequences of discrepancies. Operating characteristics were calculated for algorithm recommendations using SRA as the reference standard. Results Analysis was performed on 181 patients, 10 of whom were ruled in for HIT. The algorithm accurately stratified 98% of patients (95% CI, 95-99%), ruling out HIT in 158, ruling in HIT in 10 and recommending an SRA in 13 patients. Algorithm adherence would have obviated 165 SRAs and prevented 30 courses of unnecessary antithrombotic therapy for HIT. Diagnostic sensitivity was 0.82 (95% CI, 0.48-0.98), specificity 0.99 (95% CI, 0.97-1.00), PPV 0.90 (95% CI, 0.56-0.99) and NPV 0.99 (95% CI, 0.96-1.00). Conclusions An

  10. Coupling and power transfer efficiency enhancement of modular and array of planar coils using in-plane ring-shaped inner ferrites for inductive heating applications

    Kilic, V. T.; Unal, E.; Demir, H. V.

    2017-07-01

    We propose and demonstrate a highly effective method of enhancing coupling and power transfer efficiency in inductive heating systems composed of planar coils. The proposed method is based on locating ring-shaped ferrites in the inner side of the coils in the same plane. Measurement results of simple inductive heating systems constructed with either a single or a pair of conventional circular coils show that, with the in-plane inner ferrites, the total dissipated power of the system is increased by over 65%. Also, with three-dimensional full electromagnetic solutions, it is found that power transfer efficiency of the system is increased up to 92% with the inner ferrite placement. The proposed method is promising to be used for efficiency enhancement in inductive heating applications, especially in all-surface induction hobs.

  11. Highly efficient transition metal-free coupling of acid chlorides with terminal alkynes in [bmim]Br: A rapid route to access ynones using MgCl2

    Mohammad Navid Soltani Rad

    2018-03-01

    Full Text Available A simple, mild, highly efficient and transition metal-free protocol for synthesis of ynones in an ionic liquid is described. In this approach, the coupling reaction of different acid chlorides with terminal alkynes was efficiently carried out using 0.05 mol% MgCl2 in the presence of triethylamine in [bmim]Br at room temperature to afford the corresponding ynones in good to excellent yields. This method is highly efficient for various acid chlorides and alkynes including aliphatic, aromatic, and heteroaromatic substrates bearing different functional groups. The influence of some parameters in this reaction including type of ionic liquid, base and catalyst has been discussed.

  12. Effect of the ratio of radial gap to radius of the coils on the transmission efficiency of wireless power transfer via coupled magnetic resonances

    Gao, Pengfei; Tian, Zijian; Wang, Xuqi; Wu, Jun; Gui, Weifeng

    2018-03-01

    Wireless power transfer (WPT) via coupled magnetic resonance is a promising technology to be applied in many fields. In general, there will be a radial gap in practical application, and some special application environments need to limit the radius of the coils. Therefore, in this paper, considering the comprehensive analysis of the radial gap and the radius of the coils, the concept of the ratio of radial gap to the radius of the coils was proposed. Based on the circuit theory, the formula between the ratio and transmission efficiency of WPT was deduced, and the effects of the ratio on the transmission efficiency were studied respectively at different axial distances. Simulation experiments were carried out and the results not only demonstrate the influence law of the ratio on transmission efficiency, but also validate the value of the ratio which the axial distance has the greatest effect on the transmission efficiency. Besides, the results shows the relationship between the effect of the ratio on the efficiency and the effect of the axial distance on the efficiency. The experimental results show that the theoretical analysis is correct, thus providing an useful theoretical reference for the design and further research on the wireless power transfer system in complicated environment.

  13. Effect of the ratio of radial gap to radius of the coils on the transmission efficiency of wireless power transfer via coupled magnetic resonances

    Pengfei Gao

    2018-03-01

    Full Text Available Wireless power transfer (WPT via coupled magnetic resonance is a promising technology to be applied in many fields. In general, there will be a radial gap in practical application, and some special application environments need to limit the radius of the coils. Therefore, in this paper, considering the comprehensive analysis of the radial gap and the radius of the coils, the concept of the ratio of radial gap to the radius of the coils was proposed. Based on the circuit theory, the formula between the ratio and transmission efficiency of WPT was deduced, and the effects of the ratio on the transmission efficiency were studied respectively at different axial distances. Simulation experiments were carried out and the results not only demonstrate the influence law of the ratio on transmission efficiency, but also validate the value of the ratio which the axial distance has the greatest effect on the transmission efficiency. Besides, the results shows the relationship between the effect of the ratio on the efficiency and the effect of the axial distance on the efficiency. The experimental results show that the theoretical analysis is correct, thus providing an useful theoretical reference for the design and further research on the wireless power transfer system in complicated environment.

  14. Sensitive and selective turn off-on fluorescence detection of heparin based on the energy transfer platform using the BSA-stabilized Au nanoclusters/amino-functionalized graphene oxide hybrids.

    Lan, Jing; Zou, Hong Yan; Wang, Qiang; Zeng, Ping; Li, Yuan Fang; Huang, Cheng Zhi

    2016-12-01

    An ultra-sensitive and selective turn off-on fluorescence detection of heparin based on the energy transfer in the BSA-stabilized gold nanoclusters/amino-functionalized graphene oxide (BSA-AuNCs/NH 2 -GO) hybrids was successfully realized. The BSA-AuNCs containing amounts of carboxyl groups could be absorbed on the surface of NH 2 -GO through the electrostatic interaction, which resulted in the fluorescence quenching of BSA-AuNCs with high efficiency. However, heparin, possessing high density of negative charge, could compete with BSA-AuNCs to bind NH 2 -GO and block the energy transfer from BSA-AuNCs to NH 2 -GO. The fluorescence recovery of BSA-AuNCs was closely related to the amount of heparin and there was a good linear relationship between fluorescence recovery of BSA-AuNCs and heparin over the range of 100ng/mL to 30μg/mL with a detection limit of 40ng/mL. What's more, the fluorescence assay was successfully applied for heparin sensing in human serums and intracellular imaging. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Fragment profiling of low molecular weight heparins using reversed phase ion pair liquid chromatography-electrospray mass spectrometry.

    Xu, Xiaohui; Li, Daoyuan; Chi, Lequan; Du, Xuzhao; Bai, Xue; Chi, Lianli

    2015-04-30

    Low molecular weight heparins (LMWHs) are linear and highly charged carbohydrate polymers prepared by chemical or enzymatic depolymerization of heparin. Compared to unfractionated heparin (UFH), LMWHs are prevalently used as clinical anticoagulant drugs due to their lower side effects and better bioavailability. The work presented herein provides a rapid and powerful fragment mapping method for structural characterization of LMWHs. The chain fragments of two types of LMWHs, enoxaparin and nadroparin, were generated by controlled enzymatic digestion with each of heparinase I (Hep I, Enzyme Commission (EC) # 4.2.2.7), heparinase II (Hep II, no EC # assigned) and heparinase III (Hep III, EC # 4.2.2.8). Reversed phase ion pair high performance liquid chromatography (RPIP-HPLC) coupled with electrospray ion trap time-of-flight mass spectrometry (ESI-IT-TOF-MS) was used to profile the oligosaccharide chains ranging from disaccharides to decasaccharides. A database containing all theoretical structural compositions was established to assist the mass spectra interpretation. The six digests derived by three enzymes from two types of LMWHs exhibited distinguishable fingerprinting patterns. And a total of 94 enoxaparin fragments and 109 nadroparin fragments were detected and identified. Besides the common LMWH oligosaccharides, many components containing characteristic LMWH structures such as saturated L-idopyranosuronic acid, 2,5-anhydro-D-mannitol, 1,6-anhydro-D-aminopyranose, as well as odd number oligosaccharides were also revealed. Quantitative comparison of major components derived from innovator and generic nadroparin products was presented. This approach to profile LMWHs' fragments offers a highly reproducible, high resolution and information-rich tool for evaluating the quality of this category of anticoagulant drugs or comparing structural similarities among samples from various sources. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Optimization of membrane stack configuration for efficient hydrogen production in microbial reverse-electrodialysis electrolysis cells coupled with thermolytic solutions

    Luo, Xi

    2013-07-01

    Waste heat can be captured as electrical energy to drive hydrogen evolution in microbial reverse-electrodialysis electrolysis cells (MRECs) by using thermolytic solutions such as ammonium bicarbonate. To determine the optimal membrane stack configuration for efficient hydrogen production in MRECs using ammonium bicarbonate solutions, different numbers of cell pairs and stack arrangements were tested. The optimum number of cell pairs was determined to be five based on MREC performance and a desire to minimize capital costs. The stack arrangement was altered by placing an extra low concentration chamber adjacent to anode chamber to reduce ammonia crossover. This additional chamber decreased ammonia nitrogen losses into anolyte by 60%, increased the coulombic efficiency to 83%, and improved the hydrogen yield to a maximum of 3.5mol H2/mol acetate, with an overall energy efficiency of 27%. These results improve the MREC process, making it a more efficient method for renewable hydrogen gas production. © 2013 Elsevier Ltd.

  17. Vitamin K antagonists or low-molecular-weight heparin for the long term treatment of symptomatic venous thromboembolism

    van der Heijden, J. F.; Hutten, B. A.; Büller, H. R.; Prins, M. H.

    2002-01-01

    BACKGROUND: People with venous thromboembolism are generally treated for five days with intravenous unfractionated heparin or subcutaneous low-molecular-weight heparin followed by three months of vitamin K antagonists treatment. Treatment with vitamin K antagonists requires regular laboratory

  18. Relativistic four-component calculations of indirect nuclear spin-spin couplings with efficient evaluation of the exchange-correlation response kernel

    Křístková, Anežka; Malkin, Vladimir G. [Institute of Inorganic Chemistry, Slovak Academy of Sciences, Dúbravská cesta 9, SK-84536 Bratislava (Slovakia); Komorovsky, Stanislav; Repisky, Michal [Centre for Theoretical and Computational Chemistry, University of Tromsø - The Arctic University of Norway, N-9037 Tromsø (Norway); Malkina, Olga L., E-mail: olga.malkin@savba.sk [Institute of Inorganic Chemistry, Slovak Academy of Sciences, Dúbravská cesta 9, SK-84536 Bratislava (Slovakia); Department of Inorganic Chemistry, Comenius University, Bratislava (Slovakia)

    2015-03-21

    In this work, we report on the development and implementation of a new scheme for efficient calculation of indirect nuclear spin-spin couplings in the framework of four-component matrix Dirac-Kohn-Sham approach termed matrix Dirac-Kohn-Sham restricted magnetic balance resolution of identity for J and K, which takes advantage of the previous restricted magnetic balance formalism and the density fitting approach for the rapid evaluation of density functional theory exchange-correlation response kernels. The new approach is aimed to speedup the bottleneck in the solution of the coupled perturbed equations: evaluation of the matrix elements of the kernel of the exchange-correlation potential. The performance of the new scheme has been tested on a representative set of indirect nuclear spin-spin couplings. The obtained results have been compared with the corresponding results of the reference method with traditional evaluation of the exchange-correlation kernel, i.e., without employing the fitted electron densities. Overall good agreement between both methods was observed, though the new approach tends to give values by about 4%-5% higher than the reference method. On the average, the solution of the coupled perturbed equations with the new scheme is about 8.5 times faster compared to the reference method.

  19. Relativistic four-component calculations of indirect nuclear spin-spin couplings with efficient evaluation of the exchange-correlation response kernel

    Křístková, Anežka; Malkin, Vladimir G.; Komorovsky, Stanislav; Repisky, Michal; Malkina, Olga L.

    2015-01-01

    In this work, we report on the development and implementation of a new scheme for efficient calculation of indirect nuclear spin-spin couplings in the framework of four-component matrix Dirac-Kohn-Sham approach termed matrix Dirac-Kohn-Sham restricted magnetic balance resolution of identity for J and K, which takes advantage of the previous restricted magnetic balance formalism and the density fitting approach for the rapid evaluation of density functional theory exchange-correlation response kernels. The new approach is aimed to speedup the bottleneck in the solution of the coupled perturbed equations: evaluation of the matrix elements of the kernel of the exchange-correlation potential. The performance of the new scheme has been tested on a representative set of indirect nuclear spin-spin couplings. The obtained results have been compared with the corresponding results of the reference method with traditional evaluation of the exchange-correlation kernel, i.e., without employing the fitted electron densities. Overall good agreement between both methods was observed, though the new approach tends to give values by about 4%-5% higher than the reference method. On the average, the solution of the coupled perturbed equations with the new scheme is about 8.5 times faster compared to the reference method

  20. Assessment of HIT Antibody Complex in Hip Fracture Patients Receiving Enoxaparin or Unfractionated Heparin

    Griffin, Justin W; Hopkinson, William J; Rud-Lassen, Michael

    2011-01-01

    of antiheparin-PF4 antibodies and a greater prevalence of immunoglobulin G (IgG) subtype. Heparin and enoxaparin are capable of generating heparin-induced thrombocytopenia (HIT) antibodies in elderly patients undergoing orthopedic surgery but perhaps not to the same extent. When comparing low...

  1. Heparin induced alterations in clearance and distribution of blood-borne microparticles following operative trauma.

    Saba, T M; Antikatzides, T G

    1979-04-01

    The influence of systemic heparin administration on the vascular clearance and tissue distribution of blood-borne microparticles was evaluated in normal rats and rats after operation (laparotomy plus intestinal manipulation) utilizing an (131)I- colloid which is phagocytized by the reticuloendothelial system (RES). Intravenous heparin administration (100 USP/100g body weight) into normal animals three minutes prior to colloid injection (50 mg/lOOg) induced a significant increase in pulmonary localization of the microparticles as compared to nonheparinized control rats, while hepatic and splenic uptake were decreased. Surgical trauma decreased hepatic RE uptake and increased pulmonary localization of the microparticles when injected systemically at 60 minutes postsurgery. Heparin administration 60 minutes after surgery and three minutes prior to colloid injection, magnified the increased pulmonary localization response with an associated further depression of the RES. The ability of heparin to alter both RE clearance function and lung localization of microparticles was dose dependent and a function of the interval between heparin administration and systemic particulate infusion. Thus, low dose heparin administration was capable of stimulating RE activity while heparin in doses of excess of 50 USP units/lOOg body weight decreased RE function. These findings suggest that the functional state of the hepatic RE system can be greatly affected in a dose-dependent manner by systemic heparin administration which may influence distribution of blood-borne microparticles.

  2. Heparin Interaction with the Primed Polymorphonuclear Leukocyte CD11b Induces Apoptosis and Prevents Cell Activation

    Meital Cohen-Mazor

    2015-01-01

    Full Text Available Heparin is known to have anti-inflammatory effects, yet the mechanisms are not completely understood. In this study, we tested the hypothesis that heparin has a direct effect on activated polymorphonuclear leukocytes (PMNLs, changing their activation state, and can explain its anti-inflammatory effect. To test our hypothesis, we designed both in vitro and ex vivo studies to elucidate the mechanism by which heparin modulates PMNL functions and therefore the inflammatory response. We specifically tested the hypothesis that priming of PMNLs renders them more susceptible to heparin. Amplified levels of CD11b and increased rate of superoxide release manifested PMNL priming. Increase in cell priming resulted in a dose-dependent increase in heparin binding to PMNLs followed by augmented apoptosis. Blocking antibodies to CD11b inhibited heparin binding and abolished the apoptotic response. Moreover, heparin caused a significant dose-dependent decrease in the rate of superoxide release from PMNLs, which was blunted by blocking antibodies to CD11b. Altogether, this study shows that the interaction of heparin with the PMNL CD11b results in cell apoptosis and explains heparin’s anti-inflammatory effects.

  3. Targeting Heparin to Collagen within Extracellular Matrix Significantly Reduces Thrombogenicity and Improves Endothelialization of Decellularized Tissues.

    Jiang, Bin; Suen, Rachel; Wertheim, Jason A; Ameer, Guillermo A

    2016-12-12

    Thrombosis within small-diameter vascular grafts limits the development of bioartificial, engineered vascular conduits, especially those derived from extracellular matrix (ECM). Here we describe an easy-to-implement strategy to chemically modify vascular ECM by covalently linking a collagen binding peptide (CBP) to heparin to form a heparin derivative (CBP-heparin) that selectively binds a subset of collagens. Modification of ECM with CBP-heparin leads to increased deposition of functional heparin (by ∼7.2-fold measured by glycosaminoglycan composition) and a corresponding reduction in platelet binding (>70%) and whole blood clotting (>80%) onto the ECM. Furthermore, addition of CBP-heparin to the ECM stabilizes long-term endothelial cell attachment to the lumen of ECM-derived vascular conduits, potentially through recruitment of heparin-binding growth factors that ultimately improve the durability of endothelialization in vitro. Overall, our findings provide a simple yet effective method to increase deposition of functional heparin on the surface of ECM-based vascular grafts and thereby minimize thrombogenicity of decellularized tissue, overcoming a significant challenge in tissue engineering of bioartificial vessels and vascularized organs.

  4. Safety of low-molecular-weight heparin in pregnancy: a systematic review

    Sanson, B. J.; Lensing, A. W.; Prins, M. H.; Ginsberg, J. S.; Barkagan, Z. S.; Lavenne-Pardonge, E.; Brenner, B.; Dulitzky, M.; Nielsen, J. D.; Boda, Z.; Turi, S.; Mac Gillavry, M. R.; Hamulyák, K.; Theunissen, I. M.; Hunt, B. J.; Büller, H. R.

    1999-01-01

    Unfractionated heparin (UFH) remains the anticoagulant of choice during pregnancy. Low-molecular-weight heparins (LMWH) are an attractive alternative to UFH due to their logistic advantages and their association with a lower incidence of osteoporosis and HIT. We reviewed all published clinical

  5. Poly(vinyl alcohol)-heparin hydrogels as sensor catheter membranes

    Brinkman, E.; van der Does, L.; Bantjes, A.

    1991-01-01

    Poly(vinyl alcohol)-heparin hydrogels with varying water content were synthesized for use as sensor catheter membranes. Films were cast from aqueous mixtures of poly(viny) alcohol) (PVA), a photosensitive cross-linker p-diazonium diphenyl amine polymer (PA), glutaraldehyde (GA) and heparin. After

  6. Design of a new type of coating for the controlled release of heparin

    Hinrichs, W.L.J.; Hinrichs, W.L.J.; ten Hoopen, Hermina W.M.; Wissink, M.J.B.; Engbers, G.H.M.; Feijen, Jan

    1997-01-01

    Thrombus formation at the surface of blood contacting devices can be prevented by local release of heparin. Preferably, the release rate should be constant for prolonged periods of time. The minimum heparin release rate to achieve thromboresistance will be different for various applications and

  7. Anti-Platelet Factor 4/Heparin Antibody Formation Occurs Endogenously and at Unexpected High Frequency in Polycythemia Vera

    Sara C. Meyer

    2017-01-01

    Full Text Available Background. Myeloproliferative neoplasms (MPN encounter thromboses due to multiple known risk factors. Heparin-induced thrombocytopenia (HIT is a thrombotic syndrome mediated by anti-platelet factor 4 (PF4/heparin antibodies with undetermined significance for thrombosis in MPN. We hypothesized that anti-PF4/heparin Ab might occur in MPN and promote thrombosis. Methods. Anti-PF4/heparin antibodies were analyzed in 127 MPN patients including 76 PV and 51 ET. Screening, validation testing, and isotype testing of anti-PF4/heparin Ab were correlated with disease characteristics. Results. Anti-PF4/heparin antibodies were detected in 21% of PV and 12% of ET versus 0.3–3% in heparin-exposed patients. Validation testing confirmed anti-PF4/heparin immunoglobulins in 15% of PV and 10% of ET. Isotype testing detected 9.2% IgG and 5.3% IgM in PV and exclusively IgM in ET. IgG-positive PV patients encountered thromboses in 57.1% suggesting anti-PF4/heparin IgG may contribute to higher risk for thrombosis in MPN. Overall, 45% of PV patients experienced thromboses with 11.8% positive for anti-PF4/heparin IgG versus 7.1% in PV without thrombosis. Conclusion. Anti-PF4/heparin antibodies occur endogenously and more frequently in MPN than upon heparin exposure. Thrombotic risk increases in anti-PF4/heparin IgG-positive PV reflecting potential implications and calling for larger, confirmatory cohorts. Anti-PF4/heparin IgG should be assessed upon thrombosis in PV to facilitate avoidance of heparin in anti-PF4/heparin IgG-positive PV.

  8. High-slope-efficiency 2.06 μm Ho: YLF laser in-band pumped by a fiber-coupled broadband diode.

    Ji, Encai; Liu, Qiang; Nie, Mingming; Cao, Xuezhe; Fu, Xing; Gong, Mali

    2016-03-15

    We first demonstrate the laser performance of a compact 2.06 μm Ho: YLF laser resonantly pumped by a broadband fiber-coupled diode. In continuous-wave (CW) operation, maximum output power of 1.63 W, corresponding to a slope efficiency of 89.2%, was obtained with a near diffraction-limited beam quality. In actively Q-switched operation, maximum pulse energy of 1.1 mJ was achieved at the repetition frequency of 100 Hz. The minimum pulse duration was 43 ns. The performance in both the CW and Q-switched regimes indicates that the current fiber-coupled diode in-band pumped Ho: YLF laser has great potential in certain conditions that require several watts of output power or several millijoules of short pulse energy.

  9. Immobilized Palladium Nanoparticles on Zirconium Carboxy-Aminophosphonates Nanosheets as an Efficient Recoverable Heterogeneous Catalyst for Suzuki–Miyaura and Heck Coupling

    Vadym Kozell

    2017-06-01

    Full Text Available Zirconium phosphate glycine diphosphonate nanosheets (ZPGly have been used as support for the preparation of solid palladium nanoparticles, namely Pd@ZPGly. Thanks to the presence of carboxy-aminophosponate groups on the layer surface, ZPGly-based materials were able to stabilize a high amount of palladium (up to 22 wt % also minimizing the amount of metal leached in the final products of representative important cross-coupling processes selected for proving the catalysts’ efficiency. The catalytic systems have been fully characterized and used in low amounts (0.1 mol % in the Suzuki–Miyaura and Heck cross-couplings. Moreover, the protocols were optimized for the use of recoverable azeotropic mixtures (aq. EtOH 96% or aq. CH3CN 84%, respectively and in the flow procedure allowing one to isolate the final pure products, without any purification step, with very low residual palladium content and with a very low waste production.

  10. Improved efficiency of CdS quantum dot sensitized solar cell with an organic redox couple and a polymer counter electrode

    Shu, Ting; Li, Xiong; Ku, Zhi-Liang; Wang, Shi; Wu, Shi; Jin, Xiao-Hong; Hu, Chun-Di

    2014-01-01

    Highlights: • The organic AT - /BAT and T - /T 2 redox couples were used in CdS QDSSCs. • The AT - /BAT and PEDOT are better than polysulfide electrolyte and Pt and CoS CEs. • An improved η of 1.53% was obtained with the AT - /BAT electrolyte and the PEDOT CE. • PEDOT CE deposited at high deposition charge has better electrochemical activity. • The AT - /BAT outperformed T - /T 2 electrolyte due to suppressed charge recombination. - Abstract: Quantum dot sensitized solar cells (QDSSCs) based on an organic thiolate/disulfide redox couple (C 7 H 5 N 4 S - /C 14 H 10 N 8 S 2 or C 2 H 3 N 4 S - /C 4 H 6 N 8 S 2 ) and a polymer counter electrode [poly (3, 4-ethylenedioxythiophene), PEDOT] were fabricated and their photovoltaic performance were investigated. In CdS QDSSC, the organic C 7 H 5 N 4 S - /C 14 H 10 N 8 S 2 electrolyte shows better performance than the polysulfide electrolyte, and the PEDOT counter electrode exhibits higher efficiency than that of the Pt counter electrode and the CoS counter electrode. An efficiency of 1.53% was achieved in this QDSSC. The influences of the morphology and the deposition charge of the PEDOT counter electrodes on the cell performance were also studied. Furthermore, it was found that the C 7 H 5 N 4 S - /C 14 H 10 N 8 S 2 redox couple outperformed the C 2 H 3 N 4 S - /C 4 H 6 N 8 S 2 redox couple due to reduced electron recombination

  11. Facile one-step hydrothermal synthesis toward strongly coupled TiO2/graphene quantum dots photocatalysts for efficient hydrogen evolution

    Min, Shixiong; Hou, Jianhua; Lei, Yonggang; Ma, Xiaohua; Lu, Gongxuan

    2017-01-01

    Highlights: • TiO 2 /GQDs composites were prepared by a facile one-step hydrothermal method. • GQDs were strongly coupled onto the surface of TiO 2 nanoparticles by this method. • The TiO 2 /GQDs showed enhanced light absorption and charge separation efficiency. • The TiO 2 /GQDs exhibited higher photocatalytic H 2 evolution activity than pure TiO 2 . • GQDs play synergistic roles by acting as both photosensitizer and electron acceptor. - Abstract: The coupling of semiconductor photocatalysts with graphene quantum dots (GQDs) has been proven to be an effective strategy to enhance the photocatalytic and photoelectrical conversion performances of the resulted composites; however, the preparation of semiconductor/GQDs composites usually involves several time-inefficient and tedious post-treatment steps. Herein, we present a facile one-step hydrothermal route for the preparation of GQDs coupled TiO 2 (TiO 2 /GQDs) photocatalysts using 1,3,6-trinitropyrene (TNP) as the sole precursor of GQDs. During the hydrothermal process, TNP molecules undergo an intramolecular fusion to form GQDs, which simultaneously decorate on the surface of TiO 2 nanoparticles, leading to a strong surface interaction between the two components. The effective coupling of GQDs on TiO 2 can effectively extend the light absorption of the TiO 2 to visible region and enhance the charge separation efficiency of TiO 2 /GQDs composites as a result of GQDs acting as a photosensitizer and an excellent electron acceptor. These key advances make the TiO 2 /GQDs photocatalyst highly active towards the H 2 evolution reaction, resulting in 7 and 3 times higher H 2 evolution rate and photocurrent response at optimal GQDs content than TiO 2 alone, respectively. This study provides a new methodology for the development of high-performance GQDs modified semiconductor photocatalysts for energy conversion applications.

  12. Heparinization of alimentation solutions administered through peripheral veins in premature infants: a controlled study.

    Alpan, G; Eyal, F; Springer, C; Glick, B; Goder, K; Armon, J

    1984-09-01

    A randomized controlled study was done to determine whether the addition of heparin (1 U/mL) to peripheral intravenous alimentation solutions would affect the incidence of phlebitis and duration of patency of intravenous catheters in premature infants. Twenty-two-gauge Teflon catheters were uniformly used. One hundred five catheters infused with heparin were placed in 13 infants, and 122 catheters were placed in the control group of 13 infants. The time, nature, and incidence of complications were noted for each infusion site. Infusion of heparin was found to double the duration of patency of intravenous catheters and to reduce significantly the incidence of phlebitis. No complications related to the administration of heparin were noted. Heparinization of intravenous alimentation solutions should therefore be considered in premature infants as a means of reducing the work load and incidence of complications associated with peripheral lines.

  13. Heparin-Induced Cardiac Tamponade and Life-Threatening Hyperkalemia in a Patient with Chronic Hemodialysis

    Ho-Ming Su

    2005-03-01

    Full Text Available Heparin, a commonly used anticoagulant agent, is frequently used in patients undergoing hemodialysis. As with most medications, heparin has a significant side effect profile. Two of its most important side effects, major bleeding and hyperkalemia, may be devastating without immediate diagnosis and treatment. Major bleeding such as gastrointestinal, genitourinary or intracranial bleeding is occasionally encountered and rarely neglected. However, heparin-induced cardiac tamponade is rarely encountered and may be easily overlooked. Another side effect, heparin-induced hyperkalemia, an unusual but well-described side effect, is frequently forgotten until life-threatening arrhythmia has occurred. We report a case involving a 40-year-old male patient with uremia, who had received heparin for 10 days for deep vein thrombosis in the left lower extremity. Hemopericardium with cardiac tamponade and life-threatening hyperkalemia were both noted in this patient.

  14. The US regulatory and pharmacopeia response to the global heparin contamination crisis.

    Szajek, Anita Y; Chess, Edward; Johansen, Kristian; Gratzl, Gyöngyi; Gray, Elaine; Keire, David; Linhardt, Robert J; Liu, Jian; Morris, Tina; Mulloy, Barbara; Nasr, Moheb; Shriver, Zachary; Torralba, Pearle; Viskov, Christian; Williams, Roger; Woodcock, Janet; Workman, Wesley; Al-Hakim, Ali

    2016-06-09

    The contamination of the widely used lifesaving anticoagulant drug heparin in 2007 has drawn renewed attention to the challenges that are associated with the characterization, quality control and standardization of complex biological medicines from natural sources. Heparin is a linear, highly sulfated polysaccharide consisting of alternating glucosamine and uronic acid monosaccharide residues. Heparin has been used successfully as an injectable antithrombotic medicine since the 1930s, and its isolation from animal sources (primarily porcine intestine) as well as its manufacturing processes have not changed substantially since its introduction. The 2007 heparin contamination crisis resulted in several deaths in the United States and hundreds of adverse reactions worldwide, revealing the vulnerability of a complex global supply chain to sophisticated adulteration. This Perspective discusses how the US Food and Drug Administration (FDA), the United States Pharmacopeial Convention (USP) and international stakeholders collaborated to redefine quality expectations for heparin, thus making an important natural product better controlled and less susceptible to economically motivated adulteration.

  15. Relationship of nonreturn rates of dairy bulls to binding affinity of heparin to sperm

    Marks, J.L.; Ax, R.L.

    1985-01-01

    The binding of the glycosaminoglycan [ 3 H] heparin to bull spermatozoa was compared with nonreturn rates of dairy bulls. Semen samples from five bulls above and five below an average 71% nonreturn rate were used. Samples consisted of first and second ejaculates on a single day collected 1 d/wk for up to 5 consecutive wk. Saturation binding assays using [ 3 H] heparin were performed to quantitate the binding characteristics of each sample. Scatchard plot analyses indicated a significant difference in the binding affinity for [ 3 H] heparin between bulls of high and low fertility. Dissociation constants were 69.0 and 119.3 pmol for bulls of high and low fertility, respectively. In contrast, the number of binding sites for [ 3 H] heparin did not differ significantly among bulls. Differences in binding affinity of [ 3 H] heparin to bull sperm might be used to predict relative fertility of dairy bulls

  16. Interactions of oversulfated chondroitin sulfate (OSCS) from different sources with unfractionated heparin.

    Gray, Angel; Litinas, Evangelos; Jeske, Walter; Fareed, Jawed; Hoppensteadt, Debra

    2012-01-01

    In 2008, oversulfated chondroitin sulfate (OSCS) was identified as the main contaminant in recalled heparin. Oversulfated chondroitin sulfate can be prepared from bovine (B), porcine (P), shark (Sh), or skate (S) origin and may produce changes in the antithrombotic, bleeding, and hemodynamic profile of heparins. This study examines the interactions of various OSCSs on heparin in animal models of thrombosis and bleeding, as well as on the anticoagulant and antiprotease effects in in vitro assays. Mixtures of 70% unfractionated heparin (UFH) with 30% OSCS from different sources were tested. In the in vitro activated partial thromboplastin time (aPTT) assay, all contaminant mixtures showed a decrease in clotting times. In addition, a significant increase in bleeding time compared to the control (UFH/saline) was observed. In the thrombosis model, no significant differences were observed. The OSCSs significantly increased anti-Xa activity in ex vivo blood samples. These results indicate that various sources of OSCS affect the hemostatic properties of heparin.

  17. Enhanced basal contractility but reduced excitation-contraction coupling efficiency and beta-adrenergic reserve of hearts with increased Cav1.2 activity.

    Tang, Mingxin; Zhang, Xiaoying; Li, Yingxin; Guan, Yinzheng; Ai, Xiaojie; Szeto, Christopher; Nakayama, Hiroyuki; Zhang, Hongyu; Ge, Shuping; Molkentin, Jeffery D; Houser, Steven R; Chen, Xiongwen

    2010-08-01

    Cardiac remodeling during heart failure development induces a significant increase in the activity of the L-type Ca(2+) channel (Cav1.2). However, the effects of enhanced Cav1.2 activity on myocyte excitation-contraction (E-C) coupling, cardiac contractility, and its regulation by the beta-adrenergic system are not clear. To recapitulate the increased Cav1.2 activity, a double transgenic (DTG) mouse model overexpressing the Cavbeta2a subunit in a cardiac-specific and inducible manner was established. We studied cardiac (in vivo) and myocyte (in vitro) contractility at baseline and upon beta-adrenergic stimulation. E-C coupling efficiency was evaluated in isolated myocytes as well. The following results were found: 1) in DTG myocytes, L-type Ca(2+) current (I(Ca,L)) density, myocyte fractional shortening (FS), peak Ca(2+) transients, and sarcoplasmic reticulum (SR) Ca(2+) content (caffeine-induced Ca(2+) transient peak) were significantly increased (by 100.8%, 48.8%, 49.8%, and 46.8%, respectively); and 2) cardiac contractility evaluated with echocardiography [ejection fraction (EF) and (FS)] and invasive intra-left ventricular pressure (maximum dP/dt and -dP/dt) measurements were significantly greater in DTG mice than in control mice. However, 1) the cardiac contractility (EF, FS, dP/dt, and -dP/dt)-enhancing effect of the beta-adrenergic agonist isoproterenol (2 microg/g body wt ip) was significantly reduced in DTG mice, which could be attributed to the loss of beta-adrenergic stimulation on contraction, Ca(2+) transients, I(Ca,L), and SR Ca(2+) content in DTG myocytes; and 2) E-C couplng efficiency was significantly lower in DTG myocytes. In conclusion, increasing Cav1.2 activity by promoting its high-activity mode enhances cardiac contractility but decreases E-C coupling efficiency and the adrenergic reserve of the heart.

  18. An efficient approach to numerical study of the coupled-BBM system with B-spline collocation method

    khalid ali

    2016-11-01

    Full Text Available In the present paper, a numerical method is proposed for the numerical solution of a coupled-BBM system with appropriate initial and boundary conditions by using collocation method with cubic trigonometric B-spline on the uniform mesh points. The method is shown to be unconditionally stable using von-Neumann technique. To test accuracy the error norms2L, ?L are computed. Furthermore, interaction of two and three solitary waves are used to discuss the effect of the behavior of the solitary waves after the interaction. These results show that the technique introduced here is easy to apply. We make linearization for the nonlinear term.

  19. Surface plasmon coupling dynamics in InGaN/GaN quantum-well structures and radiative efficiency improvement

    Fadil, Ahmed; Iida, Daisuke; Chen, Yuntian

    2014-01-01

    for InGaN/GaN quantum-well structures. By using a thin SiN dielectric layer between Ag and GaN we manage to modify and improve surface plasmon coupling effects, and we attribute this to the improved scattering of the nanoparticles at the quantum-well emission wavelength. The results are interpreted using...... numerical simulations, where absorption and scattering cross-sections are studied for different sized particles on GaN and GaN/SiN substrates....

  20. An efficient protocol for copper-free palladium-catalyzed Sonogashira cross-coupling in aqueous media at low temperatures

    Marziale, Alexander N.

    2011-11-01

    A thorough study on copper-free Sonogashira cross-couplings in water was carried out using the palla-dacycle, [{Pd(μ-Cl){K2-P,C-P(iPr) 2(OC6H3-2-Ph)}}2] as pre-catalyst with different bases and palladium concentrations. The highly active pre-catalyst imparts good to near quantitative yields using a concentration of 0.25 mol % at 40 °C. This broadly applicable protocol exhibits high tolerance of functional groups and substitution patterns. © 2011 Elsevier Ltd. All rights reserved.

  1. Experimental Determination of Operating and Maximum Power Transfer Efficiencies at Resonant Frequency in a Wireless Power Transfer System using PP Network Topology with Top Coupling

    Ramachandran, Hema; Pillai, K. P. P.; Bindu, G. R.

    2017-08-01

    A two-port network model for a wireless power transfer system taking into account the distributed capacitances using PP network topology with top coupling is developed in this work. The operating and maximum power transfer efficiencies are determined analytically in terms of S-parameters. The system performance predicted by the model is verified with an experiment consisting of a high power home light load of 230 V, 100 W and is tested for two forced resonant frequencies namely, 600 kHz and 1.2 MHz. The experimental results are in close agreement with the proposed model.

  2. Top-down approach for the direct characterization of low molecular weight heparins using LC-FT-MS.

    Li, Lingyun; Zhang, Fuming; Zaia, Joseph; Linhardt, Robert J

    2012-10-16

    Low molecular heparins (LMWHs) are structurally complex, heterogeneous, polydisperse, and highly negatively charged mixtures of polysaccharides. The direct characterization of LMWH is a major challenge for currently available analytical technologies. Electrospray ionization (ESI) liquid chromatography-mass spectrometry (LC-MS) is a powerful tool for the characterization complex biological samples in the fields of proteomics, metabolomics, and glycomics. LC-MS has been applied to the analysis of heparin oligosaccharides, separated by size exclusion, reversed phase ion-pairing chromatography, and chip-based amide hydrophilic interaction chromatography (HILIC). However, there have been limited applications of ESI-LC-MS for the direct characterization of intact LMWHs (top-down analysis) due to their structural complexity, low ionization efficiency, and sulfate loss. Here we present a simple and reliable HILIC-Fourier transform (FT)-ESI-MS platform to characterize and compare two currently marketed LMWH products using the top-down approach requiring no special sample preparation steps. This HILIC system relies on cross-linked diol rather than amide chemistry, affording highly resolved chromatographic separations using a relatively high percentage of acetonitrile in the mobile phase, resulting in stable and high efficiency ionization. Bioinformatics software (GlycReSoft 1.0) was used to automatically assign structures within 5-ppm mass accuracy.

  3. How much heparin do we really need to go on pump? A rethink of current practices.

    Shuhaibar, M N

    2012-02-03

    OBJECTIVES: Patients undergoing myocardial revascularisation using extracorporeal circulation require heparin anticoagulation. We aimed to evaluate the effect of reducing heparin dosage on target activated clotting time (ACT) and postoperative blood loss. METHODS: In a prospective randomised trial, 195 patients undergoing isolated primary CABG were randomised into four groups A, B, C, and D receiving an initial heparin dosage of 100, 200, 250 and 300 iu\\/kg, respectively. Extra incremental heparin (50 iu\\/kg) was added if required to achieve a target ACT of 480 s before initiating cardiopulmonary bypass. Postoperative blood loss was measured from the time of heparin reversal to drain removal 24h later. RESULTS: Target ACT was achieved in 0, 63, 68.3 and 82.4% of patients in groups A, B, C and D, respectively, after the initial dose of heparin. In group B, of those not achieving target act a single increment of heparin was sufficient to achieve target ACT in further 18.6%. The mean ACT after the initial dose in groups B, C and D was 482.9, 519 and 588 s, respectively (P<0.05). Postoperative blood loss in millilitre per kilogram was directly proportional to preoperative heparin dose. CONCLUSIONS: Patients receiving lower dose of heparin has lower postoperative blood loss. Of those achieving the target ACT, group B was significantly the closest to the target ACT. A starting dose of 200 iu\\/kg of heparin and if necessary one 50 iu\\/kg increment achieved target ACT in 81.5% of patients. The added benefit of significant drop in postoperative blood loss is evident.

  4. A Heparin Binding Motif Rich in Arginine and Lysine is the Functional Domain of YKL-40

    Nipaporn Ngernyuang

    2018-02-01

    Full Text Available The heparin-binding glycoprotein YKL-40 (CHI3L1 is intimately associated with microvascularization in multiple human diseases including cancer and inflammation. However, the heparin-binding domain(s pertinent to the angiogenic activity have yet been identified. YKL-40 harbors a consensus heparin-binding motif that consists of positively charged arginine (R and lysine (K (RRDK; residues 144–147; but they don't bind to heparin. Intriguingly, we identified a separate KR-rich domain (residues 334–345 that does display strong heparin binding affinity. A short synthetic peptide spanning this KR-rich domain successfully competed with YKL-40 and blocked its ability to bind heparin. Three individual point mutations, where alanine (A substituted for K or R (K337A, K342A, R344A, led to remarkable decreases in heparin-binding ability and angiogenic activity. In addition, a neutralizing anti-YKL-40 antibody that targets these residues and prevents heparin binding impeded angiogenesis in vitro. MDA-MB-231 breast cancer cells engineered to express ectopic K337A, K342A or R344A mutants displayed reduced tumor development and compromised tumor vessel formation in mice relative to control cells expressing wild-type YKL-40. These data reveal that the KR-rich heparin-binding motif is the functional heparin-binding domain of YKL-40. Our findings shed light on novel molecular mechanisms underlying endothelial cell angiogenesis promoted by YKL-40 in a variety of diseases.

  5. Low-molecular weight heparin increases circulating sFlt-1 levels and enhances urinary elimination.

    Henning Hagmann

    Full Text Available RATIONALE: Preeclampsia is a devastating medical complication of pregnancy which leads to maternal and fetal morbidity and mortality. While the etiology of preeclampsia is unclear, human and animal studies suggest that excessive circulating levels of soluble fms-like tyrosine-kinase-1 (sFlt-1, an alternatively spliced variant of VEGF-receptor1, contribute to the signs and symptoms of preeclampsia. Since sFlt-1 binds to heparin and heparan sulfate proteoglycans, we hypothesized that the anticoagulant heparin, which is often used in pregnancy, may interfere with the levels, distribution and elimination of sFlt-1 in vivo. OBJECTIVE: We systematically determined serum and urine levels of angiogenic factors in preeclamptic women before and after administration of low molecular weight heparin and further characterized the interaction with heparin in biochemical studies. METHODS AND RESULTS: Serum and urine samples were used to measure sFlt-1 levels before and after heparin administration. Serum levels of sFlt-1 increased by 25% after heparin administration in pregnant women. The magnitude of the increase in circulating sFlt-1 correlated with initial sFlt-1 serum levels. Urinary sFlt-1 levels were also elevated following heparin administration and levels of elimination were dependent on the underlying integrity of the glomerular filtration barrier. Biochemical binding studies employing cation exchange chromatography revealed that heparin bound sFlt-1 had decreased affinity to negatively charged surfaces when compared to sFlt-1 alone. CONCLUSION: Low molecular weight heparin administration increased circulating sFlt1 levels and enhanced renal elimination. We provide evidence that both effects may be due to heparin binding to sFlt1 and masking the positive charges on sFlt1 protein.

  6. Modulation transfer function and detective quantum efficiency of electron bombarded charge coupled device detector for low energy electrons

    Horáček, Miroslav

    2005-01-01

    Roč. 76, č. 9 (2005), 093704:1-6 ISSN 0034-6748 R&D Projects: GA ČR(CZ) GA202/03/1575 Keywords : electron bombarded CCD * modulation transfer function * detective quantum efficiency Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering Impact factor: 1.235, year: 2005

  7. Intravitreal low molecular weight heparin in PVR surgery.

    Kumar Atul

    2003-01-01

    Full Text Available Purpose: To evaluate the efficacy of low molecular weight heparin (LMWH in prevention of postoperative fibrin formation following vitreoretinal surgery with proliferative vitreoretinopathy (PVR. Material and Methods: Thirty consecutive patients of retinal detachment with advanced PVR were enrolled in the study. They were randomised to study and control groups (n = 15 each. Study group patients received vitreoretinal surgery with 5 IU/cc of LMWH in vitrectomy infusion fluid. The control group patients received vitroretinal surgery without heparin in the infusion fluid. Patients were followed up at 1 week, 1 month and 3 months after surgery. Postoperative bleeding, media clarity, best-corrected visual acuity and success of the surgery at the end of 3 months were compared between the two groups. Results: At each follow-up visit, the study group showed a better media clarity, which was statistically significant ( P = 0.0042. The study group had a 50% better chance of retinal reattachment compared to the control group. Five patients had intraoperative bleeding in the study group (33% compared to 3 patients in the control group (20%. Conclusion: Use of intravitreal LMWH prevents postoperative fibrin formation and is beneficial in repair of retinal detachments with PVR.

  8. Multifunctional silk-heparin biomaterials for vascular tissue engineering applications

    Seib, F. Philipp; Herklotz, Manuela; Burke, Kelly A.; Maitz, Manfred F.; Werner, Carsten; Kaplan, David L.

    2013-01-01

    Over the past 30 years, silk has been proposed for numerous biomedical applications that go beyond its traditional use as a suture material. Silk sutures are well tolerated in humans, but the use of silk for vascular engineering applications still requires extensive biocompatibility testing. Some studies have indicated a need to modify silk to yield a hemocompatible surface. This study examined the potential of low molecular weight heparin as a material for refining silk properties by acting as a carrier for vascular endothelial growth factor (VEGF) and improving silk hemocompatibility. Heparinized silk showed a controlled VEGF release over 6 days; the released VEGF was bioactive and supported the growth of human endothelial cells. Silk samples were then assessed using a humanized hemocompatibility system that employs whole blood and endothelial cells. The overall thrombogenic response for silk was very low and similar to the clinical reference material polytetrafluoroethylene. Despite an initial inflammatory response to silk, apparent as complement and leukocyte activation, the endothelium was maintained in a resting, anticoagulant state. The low thrombogenic response and the ability to control VEGF release support the further development of silk for vascular applications. PMID:24099708

  9. Ways to increase efficiency of the HTGR coupled with the gas-turbine power conversion unit - HTR2008-58274

    Golovko, V. F.; Kodochigov, N. G.; Vasyaev, A. V.; Shenoy, A.; Baxi, C. B.

    2008-01-01

    The paper deals with the issue of increasing efficiency of nuclear power plants with the modular high-temperature helium reactor (HTGR) and direct gas turbine cycle. It should be noted that only this combination can highlight the advantages of the HTGR, namely the ability to heat helium to about 1000 deg. C, in comparison with other reactor plants for electricity generation. The HTGR has never been used in the direct gas turbine cycle. At present, several designs of such commercial plants are at the stage of experimental validation of main technical features. In Russia, 'OKB Mechanical Engineering' together with 'General Atomics' (USA) are developing the GT-MHR project with the reactor power of 600 MW, reactor outlet helium temperature of 850 deg. C, and efficiency of about 45.2%; the South African Republic is developing the PBMR project with the reactor power of 400 MW, reactor outlet helium temperature of 900 deg. C, and efficiency of about 42%; and Japan is developing the GTHTR-300 project with the reactor power of 600 MW, reactor outlet helium temperature of 850 deg. C, and efficiency of about 45.6%. As it has been proven by technical and economic estimations, one of the most important factors for successful promotion of reactor designs is their net efficiency, which must be not lower than 47%. A significant advantage of a reactor plant with the HTGR and gas-turbine power conversion unit over the steam cycle is considerable simplification of the power unit layout and reduction of the required equipment and systems (no steam generators, no turbine hall including steam lines, condenser, deaerator, etc.), which makes the gas-turbine power conversion unit more compact and less costly in production, operation and maintenance. However, in spite of this advantage, it seems that in the projects currently being developed, the potential of the gas-turbine cycle and high-temperature reactor to more efficiently generate electricity is not fully used. For example, in modern

  10. Nanocrystal Size-Dependent Efficiency of Quantum Dot Sensitized Solar Cells in the Strongly Coupled CdSe Nanocrystals/TiO2 System.

    Yun, Hyeong Jin; Paik, Taejong; Diroll, Benjamin; Edley, Michael E; Baxter, Jason B; Murray, Christopher B

    2016-06-15

    Light absorption and electron injection are important criteria determining solar energy conversion efficiency. In this research, monodisperse CdSe quantum dots (QDs) are synthesized with five different diameters, and the size-dependent solar energy conversion efficiency of CdSe quantum dot sensitized solar cell (QDSSCs) is investigated by employing the atomic inorganic ligand, S(2-). Absorbance measurements and transmission electron microscopy show that the diameters of the uniform CdSe QDs are 2.5, 3.2, 4.2, 6.4, and 7.8 nm. Larger CdSe QDs generate a larger amount of charge under the irradiation of long wavelength photons, as verified by the absorbance results and the measurements of the external quantum efficiencies. However, the smaller QDs exhibit faster electron injection kinetics from CdSe QDs to TiO2 because of the high energy level of CBCdSe, as verified by time-resolved photoluminescence and internal quantum efficiency results. Importantly, the S(2-) ligand significantly enhances the electronic coupling between the CdSe QDs and TiO2, yielding an enhancement of the charge transfer rate at the interfacial region. As a result, the S(2-) ligand helps improve the new size-dependent solar energy conversion efficiency, showing best performance with 4.2-nm CdSe QDs, whereas conventional ligand, mercaptopropionic acid, does not show any differences in efficiency according to the size of the CdSe QDs. The findings reported herein suggest that the atomic inorganic ligand reinforces the influence of quantum confinement on the solar energy conversion efficiency of QDSSCs.

  11. Using a coupled inductor controlled by fuzzy logic to improve the efficiency of a Buck converter in a PV system

    Abouchabana Nabil

    2017-01-01

    Full Text Available Photovoltaic generators (PVG produce a variable power according to the solar radiation (G and temperature (T. This variation affects the sizing of the components of DC / DC converters, powered by such PVG, and make it difficult. The effects may differ from one component to another. The main and critical one is presented by the inductor, the element that stores the energy during sampled periods. We propose in this work an auto-adaptation of these inductor values to maintain optimal performance of the power yield of these converters. Our idea is to replace the inductor by a coupled inductor where this adjustment is made by the addition of an adjustable electric field in the magnetic core. Low current intensities come from the PVG supply the second inductor of the coupled inductor through a circuit controlled by a fuzzy controller (FC. The whole system is modeled and simulated under MATLAB/SIMULINK for the control part of the system and under PSPICE for the power part of the system. The obtained results show good performances of the proposed converter over the standard one.

  12. Using a coupled inductor controlled by fuzzy logic to improve the efficiency of a Buck converter in a PV system

    Abouchabana, Nabil; Haddadi, Mourad; Rabhi, Abdelhamid; El Hajjaji, Ahmed

    2017-11-01

    Photovoltaic generators (PVG) produce a variable power according to the solar radiation (G) and temperature (T). This variation affects the sizing of the components of DC / DC converters, powered by such PVG, and make it difficult. The effects may differ from one component to another. The main and critical one is presented by the inductor, the element that stores the energy during sampled periods. We propose in this work an auto-adaptation of these inductor values to maintain optimal performance of the power yield of these converters. Our idea is to replace the inductor by a coupled inductor where this adjustment is made by the addition of an adjustable electric field in the magnetic core. Low current intensities come from the PVG supply the second inductor of the coupled inductor through a circuit controlled by a fuzzy controller (FC). The whole system is modeled and simulated under MATLAB/SIMULINK for the control part of the system and under PSPICE for the power part of the system. The obtained results show good performances of the proposed converter over the standard one.

  13. Highly efficient maximum power point tracking using DC-DC coupled inductor single-ended primary inductance converter for photovoltaic power systems

    Quamruzzaman, M.; Mohammad, Nur; Matin, M. A.; Alam, M. R.

    2016-10-01

    Solar photovoltaics (PVs) have nonlinear voltage-current characteristics, with a distinct maximum power point (MPP) depending on factors such as solar irradiance and operating temperature. To extract maximum power from the PV array at any environmental condition, DC-DC converters are usually used as MPP trackers. This paper presents the performance analysis of a coupled inductor single-ended primary inductance converter for maximum power point tracking (MPPT) in a PV system. A detailed model of the system has been designed and developed in MATLAB/Simulink. The performance evaluation has been conducted on the basis of stability, current ripple reduction and efficiency at different operating conditions. Simulation results show considerable ripple reduction in the input and output currents of the converter. Both the MPPT and converter efficiencies are significantly improved. The obtained simulation results validate the effectiveness and suitability of the converter model in MPPT and show reasonable agreement with the theoretical analysis.

  14. Growth of a delta-doped silicon layer by molecular beam epitaxy on a charge-coupled device for reflection-limited ultraviolet quantum efficiency

    Hoenk, Michael E.; Grunthaner, Paula J.; Grunthaner, Frank J.; Terhune, R. W.; Fattahi, Masoud; Tseng, Hsin-Fu

    1992-01-01

    Low-temperature silicon molecular beam epitaxy is used to grow a delta-doped silicon layer on a fully processed charge-coupled device (CCD). The measured quantum efficiency of the delta-doped backside-thinned CCD is in agreement with the reflection limit for light incident on the back surface in the spectral range of 260-600 nm. The 2.5 nm silicon layer, grown at 450 C, contained a boron delta-layer with surface density of about 2 x 10 exp 14/sq cm. Passivation of the surface was done by steam oxidation of a nominally undoped 1.5 nm Si cap layer. The UV quantum efficiency was found to be uniform and stable with respect to thermal cycling and illumination conditions.

  15. Strongly coupled CdS/graphene quantum dots nanohybrids for highly efficient photocatalytic hydrogen evolution: unraveling the essential roles of graphene quantum dots

    Lei, Yonggang

    2017-05-23

    It have been recognized that the coupling of graphene quantum dots (GQDs) with semiconductor photocatalysts endow the resulting nanocomposites with enhanced photocatalytic performances, however, the essential roles of GQDs have not been clearly revealed yet. Herein, we report that a high efficiency of the photocatalytic H2 evolution was achieved using strongly coupled nanohybrids of CdS with GQDs (CdS/GQDs) as visible-light-driven photocatalysts. CdS/GQDs nanohybrids were synthesized by a facile hydrothermal method in which the crystallization of CdS precursor and coupling of GQDs could be accomplished in one-step. GQDs are firmly decorated on the surface of CdS nanoparticles, forming “dot-on-particle” heterodimer structures. GQDs have no significant influence on the crystallite structure of CdS but render the nanohybrids with strong light absorption at the wavelength beyond the band edge of CdS. Under visible light irradiation (≥420nm), CdS/GQDs nanohybrids reach the highest H2 production rate of 95.4μmol·h−1, about 2.7 times higher than that of pure CdS nanoparticles, at GQDs content of 1.0wt %, and the apparent quantum efficiency (AQE) was determined to be 4.2% at 420nm. Incident light-wavelength dependent experiments reveal that the light absorption of CdS dominated the performance of nanohybrids, and the excess light absorption coming from GQDs hardly contributes to the observed higher activity. Photocurrent response, steady-state and time-resolved PL, and EIS measurements suggest that the high activity of CdS/GQDs is attributed predominantly to the graphene-like nature of GQDs, which can act as an efficient electron acceptor to induce an efficient charge separation. This work clearly reveals that GQDs mainly played a role of electron acceptor instead of a photosensitizer in enhancing the photocatalytic H2 evolution performances of CdS/GQDs nanohybrids, which offers a new insight to understand the essential roles of GQDs in semiconductor

  16. Efficient photocatalytic performance enhancement in Co-doped ZnO nanowires coupled with CuS nanoparticles

    Li, Wei; Wang, Guojing; Feng, Yimeng; Li, Zhengcao

    2018-01-01

    In this research, a kind of highly efficient semiconductor photocatalyst was fabricated by depositing CuS nanoparticles uniformly on the surface of Co-doped ZnO nanowires. ZnO nanowires were synthesized by hydrothermal method and CuS nanoparticles were modified by successive ionic layer adsorption and reaction (SILAR). By conducting methyl orange (MO) degradation experiments under the illumination of visible light, the photocatalytic activity of Co-doped ZnO nanowires modified with CuS nanoparticles was found to be nearly three times active when compared to bare ZnO nanowires. Its superior photocatalytic performance has two main reasons. The doped Co2+ ions can inhibit the recombination of photo-generated electron-hole pairs and decrease the optical bandgap, while the p-n heterostructure can enhance the visible light absorption ability and promote the separation of photo-excited charge carriers. Furthermore, the effect of the amount of deposited CuS nanoparticles on the photocatalysis was also investigated. The photocatalytic efficiency firstly raised along with the increment of SILAR cycle times and reached a maximum at 10 cycles but then decreased as the cycle times continue to increase. This originates from that an excessive amount of CuS would not only cover the active reacting sites, but also serve as recombination centers. Overall, this new nanostructure is expected to work as an efficient photocatalyst.

  17. Improving the Efficiency of 3-D Hydrogeological Mixers: Dilution Enhancement Via Coupled Engineering-Induced Transient Flows and Spatial Heterogeneity

    Di Dato, Mariaines; de Barros, Felipe P. J.; Fiori, Aldo; Bellin, Alberto

    2018-03-01

    Natural attenuation and in situ oxidation are commonly considered as low-cost alternatives to ex situ remediation. The efficiency of such remediation techniques is hindered by difficulties in obtaining good dilution and mixing of the contaminant, in particular if the plume deformation is physically constrained by an array of wells, which serves as a containment system. In that case, dilution may be enhanced by inducing an engineered sequence of injections and extractions from such pumping system, which also works as a hydraulic barrier. This way, the aquifer acts as a natural mixer, in a manner similar to the industrialized engineered mixers. Improving the efficiency of hydrogeological mixers is a challenging task, owing to the need to use a 3-D setup while relieving the computational burden. Analytical solutions, though approximated, are a suitable and efficient tool to seek the optimum solution among all possible flow configurations. Here we develop a novel physically based model to demonstrate how the combined spatiotemporal fluctuations of the water fluxes control solute trajectories and residence time distributions and therefore, the effectiveness of contaminant plume dilution and mixing. Our results show how external forcing configurations are capable of inducing distinct time-varying groundwater flow patterns which will yield different solute dilution rates.

  18. A capillary monolithic trypsin reactor for efficient protein digestion in online and offline coupling to ESI and MALDI mass spectrometry.

    Spross, Jens; Sinz, Andrea

    2010-02-15

    We describe the preparation of a capillary trypsin immobilized monolithic enzyme reactor (IMER) for a rapid and efficient digestion of proteins down to the femtomole level. Trypsin was immobilized on a poly(glycidyl methacrylate-co-acrylamide-co-ethylene glycol dimethycrylate) monolith using the glutaraldehyde technique. Digestion efficiencies of the IMER were evaluated using model proteins and protein mixtures as well as chemically cross-linked lysozyme regarding the addition of denaturants and increasing digestion temperature. The trypsin IMER described herein is applicable for the digestion of protein mixtures. Even at a 1000-fold molar excess of one protein, low-abundance proteins are readily identified, in combination with MS/MS analysis. An online setup of the IMER with reversed phase nano-HPLC separation and nano-ESI-MS/MS analysis was established. The great potential of the trypsin IMER for proteomics applications comprise short digestion times in the range of seconds to minutes, in addition to improved digestion efficiencies, compared to in-solution digestion.

  19. Pb and Sr isotope measurements by inductively coupled plasma mass spectrometer: efficient time management for precision improvement

    Monna, F.; Loizeau, J.-L.; Thomas, B. A.; Guéguen, C.; Favarger, P.-Y.

    1998-08-01

    One of the factors limiting the precision of inductively coupled plasma mass spectrometry is the counting statistics, which depend upon acquisition time and ion fluxes. In the present study, the precision of the isotopic measurements of Pb and Sr is examined. The time of measurement is optimally shared for each isotope, using a mathematical simulation, to provide the lowest theoretical analytical error. Different algorithms of mass bias correction are also taken into account and evaluated in term of improvement of overall precision. Several experiments allow a comparison of real conditions with theory. The present method significantly improves the precision, regardless of the instrument used. However, this benefit is more important for equipment which originally yields a precision close to that predicted by counting statistics. Additionally, the procedure is flexible enough to be easily adapted to other problems, such as isotopic dilution.

  20. Efficient production of membrane-integrated and detergent-soluble G protein-coupled receptors in Escherichia coli.

    Link, A James; Skretas, Georgios; Strauch, Eva-Maria; Chari, Nandini S; Georgiou, George

    2008-10-01

    G protein-coupled receptors (GPCRs) are notoriously difficult to express, particularly in microbial systems. Using GPCR fusions with the green fluorescent protein (GFP), we conducted studies to identify bacterial host effector genes that result in a general and significant enhancement in the amount of membrane-integrated human GPCRs that can be produced in Escherichia coli. We show that coexpression of the membrane-bound AAA+ protease FtsH greatly enhances the expression yield of four different class I GPCRs, irrespective of the presence of GFP. Using this new expression system, we produced 0.5 and 2 mg/L of detergent-solubilized and purified full-length central cannabinoid receptor (CB1) and bradykinin receptor 2 (BR2) in shake flask cultures, respectively, two proteins that had previously eluded expression in microbial systems.

  1. An efficient method to generate a perturbed parameter ensemble of a fully coupled AOGCM without flux-adjustment

    P. J. Irvine

    2013-09-01

    Full Text Available We present a simple method to generate a perturbed parameter ensemble (PPE of a fully-coupled atmosphere-ocean general circulation model (AOGCM, HadCM3, without requiring flux-adjustment. The aim was to produce an ensemble that samples parametric uncertainty in some key variables and gives a plausible representation of the climate. Six atmospheric parameters, a sea-ice parameter and an ocean parameter were jointly perturbed within a reasonable range to generate an initial group of 200 members. To screen out implausible ensemble members, 20 yr pre-industrial control simulations were run and members whose temperature responses to the parameter perturbations were projected to be outside the range of 13.6 ± 2 °C, i.e. near to the observed pre-industrial global mean, were discarded. Twenty-one members, including the standard unperturbed model, were accepted, covering almost the entire span of the eight parameters, challenging the argument that without flux-adjustment parameter ranges would be unduly restricted. This ensemble was used in 2 experiments; an 800 yr pre-industrial and a 150 yr quadrupled CO2 simulation. The behaviour of the PPE for the pre-industrial control compared well to ERA-40 reanalysis data and the CMIP3 ensemble for a number of surface and atmospheric column variables with the exception of a few members in the Tropics. However, we find that members of the PPE with low values of the entrainment rate coefficient show very large increases in upper tropospheric and stratospheric water vapour concentrations in response to elevated CO2 and one member showed an implausible nonlinear climate response, and as such will be excluded from future experiments with this ensemble. The outcome of this study is a PPE of a fully-coupled AOGCM which samples parametric uncertainty and a simple methodology which would be applicable to other GCMs.

  2. Human Cytochrome P450 3A4 as a Biocatalyst: Effects of the Engineered Linker in Modulation of Coupling Efficiency in 3A4-BMR Chimeras.

    Degregorio, Danilo; D'Avino, Serena; Castrignanò, Silvia; Di Nardo, Giovanna; Sadeghi, Sheila J; Catucci, Gianluca; Gilardi, Gianfranco

    2017-01-01

    Human liver cytochrome P450 3A4 is the main enzyme involved in drug metabolism. This makes it an attractive target for biocatalytic applications, such as the synthesis of pharmaceuticals and drug metabolites. However, its poor solubility, stability and low coupling have limited its application in the biotechnological context. We previously demonstrated that the solubility of P450 3A4 can be increased by creating fusion proteins between the reductase from Bacillus megaterium BM3 (BMR) and the N-terminally modified P450 3A4 (3A4-BMR). In this work, we aim at increasing stability and coupling efficiency by varying the length of the loop connecting the two domains to allow higher inter-domain flexibility, optimizing the interaction between the domains. Starting from the construct 3A4-BMR containing the short linker Pro-Ser-Arg, two constructs were generated by introducing a 3 and 5 glycine hinge (3A4-3GLY-BMR and 3A4-5GLY-BMR). The three fusion proteins show the typical absorbance at 450 nm of the reduced heme-CO adduct as well as the correct incorporation of the FAD and FMN cofactors. Each of the three chimeric proteins were more stable than P450 3A4 alone. Moreover, the 3A4-BMR-3-GLY enzyme showed the highest NADPH oxidation rate in line with the most positive reduction potential. On the other hand, the 3A4-BMR-5-GLY fusion protein showed a V max increased by 2-fold as well as a higher coupling efficiency when compared to 3A4-BMR in the hydroxylation of the marker substrate testosterone. This protein also showed the highest rate value of cytochrome c reduction when this external electron acceptor is used to intercept electrons from BMR to P450. The data suggest that the flexibility and the interaction between domains in the chimeric proteins is a key parameter to improve turnover and coupling efficiency. These findings provide important guidelines in engineering catalytically self-sufficient human P450 for applications in biocatalysis.

  3. Preparation of Low Molecular Weight Heparin by Microwave Discharge Electrodeless Lamp/TiO2 Photo-Catalytic Reaction.

    Lee, Do-Jin; Kim, Byung Hoon; Kim, Sun-Jae; Kim, Jung-Sik; Lee, Heon; Jung, Sang-Chul

    2015-01-01

    An MDEL/TiO2 photo-catalyst hybrid system was applied, for the first time, for the production of low molecular weight heparin. The molecular weight of produed heparin decreased with increasing microwave intensity and treatment time. The abscission of the chemical bonds between the constituents of heparin by photo-catalytic reaction did not alter the characteristics of heparin. Formation of by-products due to side reaction was not observed. It is suggested that heparin was depolymerized by active oxygen radicals produced during the MDEL/TiO2 photo-chemical reaction.

  4. Inductively coupled plasma torch efficiency at atmospheric pressure for organo-chlorine liquid waste removal: Chloroform destruction in oxidative conditions

    Kamgang-Youbi, Georges, E-mail: kamyougeo@yahoo.fr [French Atomic Commission-CEA, Marcoule-DTCD/SCDV/LPIC, BP 17171, 30207 Bagnols-Sur-Cèze Cedex (France); Department of Inorganic Chemistry, The University of Yaounde I, P.O Box, 812 Yaounde (Cameroon); Poizot, Karine; Lemont, Florent [French Atomic Commission-CEA, Marcoule-DTCD/SCDV/LPIC, BP 17171, 30207 Bagnols-Sur-Cèze Cedex (France)

    2013-01-15

    Highlights: ► Inductively plasma torch is used for the decomposition of organochlorine molecule. ► We examine the impact of liquid water substitution by oxygen gas as oxidant. ► Complete and safe decomposition is achieved with the presence of oxygen. ► The energy efficiency and capabilities of process are better with O{sub 2} than H{sub 2}O. -- Abstract: The performance of a plasma reactor for the degradation of chlorinated hydrocarbon waste is reported. Chloroform was used as a target for a recently patented destruction process based using an inductive plasma torch. Liquid waste was directly injected axially into the argon plasma with a supplied power of ∼4 kW in the presence of oxygen as oxidant and carrier gas. Decomposition was performed at CHCl{sub 3} feed rates up to 400 g h{sup −1} with different oxygen/waste molar ratios, chloroform destruction was obtained with at least 99% efficiency and the energy efficiency reached 100 g kWh{sup −1}. The conversion end products were identified and assayed by online FTIR spectroscopy (CO{sub 2}, HCl and H{sub 2}O) and redox titration (Cl{sub 2}). Considering phosgene as representative of toxic compounds, only very small quantities of toxics were released (<1 g h{sup −1}) even with high waste feed rates. The experimental results were very close to the equilibrium composition predicted by thermodynamic calculations. At the bottom of the reactor, the chlorinated acids were successfully trapped in a scrubber and transformed into mineral salts, hence, only CO{sub 2} and H{sub 2}O have been found in the final off-gases composition.

  5. Earth-Abundant Oxygen Evolution Catalysts Coupled onto ZnO Nanowire Arrays for Efficient Photoelectrochemical Water Cleavage

    Jiang, Chaoran; Moniz, Savio J A; Khraisheh, Majeda; Tang, Junwang

    2014-01-01

    ZnO has long been considered as a model UV-driven photoanode for photoelectrochemical water splitting, but its performance has been limited by fast charge-carrier recombination, extremely poor stability in aqueous solution, and slow kinetics of water oxidation. These issues were addressed by applying a strategy of optimization and passivation of hydrothermally grown 1D ZnO nanowire arrays. The length and diameter of bare ZnO nanowires were optimized by varying the growth time and precursor concentration to achieve optimal photoelectrochemical performance. The addition of earth-abundant cobalt phosphate (Co-Pi) and nickel borate (Ni-B) oxygen evolution catalysts onto ZnO nanowires resulted in substantial cathodic shifts in onset potential to as low as about 0.3 V versus the reversible hydrogen electrode (RHE) for Ni-B/ZnO, for which a maximum photocurrent density of 1.1 mA cm−2 at 0.9 V (vs. RHE) with applied bias photon-to-current efficiency of 0.4 % and an unprecedented near-unity incident photon-to-current efficiency at 370 nm. In addition the potential required for saturated photocurrent was dramatically reduced from 1.6 to 0.9 V versus RHE. Furthermore, the stability of these ZnO nanowires was significantly enhanced by using Ni-B compared to Co-Pi due to its superior chemical robustness, and it thus has additional functionality as a stable protecting layer on the ZnO surface. These remarkable enhancements in both photocatalytic activity and stability directly address the current severe limitations in the use of ZnO-based photoelectrodes for water-splitting applications, and can be applied to other photoanodes for efficient solar-driven fuel synthesis. PMID:25156820

  6. Covalent co-immobilization of heparin/laminin complex that with different concentration ratio on titanium surface for selectively direction of platelets and vascular cells behavior

    Wang, Jian; Chen, Yuan; Liu, Tao; Wang, Xue; Liu, Yang; Wang, Yuan; Chen, Junying; Huang, Nan

    2014-01-01

    Highlights: • Extracellular matrix inspired surface modification with fibronectin, heparin and VEGF to construct a favorable microenvironment for selectively anticoagulant and promote endothelialization. • Take the advantage of specific intermolecular interaction, the bioactivity of above biomolecules was more efficiently maintained in compared with the common used covalent immobilization method. • Poly-l-lysine was used as a novel interlayer for surface amination, and in comparison, PLL coating was more feasible and the degradation product had no harm to human body. - Abstract: Surface biofunctional modification of coronary artery stent to improve the hemocompatibility and selectively accelerate endothelium regeneration but prevent restenosis have been become a new hotspot. For this, a novel method was developed in this work by co-immobilization of Ln and heparin complex on poly-L-lysine modified Ti surface. Take the advantage of the specific interaction between Ln and heparin, Ln and heparin complexes with different concentration ratios were set up for creating different exposure density of these two types of biomolecules. According to biocompatibility evaluation results, the Hep/Ln complexes modified surface displayed less platelet adhesion and activation. Especially, on L(150)H and L(200)H surface, the AT III binding quantity, APTT value and anti-coagulation property of modified surface were significantly promoted. Furthermore, the adherent density and proliferation activity of ECs and EPCs were positively correlated with Ln concentration. Notably, the proliferation of both ECs and EPCs on L(100)H, L(150)H and L(200)H surface were greatly promoted. Another hand, the proliferation activity of SMCs was significantly inhibited on Hep/Ln modified surfaces, which was considered mainly due to the inhibitory effect of heparin to SMCs. According to the existing results, this study demonstrated that in a certain range of heparin and laminin concentration ratio

  7. Cancer Cell Adhesion and Metastasis: Selectins, Integrins, and the Inhibitory Potential of Heparins

    Gerd Bendas

    2012-01-01

    Full Text Available Cell adhesion molecules play a significant role in cancer progression and metastasis. Cell-cell interactions of cancer cells with endothelium determine the metastatic spread. In addition, direct tumor cell interactions with platelets, leukocytes, and soluble components significantly contribute to cancer cell adhesion, extravasation, and the establishment of metastatic lesions. Clinical evidence indicates that heparin, commonly used for treatment of thromboembolic events in cancer patients, is beneficial for their survival. Preclinical studies confirm that heparin possesses antimetastatic activities that lead to attenuation of metastasis in various animal models. Heparin contains several biological activities that may affect several steps in metastatic cascade. Here we focus on the role of cellular adhesion receptors in the metastatic cascade and discuss evidence for heparin as an inhibitor of cell adhesion. While P- and L-selectin facilitation of cellular contacts during hematogenous metastasis is being accepted as a potential target of heparin, here we propose that heparin may also interfere with integrin activity and thereby affect cancer progression. This review summarizes recent findings about potential mechanisms of tumor cell interactions in the vasculature and antimetastatic activities of heparin.

  8. Quantitative determination of heparin levels in serum with microtiter plate-format optode

    Kim, Sung Bae; Kang, Tae Young; Cha, Geun Sig; Nam, Hakhyun

    2006-01-01

    A new assay method has been developed for the quantitative determination of heparin in serum using a microtiter plate-format optode (MPO). Heparin and proton in physiological sample are favorably co-extracted into the solvent polymeric optode membrane containing both cationic lipophilic additive, tridodecylmethyl ammonium chloride (TDMAC), and proton-selective ionophore, 3-hydroxy-4-(4-nitrophenylazo)-phenyloctadecanoate (ETH 2412), resulting in the absorbance change of the membrane to varying heparin levels. The optimized MPO composition contains low polymer-to-plasticizer ratio compared to those of conventional ion-selective optodes or electrodes, i.e., poly(vinyl chloride) (20.0)/dioctylsebacate (76.3)/ETH 2412 (1.7)/TDMAC (1.0) (wt.%): it resulted in a quantitative response to heparin from 0 to 15 unit/mL in serum with high sensitivity. The heparin-protamine titration on the MPO could provide rapid and precise determination of heparin. It was shown that the heparin levels in serum sample could be determined from the rate of absorbance change over time (ΔA/Δt); this method was more effective than the direct absorbance measurement in minimizing the interferences from color and turbidity of serum samples. MPO has been developed as a high throughput and convenient disposable sensing device, and may find a wide application in the determination of polyions and charged macromolecules

  9. Heparin and glutathione II: correlation between decondensation of bull sperm cells and its nucleons.

    Delgado, N M; Flores-Alonso, J C; Rodríguez-Hernández, H M; Merchant-Larios, H; Reyes, R

    2001-01-01

    The correlation between the kinetics of bull sperm nuclear and nucleon decondensation induced by the action of physiological concentrations of heparin/GSH was studied. Sperm and nucleon suspensions were incubated at 37 degrees C in salt medium, at a constant concentration of either heparin or GSH and increasing concentrations of the other reagent. Even though nucleons are pretreated with DTT/CTAB, when they are incubated alone with GSH for 96 h, they remain intact, no matter which concentration is employed, and it was impossible to observe the slightest sign of nuclei decondensation. Therefore, rupture of disulfide bridges is not the main mechanism to induce nuclei decondensation and perhaps the GSH role resides in potentate the heparin effect by increasing its negative charge. Nevertheless, nucleons reach 95% of chromatin decondensation in the presence of heparin plus GSH or heparin alone. The fact that the correlation between heparin and GSH concentrations needed to induce sperm nuclei decondensation was 3- to 4-fold greater that in nucleons might be due to the complete lack of nucleon membranes. Heparin/GSH seem to induce nuclei decondensation by an ionic chromatin charge neutralization mechanism.

  10. Heparin modulates human intestinal smooth muscle (HISM) cell proliferation and matrix production

    Graham, M.; Perr, H.; Drucker, D.E.; Diegelmann, R.F.

    1986-01-01

    (HISM) cell proliferation and collagen production may play a role in the pathogenesis of intestinal stricture in Crohn's disease. The present studies were performed to evaluate the effects of heparin, a known modulator of vascular smooth muscle cells, on HISM cell proliferation and collagen production. Heparin (100 μg/ml) was added daily to HISM cell cultures for cell proliferation studies and for 24 hours at various time points during culture for collagen synthesis studies. Collagen synthesis was determined by the uptake of 3 H proline into collagenase-sensitive protein. Heparin completely inhibited cell proliferation for 7 days, after which cell numbers increased but at a slower rate than controls. Cells released from heparin inhibition demonstrated catch-up growth to control levels. Collagen production was significantly inhibited by 24 hours exposure to heparin but only at those times during culture when collagen synthesis was maximal (8 to 12 days). Non-collagen protein synthesis was inhibited by heparin at all time points during culture. Heparin through its modulation of HISM cells may play an important role in the control of the extracellular matrix of the intestinal wall

  11. Nerve growth factor loaded heparin/chitosan scaffolds for accelerating peripheral nerve regeneration.

    Li, Guicai; Xiao, Qinzhi; Zhang, Luzhong; Zhao, Yahong; Yang, Yumin

    2017-09-01

    Artificial chitosan scaffolds have been widely investigated for peripheral nerve regeneration. However, the effect was not as good as that of autologous grafts and therefore could not meet the clinical requirement. In the present study, the nerve growth factor (NGF) loaded heparin/chitosan scaffolds were fabricated via electrostatic interaction for further improving nerve regeneration. The physicochemical properties including morphology, wettability and composition were measured. The heparin immobilization, NGF loading and release were quantitatively and qualitatively characterized, respectively. The effect of NGF loaded heparin/chitosan scaffolds on nerve regeneration was evaluated by Schwann cells culture for different periods. The results showed that the heparin immobilization and NGF loading did not cause the change of bulk properties of chitosan scaffolds except for morphology and wettability. The pre-immobilization of heparin in chitosan scaffolds could enhance the stability of subsequently loaded NGF. The NGF loaded heparin/chitosan scaffolds could obviously improve the attachment and proliferation of Schwann cells in vitro. More importantly, the NGF loaded heparin/chitosan scaffolds could effectively promote the morphology development of Schwann cells. The study may provide a useful experimental basis to design and develop artificial implants for peripheral nerve regeneration and other tissue regeneration. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Chitosan-capped gold nanoparticles for selective and colorimetric sensing of heparin

    Chen, Zhanguang; Wang, Zhen; Chen, Xi; Xu, Haixiong; Liu, Jinbin

    2013-01-01

    In this contribution, novel chitosan-stabilized gold nanoparticles (AuNPs) were prepared by mixing chitosan with citrate-reductive AuNPs under appropriate conditions. The as-prepared chitosan-stabilized AuNPs were positively charged and highly stably dispersed in aqueous solution. They exhibited weak resonance light scattering (RLS) intensity and a wine red color. In addition, the chitosan-stabilized AuNPs were successfully utilized as novel sensitive probes for the detection of heparin for the first time. It was found that the addition of heparin induced a strong increase of RLS intensity for AuNPs and the color change from red to blue. The increase in RLS intensity and the color change of chitosan-stabilized AuNPs caused by heparin allowed the sensitive detection of heparin in the range of 0.2–60 μM (∼6.7 U/mL). The detection limit for heparin is 0.8 μM at a signal-to-noise ratio of 3. The present sensor for heparin detection possessed a low detection limit and wide linear range. Additionally, the proposed method was also applied to the detection of heparin in biological media with satisfactory results

  13. Characterization of currently marketed heparin products: key tests for LMWH quality assurance.

    Ye, Hongping; Toby, Timothy K; Sommers, Cynthia D; Ghasriani, Houman; Trehy, Michael L; Ye, Wei; Kolinski, Richard E; Buhse, Lucinda F; Al-Hakim, Ali; Keire, David A

    2013-11-01

    During the 2007-2008 heparin crisis it was found that the United States Pharmacopeia (USP) testing monograph for heparin sodium or low molecular weight heparins did not detect the presence of the contaminant, oversulfated chondroitin sulfate (OSCS). In response to this concern, new tests and specifications were developed by the Food and Drug Administration (FDA) and USP and put in place to detect not only the contaminant OSCS, but also to improve assurance of quality and purity of these drug products. The USP monographs for the low molecular weight heparins (LMWHs) approved for use in the United States (dalteparin, tinzaparin and enoxaparin) are also undergoing revision to include many of the same tests used for heparin sodium, including; one-dimensional (1D) 500 MHz (1)H NMR, SAX-HPLC, percent galactosamine in total hexosamine and anticoagulation time assays with purified Factor IIa or Factor Xa. These tests represent orthogonal approaches for heparin identification, measurement of bioactivity and for detection of process impurities or contaminants in these drug products. Here we describe results from a survey of multiple lots from three types of LMWHs in the US market which were collected after the 2009 heparin sodium monograph revision. In addition, innovator and generic versions of formulated enoxaparin products purchased in 2011 are compared using these tests and found to be highly similar within the discriminating power of the assays applied. Published by Elsevier B.V.

  14. Chitosan-capped gold nanoparticles for selective and colorimetric sensing of heparin

    Chen, Zhanguang, E-mail: kqlu@stu.edu.cn; Wang, Zhen; Chen, Xi [Shantou University, Department of Chemistry (China); Xu, Haixiong [Shantou Central Hospital, Affiliated Shantou Hospital of SUN YAT-SEN University (China); Liu, Jinbin [University of Texasat Dallas, Department of Chemistry (United States)

    2013-09-15

    In this contribution, novel chitosan-stabilized gold nanoparticles (AuNPs) were prepared by mixing chitosan with citrate-reductive AuNPs under appropriate conditions. The as-prepared chitosan-stabilized AuNPs were positively charged and highly stably dispersed in aqueous solution. They exhibited weak resonance light scattering (RLS) intensity and a wine red color. In addition, the chitosan-stabilized AuNPs were successfully utilized as novel sensitive probes for the detection of heparin for the first time. It was found that the addition of heparin induced a strong increase of RLS intensity for AuNPs and the color change from red to blue. The increase in RLS intensity and the color change of chitosan-stabilized AuNPs caused by heparin allowed the sensitive detection of heparin in the range of 0.2-60 {mu}M ({approx}6.7 U/mL). The detection limit for heparin is 0.8 {mu}M at a signal-to-noise ratio of 3. The present sensor for heparin detection possessed a low detection limit and wide linear range. Additionally, the proposed method was also applied to the detection of heparin in biological media with satisfactory results.

  15. Comparison of established and novel purity tests for the quality control of heparin by means of a set of 177 heparin samples.

    Alban, Susanne; Lühn, Susanne; Schiemann, Simone; Beyer, Tanja; Norwig, Jochen; Schilling, Claudia; Rädler, Oliver; Wolf, Bernhard; Matz, Magnus; Baumann, Knut; Holzgrabe, Ulrike

    2011-01-01

    The widespread occurrence of heparin contaminated with oversulfated chrondroitin sulfate (OSCS) in 2008 initiated a comprehensive revision process of the Pharmacopoeial heparin monographs and stimulated research in analytical techniques for the quality control of heparin. Here, a set of 177 heparin samples from the market in 2008 as well as pure heparin sodium spiked with defined amounts of OSCS and DS were used to evaluate established and novel methods for the quality control of heparin. Besides (1)H nuclear magnetic resonance spectroscopy (NMR), the assessment included two further spectroscopic methods, i.e., attenuated total reflection-infrared spectroscopy (ATR-IR) and Raman spectroscopy, three coagulation assays, i.e., activated partial thromboplastin time (aPTT) performed with both sheep and human plasma and the prothrombin time (PT), and finally two novel purity assays, each consisting of an incubation step with heparinase I followed by either a fluorescence measurement (Inc-PolyH-assay) or by a chromogenic aXa-assay (Inc-aXa-assay). NMR was shown to allow not only sensitive detection, but also quantification of OSCS by using the peak-height method and a response factor determined by calibration. Chemometric evaluation of the NMR, ATR-IR, and Raman spectra by statistical classification techniques turned out to be best with NMR spectra concerning the detection of OSCS. The validity of the aPTT, the current EP assay, could be considerably improved by replacing the sheep plasma by human plasma. In this way, most of the contaminated heparin samples did not meet the novel potency limit of 180 IU/mg. However, also more than 50% of the uncontaminated samples had interpretation of the results.

  16. Efficient 2,4-dichloronitrobenzene removal in the coupled BES-UASB reactor: Effect of external voltage mode.

    Chen, Hui; Gao, Xinyi; Wang, Caiqin; Shao, Junjie; Xu, Xiangyang; Zhu, Liang

    2017-10-01

    In this study, bioelectrochemical-upflow anaerobic sludge blanket (BES-UASB) system was developed for treatment of 2,4-dichloronitrobenzen (DClNB) containing wastewater to investigate the effect of external voltage with different supplying modes. Results showed that 2,4-dichloroaniline (DClAN) was under detection limit in R1 (applied with intermittent voltage) and R2 (applied with continuous voltage) when the DClNB loading increased from 25 to 100gm 3 d -1 (hydraulic retention time (HRT) was decreased from 24 to 6h) while sudden accumulation of DClAN (1.7mgL -1 ) was observed in R0 (control). Dechlorination efficiency (DE) decreased to 32.7%, 45.0% and 45.3% in R0, R1 and R2 when HRT was further shortened to 4h. Microbial community analysis indicated the significant enrichment of dechlorination-related species in R1 and R2 compared with R0, e.g., Dehalobacter and Dehalococcoides. In summary, the BES-UASB system with intermittent voltage is an alternative process for efficient treatment of DClNB containing wastewater, and the energy input was reduced markedly. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Continued advances in high brightness fiber-coupled laser modules for efficient pumping of fiber and solid-state lasers

    Hemenway, M.; Chen, Z.; Urbanek, W.; Dawson, D.; Bao, L.; Kanskar, M.; DeVito, M.; Martinsen, R.

    2018-02-01

    Both the fibber laser and diode-pumped solid-state laser market continue to drive advances in pump diode module brightness. We report on the continued progress by nLIGHT to develop and deliver the highest brightness diode-laser pumps using single-emitter technology. Continued advances in multimode laser diode technology [13] and fiber-coupling techniques have enabled higher emitter counts in the element packages, enabling us to demonstrate 305 W into 105 μm - 0.16 NA. This brightness improvement is achieved by leveraging our prior-reported package re-optimization, allowing an increase in the emitter count from two rows of nine emitters to two rows of twelve emitters. Leveraging the two rows off twelve emitter architecture,, product development has commenced on a 400 W into 200 μm - 00.16 NA package. Additionally, the advances in pump technology intended for CW Yb-doped fiber laser pumping has been leveraged to develop the highest brightness 793 nm pump modules for 2 μm Thulium fiber laser pumping, generating 150 W into 200 μm - 0.18 NA and 100 W into 105 μm - 0.15 NA. Lastly, renewed interest in direct diode materials processing led us to experiment with wavelength multiplexing our existing state of the art 200 W, 105 μm - 00.15 NA package into a combined output of 395 WW into 105 μm - 0.16 NA.

  18. Efficient Construction of Energetic Materials via Nonmetallic Catalytic Carbon-Carbon Cleavage/Oxime-Release-Coupling Reactions.

    Zhao, Gang; He, Chunlin; Yin, Ping; Imler, Gregory H; Parrish, Damon A; Shreeve, Jean'ne M

    2018-03-14

    The exploitation of C-C activation to facilitate chemical reactions is well-known in organic chemistry. Traditional strategies in homogeneous media rely upon catalyst-activated or metal-mediated C-C bonds leading to the design of new processes for applications in organic chemistry. However, activation of a C-C bond, compared with C-H bond activation, is a more challenging process and an underdeveloped area because thermodynamics does not favor insertion into a C-C bond in solution. Carbon-carbon bond cleavage through loss of an oxime moiety has not been reported. In this paper, a new observation of self-coupling via C-C bond cleavage with concomitant loss of oxime in the absence of metals (either metal-complex mediation or catalysis) results in dihydroxylammonium 5,5-bistetrazole-1,10-diolate (TKX-50) as well as N, N'-([3,3'-bi(1,2,4-oxadiazole)]-5,5'-diyl)dinitramine, a potential candidate for a new generation of energetic materials.

  19. Community nurse resource implications for a change in heparin prophylaxis policy

    Parker Martyn J.

    2015-01-01

    Full Text Available Introduction: A review was undertaken for a consecutive series of hip fracture patients for the year before and then after a change in low dose heparin prophylaxis policy. Patients and methods: For the first year heparin was administered in hospital for a maximum of 14 days only. Patients sent home before this time were not discharged taking heparin. For the second year heparin was administered as recommended by NICE guidelines for 28 days from admission regardless of whether the patient was discharged. Results: For the first year 486 patients were treated with a mean of 10.4 doses of heparin per patient. For the second year 465 patients were treated with a mean of 24.3 doses per patient. In total an extra 6,464 doses of heparin were administered. 33.8% of patients were unable to administer their heparin at home therefore a district nurse administered 2,284 of these doses of subcutaneous heparin at the patient’s home. The increased cost associated with the change in policy was estimated to be £161 per patient, with over 90% of this increase being incurred by the district nurse expense. If applied nationally for the England, using extended heparin prophylaxis for hip fracture patients would cost in excess of 12 million pounds each year. Conclusion: Whilst the necessity for and duration of thromboembolic prophylaxis for these patients remains undetermined, there is a need to re-evaluate the cost effectiveness of the current recommendations for hip fracture patients.

  20. Heparin induced thrombocytopenia type ii and myocardial infarction: Two case reports

    Antonijević Nebojša

    2004-01-01

    Full Text Available Heparin-induced thrombocytopenia (HIT type II is an acquired thrombophylic state and life-threatening immune complication of a heparin treatment mainly clinically manifested by marked thrombocytopenia, frequently by arterial and venous thrombosis, and sometimes by skin changes. Functional assay as heparin aggregation test and 14C-serotonin release assays are used in diagnostics as well as antigen assays of which detection tests for heparin-platelet factor 4 antibodies are most frequently used. Considering the fact that there is no single reliable assays for HIT II detection available, sometimes it is necessary to combine both of the above-mentioned types of assays. We present the case of a 57-year-old patient with an acute anterior myocardial infarction with cardiac insufficiency of III and IV degree according to Killip, recurrent ventricular fibrillation and diabetes mellitus type II developing thrombocytopenia to 37x10 9/l accompanied with typical skin changes. The diagnosis was confirmed by the heparin aggregation test. The second patient aged 70 undergoing the treatment for anteroseptal myocardial infarction and reinfarction of the inferior wall complicated by a cardiogenic shock and acute right bundle branch block developed thrombocytopenia 59x10 9/I on the third day of the heparin therapy, with the remark that he had received a heparin therapy during the first infarction as well. Antibodies against heparin-platelet factor 4 were detected by particle gel ID-HPF4 immunoassay. In both patients, the disease had a lethal outcome despite all then available therapeutic measures applied. Further on we discuss advantages of certain types of tests, a therapy doctrine, need for urgent therapeutic measures, inclusive of the administration of anitithrombins, avoidance of harmful procedures like low-molecular-weight heparins administration and prophylactic platelet transfusion as well as preventive measures.

  1. [Thrombocytopenia induced by type II heparin and myocardial infarct: 2 case reports].

    Antonijević, Nabojsa; Stanojević, Milica; Perunicić, Jovan; Djokić, Milan; Miković, Danijla; Kovac, Mirjana; Miljić, Predrag; Milosević, Rajko; Terzić, Branka; Vasiljević, Zorana

    2004-01-01

    Heparin-induced thrombocytopenia (HIT) type II is an acquired thrombophylic state and life-threatening immune complication of a heparin treatment mainly clinically manifested by marked thrombocytopenia, frequently by arterial and venous thrombosis, and sometimes by skin changes. Functional assay as heparin aggregation test and 14C-serotonin release assays are used in diagnostics as well as antigen assays of which detection tests for heparin-platelet factor 4 antibodies are most frequently used. Considering the fact that there is no single reliable assays for HIT II detection available, sometimes it is necessary to combine both of the above-mentioned types of assays. We present the case of a 57-year-old patient with an acute anterior myocardial infarction with cardiac insufficiency of III and IV degree according to Killip, recurrent ventricular fibrillation and diabetes mellitus type II developing thrombocytopenia to 37 x 10(9)/l accompanied with typical skin changes. The diagnosis was confirmed by the heparin aggregation test. The second patient aged 70 undergoing the treatment for anteroseptal myocardial infarction and reinfarction of the inferior wall complicated by a cardiogenic shock and acute right bundle branch block developed thrombocytopenia 59 x 10(9)/l on the third day of the heparin therapy, with the remark that he had received a heparin therapy during the first infarction as well. Antibodies against heparin-platelet factor 4 were detected by particle gel ID-HPF4 immuno-assay. In both patients, the disease had a lethal outcome despite all then available therapeutic measures applied. Further on we discuss advantages of certain types of tests, a therapy doctrine, need for urgent therapeutic measures, inclusive of the administration of antithrombins, avoidance of harmful procedures like low-molecular-weight heparins administration and prophylactic platelet transfusion as well as preventive measures.

  2. Hybrid coupling of bioenergy and geothermal energy. Efficiency through synergy; Hybride Kopplung von Bioenergie und Geothermischer Energie. Effizienz durch Synergie

    Giese, Lutz B. [Hochschule fuer Technik und Wirtschaft (HTW) Berlin (Germany). Fachbereich Ingenieurwissenschaften I; Seibt, Andrea [Boden Wasser Gesundheit (BWG) GbR, Neubrandenburg (Germany)

    2009-07-01

    Both forms of energy - geothermal energy and bioenergy - are distinguished by their storability and their capacity to provide base load electricity. In this way they can serve as an ideal supplement to other renewable energy resources, some of which are subject to considerable fluctuation. Both are readily usable for cogeneration, a form of energy production which has been accorded substantial weight in the 2050 scenario due to its high energy efficiency potential. In contrast to countries like Denmark, where cogeneration has a share of almost 50% in total energy production, its corresponding share in Germany is only just above 10%. And although the political goal is to raise the share of cogeneration to 25% by the year 2020, this will not be possible without politically painful cuts.

  3. Solid oxide fuel cell technology coupled with methane dry reforming: A viable option for high efficiency plant with reduced CO2 emissions

    Barelli, L.; Ottaviano, A.

    2014-01-01

    Nowadays the control of greenhouse gas is probably the most challenging environmental policy issue. Since CO 2 is considered the major greenhouse gas (GHG) that contributes to the global warming, enforcing technological strategies aiming to avoid or reuse CO 2 emissions becomes crucial, in order to mitigate GHG environmental impact. Currently, solutions conventionally adopted to this purpose are carbon capture and storage (CCS) technologies. In this context, instead, the followed strategy aims to further improvements in energetic conversion efficiency with related reduced specific CO 2 emissions (per produced kWh e ). Therefore, with particular reference to the electric power generation, this paper proposes an innovative energy conversion system, based on solid oxide fuel cell (SOFC), characterized by higher efficiency and reduced CO 2 emission factor respect to an analogous conventional energy plant. In particular, the innovative solution consists of combining SOFC to methane dry reforming technology, while the conventional system refers to steam methane reforming-SOFC coupling. The innovative system performance up to 65% electric efficiency as cited in the paper, was validated through simulations carried out in Aspen Plus environment. - Highlights: • An innovative high efficiency plant with low CO 2 emissions is presented. • The new solution combined SOFC to methane dry reforming technology (CDR–SOFC). • A comparison between CDR–SOFC and SMR–SOFC system was carried out in Aspen Plus. • CDR–SOFC efficiency is greater of 6.4% percentage points respect to SMR–SOFC. • A CO 2 emission factor reduction of about 10% was achieved by CDR–SOFC plant

  4. Heparan sulfate C5-epimerase is essential for heparin biosynthesis in mast cells.

    Feyerabend, Thorsten B; Li, Jin-Ping; Lindahl, Ulf; Rodewald, Hans-Reimer

    2006-04-01

    Biosynthesis of heparin, a mast cell-derived glycosaminoglycan with widespread importance in medicine, has not been fully elucidated. In biosynthesis of heparan sulfate (HS), a structurally related polysaccharide, HS glucuronyl C5-epimerase (Hsepi) converts D-glucuronic acid (GlcA) to L-iduronic acid (IdoA) residues. We have generated Hsepi-null mouse mutant mast cells, and we show that the same enzyme catalyzes the generation of IdoA in heparin and that 'heparin' lacking IdoA shows a distorted O-sulfation pattern.

  5. Increased accuracy in heparin and protamine administration decreases bleeding: a pilot study

    Runge, Marx; Møller, Christian H; Steinbrüchel, Daniel A

    2009-01-01

    Three to 5 percent of the patients undergoing cardiac surgery are reoperated because of bleeding. When a surgical cause can be excluded, heparin/protamine mismatch may be considered. Insufficient reversal of heparin and overdosing of protamine may cause postoperative bleeding. The purpose......). A reduced number of patients needed blood transfusions in the RxDx group, although this was not statistically significant (19% vs. 38%, respectively; p = .13). Initial heparin dose was significantly reduced in the RxDx group (250 mg; range, 100-375 mg) compared with the control group (300 mg; range, 200...

  6. Toll-like receptor-2 agonist-allergen coupling efficiently redirects Th2 cell responses and inhibits allergic airway eosinophilia.

    Krishnaswamy, Jayendra Kumar; Jirmo, Adan Chari; Baru, Abdul Mannan; Ebensen, Thomas; Guzmán, Carlos A; Sparwasser, Tim; Behrens, Georg M N

    2012-12-01

    Toll-like receptor (TLR) agonists beneficially modulate allergic airway inflammation. However, the efficiency of TLR agonists varies considerably, and their exact cellular mechanisms (especially of TLR 2/6 agonists) are incompletely understood. We investigated at a cellular level whether the administration of the pharmacologically improved TLR2/6 agonist S-[2,3-bispalmitoyiloxy-(2R)-propyl]-R-cysteinyl-amido-monomethoxy polyethylene glycol (BPP) conjugated to antigenic peptide (BPP-OVA) could divert an existing Th2 response and influence airway eosinophilia. The effects of BPP-OVA on airway inflammation were assessed in a classic murine sensitization/challenge model and an adoptive transfer model, which involved the adoptive transfer of in vitro differentiated ovalbumin (OVA)-specific Th2 cells. Functional T-cell stimulation by lung dendritic cells (DCs) was determined both in vitro and in vivo, combined with a cytokine secretion analysis. A single mucosal application of BPP-OVA efficiently delivered antigen, led to TLR2-mediated DC activation, and resulted in OVA-specific T-cell proliferation via lung DCs in vivo. In alternative models of allergic airway disease, a single administration of BPP-OVA before OVA challenge (but not BPP alone) significantly reduced airway eosinophilia, most likely through altered antigen-specific T-cell stimulation via DCs. Analyses of adoptively transferred Th2-biased cells after BPP-OVA administration in vivo suggested that BPP-OVA guides antigen-specific Th2 cells to produce significantly higher amounts of IFN-γ upon allergen challenge. In conclusion, our data show for the first time that a single mucosal administration of a TLR 2/6 agonist-allergen conjugate can provoke IFN-γ responses in Th2-biased cells and alleviate allergic airway inflammation.

  7. Recent developments in separation of low molecular weight heparin anticoagulants.

    Sadowski, Radosław; Gadzała-Kopciuch, Renata; Buszewski, Bogusław

    2017-10-05

    The general function of anticoagulants is to prevent blood clotting and growing of the existing clots in blood vessels. In recent years, there has been a significant improvement in developing methods of prevention as well as pharmacologic and surgical treatment of thrombosis. For over the last two decades, low molecular weight heparins (LMWHs) have found their application in the antithrombotic diseases treatment. These types of drugs are widely used in clinical therapy. Despite the biological and medical importance of LMWHs, they have not been completely characterized in terms of their chemical structure. Due to both, the structural complexity of these anticoagulants and the presence of impurities, their structural characterization requires the employment of advanced analytical techniques. Since separation techniques play the key role in these endeavors, this review will focus on the presentation of recent developments in the separation of LMWH anticoagulants. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Hyaluronan- and heparin-reduced silver nanoparticles with antimicrobial properties

    Kemp, Melissa M; Kumar, Ashavani; Clement, Dylan; Ajayan, Pulickel; Mousa, Shaker

    2009-01-01

    Aims Silver nanoparticles exhibit unique antibacterial properties that make these ideal candidates for biological and medical applications. We utilized a clean method involving a single synthetic step to prepare silver nanoparticles that exhibit antimicrobial activity. Materials & methods These nanoparticles were prepared by reducing silver nitrate with diaminopyridinylated heparin (DAPHP) and hyaluronan (HA) polysaccharides and tested for their efficacy in inhibiting microbial growth. Results & discussion The resulting silver nanoparticles exhibit potent antimicrobial activity against Staphylococcus aureus and modest activity against Escherichia coli. Silver–HA showed greater antimicrobial activity than silver–DAPHP, while silver–glucose nanoparticles exhibited very weak antimicrobial activity. Neither HA nor DAPHP showed activity against S. aureus or E. coli. Conclusion These results suggest that DAPHP and HA silver nanoparticles have potential in antimicrobial therapeutic applications. PMID:19505245

  9. Obstetric outcome with low molecular weight heparin therapy during pregnancy.

    Donnelly, J

    2012-01-01

    This was a prospective study of women attending a combined haematology\\/obstetric antenatal clinic in the National Maternity Hospital (2002-2008). Obstetric outcome in mothers treated with low molecular weight heparin (LMWH) was compared to the general obstetric population of 2006. There were 133 pregnancies in 105 women. 85 (63.9%) received prophylactic LMWH and 38 (28.6%) received therapeutic LMWH in pregnancy. 10 (7.5%) received postpartum prophylaxis only. The perinatal mortality rate was 7.6\\/1000 births. 14 (11.3%) women delivered preterm which is significantly higher than the hospital population rate (5.7%, p<0.05). Despite significantly higher labour induction rates (50% vs 29.2% p<0.01), there was no difference in CS rates compared to the general hospital population (15.4% vs 18.9%, NS). If carefully managed, these high-risk women can achieve similar vaginal delivery rates as the general obstetric population.

  10. Heparin/heparan sulfate analysis by covalently modified reverse polarity capillary zone electrophoresis-mass spectrometry.

    Sanderson, Patience; Stickney, Morgan; Leach, Franklin E; Xia, Qiangwei; Yu, Yanlei; Zhang, Fuming; Linhardt, Robert J; Amster, I Jonathan

    2018-04-13

    Reverse polarity capillary zone electrophoresis coupled to negative ion mode mass spectrometry (CZE-MS) is shown to be an effective and sensitive tool for the analysis of glycosaminoglycan mixtures. Covalent modification of the inner wall of the separation capillary with neutral or cationic reagents produces a stable and durable surface that provides reproducible separations. By combining CZE-MS with a cation-coated capillary and a sheath flow interface, a rapid and reliable method has been developed for the analysis of sulfated oligosaccharides from dp4 to dp12. Several different mixtures have been separated and detected by mass spectrometry. The mixtures were selected to test the capability of this approach to resolve subtle differences in structure, such as sulfation position and epimeric variation of the uronic acid. The system was applied to a complex mixture of heparin/heparan sulfate oligosaccharides varying in chain length from dp3 to dp12 and more than 80 molecular compositions were identified by accurate mass measurement. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Holey Reduced Graphene Oxide Coupled with an Mo2 N-Mo2 C Heterojunction for Efficient Hydrogen Evolution.

    Yan, Haijing; Xie, Ying; Jiao, Yanqing; Wu, Aiping; Tian, Chungui; Zhang, Xiaomeng; Wang, Lei; Fu, Honggang

    2018-01-01

    An in situ catalytic etching strategy is developed to fabricate holey reduced graphene oxide along with simultaneous coupling with a small-sized Mo 2 N-Mo 2 C heterojunction (Mo 2 N-Mo 2 C/HGr). The method includes the first immobilization of H 3 PMo 12 O 40 (PMo 12 ) clusters on graphite oxide (GO), followed by calcination in air and NH 3 to form Mo 2 N-Mo 2 C/HGr. PMo 12 not only acts as the Mo heterojunction source, but also provides the Mo species that can in situ catalyze the decomposition of adjacent reduced GO to form HGr, while the released gas (CO) and introduced NH 3 simultaneously react with the Mo species to form an Mo 2 N-Mo 2 C heterojunction on HGr. The hybrid exhibits superior activity towards the hydrogen evolution reaction with low onset potentials of 11 mV (0.5 m H 2 SO 4 ) and 18 mV (1 m KOH) as well as remarkable stability. The activity in alkaline media is also superior to Pt/C at large current densities (>88 mA cm -2 ). The good activity of Mo 2 N-Mo 2 C/HGr is ascribed to its small size, the heterojunction of Mo 2 N-Mo 2 C, and the good charge/mass-transfer ability of HGr, as supported by a series of experiments and theoretical calculations. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Extracellular matrix inspired surface functionalization with heparin, fibronectin and VEGF provides an anticoagulant and endothelialization supporting microenvironment

    Wang, Xue; Liu, Tao; Chen, Yuan; Zhang, Kun; Maitz, Manfred F.; Pan, Changjiang; Chen, Junying; Huang, Nan

    2014-01-01

    Highlights: • Surface modification with fibronectin, heparin and VEGF could selectively anticoagulant and promote endothelialization. • The bioactivity of biomolecules was more efficiently maintained via specific intermolecular interaction. • Poly-l-lysine interlayer was more feasible and the degradation product had no harm to human body. - Abstract: The biocompatibility of currently used coronary artery stent is still far from perfect, which closely related to insufficient endothelialization and thrombus formation. In this study, heparin, fibronectin and VEGF were immobilized on Ti surface to construct a multifunctional microenvironment with favorable properties to inhibit thrombosis formation and promote endothelialization simultaneously. The microenvironment on Ti surface was characterized in detail and demonstrated that the Hep/Fn/VEGF biofunctional coating was constructed successfully on Ti surface. The influence of surface properties such as chemical composition, roughness, hydrophilicity, and binding density of biomolecules on the performances of hemocompatibility and cytocompatibility was evaluated and discussed. Modified surface significantly enhanced the AT III binding density and prolonged the clotting time. In vitro platelet adhesion and activation assays further proved that the modified surface presented favorable anti-coagulant property. In addition, the proliferation of endothelial progenitor cells (EPCs) and endothelial cells (ECs) on the Hep/Fn/VEGF biofunctional coating was significantly promoted. In conclusion, the Hep/Fn/VEGF biofunctional coating was successfully constructed with desirable anticoagulant and endothelialization supporting properties. This work may provide a promising approach for biofunctional surface modification of coronary artery stent to acquire a desired multifunctional microenvironment

  13. Facile one-step hydrothermal synthesis toward strongly coupled TiO{sub 2}/graphene quantum dots photocatalysts for efficient hydrogen evolution

    Min, Shixiong, E-mail: sxmin@nun.edu.cn [School of Chemistry and Chemical Engineering, Beifang University of Nationalities, Yinchuan, 750021, Ningxia Province (China); Hou, Jianhua; Lei, Yonggang; Ma, Xiaohua [School of Chemistry and Chemical Engineering, Beifang University of Nationalities, Yinchuan, 750021, Ningxia Province (China); Lu, Gongxuan [State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou, 730000 (China)

    2017-02-28

    Highlights: • TiO{sub 2}/GQDs composites were prepared by a facile one-step hydrothermal method. • GQDs were strongly coupled onto the surface of TiO{sub 2} nanoparticles by this method. • The TiO{sub 2}/GQDs showed enhanced light absorption and charge separation efficiency. • The TiO{sub 2}/GQDs exhibited higher photocatalytic H{sub 2} evolution activity than pure TiO{sub 2}. • GQDs play synergistic roles by acting as both photosensitizer and electron acceptor. - Abstract: The coupling of semiconductor photocatalysts with graphene quantum dots (GQDs) has been proven to be an effective strategy to enhance the photocatalytic and photoelectrical conversion performances of the resulted composites; however, the preparation of semiconductor/GQDs composites usually involves several time-inefficient and tedious post-treatment steps. Herein, we present a facile one-step hydrothermal route for the preparation of GQDs coupled TiO{sub 2} (TiO{sub 2}/GQDs) photocatalysts using 1,3,6-trinitropyrene (TNP) as the sole precursor of GQDs. During the hydrothermal process, TNP molecules undergo an intramolecular fusion to form GQDs, which simultaneously decorate on the surface of TiO{sub 2} nanoparticles, leading to a strong surface interaction between the two components. The effective coupling of GQDs on TiO{sub 2} can effectively extend the light absorption of the TiO{sub 2} to visible region and enhance the charge separation efficiency of TiO{sub 2}/GQDs composites as a result of GQDs acting as a photosensitizer and an excellent electron acceptor. These key advances make the TiO{sub 2}/GQDs photocatalyst highly active towards the H{sub 2} evolution reaction, resulting in 7 and 3 times higher H{sub 2} evolution rate and photocurrent response at optimal GQDs content than TiO{sub 2} alone, respectively. This study provides a new methodology for the development of high-performance GQDs modified semiconductor photocatalysts for energy conversion applications.

  14. Development of a coupled tendon-driven 3D multi-joint manipulator. Investigation of tension transfer efficiency, optimal reel arrangement and tip positioning accuracy

    Horigome, Atsushi; Yamada, Hiroya; Hirose, Shigeo; Sen, Shin; Endo, Gen

    2017-01-01

    Long-reach robotic manipulators are expected to be used in the space where humans cannot work such as nuclear power plant disaster areas. We suggested a coupled tendon-driven articulated manipulator '3D CT-Arm' and developed a preliminary prototype 'Mini 3D CT-Arm' whose arm had 2.4 m length and 0.3 m width. In order to consider developing '3D CT-Arm' deeply, we discussed tension transfer efficiency of a tendon through pulleys, the arrangement of the maximum number of reels in a limited space and the tip positioning accuracy. Through many transfer efficiency experiments, we conclude that tension transfer efficiency of '3D CT-Arm' can reach over 88% in the worst case. We investigated non-interfering reels' arrangement in the base by full search in cases of up to 10 reels. In all simulations, V-shaped or W-shaped arrangement can support the most reels in a limited space. Therefore, we conclude this is the most optimal reels' arrangement. Finally, we carried out the positioning accuracy experiment with 'Mini 3D CT-Arm' via motion capture system. Although the tip position had a 2 to 41 mm error between the desired value and the measured value by potentiometer, a 29 to 95 mm error between the desired value and the measured value was measured by motion capture system. (author)

  15. Axisymmetric alternating direction explicit scheme for efficient coupled simulation of hydro-mechanical interaction in geotechnical engineering—Application to circular footing and deep tunnel in saturated ground

    Simon Heru Prassetyo

    2018-04-01

    Full Text Available Explicit solution techniques have been widely used in geotechnical engineering for simulating the coupled hydro-mechanical (H-M interaction of fluid flow and deformation induced by structures built above and under saturated ground, i.e. circular footing and deep tunnel. However, the technique is only conditionally stable and requires small time steps, portending its inefficiency for simulating large-scale H-M problems. To improve its efficiency, the unconditionally stable alternating direction explicit (ADE scheme could be used to solve the flow problem. The standard ADE scheme, however, is only moderately accurate and is restricted to uniform grids and plane strain flow conditions. This paper aims to remove these drawbacks by developing a novel high-order ADE scheme capable of solving flow problems in non-uniform grids and under axisymmetric conditions. The new scheme is derived by performing a fourth-order finite difference (FD approximation to the spatial derivatives of the axisymmetric fluid–diffusion equation in a non-uniform grid configuration. The implicit Crank-Nicolson technique is then applied to the resulting approximation, and the subsequent equation is split into two alternating direction sweeps, giving rise to a new axisymmetric ADE scheme. The pore pressure solutions from the new scheme are then sequentially coupled with an existing geomechanical simulator in the computer code fast Lagrangian analysis of continua (FLAC. This coupling procedure is called the sequentially-explicit coupling technique based on the fourth-order axisymmetric ADE scheme or SEA-4-AXI. Application of SEA-4-AXI for solving axisymmetric consolidation of a circular footing and of advancing tunnel in deep saturated ground shows that SEA-4-AXI reduces computer runtime up to 42%–50% that of FLAC's basic scheme without numerical instability. In addition, it produces high numerical accuracy of the H-M solutions with average percentage difference of only 0.5%

  16. Synthesis of palladium nanoparticles with leaf extract of Chrysophyllum cainito (Star apple) and their applications as efficient catalyst for C-C coupling and reduction reactions

    Majumdar, Rakhi; Tantayanon, Supawan; Bag, Braja Gopal

    2017-10-01

    A simple green chemical method for the one-step synthesis of palladium nanoparticles (PdNPs) has been described by reducing palladium (II) chloride with the leaf extract of Chrysophyllum cainito in aqueous medium. The synthesis of the palladium nanoparticles completed within 2-3 h at room temperature, whereas on heat treatment (70-80 °C), the synthesis of colloidal PdNPs completed almost instantly. The stabilized PdNPs have been characterized in detail by spectroscopic, electron microscopic and light scattering measurements. The synthesized PdNPs have been utilized as a green catalyst for C-C coupling reactions under aerobic and phosphine-free conditions in aqueous medium. In addition, the synthesized PdNPs have also been utilized as a catalyst for a very efficient sodium borohydride reduction of 3- and 4-nitrophenols. The synthesized PdNPs can retain their catalytic activity for several months.

  17. COMPUTATIONAL EFFICIENCY OF A MODIFIED SCATTERING KERNEL FOR FULL-COUPLED PHOTON-ELECTRON TRANSPORT PARALLEL COMPUTING WITH UNSTRUCTURED TETRAHEDRAL MESHES

    JONG WOON KIM

    2014-04-01

    In this paper, we introduce a modified scattering kernel approach to avoid the unnecessarily repeated calculations involved with the scattering source calculation, and used it with parallel computing to effectively reduce the computation time. Its computational efficiency was tested for three-dimensional full-coupled photon-electron transport problems using our computer program which solves the multi-group discrete ordinates transport equation by using the discontinuous finite element method with unstructured tetrahedral meshes for complicated geometrical problems. The numerical tests show that we can improve speed up to 17∼42 times for the elapsed time per iteration using the modified scattering kernel, not only in the single CPU calculation but also in the parallel computing with several CPUs.

  18. Acceleration of Vaporization, Atomization, and Ionization Efficiencies in Inductively Coupled Plasma by Merging Laser-Ablated Particles with Hydrochloric Acid Gas.

    Nakazawa, Takashi; Izumo, Saori; Furuta, Naoki

    2016-01-01

    To accelerate the vaporization, atomization, and ionization efficiencies in laser ablation inductively coupled plasma mass spectrometry, we merged HCl gas with laser-ablated particles before introduction into the plasma, to convert their surface constituents from oxides to lower-melting chlorides. When particles were merged with HCl gas generated from a HCl solution at 200°C, the measured concentrations of elements in the particles were 135% higher on average than the concentrations in particles merged with ultrapure water vapor. Particle corrosion and surface roughness were observed by scanning electron microscopy, and oxide conversion to chlorides was confirmed by X-ray photoelectron spectroscopy. Under the optimum conditions, the recoveries of measured elements improved by 23% on average, and the recoveries of elements with high-melting oxides (Sr, Zr, and Th) improved by as much as 36%. These results indicate that vaporization, atomization, and ionization in the ICP improved when HCl gas was merged with the ablated particles.

  19. Multielement detection limits and sample nebulization efficiencies of an improved ultrasonic nebulizer and a conventional pneumatic nebulizer in inductively coupled plasma-atomic emission spectrometry

    Olson, K.W.; Haas, W.J. Jr.; Fassel, V.A.

    1977-01-01

    Two important aspects of the analytical performance of a newly developed ultrasonic nebulizer and a specially designed pneumatic nebulizer have been compared for use in inductively coupled plasma--atomic emission spectroscopy (ICP-AES). The ultrasonic nebulizer, when combined with a conventional aerosol desolvation apparatus, provided an order of magnitude or more improvement in simultaneous multielement detection limits as compared to those obtained when the pneumatic nebulizer was used either with or without desolvation. Application of a novel method for direct measurement of the overall efficiency of nebulization to the two systems showed that an approximately tenfold greater rate of sample delivery to the plasma torch was primarily responsible for the superior detection limits afforded by the ultrasonic nebulizer. A unique feature of the ultrasonic nebulizer described is the protection against chemical attack which is achieved by completely enclosing the transducer in an acoustically coupled borosilicate glass cylinder. Direct sample introduction, convenient sample change, and rapid cleanout are other important characteristics of the system which make it an attractive alternate to pneumatic nebulizer systems

  20. Distribution of heparin-/sup 67/Ga in tumor-bearing rats

    Hiraki, T; Ando, A; Sanada, S [Kanazawa Univ. (Japan). School of Paramedicine; Ando, I; Hisada, K

    1976-06-01

    Heparin is a kind of acidic mucopolysaccharide. The distribution of heparin-/sup 67/Ga complex in tumor-bearing rats was investigated by administering it to rats into which Yoshida sarcoma had been transplanted subcutaneously. These rats were sacrificed at 10 minutes, 30 minutes, 1 hour and 3 hours after injection. Radioactivity of the tumor, blood, muscle, liver, kidney, spleen and urine were measured with a well-type scintillation counter. Retention values in these organs and excretion rates in the urine were calculated. Excretion rates (%/dose) of heparin-/sup 67/Ga in 10 min., 30 min., 1 hour, and 3 hours were 38.2%, 67.5%, 79.5% and 78.0%, respectively. From these facts, it was thought that heparin-/sup 67/Ga complex was not suitable for tumor scanning, but that this compound might be a suitable agent for the renal function test.

  1. Bilateral adrenal haemorrhage associated with heparin-induced thrombocytopaenia during treatment of Fournier gangrene.

    Tattersall, Timothy Lee; Thangasamy, Isaac A; Reynolds, Jamie

    2014-10-14

    We present a case of bilateral adrenal haemorrhage (BAH) associated with heparin-induced thrombocytopaenia (HIT) in a 61-year-old man admitted to hospital for the treatment of Fournier's gangrene. He presented to hospital with scrotal swelling and fever, and developed spreading erythaema and a gangrenous scrotum. His scrotum was surgically debrided and intravenous broad-spectrum antibiotics were administered. Unfractionated heparin was given postoperatively for venous thromboembolism prophylaxis. The patient deteriorated clinically 8-11 days postoperatively with delirium, chest pain and severe hypertension followed by hypotension and thrombocytopaenia. Abdominal CT scan revealed bilateral adrenal haemorrhage. Antibodies to the heparin-platelet factor 4 complex were present. HIT-associated BAH was diagnosed and heparin was discontinued. Intravenous bivalirudin and hydrocortisone were started, with rapid improvement in clinical status. BAH is a rare complication of HIT and should be considered in the postoperative patient with unexplained clinical deterioration. 2014 BMJ Publishing Group Ltd.

  2. Structure-Activity Relationships of Bioengineered Heparin/Heparan Sulfates Produced in Different Bioreactors

    Ha Na Kim

    2017-05-01

    Full Text Available Heparin and heparan sulfate are structurally-related carbohydrates with therapeutic applications in anticoagulation, drug delivery, and regenerative medicine. This study explored the effect of different bioreactor conditions on the production of heparin/heparan sulfate chains via the recombinant expression of serglycin in mammalian cells. Tissue culture flasks and continuously-stirred tank reactors promoted the production of serglycin decorated with heparin/heparan sulfate, as well as chondroitin sulfate, while the serglycin secreted by cells in the tissue culture flasks produced more highly-sulfated heparin/heparan sulfate chains. The serglycin produced in tissue culture flasks was effective in binding and signaling fibroblast growth factor 2, indicating the utility of this molecule in drug delivery and regenerative medicine applications in addition to its well-known anticoagulant activity.

  3. Indium-111-labeled platelets: effect of heparin on uptake by venous thrombi and relationship to the activated partial thromboplastin time

    Fedullo, P.F.; Moser, K.M.; Moser, K.S.; Konopka, R.; Hartman, M.T.

    1982-01-01

    The goal of heparin thepapy in deep vein thrombosis is to prevent thrombus extension. The relationship between thrombus extension and the results of coagulation tests used to monitor heparin thepapy is unclear. To expose this relationship, we studied the effect of several heparin regimens on the accretion of indium-111-labeled platelets on fresh venous thrombi, as detected by gamma imaging, and monitored the activated partial thromboplastin time (APTT). Six dogs were treated with a 300-U/kg bolus of heparin followed by a 90-U/kg/hour heparin infusion, a dose of heparin sufficient to increase the APTT to levels greater than eight times baseline (APTT ratio); platelet accretion (thrombus imaging) occurred only after the heparin effect was reversed with protamine sulfate. Nineteen dogs were treated with a 150-U/kg bolus of heparin followed by a 4-hour, 45-U/kg/hour heparin infusion; a thrombus was demonstrated only after protamine injection in 12 (mean APTT ratio 1.3 +/- 0.19) and before protamine injection in seven. In thirteen of these 19 dogs, 30 minutes separated the platelet injection from heparin therapy, while in six this duration was less than 30 minutes. In four of these six dogs, thrombi were demonstrated before protamine therapy and at APTT ratios greater than 3.0. Finally, 10 dogs were treated with a 100-U/kg bolus followed by a 3-hour, 50-U/kg/hour heparin infusion, after which the APTT was allowed to return to baseline values spontaneously. In all 10 dogs, a thrombus was demonstrated only after cessation of the heparin infusion, and at a mean APTT ratio of 1.4 +/- 0.15 times baseline. These results suggest that, except with very early platelet injection, platelet accretion by thrombi is consistently inhibited by heparin at APTT ratios greater than 2.5

  4. Ultrasensitive colorimetric detection of heparin based on self-assembly of gold nanoparticles on graphene oxide.

    Fu, Xiuli; Chen, Lingxin; Li, Jinhua

    2012-08-21

    A novel colorimetric method was developed for ultrasensitive detection of heparin based on self-assembly of gold nanoparticles (AuNPs) onto the surface of graphene oxide (GO). Polycationic protamine was used as a medium for inducing the self-assembly of citrate-capped AuNPs on GO through electrostatic interaction, resulting in a shift in the surface plasmon resonance (SPR) absorption of AuNPs and exhibiting a blue color. Addition of polyanionic heparin disturbed the self-assemble of AuNPs due to its strong affinity to protamine. With the increase of heparin concentration, the amounts of self-assembly AuNPs decreased and the color changed from blue to red in solution. Therefore, a "blue-to-red" colorimetric sensing strategy based on self-assembly of AuNPs could be established for heparin detection. Compared with the commonly reported aggregation-based methods ("red-to-blue"), the color change from blue to red was more eye-sensitive, especially in low concentration of target. Moreover, stronger interaction between protamine and heparin led to distinguish heparin from its analogues as well as various potentially coexistent physiological species. The strategy was simply achieved by the self-assembly nature of AuNPs and the application of two types of polyionic media, showing it to be label-free, simple, rapid and visual. This method could selectively detect heparin with a detection limit of 3.0 ng mL(-1) in standard aqueous solution and good linearity was obtained over the range 0.06-0.36 μg mL(-1) (R = 0.9936). It was successfully applied to determination of heparin in fetal bovine serum samples as low as 1.7 ng mL(-1) with a linear range of 0-0.8 μg mL(-1).

  5. Biomimetic synthesis and biocompatibility evaluation of carbonated apatites template-mediated by heparin

    Deng, Yi [Department of Oral and Maxillofacial Surgery, Laboratory of Interdisciplinary Studies, School and Hospital of Stomatology, Peking University, Beijing 100081 (China); Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871 (China); Sun, Yuhua [Department of Oral and Maxillofacial Surgery, Laboratory of Interdisciplinary Studies, School and Hospital of Stomatology, Peking University, Beijing 100081 (China); Chen, Xiaofang [Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871 (China); Zhu, Peizhi, E-mail: pzzhu@umich.edu [Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871 (China); Department of Chemistry, University of Michigan, Ann Arbor, MI 48109-1055 (United States); Wei, Shicheng, E-mail: sc-wei@pku.edu.cn [Department of Oral and Maxillofacial Surgery, Laboratory of Interdisciplinary Studies, School and Hospital of Stomatology, Peking University, Beijing 100081 (China); Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871 (China)

    2013-07-01

    Biomimetic synthesis of carbonated apatites with good biocompatibility is a promising strategy for the broadening application of apatites for bone tissue engineering. Most researchers were interested in collagen or gelatin-based templates for synthesis of apatite minerals. Inspired by recent findings about the important role of polysaccharides in bone biomineralization, here we reported that heparin, a mucopolysaccharide, was used to synthesize carbonated apatites in vitro. The results indicated that the Ca/P ratio, carbon content, crystallinity and morphology of the apatites varied depending on the heparin concentration and the initial pH value. The morphology of apatite changed from flake-shaped to needle-shaped, and the degree of crystallinity decreased with the increasing of heparin concentration. Biocompatibility of the apatites was tested by proliferation and alkaline phosphatase activity of MC3T3-E1 cells. The results suggested that carbonated apatites synthesized in the presence of heparin were more favorable to the proliferation and differentiation of MC3T3-E1 cells compared with traditional method. In summary, the heparin concentration and the initial pH value play a key role in the chemical constitution and morphology, as well as biological properties of apatites. These biocompatible nano-apatite crystals hold great potential to be applied as bioactive materials for bone tissue engineering. - Highlights: • Heparin was used as a template to synthesize needle-shaped nano-apatite. • Changing the pH value and concentration led to different properties of apatite. • Apatite prepared by heparin was more favorable to the osteogenic differentiation. • Possible synthesis mechanism of apatite templated by heparin was described.

  6. Metabolic engineering of Chinese hamster ovary cells: towards a bioengineered heparin.

    Baik, Jong Youn; Gasimli, Leyla; Yang, Bo; Datta, Payel; Zhang, Fuming; Glass, Charles A; Esko, Jeffrey D; Linhardt, Robert J; Sharfstein, Susan T

    2012-03-01

    Heparin is the most widely used pharmaceutical to control blood coagulation in modern medicine. A health crisis that took place in 2008 led to a demand for production of heparin from non-animal sources. Chinese hamster ovary (CHO) cells, commonly used mammalian host cells for production of foreign pharmaceutical proteins in the biopharmaceutical industry, are capable of producing heparan sulfate (HS), a related polysaccharide naturally. Since heparin and HS share the same biosynthetic pathway, we hypothesized that heparin could be produced in CHO cells by metabolic engineering. Based on the expression of endogenous enzymes in the HS/heparin pathways of CHO-S cells, human N-deacetylase/N-sulfotransferase (NDST2) and mouse heparan sulfate 3-O-sulfotransferase 1 (Hs3st1) genes were transfected sequentially into CHO host cells growing in suspension culture. Transfectants were screened using quantitative RT-PCR and Western blotting. Out of 120 clones expressing NDST2 and Hs3st1, 2 clones, Dual-3 and Dual-29, were selected for further analysis. An antithrombin III (ATIII) binding assay using flow cytometry, designed to recognize a key sugar structure characteristic of heparin, indicated that Hs3st1 transfection was capable of increasing ATIII binding. An anti-factor Xa assay, which affords a measure of anticoagulant activity, showed a significant increase in activity in the dual-expressing cell lines. Disaccharide analysis of the engineered HS showed a substantial increase in N-sulfo groups, but did not show a pattern consistent with pharmacological heparin, suggesting that further balancing the expression of transgenes with the expression levels of endogenous enzymes involved in HS/heparin biosynthesis might be necessary. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Elimination of heparin interference during microarray processing of fresh and biobank-archived blood samples.

    Hebels, Dennie G A J; van Herwijnen, Marcel H M; Brauers, Karen J J; de Kok, Theo M C M; Chalkiadaki, Georgia; Kyrtopoulos, Soterios A; Kleinjans, Jos C S

    2014-07-01

    In the context of environmental health research, biobank blood samples have recently been identified as suitable for high-throughput omics analyses enabling the identification of new biomarkers of exposure and disease. However, blood samples containing the anti-coagulant heparin could complicate transcriptomic analysis because heparin may inhibit RNA polymerase causing inefficient cRNA synthesis and fluorophore labelling. We investigated the inhibitory effect of heparin and the influence of storage conditions (0 or 3 hr bench times, storage at room temperature or -80°C) on fluorophore labelling in heparinized fresh human buffy coat and whole blood biobank samples during the mRNA work-up protocol for microarray analysis. Subsequently, we removed heparin by lithium chloride (LiCl) treatment and performed a quality control analysis of LiCl-treated biobank sample microarrays to prove their suitability for downstream data analysis. Both fresh and biobank samples experienced varying degrees of heparin-induced inhibition of fluorophore labelling, making most samples unusable for microarray analysis. RNA derived from EDTA and citrate blood was not inhibited. No effect of bench time was observed but room temperature storage gave slightly better results. Strong correlations were observed between original blood sample RNA yield and the amount of synthesized cRNA. LiCl treatment restored sample quality to normal standards in both fresh and biobank samples and the previously identified correlations disappeared. Microarrays hybridized with LiCl-treated biobank samples were of excellent quality with no identifiable influence of heparin. We conclude that, to obtain high quality results, in most cases heparin removal is essential in blood-derived RNA samples intended for microarray analysis. Copyright © 2014 Wiley Periodicals, Inc.

  8. Prospective multicentre cohort study of heparin-induced thrombocytopenia in acute ischaemic stroke patients

    Kawano, Hiroyuki; Yamamoto, Haruko; Miyata, Shigeki; Izumi, Manabu; Hirano, Teruyuki; Toratani, Naomi; Kakutani, Isami; Sheppard, Jo-Ann I; Warkentin, Theodore E; Kada, Akiko; Sato, Shoichiro; Okamoto, Sadahisa; Nagatsuka, Kazuyuki; Naritomi, Hiroaki; Toyoda, Kazunori; Uchino, Makoto; Minematsu, Kazuo

    2011-01-01

    Acute ischaemic stroke patients sometimes receive heparin for treatment and/or prophylaxis of thromboembolic complications. This study was designed to elucidate the incidence and clinical features of heparin-induced thrombocytopenia (HIT) in acute stroke patients treated with heparin. We conducted a prospective multicentre cohort study of 267 patients who were admitted to three stroke centres within 7 d after stroke onset. We examined clinical data until discharge and collected blood samples on days 1 and 14 of hospitalization to test anti-platelet factor 4/heparin antibodies (anti-PF4/H Abs) using an enzyme-linked immunosorbent assay (ELISA); platelet-activating antibodies were identified by serotonin-release assay (SRA). Patients with a 4Ts score ≥4 points, positive-ELISA, and positive-SRA were diagnosed as definite HIT. Heparin was administered to 172 patients (64·4%: heparin group). Anti-PF4/H Abs were detected by ELISA in 22 cases (12·8%) in the heparin group. Seven patients had 4Ts ≥ 4 points. Among them, three patients (1·7% overall) were also positive by both ELISA and SRA. National Institutes of Health Stroke Scale score on admission was high (range, 16–23) and in-hospital mortality was very high (66·7%) in definite HIT patients. In this study, the incidence of definite HIT in acute ischaemic stroke patients treated with heparin was 1·7% (95% confidence interval: 0·4–5·0). The clinical severity and outcome of definite HIT were unfavourable. PMID:21671895

  9. Purification of foot-and-mouth disease virus by heparin as ligand for certain strains.

    Du, Ping; Sun, Shiqi; Dong, Jinjie; Zhi, Xiaoying; Chang, Yanyan; Teng, Zhidong; Guo, Huichen; Liu, Zaixin

    2017-04-01

    The goal of this project was to develop an easily operable and scalable process for the recovery and purification of foot-and-mouth disease virus (FMDV) from cell culture. Heparin resins HipTrap Heparin HP and AF-Heparin HC-650 were utilized to purify FMDV O/HN/CHA/93. Results showed that the purity of AF-Heparin HC-650 was ideal. Then, the O/HN/CHA/93, O/Tibet/CHA/99, Asia I/HN/06, and A/CHA/HB/2009 strains were purified by AF-Heparin HC-650. Their affinity/virus recoveries were approximately 51.2%/45.8%, 71.5%/70.9%, 96.4%/73.5, and 59.5%/42.1%, respectively. During a stepwise elution strategy, the viral particles were mainly eluted at 300mM ionic strength peaks. The heparin affinity chromatography process removed more than 94% of cellular and medium proteins. Anion exchange resin Capto Q captured four FMD virus particles; 40% of binding proteins and 80%-90% of viral particles were eluted at 450mM NaCl. Moreover, ionic strength varied from 30 to 450mM had no effect on the immunity to FMDV. The results revealed that heparin sulfate may be the main receptor for CHA/99 strain attachment-susceptible cells. Heparin affinity chromatography can reach perfect results, especially when used as a ligand of the virus. Anion exchange is useful only as previous step for further purification. Copyright © 2016. Published by Elsevier B.V.

  10. Update on the clinical use of the low-molecular-weight heparin, parnaparin

    Giuseppe Camporese

    2009-09-01

    Full Text Available Giuseppe Camporese1, Enrico Bernardi2, Franco Noventa31Unit of Angiology and 3Department of Clinical and Experimental Medicine, Clinical Epidemiology Group, University Hospital of Padua, Italy; 2Department of Emergency and Accident Medicine, Hospital of Conegliano Veneto, ItalyAbstract: Parnaparin is a low-molecular-weight heparin that has widely shown its efficacy and safety in prevention of venous thromboembolism, in the treatment of chronic venous disorders, and in the treatment of venous and arterial (stable and unstable angina, acute ST-segment elevation myocardial infarction thrombosis. Parnaparin at the respective dosages of 3200, 4250, 6400, or 12800 IUaXa for a period ranging from 3 to 5 days to 6 months, is usually administered subcutaneously by means of once-daily regimen and is better tolerated than unfractionated heparin at the injection site. In the variety of commercially available low-molecular-weight heparins, parnaparin represents a useful therapeutic option, even though little evidence is available comparing the superiority or the equivalent efficacy and safety of parnaparin to that of the unfractionated heparin or placebo. This review summarizes the available literature on the use of parnaparin in different settings of cardiovascular diseases, including papers published during the past year and ongoing studies.Keywords: low-molecular-weight heparin, heparin, parnaparin, acute coronary syndromes, venous thromboembolism

  11. [Heparin-induced thrombocytopenia developed during the acute phase after left upper lobectomy for lung cancer].

    Mitomo, Hideki; Miyamoto, Akira; Tabata, Toshiharu; Sugawara, Takafumi; Yabuki, Hiroshi; Fujimura, Shigefumi

    2014-12-01

    Heparin-induced thrombocytopenia (HIT) is a serious adverse effect of heparin administration. This must not be rarely encountered but is not often reported in Japan compared to Western countries. A 68-year-old woman underwent left upper lobectomy for lung cancer. Low-dose unfractionated heparin was administrated to prevent thromboembolism after the operation. Two days later, sudden dyspnea appeared and ultracardiosonography showing an extensive thromboembolus from the main trunk to both main branches of pulmonary artery indicated pulmonary embolization. After the establishment of percutaneous cardiopulmonary support (PCPS) support, the embolus was removed by emergent open heart surgery. However, despite further unfractionated heparin administration following embolization surgery, other thrombus was identified in both the bi-lateral internal jagular veins and inferior vena cava by ultrasonography and contrast computed tomography( CT). Her platelet count was decreased gradually despite platelet transfusion. Plate factor 4( PF4) antibody against heparin in her blood examination was found, and HIT II was diagnosed. Discontinuation of unfractionated heparin and administration of antithrombin agent improved platelet count, and no additional embolization was identified.

  12. Prevention of equine herpesvirus myeloencephalopathy - Is heparin a novel option? A case report.

    Walter, Jasmin; Seeh, Christoph; Fey, Kerstin; Bleul, Ulrich; Osterrieder, Nikolaus

    2016-10-12

    Equine herpesvirus myeloencephalopathy (EHM) is a severe manifestation of equine herpesvirus 1 (EHV-1) infection. Prevention and treatment of EHM during EHV-1 outbreaks is critical, but no reliable and tested specific medication is available. Due to the thromboischemic nature of EHM and due to the fact that EHV-1 entry in cells is blocked by heparin, it was hypothesized that this compound may be useful in reduction of EHM incidence and severity. Therefore, during an acute EHV-1 outbreak with the neuropathogenic G 2254 /D 752 Pol variant, metaphylactic treatment with heparin to prevent EHM was initiated. Clinical signs were present in 61 horses (fever n = 55; EHM n = 8; abortion n = 6). Heparin (25000 IU subcutaneously twice daily for 3 days) was given to 31 febrile horses from day 10 of the outbreak, while the first 30 horses exhibiting fever remained untreated. Treatment outcome was analyzed retrospectively. Heparin-treated horses showed a lower EHM incidence (1/31; 3.2%) than untreated horses (7/30; 23.3%; p = 0.03). Results indicate that heparin may be useful for prevention of EHM during an EHV-1 outbreak. These promising data highlight the need for randomized and possibly blinded studies for the use of heparin in EHV-1 outbreaks.

  13. Heparin concentration is critical for cell culture with human platelet lysate.

    Hemeda, Hatim; Kalz, Jana; Walenda, Gudrun; Lohmann, Michael; Wagner, Wolfgang

    2013-09-01

    Culture media for mesenchymal stromal cells (MSCs) are generally supplemented with fetal bovine serum. Human platelet lysate (hPL) has been proven to be a very effective alternative without the risk of xenogeneic infections or immune reactions. In contrast to fetal bovine serum, hPL comprises plasma, and anticoagulants-usually unfractionated heparin (UFH)-need to be added to prevent gel formation. Cultures of MSCs in hPL media with various concentrations of UFH and enoxaparin, a low-molecular-weight heparin (LMWH), were systematically compared with regard to proliferation, fibroblastoid colony-forming unit frequency, immunophenotype and in vitro differentiation. At least 0.61 IU/mL UFH or 0.024 mg/mL LMWH was necessary for reliable prevention of coagulation of hPL pools used in this study. Higher concentrations impaired cellular proliferation in a dose-dependent manner even without benzyl alcohol, which is commonly added to heparins as a bacteriostatic agent. Colony-forming unit frequency was also reduced at higher heparin concentrations, particularly with LMWH, whereas no significant effect was observed on cellular morphology or immunophenotype. High concentrations of heparins reduced the in vitro differentiation toward adipogenic and osteogenic lineages. Heparin concentration is critical for culture of MSCs in hPL media; this is of particular relevance for cellular therapy where cell culture procedures need to be optimized and standardized. Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  14. Association between Activated Partial Thromboplastin Time and the Amount of Infused Heparin at Bone Marrow Transplantation.

    Kusuda, Machiko; Kimura, Shun-Ichi; Misaki, Yukiko; Yoshimura, Kazuki; Gomyo, Ayumi; Hayakawa, Jin; Tamaki, Masaharu; Akahoshi, Yu; Ugai, Tomotaka; Kameda, Kazuaki; Wada, Hidenori; Ishihara, Yuko; Kawamura, Koji; Sakamoto, Kana; Sato, Miki; Terasako-Saito, Kiriko; Kikuchi, Misato; Nakasone, Hideki; Kako, Shinichi; Tanihara, Aki; Kanda, Yoshinobu

    2018-03-27

    The actual heparin concentration of harvested allogeneic bone marrow varies among harvest centers. We monitor the activated partial thromboplastin time (APTT) of the patient during bone marrow infusion and administer prophylactic protamine according to the APTT. We retrospectively reviewed the charts of consecutive patients who underwent bone marrow transplantation without bone marrow processing at our center between April 2007 and March 2016 (n = 94). APTT was monitored during marrow transfusion in 52 patients. We analyzed the relationship between the APTT ratio and several parameters related to heparin administration. As a result, the weight-based heparin administration rate (U/kg/hour) seemed to be more closely related to the APTT ratio (r = .38, P = .005) than to the total amount of heparin. There was no significant correlation between the APTT ratio and renal or liver function. Bleeding complications during and early after infusion were seen in 3 of 52 patients, and included intracranial, nasal, and punctured-skin bleeding. The APTT ratio during transfusion was over 5.88 in the former 2 patients and 2.14 in the latter. All of these patients recovered without sequelae. In conclusion, slow bone marrow infusion is recommended to decrease the weight-based heparin administration rate when the heparin concentration per patient body weight is high. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  15. Analytical characterization of heparin by capillary zone electrophoresis with conductivity detection and polymeric buffer additives.

    Mikus, Peter; Valásková, Iva; Havránek, Emil

    2004-11-15

    A capillary zone electrophoresis (CZE) method for the analytical characterization of intact (high-molecular-weight) heparin was developed. For the first time, a hydrodynamically closed CZE separation system with conductivity detector was used for the separation, detection and quantitation of this highly sulfated, linear polysaccharide. Glycine (25mM) adjusted to pH 9.0 by bis-Tris-propane served as the running electrolyte system. Polymeric additives, polyvinylpyrrolidone (PVP), dextran (DEX), were used to improve the separation selectivity as they strongly retarded the heparin macromolecule while they did not practically influence comigrating inorganic anions. The proposed electrophoretic method was successfully validated. It was convenient for the sensitive, simple, rapid and reproducible assay of heparin in raw materials and isotonic saline. Here, the use of the conductivity detector was advantageous as it allowed heparin to be analyzed without a sample pretreatment. The CZE method should be an alternative to the pharmacopoeial conventional gel electrophoresis having used in the quality control of heparin so far. In addition, it should be convenient to quantitative estimation of heparin present in a preparation used, e.g., as the chiral selector in CE separations.

  16. Endostatin competes with bFGF for binding to heparin-like glycosaminoglycans

    Reis, Renata C.M.; Schuppan, Detlef; Barreto, Aline C.; Bauer, Michael; Bork, Jens P.; Hassler, Gerda; Coelho-Sampaio, Tatiana

    2005-01-01

    Endostatin is a potent inhibitor of angiogenesis and tumor growth. Here, we used human endothelial cells from lung capillaries to investigate if endostatin competes with the proangiogenic growth factors, bFGF and VEGF, for binding to costimulatory heparan sulfate molecules. Endostatin inhibited 79% and 95% of the increase in proliferation induced by bFGF and VEGF 165 , respectively. The stimulatory effect of VEGF 165 was not affected by the presence of exogenous heparin, while that of bFGF was further enhanced in the presence of up to 0.1 μg/ml heparin. The heparin-binding protein protamine completely blocked bFGF-stimulated proliferation, while it did not affect the response to VEGF 165 . Simultaneous addition of endostatin and protamine led to additive effects both in inhibition of proliferation and induction of apoptosis. Although bFGF was found to bind more strongly to heparin-Sepharose than endostatin, the latter, but not the former, displaced protamine from heparin in solution, which supports the notion that endostatin can compete with bFGF for binding to heparan sulfate in vivo. Taken as a whole, our results demonstrate that there is a direct connection between the dependence of endostatin activity on heparin-like glycosaminoglycans and its ability to antagonize bFGF

  17. Heparin binding domain of antithrombin III: Characterization using a synthetic peptide directed polyclonal antibody

    Smith, J.W.; Dey, B.; Knauer, D.J.

    1990-01-01

    Antithrombin III (ATIII) is a plasma-borne serine protease inhibitor that apparently forms covalent complexes with thrombin. The interaction between ATIII and thrombin is enhanced several thousandfold by the glycosaminoglycan, heparin. The authors have previously proposed that the heparin binding site of ATIII residues within a region extending from amino acid residues 114-156. Computer-assisted analysis of this region revealed the presence of a 22 amino acid domain (residues 124-145), part of which shows a strong potential for the formation of an amphipathic helix: hydrophobic on one face and highly positively charged on the other. In the presence studies, polyclonal antisera were generated against a synthetic peptide corresponding to residues 124-145 in native human ATIII. Affinity-purified IgG from these antisera, as well as monovalent Fab's derived from them, specifically blocked the binding of heparin to ATIII. Additionally, occupancy of the heparin binding site by these same monovalent and bivalent IgG's at least partially substituted for heparin, accelerating linkage formation between ATIII and thrombin. These results provide the first immunological evidence that region 124-145 is directly involved in the binding of heparin to ATIII and that an antibody-induced conformational change within this region can mediate ATIII activation

  18. In vitro effects of heparin and tissue factor pathway inhibitor on factor VII assays. possible implications for measurements in vivo after heparin therapy

    Bladbjerg, E-M; Larsen, L F; Ostergaard, P

    2000-01-01

    The coagulant activity of blood coagulation factor VII (FVII:C) can be lowered by changes in lifestyle and by therapeutic intervention, e.g. heparin infusion. The question is, however, whether FVII:C determined ex vivo is a valid measure of the FVII activity in vivo. We measured plasma FVII......:C, activated FVII (FVIIa), FVII protein (FVII:Ag), tissue factor pathway inhibitor (TFPI), triglycerides, and free fatty acids (FFA) before and 15 min after infusion of a bolus of unfractionated heparin (50 IU/kg body weight) in 12 healthy subjects. Additionally, we conducted in vitro experiments...

  19. Efficient coupling of Sec23-Sec24 to Sec13-Sec31 drives COPII-dependent collagen secretion and is essential for normal craniofacial development.

    Townley, Anna K; Feng, Yi; Schmidt, Katy; Carter, Deborah A; Porter, Robert; Verkade, Paul; Stephens, David J

    2008-09-15

    The COPII coat assembles on endoplasmic reticulum membranes to coordinate the collection of secretory cargo with the formation of transport vesicles. During COPII assembly, Sar1 deforms the membrane and recruits the Sec23-Sec24 complex (Sec23/24), which is the primary cargo-binding adaptor for the system, and Sec13-Sec31 (Sec13/31), which provides a structural outer layer for vesicle formation. Here we show that Sec13 depletion results in concomitant loss of Sec31 and juxtanuclear clustering of pre-budding complexes containing Sec23/24 and cargo. Electron microscopy reveals the presence of curved coated profiles on distended endoplasmic reticulum, indicating that Sec13/31 is not required for the generation or maintenance of the curvature. Surprisingly, export of tsO45-G-YFP, a marker of secretory cargo, is unaffected by Sec13/31 depletion; by contrast, secretion of collagen from primary fibroblasts is strongly inhibited. Suppression of Sec13 expression in zebrafish causes defects in proteoglycan deposition and skeletal abnormalities that are grossly similar to the craniofacial abnormalities of crusher mutant zebrafish and patients with cranio-lenticulo-sutural dysplasia. We conclude that efficient coupling of the inner (Sec23/24) and outer (Sec13/31) layers of the COPII coat is required to drive the export of collagen from the endoplasmic reticulum, and that highly efficient COPII assembly is essential for normal craniofacial development during embryogenesis.

  20. Oral heparin delivery: design and in vivo evaluation of a stomach-targeted mucoadhesive delivery system.

    Schmitz, Thierry; Leitner, Verena M; Bernkop-Schnürch, Andreas

    2005-05-01

    Low molecular weight heparin (LMWH) is an agent of choice in the anti-coagulant therapy and prophylaxis of thrombosis and coronary syndromes. However, the therapeutic use is partially limited due to a poor oral bioavailability. It was therefore the aim of this study to design and evaluate a highly efficient stomach-targeted oral delivery system for LMWH. In order to appraise the influence of the molecular weight on the oral bioavailability, mini-tablets comprising 3 kDa (279 IU) and 6 kDa (300 IU) LMWH, respectively, were generated and tested in vivo in rats. The potential of the test formulations based on thiolated polycarbophil, was evaluated in comparison to hydroxyethylcellulose (HEC) as control carrier matrix. The plasma levels of LMWH after oral versus subcutaneous administration were determined in order to calculate the relative bioavailability. With the delivery system containing 3 kDa LMWH (279 IU) a relative bioavailability of 19.1% was achieved, offering a significantly (p thiolated polymers are a promising tool for the non-invasive stomach-targeted systemic delivery of LMWH as model for a hydrophilic macromolecular polysaccharide. Copyright 2005 Wiley-Liss, Inc

  1. Elevated urine levels of heparin-binding protein in children with urinary tract infection.

    Kjölvmark, Charlott; Akesson, Per; Linder, Adam

    2012-08-01

    Urinary tract infection (UTI) is a common infection diagnosis in children, and efficient diagnosis and treatment are important to avoid serious complications. In this study we investigated whether urinary levels of neutrophil-derived heparin-binding protein (HBP) can be used as a marker of UTI in children. These results were compared to those of dipstick analysis, interleukin-6 (IL-6) analysis in urine, and bacterial culturing. Seventy-eight children aged 0-18 years with fever and/or symptoms indicating UTI were enrolled in a prospective consecutive study. Urine samples were cultured and analyzed with dipstick, and concentrations of HBP and IL-6 were measured. Fifteen patients were classified as having UTI, 30 patients had fever but were diagnosed with a non-urinary tract infection, and 33 patients had neither UTI nor fever. Using a urine HBP (U-HBP) cut-off level of 32 ng/mL, the sensitivity and specificity for detecting UTI were 93.3 and 90.3 %, respectively. Receiver operating characteristic curves demonstrated that U-HBP levels were a higher specificity indicator of UTI than urine white blood cell counts or urine IL-6 levels; they also showed a higher sensitivity than the results of the urine nitrite test. All patients with significant growth of clinically relevant bacteria had elevated U-HBP levels. The results indicate that rapid analysis of U-HBP can provide helpful guidance in the management of children with suspected UTI.

  2. Development of iodine based impinger solutions for the efficient capture of Hg{sup 0} using direct injection nebulization-inductively coupled plasma mass spectrometry analysis

    Hedrick, E.; Lee, T.G.; Biswas, P.; Zhuang, Y. [US Environmental Protection Agency, Cincinnati, OH (USA). National Exposure Research Laboratory

    2001-09-15

    Inductively coupled plasma mass spectrometry (ICP/MS) with direct injection nebulization (DIN) was used to evaluate novel impinger solution compositions capable of capturing elemental mercury (Hg{sup 0}) in EPA Method 5 type sampling. An iodine based impinger solution proved to be very efficient for Hg{sup 0} capture and was amenable to direct analysis by DIN-ICP/MS. Hg{sup 0} capture efficiency using aqueous iodine (I{sub 3}{sup -}) was comparable to Hg{sup 0} capture using acidified potassium permanganate impinger solutions which were analyzed by cold vapor atomic absorption spectrometry (CVAAS) with greater than 98% capture of Hg{sup 0} in the oxidizing impinger. Using DIN-ICP/MS, it was demonstrated for the first time that iodine can be generated just prior to impinger sampling for efficiently oxidizing Hg{sup 0} and retailing it in solution as HgI{sub 4}{sup 2-}. Due to the increased interest in Hg speciation from combustion sources and the potential for using DIN-ICP/MS for multiple metals analyses, an impinger sampling train for gaseous Hg speciation and multiple metals analyses using DIN-ICP/MS analyses is presented. The unique feature of such a sampling train is that each impinger solution in the series is amenable to direct analysis by DIN-ICP/MS. A bituminous coal was combusted in a bench scale coal system, and gaseous Hg species (oxidized and elemental) were determined using the proposed impinger train. The DIN-ICP/Ms instrumental detection limit was 0.003 ppb, and MDLs ranged from 0.007 to 0.116 {mu}g/L (ppb) in a variety of impinger solutions used for Hg capture. 33 refs., 5 figs., 7 tabs.

  3. Effect of crosslinking chemistry of albumin/heparin multilayers on FGF-2 adsorption and endothelial cell behavior

    Kumorek, Marta, E-mail: kumorek@imc.cas.cz [Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic v.v.i., Heyrovského Square 2, Prague 162 06 (Czech Republic); Janoušková, Olga, E-mail: janouskova@imc.cas.cz [Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic v.v.i., Heyrovského Square 2, Prague 162 06 (Czech Republic); Höcherl, Anita, E-mail: hocherl@imc.cas.cz [Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic v.v.i., Heyrovského Square 2, Prague 162 06 (Czech Republic); Houska, Milan, E-mail: houska@imc.cas.cz [Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic v.v.i., Heyrovského Square 2, Prague 162 06 (Czech Republic); Mázl-Chánová, Eliška, E-mail: chanova@imc.cas.cz [Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic v.v.i., Heyrovského Square 2, Prague 162 06 (Czech Republic); Kasoju, Naresh, E-mail: naresh.kasoju@eng.ox.ac.uk [Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic v.v.i., Heyrovského Square 2, Prague 162 06 (Czech Republic); Cuchalová, Lucie, E-mail: cuchaloval@gmail.com [Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic v.v.i., Heyrovského Square 2, Prague 162 06 (Czech Republic); and others

    2017-07-31

    Highlights: • Amine, carboxyl, and induced aldehyde groups of heparin were used for crosslinking of LbL film. • The carbodiimide-mediated cross-linking was the most efficient fixation method. • FGF-2 bound the most effectively to the glutaraldehyde-cross-linked LbL film. • Films cross-linked through carboxyl and aldehyde groups showed a slow FGF-2 release. • FGF-2-loaded LbL films stimulated the HUVECs growth better than the soluble FGF-2. - Abstract: The biomaterials that efficiently deliver growth factors represent an important challenge in cell-based tissue engineering. Layer-by-layer (LbL) thin films are attractive for incorporating controlled amounts of growth factors and releasing them over time. Herein, we investigated the effect of a method of cross-linking of albumin/heparin layer-by-layer (LbL) assembly ((Alb/Hep){sub 3}) on the loading and release of basic fibroblast growth factor (FGF-2), and subsequent proliferation of human endothelial cells (HUVECs). The (Alb/Hep){sub 3} assemblies were cross-linked using glutaraldehyde, reductive amination or carbodiimide chemistries, and then biofunctionalized with FGF-2. The (Alb/Hep){sub 3} assemblies were characterized by the infrared multi-internal reflection spectroscopy, atomic force microscopy, ellipsometry, and surface plasmon resonance (SPR). The FGF-2 loading was quantified by the SPR in situ analysis. Our results showed that the (Alb/Hep){sub 3} cross-linking affected the amount of the bound heparin (from 150 to 315 ng/cm{sup 2}), amount of FGF-2 loaded (from 75 to 125 ng/cm{sup 2}), FGF-2 release (from 15 to 53% over 8 days), and consequently the HUVEC cell proliferation (from 50 to 80 × 10{sup 3} cells/cm{sup 2} at day 5). All FGF-2 loaded assemblies stimulated the cell growth more than a soluble FGF-2 added into the cell media. In particular, the highest HUVECs proliferation was detected on the carbodiimide-cross-linked assembly. Overall, these biocompatible cross-linked assemblies can fine

  4. Enhancement of trophoblast differentiation and survival by low molecular weight heparin requires heparin-binding EGF-like growth factor.

    Bolnick, Alan D; Bolnick, Jay M; Kohan-Ghadr, Hamid-Reza; Kilburn, Brian A; Pasalodos, Omar J; Singhal, Pankaj K; Dai, Jing; Diamond, Michael P; Armant, D Randall; Drewlo, Sascha

    2017-06-01

    Does low molecular weight heparin (LMWH) require heparin-binding epidermal growth factor (EGF)-like growth factor (HBEGF) signaling to induce extravillous trophoblast differentiation and decrease apoptosis during oxidative stress? LMWH increased HBEGF expression and secretion, and HBEGF signaling was required to stimulate trophoblast extravillous differentiation, increase invasion in vitro and reduce trophoblast apoptosis during oxidative stress. Abnormal trophoblast differentiation and survival contribute to placental insufficiency syndromes, including preeclampsia and intrauterine growth restriction. Preeclampsia often manifests as a pro-thrombotic state, with unsuccessful transformation of the spiral arteries that reduces oxygen supply and can produce placental infarction. LMWH improves placental function by increasing blood flow. Recent data suggest that the actions of LMWH transcend its anti-coagulative properties, but the molecular mechanism is unknown. There is evidence that LMWH alters the expression of human HBEGF in trophoblast cells, which regulates human trophoblast pathophysiology. HBEGF, itself, is capable of increasing trophoblast survival and invasiveness. First-trimester placental explants and the HTR-8/SVneo cell line, established using extravillous trophoblast outgrowths from first-trimester villous explants, were treated in vitro with LMWH to examine the effects on HBEGF signaling and trophoblast function under normal physiological and pathological conditions. A highly specific antagonist of HBEGF and other inhibitors of HBEGF downstream signaling were used to determine the relationship between LMWH treatment and HBEGF. Placental tissues (n = 5) were obtained with IRB approval and patient consent from first-trimester terminations. Placental explants and HTR-8/SVneo cells were cultured on plastic or Matrigel™ and treated with a therapeutic dose of LMWH (Enoxaparin; 10 IU/ml), with or without CRM197, pan Erb-B2 Receptor Tyrosine Kinase (ERBB

  5. Heparin octasaccharide decoy liposomes inhibit replication of multiple viruses

    Hendricks, Gabriel L.; Velazquez, Lourdes; Pham, Serena; Qaisar, Natasha; Delaney, James C.; Viswanathan, Karthik; Albers, Leila; Comolli, James C.; Shriver, Zachary; Knipe, David M.; Kurt-Jones, Evelyn A.; Fygenson, Deborah K.; Trevejo, Jose M.

    2016-01-01

    Heparan sulfate (HS) is a ubiquitous glycosaminoglycan that serves as a cellular attachment site for a number of significant human pathogens, including respiratory syncytial virus (RSV), human parainfluenza virus 3 (hPIV3), and herpes simplex virus (HSV). Decoy receptors can target pathogens by binding to the receptor pocket on viral attachment proteins, acting as ‘molecular sinks’ and preventing the pathogen from binding to susceptible host cells. Decoy receptors functionalized with HS could bind to pathogens and prevent infection, so we generated decoy liposomes displaying HS-octasaccharide (HS-octa). These decoy liposomes significantly inhibited RSV, hPIV3, and HSV infectivity in vitro to a greater degree than the original HS-octa building block. The degree of inhibition correlated with the density of HS-octa displayed on the liposome surface. Decoy liposomes with HS-octa inhibited infection of viruses to a greater extent than either full-length heparin or HS-octa alone. Decoy liposomes were effective when added prior to infection or following the initial infection of cells in vitro. By targeting the well-conserved receptor-binding sites of HS-binding viruses, decoy liposomes functionalized with HS-octa are a promising therapeutic antiviral agent and illustrate the utility of the liposome delivery platform. PMID:25637710

  6. Low-molecular-weight heparins: pharmacologic profile and product differentiation.

    Fareed, J; Jeske, W; Hoppensteadt, D; Clarizio, R; Walenga, J M

    1998-09-10

    The interchangeability of low-molecular-weight heparins (LMWHs) has been the subject of discussion since these products were first introduced for the prophylaxis of deep vein thrombosis. Experimental evidence now exists to show that LMWHs differ from each other in a number of characteristics. Products have been differentiated on the basis of molecular weight and biologic properties, but only limited information derived from the clinical setting is available. Potency has been described on the basis of anti-Factor Xa activity, but at equivalent anti-Xa activities, the anti-Factor IIa activity of different products shows marked variations. At the relatively small doses used for the management of postsurgical deep vein thrombosis, the effect of these interproduct differences may be relatively minor, but as LMWHs are developed for therapeutic use at much higher doses, such differences may become clinically important. Variations in safety and efficacy reported in clinical trials of LMWHs may reflect the known differences in their molecular composition and pharmacologic properties.

  7. Thermal-based modeling of coupled carbon, water, and energy fluxes using nominal light use efficiencies constrained by leaf chlorophyll observations

    Schull, M. A.

    2015-03-11

    Recent studies have shown that estimates of leaf chlorophyll content (Chl), defined as the combined mass of chlorophyll a and chlorophyll b per unit leaf area, can be useful for constraining estimates of canopy light use efficiency (LUE). Canopy LUE describes the amount of carbon assimilated by a vegetative canopy for a given amount of absorbed photosynthetically active radiation (APAR) and is a key parameter for modeling land-surface carbon fluxes. A carbon-enabled version of the remote-sensing-based two-source energy balance (TSEB) model simulates coupled canopy transpiration and carbon assimilation using an analytical sub-model of canopy resistance constrained by inputs of nominal LUE (βn), which is modulated within the model in response to varying conditions in light, humidity, ambient CO2 concentration, and temperature. Soil moisture constraints on water and carbon exchange are conveyed to the TSEB-LUE indirectly through thermal infrared measurements of land-surface temperature. We investigate the capability of using Chl estimates for capturing seasonal trends in the canopy βn from in situ measurements of Chl acquired in irrigated and rain-fed fields of soybean and maize near Mead, Nebraska. The results show that field-measured Chl is nonlinearly related to βn, with variability primarily related to phenological changes during early growth and senescence. Utilizing seasonally varying βn inputs based on an empirical relationship with in situ measured Chl resulted in improvements in carbon flux estimates from the TSEB model, while adjusting the partitioning of total water loss between plant transpiration and soil evaporation. The observed Chl-βn relationship provides a functional mechanism for integrating remotely sensed Chl into the TSEB model, with the potential for improved mapping of coupled carbon, water, and energy fluxes across vegetated landscapes.

  8. High-Efficiency On-Line Solid-Phase Extraction Coupling to 15-150 um I.D. Column Liquid Chromatography for Proteomic Analysis

    Shen, Yufeng; Moore, Ronald J.; Zhao, Rui; Blonder, Josip; Auberry, Deanna L.; Masselon, Christophe D.; Pasa Tolic, Ljiljana; Hixson, Kim K.; Auberry, Kenneth J.; Smith, Richard D.

    2003-01-01

    Flexible manipulation of various properties of proteomic samples is important for proteomic analyses, but it has been little explored for newly developed approaches based on liquid chromatography (LC) in combination with mass spectrometry (MS). With miniaturization of the LC column inner diameter dimensions (required for improving the analysis sensitivity), this issue becomes more challenging due to the small flow rates and the increasing effects of extra column volume on the separation quality and its use for resolving complex proteomic mixtures. In this study, we used commercial switching valves (150-mm channels) to implement the on-line coupling of capillary LC columns with relatively large solid phase extraction (SPE) columns operated at 10,000 psi. With optimized column connections, switching modes, and SPE column dimensions, high-efficiency on-line SPE-capillary and nanoscale LC separations were obtained with peak capacities of ∼1000 for capillaries having inner diameters between 15 to 150 mm. The on-line coupled SPE columns increased the sample processing capabilities by ∼400-fold for sample solution volume and ∼10-fold for sample mass. The proteomic applications of this on-line SPE-capillary LC system were evaluated for analysis of both soluble and membrane protein tryptic digests. Used with an ion trap tandem MS we could typically identify 1100-1500 peptides for analyses in a single 5-hour run. Peptides extracted on the SPE column and eluted from the LC column covered a hydrophilicity/hydrophobicity range that include an estimated ∼98% of all the tryptic peptides. The present implementation also facilitates automation and enables use of both disposable SPE columns and electrospray emitters, providing a robust basis for routine proteomic analyses.

  9. Molecular Weights of Bovine and Porcine Heparin Samples: Comparison of Chromatographic Methods and Results of a Collaborative Survey

    Sabrina Bertini

    2017-07-01

    Full Text Available In a collaborative study involving six laboratories in the USA, Europe, and India the molecular weight distributions of a panel of heparin sodium samples were determined, in order to compare heparin sodium of bovine intestinal origin with that of bovine lung and porcine intestinal origin. Porcine samples met the current criteria as laid out in the USP Heparin Sodium monograph. Bovine lung heparin samples had consistently lower average molecular weights. Bovine intestinal heparin was variable in molecular weight; some samples fell below the USP limits, some fell within these limits and others fell above the upper limits. These data will inform the establishment of pharmacopeial acceptance criteria for heparin sodium derived from bovine intestinal mucosa. The method for MW determination as described in the USP monograph uses a single, broad standard calibrant to characterize the chromatographic profile of heparin sodium on high-resolution silica-based GPC columns. These columns may be short-lived in some laboratories. Using the panel of samples described above, methods based on the use of robust polymer-based columns have been developed. In addition to the use of the USP’s broad standard calibrant for heparin sodium with these columns, a set of conditions have been devised that allow light-scattering detected molecular weight characterization of heparin sodium, giving results that agree well with the monograph method. These findings may facilitate the validation of variant chromatographic methods with some practical advantages over the USP monograph method.

  10. N-acetyl-heparin attenuates acute lung injury caused by acid aspiration mainly by antagonizing histones in mice.

    Zhang, Yanlin; Zhao, Zanmei; Guan, Li; Mao, Lijun; Li, Shuqiang; Guan, Xiaoxu; Chen, Ming; Guo, Lixia; Ding, Lihua; Cong, Cuicui; Wen, Tao; Zhao, Jinyuan

    2014-01-01

    Acute lung injury (ALI) is the leading cause of death in intensive care units. Extracellular histones have recently been recognized to be pivotal inflammatory mediators. Heparin and its derivatives can bind histones through electrostatic interaction. The purpose of this study was to investigate 1) the role of extracellular histones in the pathogenesis of ALI caused by acid aspiration and 2) whether N-acetyl-heparin (NAH) provides more protection than heparin against histones at the high dose. ALI was induced in mice via intratracheal instillation of hydrochloric acid (HCl). Lethality rate, blood gas, myeloperoxidase (MPO) activity, lung edema and pathological changes were used to evaluate the degree of ALI. Heparin/NAH was administered intraperitoneally, twice a day, for 3 days or until death. Acid aspiration caused an obvious increase in extracellular histones. A significant correlation existed between the concentration of HCl aspirated and the circulating histones. Heparin/NAH (10 mg/kg) improved the lethality rate, blood gas, MPO activity, lung edema and pathological score. At a dose of 20 mg/kg, NAH still provided protection, however heparin tended to aggravate the injury due to hemorrhagic complications. The specific interaction between heparin and histones was verified by the binding assay. In summary, high levels of extracellular histones can be pathogenic in ALI caused by acid aspiration. By neutralizing extracellular histones, heparin/NAH can offer similar protection at the moderate doses. At the high dose, NAH provides better protection than heparin.

  11. Convective Leakage Makes Heparin Locking of Central Venous Catheters Ineffective Within Seconds: Experimental Measurements in a Model Superior Vena Cava.

    Barbour, Michael C; McGah, Patrick M; Ng, Chin H; Clark, Alicia M; Gow, Kenneth W; Aliseda, Alberto

    2015-01-01

    Central venous catheters (CVCs), placed in the superior vena cava (SVC) for hemodialysis or chemotherapy, are routinely filled while not in use with heparin, an anticoagulant, to maintain patency and prevent thrombus formation at the catheter tip. The heparin-locking procedure, however, places the patient at risk for systemic bleeding, as heparin is known to leak from the catheter into the blood stream. We provide evidence from detailed in vitro experiments that shows the driving mechanism behind heparin leakage to be convective-diffusive transport due to the pulsatile flow surrounding the catheter. This novel mechanism is supported by experimental planar laser-induced fluorescence (PLIF) and particle image velocimetry (PIV) measurements of flow velocity and heparin transport from a CVC placed inside a model SVC inside a pulsatile flow loop. The results predict an initial, fast (<10 s), convection-dominated phase that rapidly depletes the concentration of heparin in the near-tip region, the region of the catheter with side holes. This is followed by a slow, diffusion-limited phase inside the catheter lumen, where the concentration is still high, that is insufficient at replenishing the lost heparin concentration in the near-tip region. The results presented here, which are consistent with previous in vivo estimates of 24 hour leakage rates, predict that the concentration of heparin in the near-tip region is essentially zero for the majority of the interdialytic phase, rendering the heparin locking procedure ineffective.

  12. Molecular Weights of Bovine and Porcine Heparin Samples: Comparison of Chromatographic Methods and Results of a Collaborative Survey.

    Bertini, Sabrina; Risi, Giulia; Guerrini, Marco; Carrick, Kevin; Szajek, Anita Y; Mulloy, Barbara

    2017-07-19

    In a collaborative study involving six laboratories in the USA, Europe, and India the molecular weight distributions of a panel of heparin sodium samples were determined, in order to compare heparin sodium of bovine intestinal origin with that of bovine lung and porcine intestinal origin. Porcine samples met the current criteria as laid out in the USP Heparin Sodium monograph. Bovine lung heparin samples had consistently lower average molecular weights. Bovine intestinal heparin was variable in molecular weight; some samples fell below the USP limits, some fell within these limits and others fell above the upper limits. These data will inform the establishment of pharmacopeial acceptance criteria for heparin sodium derived from bovine intestinal mucosa. The method for MW determination as described in the USP monograph uses a single, broad standard calibrant to characterize the chromatographic profile of heparin sodium on high-resolution silica-based GPC columns. These columns may be short-lived in some laboratories. Using the panel of samples described above, methods based on the use of robust polymer-based columns have been developed. In addition to the use of the USP's broad standard calibrant for heparin sodium with these columns, a set of conditions have been devised that allow light-scattering detected molecular weight characterization of heparin sodium, giving results that agree well with the monograph method. These findings may facilitate the validation of variant chromatographic methods with some practical advantages over the USP monograph method.

  13. Cost-utility of enoxaparin compared with unfractionated heparin in unstable coronary artery disease

    Milne Ruairidh

    2001-10-01

    Full Text Available Abstract Background Low molecular weight heparins hold several advantages over unfractionated heparin including convenience of administration. Enoxaparin is one such heparin licensed in the UK for use in unstable coronary artery disease (unstable stable angina and non-Q wave myocardial infarction. In these patients, two large randomised controlled trials and their meta-analysis showed small benefits for enoxaparin over unfractionated heparin at 30–43 days and potentially at one year. We found no relevant published full economic evaluations, only cost studies, one of which was conducted in the UK. The other studies, from the US, Canada and France, are difficult to interpret since their resource use and costs may not reflect UK practice. Methods We aimed to compare the benefits and costs of short-term treatment (two to eight days with enoxaparin and unfractionated heparin in unstable coronary artery disease. We used published data sources to estimate the incremental cost per quality adjusted life year (QALY, adopting a NHS perspective and using 1998 prices. Results The base case was a 0.013 QALY gain and net cost saving of £317 per person treated with enoxaparin instead of unfractionated heparin. All but one sensitivity analysis showed net savings and QALY gains, the exception (the worst case being a cost per QALY of £3,305. Best cases were a £495 saving and 0.013 QALY gain, or a £317 saving and 0.014 QALY gain per person. Conclusions Enoxaparin appears cost saving compared with unfractionated heparin in patients with unstable coronary artery disease. However, cost implications depend on local revascularisation practice.

  14. Effects of heparin on platelet aggregation and release and thromboxane A2 production

    Mohammad, S.F.; Anderson, W.H.; Smith, J.B.; Chuang, H.Y.; Mason, R.G.

    1981-01-01

    Heparin, when added to citrated platelet-rich plasma (PRP), caused potentiation of platelet aggregation and the release reaction induced by the aggregating agents adenosine diphosphate (ADP), arachidonic acid, collagen, and epinephrine. At low concentrations (4.7 x 10(-5) M) arachidonic acid failed to cause aggregation of platelets in citrated PRP. However, in the presence of heparin, the same concentration of arachidonic acid caused aggregation. Examination of PRP for the presence of thromboxane A2 (TxA2) by use of a bioassay revealed that heparin also stimulated release of TxA2. This finding indicated that platelets released more TxA2 when they were challenged by low concentrations of arachidonic acid in the presence of heparin than in its absence. Platelets were labeled with 3 H-arachidonic acid and 14 C-serotonin, and attempts were made to determine whether heparin stimulated the platelet release reaction first with subsequent increased production of TxA2, or alternatively, whether heparin stimulated TxA2 production first with subsequent enhancement of the release reaction. In view of the demonstrated simultaneous release of 14 C-serotonin and 3 H-arachidonic acid metabolites, it appeared that either release of 14 C and 3 H occurs concurrently or, even if one of these events is dependent on the other, both events take place in rapid succession. Timed sequential studies revealed that in the presence of arachidonic acid, the addition of heparin hastened the apparently simultaneous release of both 14 C and 3 H

  15. Voltammetric determination of heparin based on its interaction with malachite green

    Xueliang Niu

    2008-08-01

    Full Text Available In this paper malachite green (MG was used as a bioprobe to determine heparin concentration by linear sweep voltammetry on the dropping mercury working electrode (DME. In Britton-Robinson (B-R buffer solution of pH 1.5, MG had a well-defined second order derivative linear sweep voltammetric reductive peak at –0.618 V (vs. SCE. After the addition of heparin into the MG solution, the reductive peak current decreased apparently without the movement of peak potential. Based on the difference of the peak current, a new voltammetric method for the determination of heparin was established. The conditions for the binding reaction and the electrochemical detection were optimized. Under the selected experimental conditions the difference of peak current was directly proportional to the concentration of heparin in the range from 0.3 to 10.0 mg/L with the linear regression equation as ∆ip″ (nA = 360.19 C (mg/L + 178.88 (n = 15, γ = 0.998 and the detection limit as 0.28 mg/L (3σ. The effects of coexisting substances such as metal ions, amino acids on the determination of heparin were investigated and the results showed that this method had good selectivity. This method was further applied to determine the heparin content in heparin sodium injection samples with satisfactory results and good recovery. The stoichiometry of the biocomplex was calculated by the electrochemical method and the binding mechanism was further discussed.

  16. Prevention of fatal postoperative pulmonary embolism by low doses of heparin. An international multicentre trial.

    1975-07-12

    The efficacy of low-dose heparin in preventing fatal postoperative pulmonary embolism has been investigated in a multicentre prospective randomised trial. 4121 patients over the age of forty years undergoing a variety of elective major surgical procedures were included in the trial; 2076 of these were in the control group and 2045 patients received heparin. The two groups were well matched for age, sex, weight, blood-group, and other factors which could predispose to the development of venous thromboembolism. 180 (4-4 %) patients died during the postoperative period, 100 in the control and 80 in the heparin group: 72% of deaths in the control and 66% in the heparin group had necropsy examination. 16 patients in the control group and 2 in the heparin group were found at necropsy to have died due to acute massive pulmonary embolism (P smaller than 0-005). In addition, emboli found at necropsy in 6 patients in the control group and 3 in the heparin group were considered either contributory to death or an incidental finding since death in these patients was attributed to other causes. Taking all pulmonary emboli together, the findings were again significant (P smaller than 0-005). Of 1292 patients in whom the 125-I-fibrinogen test was performed to detect deep-vein thrombosis (D.V.T.) 667 were in the control group and 625 in the heparin group. The frequency of isotopic D.V.T. was reduced from 24-6% in the control group 7-7% in the heparin group (P smaller 0-005). In 30 patients D.V.T. was detected at necropsy; 24 in the control and 6 in the heparin group (P smaller 0-005). 32 patients in the control group and 11 in the heparin group developed clinically diagnosed D.V.T. which was confirmed by venography (P smaller than 0-005). In addition, 24 patients in the control and 8 in the heparin group were treated for clinically suspected pulmonary emoblism. The difference in the number of patients requiring treatment for D.V.T. and/or pulmonary embolism in the two groups was

  17. Morbidity associated with heparin therapy in spinal surgery patients with cardiovascular diseases

    Sawakami, Kimihiko; Ishikawa, Seiichi; Ito, Takui

    2011-01-01

    The objectives of this study were to investigate morbidity associated with heparin therapy in spinal surgery patients. The management of patients on anticoagulant therapy who undergo spinal surgery is becoming a common clinical problem. Although guidelines for the management of gastrointestinal endoscopy patients on heparin therapy have been published, spinal surgery may lead to specific complications, especially because of heparin therapy. However, only few studies have examined the clinical significance of heparin therapy in spinal surgery patients. The subjects of this study were 116 consecutive patients who were on anticoagulant or antiplatelet therapy. This says that all of the patients were receiving heparin or another anticoagunt. The patients were divided into 2 groups: a group that received heparin therapy before and after surgery (H group, n=25) and a group that did not receive heparin therapy (NH group, n=91). The results of clinical examinations and magnetic resonance imaging (MRI) in the 2 groups were compared. There were no significant differences between the 2 groups in baseline data. Comorbidities in both groups included valvular heart disease, atrial fibrillation, angina pectoris/myocardial infarction, and cerebral infarction. Mean intraoperative and postoperative blood loss in the H group were 324 ml and 536 ml, respectively, and the corresponding values in the NH group were 431 ml and 449 ml, respectively. MRI of all patients was performed within 10 days after surgery and T2-weighted images in the axial plane were examined for evidence of an epidural hematoma. Although the proportion of patients with an epidural hematoma, detected by MRI was higher in the H group than in the NH group (71% vs. 64%), none of the patients in either group required revision surgery because of intolerable pain or muscle weakness. Thrombocytopenia and skin necrosis were observed as complications of the heparin therapy in 1 patient in the H group (4%). The rate of

  18. Preparation and characterization of chitosan-heparin composite matrices for blood contacting tissue engineering

    He Qing; Gong Kai; Gong Yandao; Zhang Xiufang; Ao Qiang; Zhang Lihai; Hu Min

    2010-01-01

    Chitosan has been widely used for biomaterial scaffolds in tissue engineering because of its good mechanical properties and cytocompatibility. However, the poor blood compatibility of chitosan has greatly limited its biomedical utilization, especially for blood contacting tissue engineering. In this study, we exploited a polymer blending procedure to heparinize the chitosan material under simple and mild conditions to improve its antithrombogenic property. By an optimized procedure, a macroscopically homogeneous chitosan-heparin (Chi-Hep) blended suspension was obtained, with which Chi-Hep composite films and porous scaffolds were fabricated. X-ray photoelectron spectroscopy and sulfur elemental analysis confirmed the successful immobilization of heparin in the composite matrices (i.e. films and porous scaffolds). Toluidine blue staining indicated that heparin was distributed homogeneously in the composite matrices. Only a small amount of heparin was released from the matrices during incubation in normal saline for 10 days. The composite matrices showed improved blood compatibility, as well as good mechanical properties and endothelial cell compatibility. These results suggest that the Chi-Hep composite matrices are promising candidates for blood contacting tissue engineering.

  19. Laboratory tests for identification or exclusion of heparin induced thrombocytopenia: HIT or miss?

    Favaloro, Emmanuel J

    2018-02-01

    Heparin induced thrombocytopenia (HIT) is a potentially fatal condition that arises subsequent to formation of antibodies against complexes containing heparin, usually platelet-factor 4-heparin ("anti-PF4-heparin"). Assessment for HIT involves both clinical evaluation and, if indicated, laboratory testing for confirmation or exclusion, typically using an initial immunological assay ("screening"), and only if positive, a secondary functional assay for confirmation. Many different immunological and functional assays have been developed. The most common contemporary immunological assays comprise enzyme-linked immunosorbent assay [ELISA], chemiluminescence, lateral flow, and particle gel techniques. The most common functional assays measure platelet aggregation or platelet activation events (e.g., serotonin release assay; heparin-induced platelet activation (HIPA); flow cytometry). All assays have some sensitivity and specificity to HIT antibodies, but differ in terms of relative sensitivity and specificity for pathological HIT, as well as false negative and false positive error rate. This brief article overviews the different available laboratory methods, as well as providing a suggested approach to diagnosis or exclusion of HIT. © 2017 Wiley Periodicals, Inc.

  20. Heparin-independent, PF4-dependent binding of HIT antibodies to platelets: implications for HIT pathogenesis.

    Padmanabhan, Anand; Jones, Curtis G; Bougie, Daniel W; Curtis, Brian R; McFarland, Janice G; Wang, Demin; Aster, Richard H

    2015-01-01

    Antibodies specific for platelet factor 4 (PF4)/heparin complexes are the hallmark of heparin-induced thrombocytopenia and thrombosis (HIT), but many antibody-positive patients have normal platelet counts. The basis for this is not fully understood, but it is believed that antibodies testing positive in the serotonin release assay (SRA) are the most likely to cause disease. We addressed this issue by characterizing PF4-dependent binding of HIT antibodies to intact platelets and found that most antibodies testing positive in the SRA, but none of those testing negative, bind to and activate platelets when PF4 is present without any requirement for heparin (P HIT antibodies recognize PF4 in a complex with heparin, only a subset of these antibodies recognize more subtle epitopes induced in PF4 when it binds to CS, the major platelet glycosaminoglycan. Antibodies having this property could explain "delayed HIT" seen in some individuals after discontinuation of heparin and the high risk for thrombosis that persists for weeks in patients recovered from HIT. © 2015 by The American Society of Hematology.

  1. Hemocompatible ɛ-polylysine-heparin microparticles: A platform for detecting triglycerides in whole blood.

    Xu, Tingting; Chi, Bo; Chu, Meilin; Zhang, Qicheng; Zhan, Shuyue; Shi, Rongjia; Xu, Hong; Mao, Chun

    2018-01-15

    Triglycerides are clinically important marker for atherosclerosis, heart disease and hypertension. Here, a platform for detecting triglycerides in whole blood directly was developed based on hemocompatible ɛ-polylysine-heparin microparticles. The obtained products of ɛ-polylysine-heparin microparticles were characterized by fourier transform infrared (FT-IR) spectra, transmission electron microscopy (TEM) and ζ-potential. Moreover, the blood compatibility of ɛ-polylysine-heparin microparticles was characterized by in vitro coagulation tests, hemolysis assay and whole blood adhesion tests. Considering of uniform particle size, good dispersibility and moderate long-term anticoagulation capability of the microparticles, a Lipase-(ɛ-polylysine-heparin)-glassy carbon electrode (GCE) was constructed to detect triglycerides. The proposed biosensor had good electrocatalytic activity towards triglycerides, in which case the sensitivity was 0.40μAmg -1 dLcm -2 and the detection limit was 4.67mgdL -1 (S/N = 3). Meanwhile, the Lipase-(ɛ-polylysine-heparin)-GCE electrode had strong anti-interference ability as well as a long shelf-life. Moreover, for the detection of triglycerides in whole blood directly, the detection limit was as low as 5.18mgdL -1 . The new constructed platform is suitable for detecting triglycerides in whole blood directly, which provides new analytical systems for clinical illness diagnosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Evidence for a saturable mechanism of disappearance of standard heparin in rabbits

    Boneu, B.; Caranobe, C.; Gabaig, A.M.; Dupouy, D.; Sie, P.; Buchanan, M.R.; Hirsh, J.

    1987-01-01

    This work demonstrates that after bolus intravenous injection standard heparin (SH) disappearance results from the combination of a saturable and a non saturable mechanism. Pharmacokinetics and pharmacodynamics of SH were studied by measuring the disappearance of increasing doses (5 - 500 anti-factor Xa U/kg) of 125 I-heparin and of its biological effects. CPM curves allowed the determination of the half lives of heparin according to the dose injected. The half lives were clearly dose dependent and reached a plateau over 100 anti-factor Xa U/kg. The complex curve which describes the amount of heparin cleared per time unit after any given dose has been resolved into its two components reflecting a saturable and a non saturable mechanism of disappearance. For the doses less than 100 anti-factor Xa U/kg the saturable mechanism was preeminent and the anti-factor Xa activity disappearance followed an exponential pattern; for the doses less than 100 anti-factor Xa U/kg the contribution of the non saturable mechanism becomes more important and the anti-factor Xa activity disappearance followed a concave-convex pattern. Further experiments showed that the heparin half life shortened as the circulating anti-factor Xa activity decreased; this phenomenon may explain the concave-convex pattern of the curve of the anticoagulant effect observed after injection of large doses of SH

  3. Effect of heparin calcium different concentrations on some physical properties and structure in polyacrylamide matrix

    Abdelrazek, E.M.; Ibrahim, Hosam S.

    2010-01-01

    Films of polyacrylamide (PAAm) doped with different concentrations of heparin calcium, from 0.0 to 8 wt%, have been prepared by casting method. Studies were carried out utilizing X-ray, FT-IR, UV/VIS, DSC and DC electrical conduction to characterize the structural, optical and thermal properties of the films. Results revealed that the structural and chemical characterizations of PAAm films are affected by the addition of heparin calcium content. XRD spectra revealed that the amorphous phases increase with increase in filling levels of heparin (FLs). FT-IR analysis revealed that incorporation of heparin calcium leads to a small modification in the spectra of films. The optical absorption spectra in the UV/VIS region revealed structural variation increases with increase in concentration, which is reflected in the form of decrease in the energy band gap E g . Significant changes of DSC curves of the films suggest that strong interaction established between heparin calcium and PAAm molecules. The DC electric conduction data were interpreted on the basis of an intrachain one-dimensional interpolaron hopping model of Kuivalainen.

  4. Heparin-Induced Thrombocytopenia in a Patient with Essential Thrombocythemia: A Case Based Update

    Edva Noel

    2015-01-01

    Full Text Available Vascular thrombosis is a common clinical feature of both essential thrombocythemia (ET and heparin-induced thrombocytopenia (HIT. The development of HIT in a patient with ET is rare and underrecognized. We report the case of a 77-year-old woman with preexisting ET, who was admitted with acute coronary syndrome, and IV heparin was started. She was exposed to unfractionated heparin (UFH 5 days prior to this admission. Decrease in platelet count was noted, and HIT panel was sent. Heparin was discontinued. Patient developed atrial fibrillation, and Dabigatran was started. On day three, patient also developed multiple tiny cerebral infarctions and acute right popliteal DVT. On day ten of admission, HIT panel was positive, and Dabigatran was changed to Lepirudin. Two days later, Lepirudin was also discontinued because patient developed pseudoaneurysm on the right common femoral artery at the site of cardiac catheterization access. A progressive increase in the platelet count was noted after discontinuing heparin. Physicians should be aware of the coexistence of HIT and ET, accompanied challenges of the prompt diagnosis, and initiation of appropriate treatment.

  5. Nycthemeral variations of 99Tcsup(m)-labelled heparin pharmacokinetic parameters

    Decousus, M.; Gremillet, E.; Decousus, H.; Champailler, A.; Houzard, C.; Perpoint, B.; Jaubert, J.

    1985-01-01

    Six healthy volunteers received four i.v.boluses of 99 Tcsup(m)-heparin at 8.00, 14.00, 20.00 and 02.00 hours at seven-day intervals. Nine blood samples were taken covering a period of 2 h after administration. Simultaneously urine was collected and diuresis not noted. Plasma and urinary radioactivity were measured and standard pharmacokinetic parameters were calculated. Nycthemeral variations of these kinetic parameters were detected by means of distribution-free tests. Circadian rhythms were analysed by means of the cosinor method and the Gauss-Marquardt method. The mean raw value of the following parameters: apparent volume of distribution, plasmatic clearance and extra-renal metabolic clearance, increased significantly between 8.00 and 14.00 and decreased between 14.00 and 20.00. A circadian rhythm was found for the plasmatic clearance only. On the other hand the elimination half-lives and the renal clearance were unaffected by the time of the injections. These results obtained for low doses of 99 Tcsup(m)-heparin suggest a circadian rhythm of the bio-availability of heparin in man. This fact should be taken into account for the use of 99 Tcsup(m)-heparin in the diagnosis of deep-vein thrombosis and for the safe adjustment of the heparin dosages in the treatment of severe thromboembolism. (author)

  6. Heparin-induced increase in serum levels of aminotranferases. A controlled clinical trial.

    Nielsen, H K; Husted, S E; Koopmann, H D; Fasting, H; Simonsen, O; Andersen, K; Husegaard, H C; Petersen, T K

    1984-01-01

    Sixty-four patients over the age of 40 years, undergoing elective surgery of at least one hour's duration, were randomized to treatment with either a thromboembolic deterrent ( TED ) stocking (Kendall Co.) or subcutaneous low-dose heparin 5 000 IU every 12 hours. Serum levels of alanine aminotransferase (S-ALAT), aspartate aminotransferase (S-ASAT), gamma-glutamyl transpeptidase (S-gamma-GT) and alkaline phosphatase (S-ALP) were measured. S-ALAT increased significantly on the 5th and 10th postoperative day, from 27 +/- 2 (x +/- SE) to 40 +/- 4 (p less than 0.01) and 55 +/- 7 U/l (p less than 0.001), respectively, in the heparin group and was significantly higher in the heparin than in the TED group both on the 5th (p less than 0.01) and 10th (p less than 0.05) postoperative day. S-ASAT and S-gamma-GT increased significantly during heparin treatment, but did not differ significantly from the values of the TED group. No change in S-ALP was registered in either group. It is concluded that prophylactic treatment with low-dose heparin induces a significant increase in S-aminotransferase levels, especially in S-ALAT. The phenomenon has profound differential diagnostic implications in conditions such as pulmonary embolism and acute myocardial infarction.

  7. Assessment of Heparin Anticoagulation Measured Using i-STAT and Hemochron Activated Clotting Time.

    Maslow, Andrew; Chambers, Alison; Cheves, Tracey; Sweeney, Joseph

    2018-01-31

    Adequate anticoagulation, measured using activated clotting time (ACT), is important during vascular and cardiac surgeries. Unfractionated heparin is the most common anticoagulant used. The purpose of this analysis was to compare the i-STAT ACT (iACT) to the Hemochron ACT (hACT), both of which were then compared to anti-factor Xa (anti-Xa) assay, a representation of heparin level and activity. Prospective study. Tertiary care cardiovascular center. Eleven consecutive elective adult cardiac surgical patients. Prior to cardiopulmonary bypass, ACTs were measured using i-STAT and Hemochron technologies and compared to each other and to anti-Xa assay prior to and during a cumulative administration of heparin. Data were compared using bias analyses. Heparin (300 U/kg) was administered in quarterly doses. Coagulation labs were collected prior to and 3 minutes after each quarterly dose of heparin. The baseline ACTs for i-STAT and Hemochron were 147 and 142 seconds, respectively. A significant association was found between iACT and hACT (p = 0.002). The iACT measurements underestimated hACT at ACT levels >180 seconds or anti-Xa levels >0.75 U/mL. No significant difference was found between ACT data at anti-Xa levels 0.75 U/mL. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Detection of growth factor binding to gelatin and heparin using a photonic crystal optical biosensor

    Morgan, Abby W.; Chan, Leo L.; Sendemir-Urkmez, Aylin; Cunningham, Brian T.; Jamison, Russell D.

    2010-01-01

    Drug-carrier interactions are important to protein controlled release systems to protect the protein from denaturation and ensure properly timed release. A novel photonic crystal biosensor was used to investigate a gelatin-protein controlled release system to determine the amount of protein bound to the carrier at physiological conditions. The Biomolecular Interaction Detection (BIND) system reflects a narrow band of wavelengths when white light is shone incident to the grating. As mass is deposited onto the surface, the peak wavelength value is shifted due to changes in the optical density of the biosensor. The BIND system was used to detect the binding of growth factors onto acidic gelatin, basic gelatin, and heparin on the sensor surface. Through a series of experiments, including functionalizing the sensor, adjusting the ionic strength of the solution, adjusting the substrate concentration, and minimizing non-specific signal, the adsorption of the gelatins and heparin on the sensor was enhanced. The binding interaction of recombinant human transforming growth factor (rhTGF)-β1 and bone morphogenetic protein (rhBMP)-2 with the two types of gelatin and heparin were investigated. The strength of the interaction between rhTGF-β1 and the substrates is in the following order: heparin > acidic gelatin > basic gelatin. RhBMP-2 bound to the substrates but with less intensity than TGF-β1: heparin > basic gelatin > acidic gelatin. This work provides support for the controlled release mechanism through degradation of the gelatin carrier.

  9. The role of heparin in sepsis: much more than just an anticoagulant.

    Li, Xu; Ma, Xiaochun

    2017-11-01

    Despite progress in antibiotic treatment, mechanical ventilation, fluid resuscitation and blood glucose maintenance, sepsis remains a cause of high mortality in the intensive care unit to date, there are no proven treatment strategies for the routine management of septic patients. The extensive interaction between inflammation and coagulation contributes to the basic pathophysiology of sepsis. Thus, the agents that attenuate the activation of both inflammation and coagulation may improve the outcome in sepsis. Apart from the well-known anticoagulant effects of heparin, it also possesses various immunomodulatory properties and protects glycocalyx from shedding. Hence, heparin seems to be such an agent. Immunothrombosis plays an important role in early host defence against bacterial dissemination, thus the proper timing for anticoagulant therapy should be determined. We review the available experimental and clinical data supporting the use of heparin in sepsis. At this time the use of heparin in the treatment of sepsis is conflicting. Future trials of heparin therapy for sepsis should concentrate on the very severely ill patients, in whom benefit is most likely to be demonstrated. © 2017 John Wiley & Sons Ltd.

  10. Characterization of currently marketed heparin products: key tests for quality assurance.

    Keire, David A; Ye, Hongping; Trehy, Michael L; Ye, Wei; Kolinski, Richard E; Westenberger, Benjamin J; Buhse, Lucinda F; Nasr, Moheb; Al-Hakim, Ali

    2011-01-01

    During the 2007-2008 heparin crisis, it was found that the United States Pharmacopeia (USP) testing monograph for unfractionated heparin sodium (UFH) did not detect the presence of the contaminant, oversulfated chondroitin sulfate (OSCS) in heparin. In response to this concern, new tests and specifications were developed by the Food and Drug Administration (FDA) and USP and put in place to not only detect the contaminant OSCS but also to improve assurance of quality and purity of the drug product. Additional tests were also developed to monitor the heparin supply chain for other possible economically motivated additives or impurities. In 2009, a new USP monograph was put in place that includes 500 MHz (1)H NMR, SAX-HPLC, %galactosamine in total hexosamine, and anticoagulation time assays with purified factor IIa or factor Xa. These tests represent orthogonal approaches for UFH identification, measurement of bioactivity, and for detection of process impurities or contaminants in UFH. The FDA has applied these analytical approaches to the study of UFH active pharmaceutical ingredients in the marketplace. Here, we describe results from a comprehensive survey of UFH collected from seven different sources after the 2009 monograph revision and compare these data with results obtained on other heparin samples collected during the 2007-2008 crisis.

  11. Analysis of the complex formation of heparin with protamine by light scattering and analytical ultracentrifugation: implications for blood coagulation management.

    Maurer, Jürgen; Haselbach, Stephanie; Klein, Oliver; Baykut, Doan; Vogel, Vitali; Mäntele, Werner

    2011-02-02

    Heparin, a linear glycosaminoglycan, is used in different forms in anticoagulation treatment. Protamine, a highly positive charged peptide containing about 32 amino acids, acts as an antagonist for heparin to restore normal blood coagulation. The complex formation of protamine with heparin was analyzed by a combination of analytical ultracentrifugation and light scattering. Titration of heparin with protamine in blood plasma preparations results in a drastic increase of turbidity, indicating the formation of nanoscale particles. A similar increase of turbidity was observed in physiological saline solution with or without human serum albumin (HSA). Particle size analysis by analytical ultracentrifugation revealed a particle radius of approximately 30 nm for unfractionated heparin and of approximately 60 nm for low molecular weight heparin upon complexation with excess protamine, in agreement with atomic force microscopy data. In the absence of HSA, larger and more heterogeneous particles were observed. The particles obtained were found to be stable for hours. The particle formation kinetics was analyzed by light scattering at different scattering angles and was found to be complete within several minutes. The time course of particle formation suggests a condensation reaction, with sigmoidal traces for low heparin concentrations and quasi-first-order reaction for high heparin concentrations. Under all conditions, the final scattering intensity reached after several minutes was found to be proportional to the amount of heparin in the blood plasma or buffer solution, provided that excess protamine was available and no multiple scattering occurred. On the basis of a direct relation between particle concentration and the heparin concentration present before protaminization, a light scattering assay was developed which permits the quantitative analysis of the heparin concentration in blood plasma and which could complement or even replace the activated clotting time test

  12. Evaluation of a novel thermosensitive heparin-poloxamer hydrogel for improving vascular anastomosis quality and safety in a rabbit model.

    Ying-Zheng Zhao

    Full Text Available Despite progress in the design of advanced surgical techniques, stenosis recurs in a large percentage of vascular anastomosis. In this study, a novel heparin-poloxamer (HP hydrogel was designed and its effects for improving the quality and safety of vascular anastomosis were studied. HP copolymer was synthesized and its structure was confirmed by Fourier transform infrared spectroscopy (FTIR and nuclear magnetic resonance spectroscopy ((1H-NMR. Hydrogels containing HP were prepared and their important characteristics related to the application in vascular anastomosis including gelation temperature, rheological behaviour and micromorphology were measured. Vascular anastomosis were performed on the right common carotid arteries of rabbits, and the in vivo efficiency and safety of HP hydrogel to achieve vascular anastomosis was verified and compared with Poloxamer 407 hydrogel and the conventional hand-sewn method using Doppler ultrasound, CT angiograms, scanning electron microscopy (SEM and histological technique. Our results showed that HP copolymer displayed special gel-sol-gel phase transition behavior with increasing temperature from 5 to 60 °C. HP hydrogel prepared from 18 wt% HP solution had a porous sponge-like structure, with gelation temperature at approximately 38 °C and maximum elastic modulus at 10,000 Pa. In animal studies, imaging and histological examination of rabbit common jugular artery confirmed that HP hydrogel group had similar equivalent patency, flow and burst strength as Poloxamer 407 group. Moreover, HP hydrogel was superior to poloxamer 407 hydrogel and hand-sewn method for restoring the functions and epithelial structure of the broken vessel junctions after operation. By combining the advantages of heparin and poloxamer 407, HP hydrogel holds high promise for improving vascular anastomosis quality and safety.

  13. Managing cancer-related venous thromboembolic disease: low-molecular-weight heparins and beyond.

    O'Connell, Casey L; Liebman, Howard A

    2008-12-01

    Venous thromboembolism is a major contributor to the morbidity and mortality of patients with cancer. For patients undergoing cancer surgery, several trials support the safety and efficacy of unfractionated heparin and of low-molecular-weight heparin for the prevention of venous thromboembolism, while data regarding the efficacy and safety of these agents in the setting of medical hospitalization is less definitive and must be extracted from trials including noncancer patients with different thrombotic risk factors. Randomized clinical studies confirm that patients with cancer who develop venous thromboembolism have superior outcomes when treated with long-term low-molecular-weight heparin as compared with warfarin. Novel anticoagulants that are orally bioavailable and function by directly inhibiting factor Xa or thrombin are entering the market. To date, data regarding the efficacy and safety of these novel anticoagulants as venous thromboembolism prophylaxis and treatment in cancer patients are not available and must be extracted from larger trials with heterogeneous patient populations.

  14. Safety and Efficacy of Argatroban in the Management of Heparin-Induced Thrombocytopenia

    Bernd Saugel

    2011-01-01

    Full Text Available Heparin-induced thrombocytopenia (HIT is a life-threatening adverse reaction to heparin therapy that is characterized by thrombocytopenia and an increased risk of venous and arterial thrombosis. According to guidelines, in patients with strongly suspected or confirmed HIT all sources of heparin have to be discontinued and an alternative, nonheparin anticoagulant for HIT treatment must immediately be started. For both the prophylaxis of thrombembolic events in HIT and the treatment of HIT with thrombosis the direct thrombin inhibitor argatroban is approved in the United States. The objective of this review is to describe the mechanism of action and the pharmacokinetic profile of argatroban, to characterize argatroban regarding its safety and therapeutic efficacy and to discuss its place in therapy in HIT.

  15. Furin proteolytically processes the heparin-binding region of extracellular superoxide dismutase

    Bowler, Russell P; Nicks, Mike; Olsen, Dorte Aa

    2002-01-01

    Extracellular superoxide dismutase (EC-SOD) is an antioxidant enzyme that attenuates brain and lung injury from oxidative stress. A polybasic region in the carboxyl terminus distinguishes EC-SOD from other superoxide dismutases and determines EC-SOD's tissue half-life and affinity for heparin....... There are two types of EC-SOD that differ based on the presence or absence of this heparin-binding region. It has recently been shown that proteolytic removal of the heparin-binding region is an intracellular event (Enghild, J. J., Thogersen, I. B., Oury, T. D., Valnickova, Z., Hojrup, P., and Crapo, J. D...... of intracellular proteases implicate furin as a processing protease. In vitro experiments using furin and purified EC-SOD suggest that furin proteolytically cleaves EC-SOD in the middle of the polybasic region and then requires an additional carboxypeptidase to remove the remaining lysines and arginines...

  16. Platelet count recovery and seroreversion in immune HIT despite continuation of heparin: further observations and literature review.

    Shih, Andrew W; Sheppard, Jo-Ann I; Warkentin, Theodore E

    2017-10-05

    One of the standard distinctions between type 1 (non-immune) and type 2 (immune-mediated) heparin-induced thrombocytopenia (HIT) is the transience of thrombocytopenia: type 1 HIT is viewed as early-onset and transient thrombocytopenia, with platelet count recovery despite continuing heparin administration. In contrast, type 2 HIT is viewed as later-onset (i. e., 5 days or later) thrombocytopenia in which it is generally believed that platelet count recovery will not occur unless heparin is discontinued. However, older reports of type 2 HIT sometimes did include the unexpected observation that platelet counts could recover despite continued heparin administration, although without information provided regarding changes in HIT antibody levels in association with platelet count recovery. In recent years, some reports of type 2 HIT have confirmed the observation that platelet count recovery can occur despite continuing heparin administration, with serological evidence of waning levels of HIT antibodies ("seroreversion"). We now report two additional patient cases of type 2 HIT with platelet count recovery despite ongoing therapeutic-dose (1 case) or prophylactic-dose (1 case) heparin administration, in which we demonstrate concomitant waning of HIT antibody levels. We further review the literature describing this phenomenon of HIT antibody seroreversion and platelet count recovery despite continuing heparin administration. Our observations add to the concept that HIT represents a remarkably transient immune response, including sometimes even when heparin is continued.

  17. Anticoagulant effects of inhaled unfractionated heparin in the dog as determined by partial thromboplastin time and factor Xa activity.

    Manion, Jill S; Thomason, John M; Langston, Vernon C; Claude, Andrew K; Brooks, Marjory B; Mackin, Andrew J; Lunsford, Kari V

    2016-01-01

    To evaluate the anticoagulant effects of inhaled heparin in dogs. This study was conducted in 3 phases. In phase 1, bronchoalveolar lavage fluid (BALf) was collected to generate an in vitro calibration curve to relate heparin concentration to the activated partial thromboplastin time (aPTT). In phase 2, heparin was administered via nebulization to determine the threshold dose needed to prolong systemic aPTT. In phase 3, the local anticoagulant activity of inhaled heparin was determined by measurement of BALf anti-Xa activity and aPTT. University teaching hospital. Six healthy intact female Walker Hounds were used in this study. Two dogs were used for each phase. Inhaled unfractionated sodium heparin was administered in doses ranging from 50,000 to 200,000 IU. In vitro addition of heparin to BALf caused a prolongation in aPTT. Inhaled heparin at doses as high as 200,000 IU failed to prolong systemic aPTT, and a threshold dose could not be determined. No significant local anticoagulant effects were detected. Even at doses higher than those known to be effective in people, inhaled heparin appears to have no detectable local or systemic anticoagulant effects in dogs with the current delivery method. © Veterinary Emergency and Critical Care Society 2015.

  18. Safety and potential anticoagulant effects of nebulised heparin in burns patients with inhalational injury at Singapore General Hospital Burns Centre.

    Yip, Lian Yee; Lim, Yen Fang; Chan, Hong Ngee

    2011-11-01

    Nebulised heparin, N-acetylcysteine (NAC) and salbutamol were shown to decrease reintubation rates, incidence of atelectasis and mortality in paediatric patients and reduce lung injury scores in adult burns patients with inhalational lung injury (ILI). Nebulised heparin, NAC and salbutamol treatment protocol was introduced in Singapore General Hospital (SGH) Burns Centre in 2006. However, safety data on the use of nebulised heparin and NAC for burns patients with ILI is not well established. In this study, we investigated the safety and potential anticoagulant effects of nebulised heparin in burns patients with ILI. A retrospective study with historical control was conducted. The treatment group consisted of 52 mechanically ventilated adult patients, with a diagnosis of ILI as confirmed by bronchoscopy, admitted to burn intensive care unit (BICU) from the year 2006 to 2009. The group was treated with nebulised heparin, NAC and salbutamol. The control group consists of 11 mechanically ventilated BICU ILI patients treated from year 2001 to 2005 before protocol initiation. Blood coagulation indices (prothrombin time (PT), activated partial thromboplastin time (APTT) and platelet count) were monitored and bleeding incidences were assessed. Blood coagulation indices did not suggest an increase risk of bleeding with nebulised heparin. The APTT, PT and platelet count followed a similar trend for both groups over 7 days. No clinically significant increase in bleeding risk was found to be associated with nebulised heparin. Nebulised heparin was not found to potentiate the risk of bleeding in burns patients with ILI. Copyright © 2011 Elsevier Ltd and ISBI. All rights reserved.

  19. The effect of heparin on pregnancy associated plasma protein-A concentration in healthy, non-pregnant individuals

    Jespersen, Camilla H B; Vestergaard, Kirstine R.; Schou, Morten

    2015-01-01

    Objectives: The objective of this study was to determine the differences in pregnancy associated plasma protein-A (PAPP-A) concentrations in heparin naive and heparin treated healthy men and non-pregnant women, to find a possible difference in different age groups, and to determine the response...

  20. Vitamin K antagonists or low-molecular-weight heparin for the long term treatment of symptomatic venous thromboembolism

    van der Heijden, J. F.; Hutten, B. A.; Büller, H. R.; Prins, M. H.

    2000-01-01

    Patients who have had an episode of symptomatic venous thromboembolism are usually treated for at least five days with intravenous unfractionated heparin or subcutaneous low-molecular-weight heparin. Thereafter, they received a three month course of a vitamin K antagonist, with a dose adjusted to

  1. Vascular access site complication in transfemoral coronary angiography between uninterrupted warfarin and heparin bridging.

    Wongcharoen, Wanwarang; Pinyosamosorn, Kittipong; Gunaparn, Siriluck; Boonnayhun, Suchada; Thonghong, Tasalak; Suwannasom, Pannipa; Phrommintikul, Arintaya

    2017-08-01

    Warfarin discontinuation with heparin bridging is a common practice in patients receiving warfarin prior to elective coronary angiography (CAG). The uninterrupted warfarin strategy has been suggested to be alternative option for patients with high thromboembolic risk. Therefore, we aimed to assess the safety of elective transfemoral CAG during uninterrupted warfarin therapy compared to heparin bridging. This study was a randomized open-label design with blinded event evaluation. The 110 consecutive patients (age ≥ 18 years) receiving warfarin before the planned transfemoral CAG were randomly assigned to either heparin bridging or uninterrupted warfarin with targeted INR (2.0-3.0). The primary outcome was the incidence of major vascular access site complications. The baseline characteristics were comparable between two groups (mean age was 60.1 ± 7.8 years, 49 males). The mean INR on the day of CAG of heparin bridging and uninterrupted warfarin groups was 1.2 ± 0.3 and 2.2 ± 0.5 (P warfarin patients (P = 0.243). The total vascular access site complications occurred in 6 (10.9%) heparin-bridging and one (1.8%) uninterrupted warfarin patients (P = 0.113). No patient developed either other bleeding or thromboembolic events during 7 days after CAG. We demonstrated that an uninterrupted warfarin strategy did not increase vascular access site complications in patients undergoing transfemoral CAG compared to heparin bridging therapy. Due to the safety and the ease of uninterrupted warfarin strategy, this approach should be encouraged in patients receiving long-term warfarin who undergo elective transfemoral CAG. © 2017, Wiley Periodicals, Inc.

  2. High-throughput differentiation of heparin from other glycosaminoglycans by pyrolysis mass spectrometry.

    Nemes, Peter; Hoover, William J; Keire, David A

    2013-08-06

    Sensors with high chemical specificity and enhanced sample throughput are vital to screening food products and medical devices for chemical or biochemical contaminants that may pose a threat to public health. For example, the rapid detection of oversulfated chondroitin sulfate (OSCS) in heparin could prevent reoccurrence of heparin adulteration that caused hundreds of severe adverse events including deaths worldwide in 2007-2008. Here, rapid pyrolysis is integrated with direct analysis in real time (DART) mass spectrometry to rapidly screen major glycosaminoglycans, including heparin, chondroitin sulfate A, dermatan sulfate, and OSCS. The results demonstrate that, compared to traditional liquid chromatography-based analyses, pyrolysis mass spectrometry achieved at least 250-fold higher sample throughput and was compatible with samples volume-limited to about 300 nL. Pyrolysis yielded an abundance of fragment ions (e.g., 150 different m/z species), many of which were specific to the parent compound. Using multivariate and statistical data analysis models, these data enabled facile differentiation of the glycosaminoglycans with high throughput. After method development was completed, authentically contaminated samples obtained during the heparin crisis by the FDA were analyzed in a blinded manner for OSCS contamination. The lower limit of differentiation and detection were 0.1% (w/w) OSCS in heparin and 100 ng/μL (20 ng) OSCS in water, respectively. For quantitative purposes the linear dynamic range spanned approximately 3 orders of magnitude. Moreover, this chemical readout was successfully employed to find clues in the manufacturing history of the heparin samples that can be used for surveillance purposes. The presented technology and data analysis protocols are anticipated to be readily adaptable to other chemical and biochemical agents and volume-limited samples.

  3. Efficient generation of volatile species for cadmium analysis in seafood and rice samples by a modified chemical vapor generation system coupled with atomic fluorescence spectrometry

    Yang, Xin-an; Chi, Miao-bin; Wang, Qing-qing; Zhang, Wang-bing

    2015-01-01

    Highlights: • We develop a modified chemical vapor generation method coupled with AFS for the determination of cadmium. • The response of Cd could be increased at least four-fold compared to conventional thiourea and Co(II) system. • A simple mixing sequences experiment is designed to study the reaction mechanism. • The interference of transition metal ions can be easily eliminated by adding DDTC. • The method is successfully applied in seafood samples and rice samples. - Abstract: A vapor generation procedure to determine Cd by atomic fluorescence spectrometry (AFS) has been established. Volatile species of Cd are generated by following reaction of acidified sample containing Fe(II) and L-cysteine (Cys) with sodium tetrahydroborate (NaBH 4 ). The presence of 5 mg L −1 Fe(II) and 0.05% m/v Cys improves the efficiency of Cd vapor generation substantially about four-fold compared with conventional thiourea and Co(II) system. Three experiments with different mixing sequences and reaction times are designed to study the reaction mechanism. The results document that the stability of Cd(II)–Cys complexes is better than Cys–THB complexes (THB means NaBH 4 ) while the Cys–THB complexes have more contribution to improve the Cd vapor generation efficiency than Cd(II)–Cys complexes. Meanwhile, the adding of Fe(II) can catalyze the Cd vapor generation. Under the optimized conditions, the detection limit of Cd is 0.012 μg L −1 ; relative standard deviations vary between 0.8% and 5.5% for replicate measurements of the standard solution. In the presence of 0.01% DDTC, Cu(II), Pb(II) and Zn(II) have no significant influence up to 5 mg L −1 , 10 mg L −1 and 10 mg L −1 , respectively. The accuracy of the method is verified through analysis of the certificated reference materials and the proposed method has been applied in the determination of Cd in seafood and rice samples

  4. Efficient generation of volatile species for cadmium analysis in seafood and rice samples by a modified chemical vapor generation system coupled with atomic fluorescence spectrometry

    Yang, Xin-an, E-mail: 13087641@qq.com; Chi, Miao-bin, E-mail: 1161306667@qq.com; Wang, Qing-qing, E-mail: wangqq8812@163.com; Zhang, Wang-bing, E-mail: ahutwbzh@163.com

    2015-04-15

    Highlights: • We develop a modified chemical vapor generation method coupled with AFS for the determination of cadmium. • The response of Cd could be increased at least four-fold compared to conventional thiourea and Co(II) system. • A simple mixing sequences experiment is designed to study the reaction mechanism. • The interference of transition metal ions can be easily eliminated by adding DDTC. • The method is successfully applied in seafood samples and rice samples. - Abstract: A vapor generation procedure to determine Cd by atomic fluorescence spectrometry (AFS) has been established. Volatile species of Cd are generated by following reaction of acidified sample containing Fe(II) and L-cysteine (Cys) with sodium tetrahydroborate (NaBH{sub 4}). The presence of 5 mg L{sup −1} Fe(II) and 0.05% m/v Cys improves the efficiency of Cd vapor generation substantially about four-fold compared with conventional thiourea and Co(II) system. Three experiments with different mixing sequences and reaction times are designed to study the reaction mechanism. The results document that the stability of Cd(II)–Cys complexes is better than Cys–THB complexes (THB means NaBH{sub 4}) while the Cys–THB complexes have more contribution to improve the Cd vapor generation efficiency than Cd(II)–Cys complexes. Meanwhile, the adding of Fe(II) can catalyze the Cd vapor generation. Under the optimized conditions, the detection limit of Cd is 0.012 μg L{sup −1}; relative standard deviations vary between 0.8% and 5.5% for replicate measurements of the standard solution. In the presence of 0.01% DDTC, Cu(II), Pb(II) and Zn(II) have no significant influence up to 5 mg L{sup −1}, 10 mg L{sup −1}and 10 mg L{sup −1}, respectively. The accuracy of the method is verified through analysis of the certificated reference materials and the proposed method has been applied in the determination of Cd in seafood and rice samples.

  5. Determination of extremely low 236U/238U isotope ratios in environmental samples by sector-field inductively coupled plasma mass spectrometry using high-efficiency sample introduction

    Boulyga, Sergei F.; Heumann, Klaus G.

    2006-01-01

    A method by inductively coupled plasma mass spectrometry (Icp-Ms) was developed which allows the measurement of 236 U at concentration ranges down to 3 x 10 -14 g g -1 and extremely low 236 U/ 238 U isotope ratios in soil samples of 10 -7 . By using the high-efficiency solution introduction system APEX in connection with a sector-field ICP-MS a sensitivity of more than 5000 counts fg -1 uranium was achieved. The use of an aerosol desolvating unit reduced the formation rate of uranium hydride ions UH + /U + down to a level of 10 -6 . An abundance sensitivity of 3 x 10 -7 was observed for 236 U/ 238 U isotope ratio measurements at mass resolution 4000. The detection limit for 236 U and the lowest detectable 236 U/ 238 U isotope ratio were improved by more than two orders of magnitude compared with corresponding values by alpha spectrometry. Determination of uranium in soil samples collected in the vicinity of Chernobyl nuclear power plant (NPP) resulted in that the 236 U/ 238 U isotope ratio is a much more sensitive and accurate marker for environmental contamination by spent uranium in comparison to the 235 U/ 238 U isotope ratio. The ICP-MS technique allowed for the first time detection of irradiated uranium in soil samples even at distances more than 200 km to the north of Chernobyl NPP (Mogilev region). The concentration of 236 U in the upper 0-10 cm soil layers varied from 2 x 10 -9 g g -1 within radioactive spots close to the Chernobyl NPP to 3 x 10 -13 g g -1 on a sampling site located by >200 km from Chernobyl

  6. Determination of extremely low (236)U/(238)U isotope ratios in environmental samples by sector-field inductively coupled plasma mass spectrometry using high-efficiency sample introduction.

    Boulyga, Sergei F; Heumann, Klaus G

    2006-01-01

    A method by inductively coupled plasma mass spectrometry (ICP-MS) was developed which allows the measurement of (236)U at concentration ranges down to 3 x 10(-14)g g(-1) and extremely low (236)U/(238)U isotope ratios in soil samples of 10(-7). By using the high-efficiency solution introduction system APEX in connection with a sector-field ICP-MS a sensitivity of more than 5,000 counts fg(-1) uranium was achieved. The use of an aerosol desolvating unit reduced the formation rate of uranium hydride ions UH(+)/U(+) down to a level of 10(-6). An abundance sensitivity of 3 x 10(-7) was observed for (236)U/(238)U isotope ratio measurements at mass resolution 4000. The detection limit for (236)U and the lowest detectable (236)U/(238)U isotope ratio were improved by more than two orders of magnitude compared with corresponding values by alpha spectrometry. Determination of uranium in soil samples collected in the vicinity of Chernobyl nuclear power plant (NPP) resulted in that the (236)U/(238)U isotope ratio is a much more sensitive and accurate marker for environmental contamination by spent uranium in comparison to the (235)U/(238)U isotope ratio. The ICP-MS technique allowed for the first time detection of irradiated uranium in soil samples even at distances more than 200 km to the north of Chernobyl NPP (Mogilev region). The concentration of (236)U in the upper 0-10 cm soil layers varied from 2 x 10(-9)g g(-1) within radioactive spots close to the Chernobyl NPP to 3 x 10(-13)g g(-1) on a sampling site located by >200 km from Chernobyl.

  7. Technical note: optimization for improved tube-loading efficiency in the dual-energy computed tomography coupled with balanced filter method.

    Saito, Masatoshi

    2010-08-01

    This article describes the spectral optimization of dual-energy computed tomography using balanced filters (bf-DECT) to reduce the tube loadings and dose by dedicating to the acquisition of electron density information, which is essential for treatment planning in radiotherapy. For the spectral optimization of bf-DECT, the author calculated the beam-hardening error and air kerma required to achieve a desired noise level in an electron density image of a 50-cm-diameter cylindrical water phantom. The calculation enables the selection of beam parameters such as tube voltage, balanced filter material, and its thickness. The optimal combination of tube voltages was 80 kV/140 kV in conjunction with Tb/Hf and Bi/Mo filter pairs; this combination agrees with that obtained in a previous study [M. Saito, "Spectral optimization for measuring electron density by the dual-energy computed tomography coupled with balanced filter method," Med. Phys. 36, 3631-3642 (2009)], although the thicknesses of the filters that yielded a minimum tube output were slightly different from those obtained in the previous study. The resultant tube loading of a low-energy scan of the present bf-DECT significantly decreased from 57.5 to 4.5 times that of a high-energy scan for conventional DECT. Furthermore, the air kerma of bf-DECT could be reduced to less than that of conventional DECT, while obtaining the same figure of merit for the measurement of electron density and effective atomic number. The tube-loading and dose efficiencies of bf-DECT were considerably improved by sacrificing the quality of the noise level in the images of effective atomic number.

  8. A new approach for heparin standardization: combination of scanning UV spectroscopy, nuclear magnetic resonance and principal component analysis.

    Marcelo A Lima

    Full Text Available The year 2007 was marked by widespread adverse clinical responses to heparin use, leading to a global recall of potentially affected heparin batches in 2008. Several analytical methods have since been developed to detect impurities in heparin preparations; however, many are costly and dependent on instrumentation with only limited accessibility. A method based on a simple UV-scanning assay, combined with principal component analysis (PCA, was developed to detect impurities, such as glycosaminoglycans, other complex polysaccharides and aromatic compounds, in heparin preparations. Results were confirmed by NMR spectroscopy. This approach provides an additional, sensitive tool to determine heparin purity and safety, even when NMR spectroscopy failed, requiring only standard laboratory equipment and computing facilities.

  9. The effect of heparin administration on the FT4-levels and on an unspecific peripheral thyroid parameter

    Eber, B.; Borkenstein, J.; Leb, G.

    1984-01-01

    Heparin produces changes in FT 4 -levels both in vivo and in vitro as determined by commercial kits. Methods utilising the principle of equilibrium dialysis show significant increases whereas methods using T 4 -tracer analogue techniques reveal marked decreases in FT 4 -values. Possible clinical side-effects of heparin administration such as heparin-induced hyperthyroidism and tachyarrhythmias are discussed. The present results confirm the FT 4 -decreasing effect of in vivo and in vitro administration of heparin with FT 4 -RIAs based on the tracer analogue technique; however, the unspecific peripheral thyroid parameter of systolic time-intervals did not reveal any tendency towards hyperthyroidism. Also the discrepant results dependent on the method used, indicate that, following heparin administration FT 4 -levels do not reflect that hormone concentration is relevant to the metabolism of the whole body. (orig.) [de

  10. The physiologic and therapeutic role of heparin in implantation and placentation

    Michela Quaranta

    2015-01-01

    Full Text Available Implantation, trophoblast development and placentation are crucial processes in the establishment and development of normal pregnancy. Abnormalities of these processes can lead to pregnancy complications known as the great obstetrical syndromes: preeclampsia, intrauterine growth restriction, fetal demise, premature prelabor rupture of membranes, preterm labor, and recurrent pregnancy loss. There is mounting evidence regarding the physiological and therapeutic role of heparins in the establishment of normal gestation and as a modality for treatment and prevention of pregnancy complications. In this review, we will summarize the properties and the physiological contributions of heparins to the success of implantation, placentation and normal pregnancy.

  11. Heparin as a pharmacologic intervention to induce positive scintiscan in occult gastrointestinal bleeding

    Chaudhuri, T.K.; Brantly, M.

    1984-01-01

    The value of using heparin as a pharmacologic intervention to induce a positive scintiscan was studied in a patient with chronic occult gastrointestinal bleeding. When all standard diagnostic tests (upper and lower gastrointestinal series, upper and lower endoscopy, and conventional noninterventional Tc-99m RBC imaging) fail to detect and localize gastrointestinal bleeding in a patient who has definite clinical evidence (guaiac positive stool and dropping hemoglobin, hematocrit) of chronic occult gastrointestinal oozing, heparin may be used (with proper precaution) as a last resort to aid in the scintigraphic detection and localization of chronic occult gastrointestinal bleeding

  12. Spurious hypocalcemia in hemodialysis patients after heparinization. In-vitro formation of calcium soaps.

    Godolphin, W; Cameron, E C; Frohlich, J; Price, J D

    1979-02-01

    Patients on long-term hemodialysis via arteriovenous fistula received heparin when the fistula needle was inserted, before a sample of blood was obtained for chemical analysis. The resultant release of lipoprotein lipase activity in vivo and continued lipolytic activity in vitro sometimes produced sufficient free fatty acid to precipitate calcium soaps. The consequent spurious hypocalcemia was most frequently observed when the patients had chylomicronemia. This cause of apparent hypocalcemia was eliminated either by immediate analyses of the blood samples or by obtaining samples before systemic heparinization.

  13. Investigation of a Potential Protective Mechanism Against Heparin-Induced Thrombocytopenia in Patients on Chronic Intermittent Hemodialysis

    Tanhehco, Yvette C.; Cuker, Adam; Rudnick, Michael; Sachais, Bruce S.

    2015-01-01

    BACKGROUND Heparin-induced thrombocytopenia (HIT) develops as a result of platelet (PLT) activation by anti-platelet factor 4 (PF4)/heparin complex antibodies. Despite repeated exposure to heparin, patients undergoing chronic intermittent hemodialysis (HD) rarely develop HIT. We investigated the possibility that HD decreases/removes PF4 from PLT surfaces and/or plasma, thereby disfavoring immune complex formation as a mechanism of protection against HIT. MATERIALS AND METHODS We enrolled 20 patients undergoing chronic HD at the Penn Presbyterian Medical Center. Blood samples were drawn before, during and after treatment in the presence and absence of heparin. PF4, PF4/heparin antibody, heparin, and P-selectin levels were measured. RESULTS No patients demonstrated clinical symptoms of HIT. PLT surface PF4 levels decreased and plasma PF4 levels increased concurrently with increase in plasma heparin concentration. In the absence of heparin, PLT surface and plasma PF4 levels were unchanged. Anti-PF4/heparin antibodies, which were non-functional by the serotonin release assay, were detectable in 8 patients. PLT surface P-selectin levels did not change during treatment. CONCLUSIONS Removal of PLT surface and/or plasma PF4 as a mechanism of protection against HIT in patients undergoing HD is not supported by the results of our study, although the transient decrease in PLT surface PF4 in the presence of large amounts of heparin remains a candidate mechanism. The small sample size, single type of dialyzer membrane, and early sampling time points may have led to the inability to detect changes in PF4 levels. Future studies should explore other potential protective mechanisms. PMID:23305841

  14. Blood interaction with a Bioline heparin coated HIA-VAD : A study on calves

    vanderKamp, KWHJ; Magielse, CPE; Elstrodt, JM; vanderMeer, J; vanOeveren, W; Rakhorst, G

    The blood compatibility of ventricular assist devices developed by the Helmholtz institute Aachen (HA-VAD's) was tested on calves. Seven calves received a non-coated HIA-VAD (control) and three a Bioline heparin coated device. The circulatory support of these HIA-VAD's lasted one week. Mechanical

  15. Cooperative control of blood compatibility and re-endothelialization by immobilized heparin and substrate topography.

    Ding, Yonghui; Yang, Meng; Yang, Zhilu; Luo, Rifang; Lu, Xiong; Huang, Nan; Huang, Pingbo; Leng, Yang

    2015-03-01

    A wide variety of environmental cues provided by the extracellular matrix, including biophysical and biochemical cues, are responsible for vascular cell behavior and function. In particular, substrate topography and surface chemistry have been shown to regulate blood and vascular compatibility individually. The combined impact of chemical and topographic cues on blood and vascular compatibility, and the interplay between these two types of cues, are subjects that are currently being explored. In the present study, a facile polydopamine-mediated approach is introduced for immobilization of heparin on topographically patterned substrates, and the combined effects of these cues on blood compatibility and re-endothelialization are systematically investigated. The results show that immobilized heparin and substrate topography cooperatively modulate anti-coagulation activity, endothelial cell (EC) attachment, proliferation, focal adhesion formation and endothelial marker expression. Meanwhile, the substrate topography is the primary determinant of cell alignment and elongation, driving in vivo-like endothelial organization. Importantly, combining immobilized heparin with substrate topography empowers substantially greater competitive ability of ECs over smooth muscle cells than each cue individually. Moreover, a model is proposed to elucidate the cooperative interplay between immobilized heparin and substrate topography in regulating cell behavior. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  16. Low-molecular-weight heparin in the treatment of patients with venous thromboembolism

    tenCate, JW; Buller, HR; Gent, M; Hirsh, J; Prins, MH; Baildon, R; Lensing, AWA; Anderson, DR; vanBeek, EJR; Fiesinger, JN; Tijssen, JGP; vanBarneveld, A; Eimers, LT; Graafsma, YP; Hettiarachchi, R; Hutten, B; Redekop, K; Haley, S; LIberale, L; Finch, T; Whittaker, S; Wilkinson, L; Prandoni, P; Villalta, S; Girolami, B; Bagatella, P; Rossi, L; Girolami, A; Piovella, F; Barone, M; Beltrametti, C; Serafini, S; Siragusa, S; Ascari, E; Kovacs, MJ; Morrow, B; Kovacs, J; Kuijer, PMM; Koopman, MMW; Jagt, H; Weitz, J; Kearon, C; Biagioni, L; Haas, S; Lossner, F; Spengel, FA; Berger, M; Demers, C; Poulin, J; vanderMeer, J; Que, GTH; Smid, WM; Robinson, KS; Boyle, E; Leclerc, [No Value; StJacques, B; Finkenbine, S; Gallus, AS; Cohlan, D; Rich, C; Brandjes, DPM; Hoefnagel, CA; deRijk, M; Turkstra, F; Desjardins, L; CoteDesjardins, J; Couture, L; Ruel, M; Villenueve, J; Geerts, WH; Jay, RM; Code, EKI; Turpie, AGG; Johnson, J; Nguyen, P; Cusson, [No Value; Roy, S; Wells, PS; Bormanis, J; Goudie, D; Cruickshank, M; vonLewinski, M; Monreal, M; Sahuquillo, JC; Lafoz, E; Simonneau, G; Parent, F; Jagot, J; Douketis, JD; Kinnon, K; Ginsberg, JS; BrillEdwards, P; Donovan, D; Ockelford, PA; Kassis, J; Bornais, S; Planchon, B; ElKouri, D; Pistorius, MA; Escribano, M; Garrido, G; Chesterman, CN; Chong, BH; Pritchard, S; Cade, JF; Bynon, T; Stanford, J; Brien, WM; Palmer, B; Faivre, R; Petiteau, B; Manucci, PM; Moia, M; Bucciarelli, P

    1997-01-01

    Background Low-molecular-weight heparin is known to be safe and effective for the initial Treatment of patients with proximal deep-vein thrombosis. However, its application to patients with pulmonary embolism or previous episodes of thromboembolism has not been studied. Methods We randomly assigned

  17. Improved distribution and reduced toxicity of adriamycin bound to albumin-heparin microspheres

    Cremers, Harry; Cremers, H.F.M.; Bayon, L.G.; Verrijk, R.; Wesseling, M.M.; Wondergem, J.; Heuff, G.; Kwon, G.S.; Bae, Y.H.; Feijen, Jan; Kim, S.W.

    1995-01-01

    Adriamycin (ADR) was formulated in albumin-heparin conjugate microspheres (AHCMS) to improve site-specific delivery and to reduce the toxicity of the drug. The effect of formulating ADR in AHCMS was investigated upon intrahepatic administration to male Wag/Rij rats. After intraveno-portal (i.v.p.)

  18. Transfer of heparin polyion across a polarized water/ionic liquid membrane interface

    Langmaier, Jan; Samec, Zdeněk; Samcová, E.; Tůma, P.

    2012-01-01

    Roč. 24, OCT 2012 (2012), s. 25-27 ISSN 1388-2481 R&D Projects: GA ČR GAP206/11/0707 Institutional support: RVO:61388955 Keywords : heparin polyion * ionic liquid membrane * amperometric detection Subject RIV: CG - Electrochemistry Impact factor: 4.425, year: 2012

  19. Immobilization of heparin to EDC/NHS-crosslinked collagen. Characterization and in vitro evaluation

    Wissink, M.J.B.; Beernink, R.; Pieper, J.S.; Poot, Andreas A.; Engbers, G.H.M.; Beugeling, T.; Beugeling, T.; van Aken, W.G.; Feijen, Jan

    2001-01-01

    In the present study, heparin immobilization to a non-cytotoxic crosslinked collagen substrate for endothelial cell seeding was investigated. Crosslinking of collagen using N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (EDC) and N-hydroxysuccinimide (NHS) resulted in a material containing 14 free

  20. Effect of low-dose heparin on urinary albumin excretion in insulin-dependent diabetes mellitus

    Myrup, B; Hansen, P M; Jensen, T

    1995-01-01

    We investigated the effect of heparin on urinary albumin excretion in patients with insulin-dependent diabetes mellitus. 39 patients with persistent urinary albumin excretion of 30-300 mg/24 h were randomly treated for 3 months with subcutaneous injections twice daily of isotonic saline, 5000 IU...

  1. Amperometric Sensor for Heparin: Sensing Mechanism and Application in Human Blood Plasma Analysis

    Langmaier, Jan; Olšák, J.; Samcová, E.; Samec, Zdeněk; Trojánek, Antonín

    2006-01-01

    Roč. 18, 13-14 (2006), s. 1329-1338 ISSN 1040-0397 R&D Projects: GA ČR GA203/04/0424 Institutional research plan: CEZ:AV0Z40400503 Keywords : heparin * amperometry * PVC membrane electrode * sensing mechanism * human blood plasma Subject RIV: CG - Electrochemistry Impact factor: 2.444, year: 2006

  2. Early Heparin Administration Reduces Risk for Left Atrial Thrombus Formation during Atrial Fibrillation Ablation Procedures

    Stefan Asbach

    2011-01-01

    Full Text Available Objective. Despite the use of anticoagulation during left atrial (LA ablation procedures, ischemic cerebrovascular accidents (CVAs are recognized as a serious complication. Heparin is usually given after safe transseptal access has been obtained, resulting in a short unprotected dwell time of catheters within the LA, which may account for CVAs. We investigated the frequency of CVAs and LA thrombus formation as detected by intracardiac ultrasound (ICE depending on the timing of heparin administration. Methods and Results. Sixty LA ablation procedures with the use of ICE were performed in 55 patients. Patients were grouped by heparin administration after (Group I, =13 and before (Group II, =47 transseptal access. Group I patients were younger (56.6±13.7 versus 65.9±9.9 years, =.01; other clinical and echocardiographic characteristics did not differ between groups. Early thrombus formation was observed in 2 (15.4% of group I patients as compared to 0% of group II patients (=.04. One CVA (2.1% occurred in one group II patient without prior thrombus detection, and none occurred in group I patients (=ns. Conclusion. Early administration of heparin reduces the risk of early intracardiac thrombus formation during LA ablation procedures. This did not result in reduced rate of CVAs.

  3. Extrapulmonary colony formation after intravenous injection of tumour cells into heparin treated animals

    Maat, B.

    1978-01-01

    Recent data on extrapulmonary colony formation after heparin administration are inconclusive. A systemic study of this topic was undertaken with 4 experimental tumour systems and 2 distinct periods of reduced clotting capacity in rats and mice. I.v. injection of various numbers of tumour cells into

  4. Influence of heparin on the assay of amitriptyline, clomipramine, and their metabolites

    Levering, S.C.M.; Oostelbos, M.C.J.M.; Toll, P.J.M.M.; Loonen, A.J.M.

    1996-01-01

    In this study the effect of the use of lithium heparin containers on the plasma levels of amitriptyline, clomipramine, and their metabolites was investigated. Twenty-five patients (10 men and 15 women, mean age 51.8 ± 14.9 years) taking either amitriptyline or clomipramine in a daily dosage varying

  5. Biosynthesis of heparin. Effects of n-butyrate on cultured mast cells

    Jacobsson, K.G.; Riesenfeld, J.; Lindahl, U.

    1985-01-01

    Murine mastocytoma cells were incubated in vitro with inorganic [ 35 S]sulfate, in the absence or presence of 2.5 mM n-butyrate, and labeled heparin was isolated. The polysaccharide produced in the presence of butyrate showed a lower charge density on anion exchange chromatography than did the control material and a 3-fold increased proportion of components with high affinity for antithrombin. Structural analysis of heparin labeled with [ 3 H] glucosamine in the presence of butyrate showed that approximately 35% of the glucosamine units were N-acetylated, as compared to approximately 10% in the control material; the nonacetylated glucosamine residues were N-sulfated. The presence of butyrate thus leads to an inhibition of the N-deacetylation/N-sulfation process in heparin biosynthesis, along with an augmented formation of molecules with high affinity for antithrombin. Preincubation of the mastocytoma cells with butyrate was required for manifestation of either effect; when the preincubation period was reduced from 24 to 10 h the effects of butyrate were no longer observed. A polysaccharide formed on incubating mastocytoma microsomal fraction with UDP-[ 3 H]glucuronic acid, UDP-N-acetylglucosamine, and 3'-phosphoadenylylsulfate in the presence of 5 mM butyrate showed the same N-acetyl/N-sulfate ratio as did the corresponding control polysaccharide, produced in the absence of butyrate. These findings suggest that the effect of butyrate on heparin biosynthesis depends on the integrity of the cell

  6. Synthesis and characterization of polystyrene-poly(ethylene oxide)-heparin block copolymers

    Vulić, I.; Okano, T.; Kim, S.W.; Feijen, Jan

    1988-01-01

    A procedure for the preparation of new block copolymers composed of a hydrophobic block of polystyrene, a hydrophilic spacer-block of poly(ethylene oxide) and a bioactive block of heparin was investigated. Polystyrene with one amino group per chain was synthesized by free radical oligomerization of

  7. Improved synthesis of polystyrene-poly(ethylene oxide)-heparin block copolymers

    Vulic, I.; Loman, A.J.B.; Feijen, Jan; Okano, T.; Kim, S.W.

    1990-01-01

    A novel procedure for the synthesis of block copolymers composed of a hydrophobic block of polystyrene, a hydrophilic block of poly(ethylene oxide) and a bioactive block of nitrous acid-degraded heparin was developed. Amino-semitelechelic polystyrene was prepared by anionic polymerization of styrene

  8. Heparin interferes with the radioenzymatic and homogeneous enzyme immunoassays for aminoglycosides

    Krogstad, D.J.; Granich, G.G.; Murray, P.R.; Pfaller, M.A.; Valdes, R.

    1981-01-01

    Heparin interferes with measurement of aminoglycosides in serum by biological, radioenzymatic, and homogeneous enzyme immunoassay techniques, but not with radioimmunoassay. At concentrations greater than or equal to 10 5 and greater than or equal to 3 X 10 6 USP units/L, respectively, it interferes with the radioenzymatic assay by inhibiting the gentamicin 3-acetyltransferase and kanamycin 6'-acetyltransferase enzymes used in the assay. It interferes with the homogeneous enzyme immunoassays for gentamicin and tobramycin (at concentrations greater than or equal to 10 5 and greater than or equal to10 4 USP units/L, respectively), but not with the commercially available homogeneous enzyme immunoassays for other drugs. Heparin interference with the homogeneous enzyme immunoassay for aminoglycosides requires both the heparin polyanion and glucose-6-phosphate dehydrogenase bound to a cationic aminoglycoside. This interference can be reproduced with dextran sulfate (but not dextran), and does not occur with free enzyme (glucose-6-phosphate dehydrogenase) alone. Heparin interference with these two assays and at concentrations that may be present in intravenous infusions or in seriously underfilled blood-collection tubes is described

  9. In vitro Heparin Precipitation in the Plasma of Euthyroid women with ...

    OBJECTIVE: Women with elevated Lp(a), who are susceptible to atherosclerosis, get to reduce, their cardiovascular disease by in-vivo administration of low dose heparin. And history of recurrent miscarriage associated with auto antibodies have had a high rate of life births in subsequent pregnancies when they were ...

  10. Ergotism of the lower limb complicating DHE-heparin thrombosis prophylaxis. Observation by serial angiography

    Warmuth-Metz, M.

    1988-10-01

    Today ergotism is becoming more and more important as a complication in the treatment of migraine headache or thrombosis prophylaxis with DHE heparin. Although complete recovery is seldom reported in the current literature, in our case it was possible to resolve a spasm of the left lower limb completely by early diagnosis and adaequate pharmacological treatment. The case was well documented by serial angiography.

  11. Endothelial glycocalyx degradation induces endogenous heparinization in patients with severe injury and early traumatic coagulopathy

    Ostrowski, Sisse R; Johansson, Pär I

    2012-01-01

    There is emerging evidence that early trauma-induced coagulopathy (TIC) is mechanistically linked to disruption of the vascular endothelium and its glycocalyx, assessed by thrombomodulin and syndecan 1, respectively. This study evaluated if degradation of the endothelial glycocalyx and ensuing...... release of its heparin-like substances induce autoheparinization and thereby contributes to TIC....

  12. Low dose intravesical heparin as prophylaxis against recurrent noninvasive (stage Ta) bladder cancer

    Bitsch, M; Hermann, G G; Andersen, J P

    1990-01-01

    A controlled randomized clinical trial was conducted to examine the efficacy of topical low dose heparin (0.125 gm./l., 25,000 units per l.) as prophylaxis against recurrent noninvasive (stage Ta) transitional cell bladder cancer. Transurethral tumor resection was done with irrigation fluid conta...

  13. Heparin binding chitosan derivatives for production of pro-angiogenic hydrogels for promoting tissue healing

    Yar, Muhammad, E-mail: drmyar@ciitlahore.edu.pk [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000 (Pakistan); Shahzad, Sohail [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000 (Pakistan); Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100 (Pakistan); Shahzadi, Lubna [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000 (Pakistan); Shahzad, Sohail Anjum [Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad 22060 (Pakistan); Mahmood, Nasir [Department of Allied Health Sciences and Chemical Pathology, University of Health Sciences, Lahore (Pakistan); Department of Human Genetics and Molecular Biology, University of Health Sciences, Lahore (Pakistan); Chaudhry, Aqif Anwar [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000 (Pakistan); Rehman, Ihtesham ur [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000 (Pakistan); Materials Science and Engineering, North Campus, University of Sheffield, Broad Lane, Sheffield S3 7HQ (United Kingdom); MacNeil, Sheila, E-mail: s.macneil@sheffield.ac.uk [Materials Science and Engineering, North Campus, University of Sheffield, Broad Lane, Sheffield S3 7HQ (United Kingdom)

    2017-05-01

    Our aim was to develop a biocompatible hydrogel that could be soaked in heparin and placed on wound beds to improve the vasculature of poorly vascularized wound beds. In the current study, a methodology was developed for the synthesis of a new chitosan derivative (CSD-1). Hydrogels were synthesized by blending CSD-1 for either 4 or 24 h with polyvinyl alcohol (PVA). The physical/chemical interactions and the presence of specific functional groups were confirmed by Fourier transform infrared (FT-IR) spectroscopy and proton nuclear magnetic resonance ({sup 1}H NMR). The porous nature of the hydrogels was confirmed by scanning electron microscopy (SEM). Thermal gravimetric analysis (TGA) showed that these hydrogels have good thermal stability which was slightly increased as the blending time was increased. Hydrogels produced with 24 h of blending supported cell attachment more and could be loaded with heparin to induce new blood vessel formation in a chick chorionic allantoic membrane assay. - Highlights: • Chitosan based hydrogels were designed to stimulate angiogenesis. • Two new derivatives of chitosan were produced using a Mannich type reaction. • Blending a chitosan derivative with PVA gave a porous biocompatible hydrogel. • Heparin bound to the hydrogel on immersion changing its morphology. • Heparin loaded hydrogel stimulated blood vessel formation in a chick model.

  14. Optical sensing of sulfate by polymethinium salt receptors: colorimetric sensor for heparin

    Bříza, T.; Kejík, Z.; Císařová, I.; Králová, Jarmila; Martásek, P.; Král, V.

    2008-01-01

    Roč. 16, - (2008), s. 1901-1903 ISSN 1359-7345 R&D Projects: GA AV ČR KAN200200651; GA ČR(CZ) GA203/06/1038 Institutional research plan: CEZ:AV0Z50520514 Keywords : colorimetric sensor * heparin * polymethinium salt Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.340, year: 2008

  15. Venous thromboembolism in pregnancy: prophylaxis and treatment with low molecular weight heparin

    Andersen, Anita Sylvest; Berthelsen, Jørgen G; Bergholt, Thomas

    2010-01-01

    OBJECTIVE: To evaluate the safety of individually dosed low molecular weight heparin (LMWH) for prophylaxis and treatment of thromboembolic complications in pregnancy. DESIGN: Cohort study with a chronologic register-based control group. SETTING: Department of Obstetrics and Gynecology, Hillerød ...

  16. Venous thromboembolism in pregnancy: prophylaxis and treatment with low molecular weight heparin

    Andersen, Anita Sylvest; Berthelsen, Jørgen G.; Bergholt, Thomas

    2010-01-01

    OBJECTIVE: To evaluate the safety of individually dosed low molecular weight heparin (LMWH) for prophylaxis and treatment of thromboembolic complications in pregnancy. DESIGN: Cohort study with a chronologic register-based control group. SETTING: Department of Obstetrics and Gynecology, Hillerød...

  17. The impact of heparin-coated circuits on hemodynamics during and after cardiopulmonary bypass

    de Vroege, R; Huybregts, R; van Oeveren, W; van Klarenbosch, J; Linley, G; Mutlu, J; Jansen, E; Hack, E; Eijsman, L; Wildevuur, C

    This study was performed to investigate if heparin-coated extracorporeal circuits can reduce the systemic inflammatory reaction with the subsequent release of vasoactive substances during and after cardiopulmonary bypass. Fifty-one patients scheduled for coronary artery bypass grafting were perfused

  18. ADRIAMYCIN-LOADED ALBUMIN-HEPARIN CONJUGATE MICROSPHERES FOR INTRAPERITONEAL CHEMOTHERAPY

    CREMERS, HFM; SEYMOUR, LW; LAM, K; LOS, G; KWON, G; BAE, YH; KIM, SW; FEIJEN, J

    1994-01-01

    Adriamycin-loaded albumin-heparin conjugate microspheres (ADR-AHCMS) were evaluated as possible intraperitoneal (i.p.) delivery systems for site-specific cytotoxic action. The biocompatibility of the microspheres after intraperitoneal injection was tested first. 1 day after i.p. administration of

  19. Release of proteins via ion exchange from albumin-heparin microspheres

    Kwon, Glen S.; Bae, You Han; Cremers, H.F.M.; Cremers, Harry; Feijen, Jan; Kim, Sung Wan

    1992-01-01

    Albumin-heparin and albumin microspheres were prepared as ion exchange gels for the controlled release of positively charged polypeptides and proteins. The adsorption isotherms of chicken egg and human lysozyme, as model proteins, on microspheres were obtained. An adsorption isotherm of chicken egg

  20. Role of the A+ helix in heparin binding to protein C inhibitor

    Elisen, M. G.; Maseland, M. H.; Church, F. C.; Bouma, B. N.; Meijers, J. C.

    1996-01-01

    Interactions between proteins and heparin(-like) structures involve electrostatic forces and structural features. Based on charge distributions in the linear sequence of protein C inhibitor (PCI), two positively charged regions of PCI were proposed as possible candidates for this interaction. The

  1. Effect of low-dose heparin on urinary albumin excretion in insulin-dependent diabetes mellitus

    Myrup, B.; Hansen, P.M.; Jensen, T.; Kofoed-Enevoldsen, A.; Feldt-Rasmussen, B.; Gram, J.; Kluft, C.; Jespersen, J.; Deckert, T.

    1995-01-01

    We investigated the effect of heparin on urinary albumin excretion in patients with insulin-dependent diabetes mellitus. 39 patients with persistent urinary albumin excretion of 30-300 mg/24 h were randomly treated for 3 months with subcutaneous injections twice daily of isotonic saline, 5000 IU

  2. Heparin-Functionalized chitosan/ κ-carrageenan complexes as potential scaffolds for tissue engineering

    Dofeliz, Joni L.; Rojas, Nina Rosario L.

    2015-01-01

    Cell-based approaches to tissue regeneration are playing an increasingly important role in bone and cartilage repair. This is made possible through the use of growth factors, which are signaling molecules that induce a number of effects such as cell proliferation, migration and differentiation. But problems arise as these growth factors tend to be expensive, short-lived and slow moving through the extracellular matrix, making them very inefficient in their current form of introduction. One such growth factor is basic fibroblast growth factor (bFGF). The general objective of this study is to construct heparin-functionalized chitosan/κ-carrageenan scaffolds, which when bound to basic fibroblast growth factor (bFGF), may be used in the culture of mesenchymal stem cells for differentiation into cartilage. In this study, gels of semi-interpenetrating networks (semi-IPN) of chitosan and κ-carrageenan (2:4:1 blend ration) were prepared using calcium chloride as a cross-linker. The gels were then functionalized with heparin, which is known for its growth factor binding ability, using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) as cross-linker. The functionalized gels were then reshaped into scaffold on the wells of 48-well plates through freeze-dry method. The scaffolds were found to be realatively porous with pore sizes larger than 100 μm which satisfies the requirements for cell culture. Subsequent thermogravimetric analysis shows that the scaffolds were relatively stable with a degradation temperature of 277°C. Additionally, there was no observable separation of the individual degradation temperatures of chitosan and κ-carrageenan, confirming that a single miscible phase in the form of a semi-IPN structure was created. Results of scanning electron microscopy also showed that the scaffolds were stable under 2 hours of UV sterilization. The FTIR spectra of the heparinized PEC showed characteristic absorption bands (S=O asymetric stretch) in the area of 1160

  3. Heparin-binding peptide amphiphile supramolecular architectures as platforms for angiogenesis and drug delivery

    Chow, Lesleyann W.

    A fascinating phenomenon in nature is the self-assembly of molecules into a functional, hierarchical structure. In the past decade, the Stupp Laboratory has developed several classes of self-assembling biomaterials, one of which is the synthetic peptide amphiphile (PA). Self-assembling PAs are attractive and versatile biomolecules that can be customized for specific applications in regenerative medicine. In particular, a heparin-binding peptide amphiphile (HBPA) containing a specific heparin-binding peptide sequence was used here to induce angiogenesis and serve as a delivery vehicle for growth factors and small hydrophobic molecules. Throughout this dissertation, the HBPA/heparin system is used in different architectures for a variety of regenerative medicine applications. In one aspect of this work, hybrid scaffolds made from HBPA/heparin gelled on a poly(L-lactic acid) (PLLA) fiber mesh were used to promote angiogenesis to facilitate pancreatic islet transplantation for the treatment of type 1 diabetes. Delivery of growth factors with HBPA/PLLA scafflolds increased vessel density in vivo and correlated with improved transplant outcomes in a streptozotocin-induced diabetic mouse model. Soluble HBPA nanofiber architectures were also useful for islet transplantation applications. These nanofibers were used at concentrations below gelation to deliver growth factors into the dense islet cell aggregate, promoting cell survival and angiogenesis in vitro. The nanostructures infiltrated the islets and promoted the retention of heparin and growth factors within the islet. Another interesting growth factor release system discussed here is the HBPA membrane structure. HBPA was found to self-assemble with hyaluronic acid, a large biopolymer found in the body, into macroscopic, hierarchically-ordered membranes. Heparin was incorporated into these membranes and affected the membrane's mechanical properties and growth factor release. Human mesenchymal stem cells were also shown

  4. Heparin for prolonging peripheral intravenous catheter use in neonates: a randomized controlled trial.

    Upadhyay, A; Verma, K K; Lal, P; Chawla, D; Sreenivas, V

    2015-04-01

    To determine the efficacy of heparinized saline administered as intermittent flush on functional duration of the peripheral intravenous catheter (PIVC) in neonates. Randomized, double-blind and placebo-controlled trial. Neonatal intensive care unit of a teaching hospital. Term and preterm neonates born at >32 weeks of gestation who required PIVC only for intermittent administration of antibiotics. Eligible neonates were randomized to receive 1 ml of either heparinized saline (10 U ml(-1)) (n=60) or normal saline (n=60) every 12 h before and after intravenous antibiotics. Functional duration of first peripheral intravenous catheter. A total of 120 neonates were randomized to two groups of 60 neonates each. The mean (s.d.) of age of babies in case and control group was 5.7 (2.5) days and 4.6 (3.1) days, respectively. The average weight of babies in both the groups was 2.1 kg. Mean functional duration of first catheter was more in heparinized saline group, mean (s.d.) of 71.68 h  (27.3) as compared with 57.7 h (23.6) in normal saline group (P<0.005). The mean (95% confidence interval) difference in functional duration in the two groups was 13.9 h (4.7-23.15). Mean duration of patency for any catheter was also significantly more in heparinized saline group than control group. Heparinized saline flush increases the functional duration of peripheral intravenous catheter.

  5. Selective interaction of heparin with the variable region 3 within surface glycoprotein of laboratory-adapted feline immunodeficiency virus.

    Qiong-Ying Hu

    Full Text Available Heparan sulfate proteoglycans (HSPG can act as binding receptors for certain laboratory-adapted (TCA strains of feline immunodeficiency virus (FIV and human immunodeficiency virus (HIV. Heparin, a soluble heparin sulfate (HS, can inhibit TCA HIV and FIV entry mediated by HSPG interaction in vitro. In the present study, we further determined the selective interaction of heparin with the V3 loop of TCA of FIV. Our current results indicate that heparin selectively inhibits infection by TCA strains, but not for field isolates (FS. Heparin also specifically interferes with TCA surface glycoprotein (SU binding to CXCR4, by interactions with HSPG binding sites on the V3 loop of the FIV envelope protein. Peptides representing either the N- or C-terminal side of the V3 loop and containing HSPG binding sites were able to compete away the heparin block of TCA SU binding to CXCR4. Heparin does not interfere with the interaction of SU with anti-V3 antibodies that target the CXCR4 binding region or with the interaction between FS FIV and anti-V3 antibodies since FS SU has no HSPG binding sites within the HSPG binding region. Our data show that heparin blocks TCA FIV infection or entry not only through its competition of HSPG on the cell surface interaction with SU, but also by its interference with CXCR4 binding to SU. These studies aid in the design and development of heparin derivatives or analogues that can inhibit steps in virus infection and are informative regarding the HSPG/SU interaction.

  6. Dual Affinity Heparin-Based Hydrogels Achieve Pro-Regenerative Immunomodulation and Microvascular Remodeling.

    Ogle, Molly E; Krieger, Jack R; Tellier, Liane E; McFaline-Figueroa, Jennifer; Temenoff, Johnna S; Botchwey, Edward A

    2018-04-09

    The immune response to biomaterial implants critically regulates functional outcomes such as vascularization, transplant integration/survival, and fibrosis. To create "immunologically smart" materials, the host-material response may be engineered to optimize the recruitment of pro-regenerative leukocyte subsets which mature into corresponding wound-healing macrophages. We have recently identified a unique feature of pro-regenerative Ly6C low monocytes that is a higher expression of both the bioactive lipid receptor sphingosine-1-phosphate receptor 3 (S1PR3) and the stromal derived factor-1α (SDF-1α) receptor CXCR4. Therefore, we designed a bifunctional hydrogel to harnesses a mechanistic synergy between these signaling axes to enhance the recruitment of endogenous pro-regenerative monocytes. To overcome the challenge of codelivering two physiochemically distinct molecules-a large hydrophilic protein and hydrophobic small molecule-we engineered a dual affinity hydrogel that exploits the growth factor affinity of a heparin derivative (Hep -N ) and lipid chaperone activity of albumin. The sphingosine analog FTY720 and SDF-1α are successfully loaded and coreleased from the Hep -N -functionalized PEG-DA hydrogels while maintaining bioactivity. Placement of these hydrogels into a murine partial thickness skin wound demonstrates that corelease of FTY720 and SDF-1α yields superior recruitment of myeloid cells to the implant interface compared to either factor alone. Although in vivo delivery of FTY720 or SDF-1α individually promotes the enhanced recruitment of Ly-6C low anti-inflammatory monocytes, codelivery enhances the early accumulation and persistence of the differentiated wound healing CD206 + macrophages in the tissue surrounding the gel. Co-delivery similarly promoted the synergistic expansion of vasculature adjacent to the implant, a key step in tissue healing. Taken together, these findings suggest that the combination of chemotactic molecules may provide

  7. 111In-labeled platelets: effects of heparin on uptake by venous thrombi and relationship to the activated partial thromboplastin time

    Fedullo, P.F.; Moser, K.M.; Moser, K.S.; Konopka, R.; Hartman, M.T.

    1982-01-01

    The goal of heparin therapy in deep vein thrombosis is to prevent thrombus extension. The relationship between thrombus extension and the results of coagulation tests used to monitor heparin therapy is unclear. To explore this relationship, we studied the effect of several heparin regimens on the accretion of 111 In-labeled platelets on fresh venous thrombi, as detected by gamma imaging, and monitored the activated partial thromboplastin time (APTT). Six dogs were treated with a 300-U/kg bolus of heparin followed by a 90-U/kg/hour heparin infusion, a dose of heparin sufficient to increase the APTT to levels greater than eight times baseline (APTT ratio); platelet accretion (thrombus imaging) occurred only after the heparin effect was reversed with protamine sulfate. Nineteen dogs were treated with a 150-U/kg bolus of heparin followed by a 4-hour, 45-U/kg/hour heparin infusion; a thrombus was demonstrated only after protamine injection in 12 (mean APTT ratio 1.3 +/- 0.19) and before protamine injection in seven. In thirteen of these 19 dogs, 30 minutes separated the platelet injection from heparin therapy, while in six this duration was less than 30 minutes. In four of these six dogs, thrombi were demonstrated before protamine therapy and at APTT ratios greater than 3.0. Finally, 10 dogs were treated with a 100-U/kg bolus followed by a 3-hour, 50-U/kg/hour heparin infusion, after which the APTT was allowed to return to baseline values spontaneously. In all 10 dogs, a thrombus was demonstrated only after cessation of the heparin infusion, and at a mean APTT ratio of 1.4 +/- 0.15 times baseline. These results suggest that, except with very early platelet injection, platelet accretion by thrombi is consistently inhibited by heparin at APTT ratios greater than 2.5. Platelet accretion by venous thrombi occurs within narrow limits of heparin effect as reflected by the APTT

  8. Subtle differences in commercial heparins can have serious consequences for cardiopulmonary bypass patients: A randomized controlled trial.

    Arsenault, Kyle A; Paikin, Jeremy S; Hirsh, Jack; Dale, Brian; Whitlock, Richard P; Teoh, Kevin; Young, Ed; Ginsberg, Jeffrey S; Weitz, Jeffrey I; Eikelboom, John W

    2012-10-01

    To compare the potency, reversibility, and perioperative bleeding risk of Hepalean with those of PPC heparin. Because in vitro testing failed to detect differences in the potency or protamine reversibility of the 2 heparin preparations, we conducted a parallel group, single-center, double-blind, randomized, controlled trial to compare the anticoagulant effects of Hepalean to those of PPC heparin in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass. From June 1, 2011, to June 30, 2011, we randomly assigned 11 patients to receive PPC heparin and 10 to receive Hepalean. Despite similar initial doses of heparin, the median initial activated clotting time was numerically lower in the PPC heparin group than in the Hepalean group (median, 516.0 seconds; interquartile range, 481.0-633.0; vs median, 584.0 seconds, interquartile range, 520.0-629.0; P = .418). Those given PPC heparin required a greater total heparin dose (median, 46,000.0 U; interquartile range, 39,500.0-60,000.0 vs median, 34,500.0 U; interquartile range, 32,250.0-37,000.0; P = .011) and a greater dose of heparin per kilogram than those given Hepalean (median, 572.9 U/kg; interquartile range, 443.0-659.7 vs median, 401.1 U/kg; interquartile range, 400.0-419.4; P = .003). The key secondary results included an increased median total protamine dose (median, 600.0 mg; interquartile range, 550.0-700.0; vs median, 500.0 mg; interquartile range, 425.0-542.5; P = .026) and a trend toward increased chest tube output within 24 hours (median, 830.0 mL; interquartile range, 425.0-1135.0; vs median, 702.5 mL; interquartile range, 550.0-742.5; P = .324). PPC heparin use was associated with greater heparin and protamine dose requirements than Hepalean. These findings indicate that heparin preparations are not interchangeable and suggest that a direct comparison of the potency with the brand in use is needed if a change is made to ensure that the agents exert similar anticoagulant

  9. Profiling analysis of low molecular weight heparins by multiple heart-cutting two dimensional chromatography with quadruple time-of-flight mass spectrometry.

    Ouyang, Yilan; Zeng, Yangyang; Rong, Yinxiu; Song, Yue; Shi, Lv; Chen, Bo; Yang, Xinlei; Xu, Naiyu; Linhardt, Robert J; Zhang, Zhenqing

    2015-09-01

    Low molecular weight heparins (LMWHs) are polydisperse and microheterogenous mixtures of polysaccharides used as anticoagulant drugs. Profiling analysis is important for obtaining deeper insights into the structure of LMWHs. Previous oligosaccharide mapping methods are relatively low resolution and are unable to show an entire picture of the structural complexity of LMWHs. In the current study a profiling method was developed relying on multiple heart-cutting, two-dimensional, ultrahigh performance liquid chromatography with quadruple time-of-flight mass spectrometry. This represents an efficient, automated, and robust approach for profiling LMWHs. Using size-exclusion chromatography and ion-pairing reversed-phase chromatography in a two-dimensional separation, LMW components of different sizes and LMW components of the same size but with different charges and polarities can be resolved, providing a more complete picture of a LMWH. Structural information on each component was then obtained with quadrupole time-of-flight mass spectrometry. More than 80 and 120 oligosaccharides were observed and unambiguously assigned from the LMWHs, nadroparin and enoxaparin, respectively. This method might be useful for quality control of LMWHs and as a powerful tool for heparin-related glycomics.

  10. Gene therapy for C-26 colon cancer using heparin-polyethyleneimine nanoparticle-mediated survivin T34A

    Zhang L

    2011-10-01

    Full Text Available Ling Zhang1,*, Xiang Gao1,2,*, Ke Men1, BiLan Wang1, Shuang Zhang1, Jinfeng Qiu1, Meijuan Huang1, MaLing Gou1, Ning Huang2, ZhiYong Qian1, Xia Zhao1, YuQuan Wei11State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, 2Department of Pathophysiology, College of Preclinical and Forensic Medical Sciences, Sichuan University, Chengdu, People’s Republic of China*These authors contributed equally to this workBackground: Gene therapy provides a novel method for the prevention and treatment of cancer, but the clinical application of gene therapy is restricted, mainly because of the absence of an efficient and safe gene delivery system. Recently, we developed a novel nonviral gene carrier, ie, heparin-polyethyleneimine (HPEI nanoparticles for this purpose.Methods and results: HPEI nanoparticles were used to deliver plasmid-expressing mouse survivin-T34A (ms-T34A to treat C-26 carcinoma in vitro and in vivo. According to the in vitro studies, HPEI nanoparticles could efficiently transfect the pGFP report gene into C-26 cells, with a transfection efficiency of 30.5% ± 2%. Moreover, HPEI nanoparticle-mediated ms-T34A could efficiently inhibit the proliferation of C-26 cells by induction of apoptosis in vitro. Based on the in vivo studies, HPEI nanoparticles could transfect the Lac-Z report gene into C-26 cells in vivo. Intratumoral injection of HPEI nanoparticle-mediated ms-T34A significantly inhibited growth of subcutaneous C-26 carcinoma in vivo by induction of apoptosis and inhibition of angiogenesis.Conclusion: This research suggests that HPEI nanoparticle-mediated ms-T34A may have a promising role in C-26 colon carcinoma therapy.Keywords: gene therapy, mouse survivin-T34A, colon cancer, polyethyleneimine, nanoparticles, cancer therapy

  11. [Morphology research of the rat sciatic nerve bridged by collage-heparin sulfate scaffold].

    Wang, Shu-sen; Hu, Yun-yu; Luo, Zhuo-jing; Chen, Liang-wei; Liu, Hui-ling; Meng, Guo-lin; Lü, Rong; Xu, Xin-zhi

    2005-04-15

    To observe the treating effect of collage-heparin sulfate after the 10 mm rat sciatic nerve defect was bridged by it. A new kind of nervous tissue engineering scaffold was produced by freeze-drying technique from collagen-heparin sulfate. Thirty-two SD rats were randomly divided into A, B, C and D groups. Sciatic nerve defect in group A was bridged by collagen-heparin sulfate. In group B, sciatic nerve was bridged by auto-nerve transplantation. Group C was the blank control group. Animals in group D were normal. And 10 mm sciatic nerve defect was bridged in the experiment. Thirty-six weeks after the operation, the experimental animals were detected by HRP labeled retrograde trace, HE staining, toluidine staining, silvering staining, S100, GAP-43 and NF immunohistological staining, MBP immunofluorescence staining and transmission electron microscope to observe the nerve regeneration inducing effect of this new scaffold. Nine months after operation, the collage-heparin sulfate scaffold was replaced by newly regenerated nerve. The number of HRP labeled spinal cord anterior horn cells and the area of sensation nerve fiber at the posterior horn were similar with that was repaired by auto-nerve. GAP-43, NF and S100 labeled regenerated nerve fiber had passed the total scaffold and entered the distal terminal. The regenerated nerve fibers were paralleled, lineage arranged, coincide with the prearranged regenerating "channel" in the collagen-heparin sulfate scaffold. MBP immunofluorescence staining also proved that the newly regenerated nerve fiber could be ensheathed. In the experimental group, the area of myelinated nerve fiber and the thickness of the myelin sheath had no obvious difference with that of the group repaired by auto-nerve, except that the density of the regenerated myelinated sheath fiber was lower than that of the control group. Nervous tissue engineering scaffold produced by collagen-heparin sulfate can guide the regeneration of nerve fibers. The nerve

  12. Strongly coupled CdS/graphene quantum dots nanohybrids for highly efficient photocatalytic hydrogen evolution: unraveling the essential roles of graphene quantum dots

    Lei, Yonggang; Yang, Cheng; Hou, Jianhua; Wang, Fang; Min, Shixiong; Ma, Xiaohua; Jin, Zhiliang; Xu, Jing; Lu, Gongxuan; Huang, Kuo-Wei

    2017-01-01

    hydrothermal method in which the crystallization of CdS precursor and coupling of GQDs could be accomplished in one-step. GQDs are firmly decorated on the surface of CdS nanoparticles, forming “dot-on-particle” heterodimer structures. GQDs have no significant

  13. Efficient one-pot enzymatic synthesis of alpha-(1 -> 4)-glucosidic disaccharides through a coupled reaction catalysed by Lactobacillus acidophilus NCFM maltose phosphorylase

    Nakai, Hiroyuki; Dilokpimol, Adiphol; Abou Hachem, Maher

    2010-01-01

    Lactobacillus acidophilus NCFM maltose phosphorylase (LaMalP) of glycoside hydrolase family 65 catalysed enzymatic synthesis of alpha-(1 -> 4)-glucostdic disacchandes from maltose and five monosacchandes in a coupled phosphorolysis/reverse phosphorolysis one-pot reaction Thus phosphorolysis...

  14. Using Pd-salen complex as an efficient catalyst for the copper- and solvent-free coupling of acyl chlorides with terminal alkynes under aerobic conditions

    Mohammad

    2010-01-01

    The palladium-salen complex palladium(Ⅱ) N,N'-bis{[5-(triphenylphosphonium)-methyl]salicylidene}-l,2-ethanediamine chloride was found to be a highly active catalyst for the copper- and solvent-free coupling reaction of terminal alkynes with different acyl chlorides in the presence of triethylamine as base, giving excellent ynones under aerobic conditions.

  15. Subnanometer Gold Clusters on Amino-Functionalized Silica: An Efficient Catalyst for the Synthesis of 1,3-Diynes by Oxidative Alkyne Coupling

    Vilhanová, B.; Václavík, Jiří; Artiglia, L.; Ranocchiari, M.; Togni, A.; van Bokhoven, J. A.

    2017-01-01

    Roč. 7, č. 5 (2017), s. 3414-3418 ISSN 2155-5435 Institutional support: RVO:61388963 Keywords : alkyne coupling * gold * heterogeneous catalysis * hypervalent iodine * subnanometer Subject RIV: CC - Organic Chemistry OBOR OECD: Organic chemistry Impact factor: 10.614, year: 2016

  16. THE DEVELOPMENT OF IODINE BASED IMPINGER SOLUTIONS FOR THE EFFICIENT CAPTURE OF HG USING DIRECT INJECTION NEBULIZATION - INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY ANALYSIS

    Inductively coupled plasma mass spectrometry (ICP/MS) with direct injection nebulization (DIN) was used to evaluate novel impinger solution compositions capable of capturing elemental mercury (Hgo) in EPA Method 5 type sampling. An iodine based impinger solutoin proved to be ver...

  17. Prolonged Activated Clotting Time after Protamine Administration Does Not Indicate Residual Heparinization after Cardiopulmonary Bypass in Pediatric Open Heart Surgery.

    Yamamoto, Tomohiro; Wolf, Hans-Gerd; Sinzobahamvya, Nicodème; Asfour, Boulos; Hraska, Victor; Schindler, Ehrenfried

    2015-08-01

    In open heart surgery, heparinization is commonly neutralized using an empirical heparin:protamine ratio ranging between 1:1 and 1:1.5. However, these ratios may result in protamine overdose that should be avoided for its negative side effects on the coagulation system. This study aimed to indicate the appropriate treatment for prolonged activated clotting time (ACT) after protamine administration following cardiopulmonary bypass (CPB) in pediatric open heart surgery by investigating the underlying reasons for it. Twenty-seven children (open heart surgery were included. Heparin was administered only before CPB (400 IU/kg) and in the pump priming volume for CPB (2,000 IU) and was neutralized by 1:1 protamine after CPB. The blood heparin concentration was measured using anti-Xa assay. ACT and blood concentrations of heparin, coagulation factors, thrombin-antithrombin complex, and prothrombin fragment 1 + 2 were assessed. A rotational thromboelastometry (ROTEM; Tem International GmbH, München, Bayern, Germany) was used to confirm the coagulation status and residual heparin after protamine administration. Anti-Xa assay showed that there is no residual heparin in the blood after 1:1 protamine administration. Nevertheless, ACT (128.89 ± 3.09 seconds before heparin administration) remained prolonged (177.14 ± 5.43 seconds at 10 minutes after protamine, 182.00 ± 5.90 seconds at 30 minutes after protamine). The blood concentrations of coagulation factors were significantly lower than those before heparin administration (p < 0.01). The low FIBTEM MCF of ROTEM (4.43 ± 0.32 mm) at 10 minutes after protamine indicated low fibrinogen concentration. Prolonged ACT after heparin neutralization by 1:1 protamine administration does not necessarily indicate residual heparin, but low blood concentrations of coagulation factors should be considered as a reason as well. Accordingly, supply of coagulation factors instead of additional protamine should be

  18. Taurolidine lock is superior to heparin lock in the prevention of catheter related bloodstream infections and occlusions.

    Evelyn D Olthof

    Full Text Available Patients on home parenteral nutrition (HPN are at risk for catheter-related complications; mainly infections and occlusions. We have previously shown in HPN patients presenting with catheter sepsis that catheter locking with taurolidine dramatically reduced re-infections when compared with heparin. Our HPN population therefore switched from heparin to taurolidine in 2008. The aim of the present study was to compare long-term effects of this catheter lock strategy on the occurrence of catheter-related bloodstream infections and occlusions in HPN patients.Data of catheter-related complications were retrospectively collected from 212 patients who received HPN between January 2000 and November 2011, comprising 545 and 200 catheters during catheter lock therapy with heparin and taurolidine, respectively. We evaluated catheter-related bloodstream infection and occlusion incidence rates using Poisson-normal regression analysis. Incidence rate ratios were calculated by dividing incidence rates of heparin by those of taurolidine, adjusting for underlying disease, use of anticoagulants or immune suppressives, frequency of HPN/fluid administration, composition of infusion fluids, and duration of HPN/fluid use before catheter creation.Bloodstream infection incidence rates were 1.1/year for heparin and 0.2/year for taurolidine locked catheters. Occlusion incidence rates were 0.2/year for heparin and 0.1/year for taurolidine locked catheters. Adjusted incidence ratios of heparin compared to taurolidine were 5.9 (95% confidence interval, 3.9-8.7 for bloodstream infections and 1.9 (95% confidence interval, 1.1-3.1 for occlusions.Given that no other procedural changes than the catheter lock strategy were implemented during the observation period, these data strongly suggest that taurolidine decreases catheter-related bloodstream infections and occlusions in HPN patients compared with heparin.

  19. Basic fibroblast growth factor binds to subendothelial extracellular matrix and is released by heparitinase and heparin-like molecules

    Bashkin, P.; Doctrow, S.; Klagsbrun, M.; Svahn, C.M.; Folkman, J.; Vlodavsky, I.

    1989-01-01

    Basic fibroblast growth factor (bFGF) exhibits specific binding to the extracellular matrix (ECM) produced by cultured endothelial cells. Binding was saturable as a function both of time and of concentration of 125 I-bFGF. Scatchard analysis of FGF binding revealed the presence of about 1.5 x 10 12 binding sites/mm 2 ECM with an apparent k D of 610 nM. FGF binds to heparan sulfate (HS) in ECM as evidenced by (i) inhibition of binding in the presence of heparin or HS at 0.1-1 μg/mL, but not by chondroitin sulfate, keratan sulfate, or hyaluronic acid at 10 μg/mL, (ii) lack of binding to ECM pretreated with heparitinase, but not with chondroitinase ABC, and (iii) rapid release of up to 90% of ECM-bound FGF by exposure to heparin, HS, or heparitinase, but not to chondroitin sulfate, keratan sulfate, hyaluronic acid, or chondroitinase ABC. Oligosaccharides derived from depolymerized heparin, and as small as the tetrasaccharide, released the ECM-bound FGF, but there was little or no release of FGF by modified nonanticoagulant heparins such as totally desulfated heparin, N-desulfated heparin, and N-acetylated heparin. FGF released from ECM was biologically active, as indicated by its stimulation of cell proliferation and DNA synthesis in vascular endothelial cells and 3T3 fibroblasts. Similar results were obtained in studies on release of endogenous FGF-like mitogenic activity from Descement's membranes of bovine corneas. It is suggested that ECM storage and release of bFGF provide a novel mechanism for regulation of capillary blood vessel growth. Whereas ECM-bound FGF may be prevented from acting on endothelial cells, its displacement by heparin-like molecules and/or HS-degrading enzymes may elicit a neovascular response

  20. Heparin modulates the endopeptidase activity of Leishmania mexicana cysteine protease cathepsin L-Like rCPB2.8.

    Wagner A S Judice

    Full Text Available Cysteine protease B is considered crucial for the survival and infectivity of the Leishmania in its human host. Several microorganism pathogens bind to the heparin-like glycosaminoglycans chains of proteoglycans at host-cell surface to promote their attachment and internalization. Here, we have investigated the influence of heparin upon Leishmania mexicana cysteine protease rCPB2.8 activity.THE DATA ANALYSIS REVEALED THAT THE PRESENCE OF HEPARIN AFFECTS ALL STEPS OF THE ENZYME REACTION: (i it decreases 3.5-fold the k 1 and 4.0-fold the k -1, (ii it affects the acyl-enzyme accumulation with pronounced decrease in k 2 (2.7-fold, and also decrease in k 3 (3.5-fold. The large values of ΔG  =  12 kJ/mol for the association and dissociation steps indicate substantial structural strains linked to the formation/dissociation of the ES complex in the presence of heparin, which underscore a conformational change that prevents the diffusion of substrate in the rCPB2.8 active site. Binding to heparin also significantly decreases the α-helix content of the rCPB2.8 and perturbs the intrinsic fluorescence emission of the enzyme. The data strongly suggest that heparin is altering the ionization of catalytic (Cys(25-S(-/(His(163-Im(+ H ion pair of the rCPB2.8. Moreover, the interaction of heparin with the N-terminal pro-region of rCPB2.8 significantly decreased its inhibitory activity against the mature enzyme.Taken together, depending on their concentration, heparin-like glycosaminoglycans can either stimulate or antagonize the activity of cysteine protease B enzymes during parasite infection, suggesting that this glycoconjugate can anchor parasite cysteine protease at host cell surface.